Yamini Ai Board Review 1A

Front 1

Types of Adjuvants

Back 1

Alum
Freund's adjuvant (emulsified bacterial products)
Incomplete Freund's (water in oil)
Ribi adjuvant (Squalene–Tween80, water, oil)
Titermax (copolymers POP and POE)

Front 2

Strep Pyogenes superantigen toxin and disease

Back 2

SEC2 ––> food poisoning
TSST ––> toxic shock syndrome
SPE–C ––> strep toxic schock syndrome

Front 3

Super antigens bind _____ on TCRS and ____ on MHC

Back 3

V–beta region of TCR on the CDR4 and outside the peptide binding groove on Beta2 region of MHC

Front 4

Characteristics of epitopes recognized by
(1) B cells
(2) T cells

Back 4

(1) B cells ––> linear determinants or tertiary, carbs/4–8 aa residues / nucleic acids

(2) T cells ––> linear only, amino acids only
(8–30 aa in length; MHC Class I 8–11, MHC Class II 10–30)

Front 5

Examples of Conjugated vaccines and purpose

Back 5

Prevnar 13 (pneumococcal)
Hib
MCV4–Menactra, Menveo (meningococcal)

T independent antigens linked to a carrier protein ––> triggers a T dependent response and memory

Front 6

Examples of polysaccharide vaccines and purpose for testing

Back 6

MSPV4 (menomune) ––> meningococcal vaccine
Pneumococcal vaccine 23 valent

Front 7

Type of cell that recognizes each antigen
(1) Protein
(2) Polysaccharide
(3) Nucleic acid
(4) Lipids

Back 7

(1) T cells and B cells
(2) Marginal zone B cells and B1 cells (T indpdt)
(3) CTLs and DCs (via TLR9)
(4) NKT cells (via CD1) and gamma–delta T cells

Front 8

MHC Class I
(1) Expression
(2) Genes
(3) polypeptide chains
(4) CD restriction
(5) Peptide binding site
(6) Antigenic sampling
(7) Inducting cytokines

Back 8

(1) Most nucleated cells
(2) HLA–A, B, C
(3) CD8 binds a3
(4) alpha chain (a1, a2,a3) and beta–2 microglobulin
(5) alpha 1 and 2 to peptides 8–11 aa
(6) intracellular
(7) IFN alpha, beta, gamma

Front 9

MHC Class II
(1) Expression
(2) Genes
(3) polypeptide chains
(4) CD restriction
(5) Peptide binding site
(6) Antigenic sampling
(7) Inducting cytokines

Back 9

(1) APCs (DCs, macs, B cells), thymic epithelia, activated T cells
(2) HLA–DP, DQ, DR
(3) CD4 binds beta–2
(4) alpha chain (a1, a2) and beta chain (b1, b2)
(5) alpha 1 & beta 1 to peptides 10–30 aa
(6) extracellular
(7) IFN gamma

Front 10

Products of MHC Class III region

Back 10

Complement (Factor B, C4a, C4b, C2)
Cytokines (TNF alpha, lymphotoxins alpha, beta)
Heat Shock Proteins

Front 11

Products of MHC Class I region

Back 11

HLA A, B, C and Class I–like proteins...
HLA E ––> NK cell recognition (via NKG2C for activation and NKG2A/B for inhibition)
HLA F ––> localize to ER and golgi, also protects fetus from rejection
HLA G ––> on fetal derived placental cells, protects fetus from rejection
HLA H ––> iron metabolism

Front 12

Products of MHC Class II region

Back 12

DP, DQ, DR
TAP1 and TAP2 ––> two subunits that transport antigen peptides into ER

Front 13

Steps of MHC Class I pathway

Back 13

1. New MHC–I stay in ER b/c of calnexin, calreticulin, ERP57, tapasin
2. cytoplasmic proteins degraded by proteasome (made up of subunits LMPs)
3. peptides transported to ER by TAP proteins
4. peptides loaded on to NEW MHC
5. MHC–I and antigen are transported to surface

Front 14

How HSV and CMV avoid presentation

Back 14

HSV blocks TAP transportation (prevents antigen binding with MHC–I)
CMV removes MHC–I from the ER

Front 15

Steps of MHC Class II pathway

Back 15

1. extracellular antigen endocytosed into phagosomes
2. Phagosome and lysosome fusion ––> degradation of proteins
3. new MHC–II made in ER and transported to phagolysosome. Binding cleft occupied by invariant chain (Ii)
4. Ii degraded, leaving behind CLIP
5. HLA–DM removes CLIP and peptides are loaded
6. MHC class II and peptide are transported to surface

Front 16

MHC Class I deficiency features (name, mutation, sx, lab, tx)

Back 16

Name: Bare lymphocyte syndrome
Common: Both aut rec
Mutation: TAP.
Sx: inopulm infxn, granulomatous skin lesions, necrobiosis lipoidica
Lab: low CD8, no MHCI
Tx: treat pulm infections like CF (airway clearance and chest PT)

Front 17

MHC Class II deficiency features (name, mutation, sx, lab, tx)

Back 17

Name: Bare lymphocyte syndrome
Common: Both aut rec
Mutation: TFs required for MHC expression (MHC2TA, RFX5, FRXAP, FRXANK)
Sx: diarrhea, HSM, incr LFTs, sclerosing cholangitis (Cryptosporidium), pulm infxn(PJP, encapsulated bacteria, HSV, RSV), meningitis
Lab: low CD4, reversed CD4:8, no HLA DR/DP/DQ on lymphocytes, hypogam, missing germinal centers
Tx: HSCT

Front 18

AIRE function and mutation leads to...

Back 18

Fxn: promotes expression of nonthymic antigens in the thymus.
APS (autoimmune polyglandular syndrome)
lymphocytes not deleted or tolerized to endocrine–related self–anteigens

Front 19

Maintenance of Anergy in T cells requires...

Back 19

Blockade of TCR signaling
Ubiquitin ligases (target proteins for degradtion)
Inhibitor costim (CTLA4 & PD–1)
DCs expressing self antigen w/o co–stim to maintain anergy

Front 20

T cell selection fate depends on _____ and ______.
Three fates are _____ and require _______.

Back 20

Concentration and affinity.
Strong affinity to self antigen ––> apoptosis
Weak affinity ––> positive selection ––> effector cells
Intermediate affinity ––> T regs.

Front 21

T reg markers
T reg survival factors
T reg maintenance factors

Back 21

CD4, CD25 (IL–2R alpha chain), FoxP3
IL–2, TGF–beta
IL–10, TGF–beta

Front 22

IPEX syndrome (mutation, features

Back 22

FoxP3 mutation
Autoimmune disorder with triad of watery diarrhea, eczema, endocrinopathy

Front 23

Neg selection via apoptosis happens via these pathways

Back 23

1. Bim (part of Bcl–2 family) ––> apoptosis via mitochondrial pathway
2. Fas ligand (CD95L) on T cells ––> interacts with Fas (CD95) on same cell or nearby cells ––> apoptosis via caspase system. If caspase/FAS absent ––> ALPS

Front 24

Mechanism of peripheral B cell tolerance

Back 24

chronic antigen recognition without T cell help ––> downregulates CXCR5 ––> inhibits B cell homing and B/T interaction ––> death

Front 25

What types of nucleic acids are A, G, T, C?

Back 25

A & G are purines. T&C are pyrimidines (along with uracil for RNA)

Front 26

In COPD, histone deacetylation is increased/decreased?

Back 26

Decreased deacetylation = increased gene expression.

Front 27

SNPs and Disease: Fillagrin

Back 27

Disease: Eczema
Gene: fillagrin
Function: epidermal barrier

Front 28

SNPs and Disease: ORMDL3

Back 28

Disease: Asthma
Gene: 17q12–21
Function: unknown

Front 29

SNPs and Disease: CD14

Back 29

Disease: Incr and decr Atopy/Asthma
Gene: 5q22–32
Function: LPS receptor

Front 30

SNPs and Disease: CCR5

Back 30

Disease: protects a/nonatopic asthma
Gene: 3p21–22
Function: chemokine receptor

Front 31

SNPs and Disease: TLR7 and 8

Back 31

Disease: Incr risk of asthma/AR/AD/specific IgE
Gene: Xp22
Function: pattern recognition receptor for viral ssRNA

Front 32

SNPs and Disease: IL–13

Back 32

Disease: Incr risk asthma, hyperreactivity, SPT responsiveness. Linked to singulair response.
Gene: 5q31
Function: Induces IgE secretion, mucus, collagen synthesis

Front 33

SNPs and Disease: Beta–2 adrenergic receptor

Back 33

Disease: Arg/arg ––> decreased albuterol response (v. gly/gly 16)
Gene: ADRB2
Function: adrenaline/noradrenaline receptor

Front 34

SNPs and Disease: Type 1 transmembrane protein

Back 34

Disease: Incr risk asthma and hyperreactive airway
Gene: ADAM33
Function: Cell–to–cell interactions

Front 35

Histone __________ opens chromatin to allow transcription.

Back 35

Acetylation (deacetylation represses expression)

Front 36

An adult human makes ______ Ig every day

Back 36

2–3 grams

Front 37

How many constant regions do the different Ig isotypes have?

Back 37

G, A, D ––> three Ch domains
M, E ––> 4 Ch domains

Front 38

Omalizumab binds to....

Back 38

Ch3 on IgE

Front 39

Where do papain and pepsin cleave Ig?

Back 39

Papain cleaves Ig above the hinge ––> two Fab (antigen binding) fragments and one Fc (crystallizable) ––> Fabs can bind but not crosslink

Pepsin cleaves below the hinge ––> F(ab')2 ––> can bind and crosslink

Neither fix complement or bind Fc receptor

Front 40

Variable regions on Ig have ____ CDRs and which is most variable?

Back 40

3 CDRs of 10 aa length,
CDR3 is most variable.

Front 41

Glycosylation of Ig is ! for____
Conserved sites include____

Back 41

(1) maintaining structural stability and effector functions (for IgG, binding Fc–gamma–R and C1q)
(2) Asparagine–297 on Ch2 of IgG

Front 42

Decreased galatosylation is associated with...

Back 42

Rheumatoid arthritis, SLE, Crohn's, TB,

Front 43

This enrichment increases IVIG antiinflammatory properties

Back 43

Sialic Acid

Front 44

Which Ig form which ___–mers?

Back 44

Monomers (all Ig)
Dimers (IgA)
Pentamers (IgM)

Front 45

The IgG subclass with the shortest half life

Back 45

IgG3

Front 46

The Ig that fixes complement most efficiently

Back 46

IgM

Front 47

Rheumatoid factor is an _____ antibody against ___

Back 47

RF is an IgM antibody against
Fc portion of IgG.

Front 48

Ig super family consists of....

Back 48

TCR, MHC, CD4, CD8, CD19, B7–1, B7–2, Fc receptors, KIR (Killer cell Ig–like receptor), VCAM–1

All 70–110 aa, and usu with disulfide loop.

Front 49

Which Ig crosses the placenta

Back 49

IgG

Front 50

Which Ig has the highest plasma concentration

Back 50

IgG

Front 51

Which Ig has the highest total body concentration and daily production

Back 51

IgA

Front 52

What transports IgA across the mucosal epithelium

Back 52

poly–Ig receptor (via transcytosis)

Front 53

Ways Ig gets diversity...

Back 53

Germline variation (diff inherited V, D, Js)
Combinatorial diversity (somatic recombination of V, D, Js)
Junctional diversity (+/– nucleotides at junctions)
Somatic hypermutation (point mut in V's in rapidly dividing lymphocytes, affinity maturation)
Receptor editing (changes in Ig specificity if self–reactive ab made)

Front 54

Alternative Splicing is....

Back 54

– splicing at different C regions to make membrane v. secreted Ig
– splicing at different location of IgM to make IgD (not conventional class switch).

Front 55

Which cytokines induce which class switching for Ig?

Back 55

G1 ––> IFN gamma, IL–4
G2 ––> IFN gamma, TGF beta
G3 ––> IFN gamma
G4 ––> IL4, 13
A ––> TGF beta, IL–5
M ––> n/a
E ––> IL–4, 13
D ––> n/a

Front 56

Which Ig can activate complement

Back 56

IgG1–3, IgM

Front 57

Functions of Ig isotypes

Back 57

IgG1 ––> Th1 response, opsonization, best at ADCC
IgG2 ––> antipolysaccharide. last to get to adult levels
IgG3 ––> opsonization
IgG4 ––> antipolysaccharide. Th2. Incr in IT.
IgA ––> mucosal immunity (A1 in serum/resp. A2 GI)
M ––> primary response
E ––> allergy. only ig that binds mast cells
D ––> B cell maturation marker. Function unknown.

Front 58

Fc receptors for IgE (CD marker, affinity, cell distribution, function)

Back 58

FceRI: high affinity, on mast/baso/eos, degranulation and ADCC
FceRII: aka CD23, low affinity, on neut/eos/monos, fxn unknown

Front 59

Fc receptors for IgE (CD marker, affinity, cell distribution, function)

Back 59

FcgRI: aka CD64, high affinity, macs/neut/eos, phagocytosis
FcgRIIa: aka CD32, low, macs/neut/eos/plt, poor phagocytosis
FcgRIIb: aka CD32, low, B, feedback inhibition of B cells
FcgRIIIA: aka CD16, low, NK/macs, ADCC
FCgRIIIb: aka CD16, low, neut/mac/eos, poor phagocytosis

Front 60

Most important cytokine produced in activation of T cells (after TCR–HLA complex formed)

Back 60

IL–2 (receptor CD25), T cell survival signal, stimulates clonal proliferation

Front 61

What are the costim molecules/receptors/function?

Back 61

(1) APC: CD80 (B7–1)/CD86 (B7–2) and CD28 on T ––> activates naive T cells (induces CD40L, OX40, CXR5, ICOS, CTLA4)
(2) APC: CD80 (B7–1)/CD86 (B7–2) and CTLA4(CD152) on T ––> T cell tolerance and Th1 devt
(3) APC: ICOS–L and ICOS on T ––> costim of effector T cells, class switching
(4) APC cD40 and CD40L on T ––> APC activation, germ ctr devt, class switch, stim AID for somatic hypermutation
(5) APC: PDL1/PDL2 & PD–1 on T –> neg regulation and cell death

Front 62

Contents of tCR complex

Back 62

TCR alpha/beta chains (or delta/gamma – not HLA restricted, don't need CD4/8)
CD3 (epsilon, gamma, delta, zeta chains)
CD4 or 8

Front 63

TCR signaling pathway

Back 63

HLA binds TCR, costim ––> SLAM (signaling lymphocytic activation molecule) binds SAP (SLAM associated protein linking SLAM to Fyn ––> Fyn associates with CD3 and Lck associates with CD4/8 and P–lates them ––> Zap70 binds to P on zeta chain, docks, P–lates LAT ––> LAT recruits adapter proteins
(1) Grb2–SoS ––> Ras GDP/GTP ––> MEK1 ––> ERK ––> ELK ––> Fox ––> AP–1 ––> IL–2
(2)PLC ––> DAG and IP3 ––> PKC ––> I kappaB ––> NFkappaB ––> IL2
(3) IP3 ––> Ca flux through CRAC (Ca release activated Ca chanel) ––> calmodulin ––> calcineurine ––> NFAT(TF for IL–2/IL4, TNF)

Front 64

CD4 and CD8 bind which HLA, where?

Back 64

CD4 ––> MHC 2, beta2
CD8 ––> MHC 1, alpha 3

Front 65

Deficiency in SAP causes

Back 65

X linked lymphoproliferative syndrome

Front 66

Types of Src family kinaseas
Type of Syk family kinase
Type of MAP kinase

Back 66

Lck, Fyn
ZAP70
ERK

Front 67

B cell receptor signaling

Back 67

BCR cross links and associates with IGa/Igb (similar to CD3) ––> lipid raft of Src family kinases (lyn, fyn, btk) P–late ITAMS ––> Syk docks and p–lates BLNK ––> activates Ras, RAC, PLC, BTK
– BTK ––> activates PLC ––> PIP2, IP3, DAG ––> NFkappaB pathway via DAG, NFAT pathway via IP3, AP–1 pathway via Grb2/SOs

Front 68

Role of CD21 in BCR signaling

Back 68

Signal enhancement from cD21 (CR2) if antigen opsonized by C3b ––> degraded to c3d which binds CD21 ––> brings CD21/CD19/CD81 complex into BCR ––> recruits Lyn and activates IP3 kinase

Front 69

Cytokines of Innate Immune system

Back 69

TNF, IL1, IL12, IFNa, IFNb, IL10, IL–6, IL15, IL18, IL–23, IL27

Front 70

Chemokine Families (C, CC, CXC, CX3)

Back 70

C
CC ––> Eos, Baso's, Mono ––> allergy
CXC ––> PMNs ––> Inflammation
CX3

Front 71

Alternative pathway for complement

Back 71

Baseline C3 tickover to c3b. C3b binds bacteria. C3b binds factor b ––> C3bB. Factor D cleaves B ––> C3bBb, stabilized by properdin.
Regulated by factor I mediated cleavage of C3b.
Factors H, MCP (CD46), and DAF (CD55) are cofactors

Front 72

Classical pathway for complement

Back 72

C1q binds Fc of Ig crosslinked by antigen. C1q asssociates with C1r serine proteases ––> cleave c1s proteins. C1s cleaves C4 and C2 ––> C4b2a = C3 convertase
C1 inhibitor blocks C1r and c1s.
C4b is bound by DAF, CR1, and C4bindingprotein to block cascade.
Factor I inactivates C4b into C4bi

Front 73

Lectin pathway for complement

Back 73

Absence of Ab!
MBL binds mannose on microbial polysaccharides. MBL binds MBL–assoc protease1 (MASP1 and 2) ––> cleaves C4 and C2 ––> C3 convertase C4b2a

Front 74

Common path in all complement pathways

Back 74

C3 cleaves C3 to C3b ––> C3b binds C3 convertase ––> C5 convertase (C3bBb3b in AP and C4b1a3b in CP/LP) ––> cleabes C5 ––> releases C5a and starts formation of MAC (C5b –8).
C9 siilar to perforin
S protein and CD59 block MAC formation

Front 75

Chemotaxis of C5a and C3a

Back 75

C5 a most potent mediator of basophil/cutaneous mast cell degranulation.
C5a chemotactic for neut/eos/monos/baso
C3a chemotactic for eos

Front 76

ranking the isotypes in binding affinity for C1q

Back 76

IgM>IgG3>IgG1>IgG2

Front 77

CR3 or CR4 deficiency leads to...

Back 77

LAD type 1 (due to rare mutation in beta chain CD18 common to CD11 and CD18)

Front 78

CR1 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 78

aka CD35
C3b, C4b, iC3b
regulates complement activation, phagocytosis, clearance of immune complexes
HIV

Front 79

CR2 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 79

aka CD21
C3d, iC3b, C3d
part of B cell co receptor
trapping antigesn in germinal center
EBV, HIV

Front 80

CR3 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 80

aka Mac–1, CD11b/CD18
iC3b, ICAM–1
Phagocytosis, leukocyte adhesion to endothelial cells
LAD type I
TB, HIV, West Nile

Front 81

CR4 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 81

aka gp 150/95, CD11c/CD18)
iC3b
Phagocytosis
LAD type I
none

Front 82

Cd46 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 82

aka MCP
––
––
––
measles virus

Front 83

Cd55 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 83

aka DAF
C4b and capsid
regulates C3 convertase formation
PNH
echovirus and coxsackie virus

Front 84

Cd59 (other name, ligand, function, deficiency disease, microbe that uses this receptor)

Back 84

aka protectin
C5b–8 and C9
disrupts MAC formation
PNH
–––

Front 85

What is C3 nephritic factor and what does it cause.

Back 85

Autoantibody that stabilizes C3bBb and protects from degradation by factors H/I ––> unregulated C3 consumption
SLE, MPGN, partial lipodystrophy (fat loss in upper body due to gradient in factor D concentration which completes C3bBb formation)

Front 86

What is anti–C1q antibody and what does it cause.

Back 86

Autoantibody to C1q ––> activation of creatine phosphate pathway with immune complex deposition
Hypocomplemetemic urticarial vasculitis (HUVS) (tx with hydroxychloroquine)

Front 87

Complement deficiency and disease:
(1) No CH50, AH50 ok
(2) CH50 ok, no AH50
(3) No CH50 and No AH50
(4) No CH50, AH50 or C3

Back 87

(1) No c1q, C1r, c1s, c2 or c4
(2) No Factor B, D or properdin
(3) No C3, 5–9
(4) No Factor H, I

Front 88

Disease and associated complement deficiency
SLE
MPGN
HUS
HAE
PNH

Back 88

SLE ––> C1q, C1r, C1s, C4, C2, MBL
MPGN ––> C1q, C1r, C1s, C4, C2, C3, Factor H, Factor I, MCP
HUS ––> Factor H
HAE ––> C1 inhibitor
PNH ––> CD59 (MAC) and CD55 (DAF)

Front 89

What is the bradykinin pathway

Back 89

First simple way. Kallikrein cleaves LMW kininogen ––> lys–bradykinin. Cleaved by aminopeptidase ––> bradykinin.

Bradykinin binds B2 receptor

Contact Activation. Factor XII (HAgeman) binds neg charged surface ––> makes XIIa. Prekallikrein complexes with HMW kininogen, binds surface, gets cleaved by XIIa ––> kallikrein. Kallikrein digests HMW kininogen ––> bradykinin.
XIIa also cleaves XI to make XIa ––> coagulation

HSP90 and prolylcarboxypeptidase can also activated prekallikrein–HMWkininogen complex to make kallikrein.

Front 90

What does C1 inhibitor inhibit?
What is it consumed by

Back 90

Inmhibits factor XIIa and XIIf, kallikrein, factor XIa, and C1r & s.
Consumed by plasmin

Front 91

Major enzyme responsible for bradykinin degradation

Back 91

Kininase II (identical to angiotensin–converting enzyme)

Front 92

In the bradykinin pathway, what receptors do factor XII and HK bind?

Back 92

uPAR (urokinase plasminogen activator receptor)
cytokeratin 1
receptor for the globular head of C1q (gC1qR)

Front 93

What are M cells

Back 93

membranous cells that deliver antigens to peyer's patches (not APCs) by making a pocket where T/B cells can interact with antigen

Front 94

REgions of the GI tract mucosa and their cells/functions

Back 94

Epithelial: mostly CD8+ T cells. Also paneth

Lamina Propria: mostly mixed with activated CD4+ T. Also, epithelial, intraepithelial lymphs, activated B/plasma, Ts.

Peyer's: Mostly CD4+T. Also M

Other: Mac/mast/eos/B

Front 95

How to T cells localize to the small intestine

Back 95

alpha4Beta7 binding CCR9
MAdCAM–1

Front 96

Intraepithelial lymphocytes (IELs)
where?
migration?
expression pattern?

Back 96

Above basement membrane between epithelial cells

Migration by CCR9, or CCL25 & cD103 (E cadherin)

Express CD8alpha–alpha, common for activated mucosal T cells. Mostly effector cells

Front 97

Intestinal immunity regulatory t cells

Back 97

Th3 cells (subset of CD4+ that make TGFb)
TR1 (CD4 that make IL–10)
CD4+CD25+ T regs
CD8+ suppressor T cells
delta/gamma T cells

Front 98

What cytokines trigger class switching to IgA

Back 98

TGFb and IL–5

Front 99

Main breast milk components

Back 99

IgA, lysozyme, lactoferrin, TNF alpha.

Front 100

Methods for detecting antibody mismatches

Back 100

(1) Cross–matching. testing serum from recipient against cells from donor for RBC/HLA antigens. Absolute contraind.
(2) Donor–recipient matching: matching by HLA typing. Measure response of immunocompetetnt cells from recipient to antigens present on donor cells.

Front 101

Types and Mechanisms of transplant rejection

Back 101

(1) Hyperacute (<24h): from preformed ABO abs, HLA abs, complement. Neutrophils.
(2) Accelerated rejection (3–5d): Noncomplement fixing abs, NK, monos.
(3) Acute (6–90 d): T cells, antibodies.
(4) Chronic (>60d): Antibodies. (delayed type hypersensitivity)

Front 102

Cytokines released in acute rejection

Back 102

IL2, 4, 5, 7, 10, 15 TNFa, IFNg

Front 103

Costimulation methods in transplant rejection for CD4+ and CD8+ T cells

Back 103

4: Receptor ligand interactions
IL–1 and IL–6 on APCs


8: IL–2

Front 104

Activation of CD4+ T cells (5 combos of ligand and receptor)

Back 104

CD2 and CD58
CD11a/CD18 and CD54
CD5 and CD72
CD40L and CD40
CD28 and CD80/86
(T cell & APC)

Front 105

Cyclosporine and tacrolimus (FK506) mechanism

Back 105

Inhibits T cell and activation.
CSA binds cyclophilin ––> inhibition of calcineurin ––> blockade of NFAT activation ––> no transcription of IL2 ––> no T cell differentiation

Front 106

Rapamycin mechanism

Back 106

Inhibits T cell and activation

Rapamycin binds FKBP ––> binds and inhibits mTOR ––> blocks T cell prolif

Front 107

Mycophenolate mofetil (MMF) mechanism

Back 107

Inhibits guanine nucleotide synthesis ––> stops T cell prolif

Front 108

Azathioprine mechanism

Back 108

Blocks lymphocyte precursors (less specific than MMF so higher toxicity)

Front 109

Mechanism of Anti–CD3

Back 109

Binds CD3 ––> promotes phagocytosis or complement mediated lysis of T cells

Front 110

Mechanism of Anti–CD25 (alpha subunit of IL2R)

Back 110

Blockade of IL2 binding to activated T cells expressing CD25 ––> prevention of T cell activation

Front 111

Mechanism of corticosteroids

Back 111

Block synthesis and secretion of cytokines from macrophages

Front 112

Improved patient survival in cancer associated with...

Back 112

TILs with a normal zeta chain. Usuall CD95+ (FAS)

Front 113

Tumor immune inhibitors?

Back 113

TNF ligands (FASL, TRAIL, TNF)
Cytokines (TGFbeta, IL–10, GMCSF, ZIP)
Small molecules (PGE2, epi, ROS)
Virally related products (p15E, EBI–3)
Tumor associated gangliosides – block IL–2 depdt prolif

Front 114

What are KIR?

Back 114

Inhibitor receptors on NK cell
Recognize MHC class I
Help scavenging for abnormal tumor cells

Front 115

What are AMP?

Back 115

Antimicrobial peptides.
Cationic proteins involved in innate immunity a/bacteria, fungi, viruses
Made by keratinocytes
Two families (defensins (HBD1,2,3), cathelicidins (LL37), Lactoferrins (hlF–11), Histatins
Interact with microbe membrane phospholipids, antiproliferative effects

Front 116

What are PAMPs

Back 116

Pathogen associated molecular patterns
Conserved microbial sequences
Ex: LPS (on gram neg bacteria), teichoic acid (GP)
Recognized by PRRs (pattern recognition receptors to detect infection

Front 117

fMLP (full receptor name, location, class, structure, function)

Back 117

Receptor: N–formyl Met–leu Phe receptors
Location: cell surface
Class: signaling
Structure: GPCR
Function: antibacterial

Front 118

CARD (full receptor name, location, class, structure, function)

Back 118

Caspase Activation and Recruitment Domains (ex: retinoic acid inducible gene I like receptors)
Location: cytoplasm
Class: signaling:
Structure: RNA helicase and caspase recruitment domains (part of inflammasome)
Function: cytoplasmic virus detection ––> type1 IFN production

Front 119

CLR (full receptor name, location, class, structure, function)

Back 119

C–type lectin receptors (MBL and macrophage mannose receptor)
Loc: cell surface
Class:secreted or endocytic
Structure: Ca dpdt carbohydrate binding domains
Fxn: antifungal

Front 120

NLR or NACT–LRR (full receptor name, location, class, structure, function)

Back 120

Nucleotide binding Oligomerization domains
Loc: cytoplasm
Class: signaling
Structure: C terminal leucine rich repeat and nucleotide binding domain (central proteins of inflammasome)
Fxn: IL–1b and IL18 secretion

Front 121

TLR (full receptor name, location, class, structure, function)

Back 121

Toll–like receptors
Loc: cell–surface cytoplasm (TLR3)
Class: signaling
Fxn: antibacterial/fungal/viral

Front 122

Function of the inflammasome (associated diseases)

Back 122

Located in cytoplasm, activates caspases 1 and 5 ––> production/secretion of IL–1 and IL–18

Activating mutations in Cold induced autoinflammatory syndrome (CIAS1), Muckle–wells, familial cold urticaria, CINCA

Front 123

TLR 1 (ligand and source)

Back 123

Lipoarabinomannan
Mycobacteria

Front 124

TLR 2 (ligand and source)

Back 124

Zymosan
Fungi

Front 125

TLR 3 (ligand and source)

Back 125

dsRNA
Virus

Front 126

TLR 4 (ligand and source)

Back 126

LPS, peptidoglycan, RSV fusion protein, HSP70, HSP90

Gram neg bacteria, gram positive bacteria, RSV, acute phase proteins

Front 127

TLR 5 (ligand and source)

Back 127

Flagellin

Flagellated bacteria

Front 128

TLR 6 (ligand and source)

Back 128

Diacyl lipopeptides

Mycoplasma

Front 129

TLR 7 (ligand and source)

Back 129

Imidazoloquinolones

Synthetic

Front 130

TLR 8 (ligand and source)

Back 130

ssRNA

Virus

Front 131

TLR 9 (ligand and source)

Back 131

Unmethylated CpG motifs

Bacteria and DNA viruses

Front 132

TLR 10 (ligand and source)

Back 132

Unknown

Front 133

TLR 11 (ligand and source)

Back 133

Profilin

Toxoplasma gondii

Front 134

TLR 4 signaling MyD88 dependent pathway

Back 134

TLR4 & MD2 ––> TIRAP ––> MyD88 ––> IRAK + TRAF6 ––> NEMO/IKKg + IKKa + IKKb ––> NFkB ––> into nucleus ––> transcription of inflammatory cytokines

Front 135

TLR4 signaling MyD88 independent pathway

Back 135

TLR4 & MD2 –> TRAM –> TRIF

––> TRAF ––> NFkB
––> RIP1 ––> NFkB
––> TBK1 + IKKe/i ––> IRF3
all lead to IFN beta transcription

Front 136

What is in the TLR4 complex?

Back 136

TLR4 (binds LPS via LPS binding protein)
MD2 (lymphocyte antigen 96)
CD14

Front 137

Only TLR that never signals through MyD88

Back 137

TLR3

Front 138

TLRs or pathway involved in HSV1 encephalitis

Back 138

TLR 3, 7, 8, 9

Front 139

TLRs or pathway involved in aspergillosis

Back 139

TLR4

Front 140

TLRs or pathway involved in ADrenal insufficiency

Back 140

TLR2 and 4

Front 141

TLRs or pathway involved in Crohn's dsease or Blau's syndrome

Back 141

NOD2

Front 142

TLRs or pathway involved in Leprosy and TB

Back 142

TLR2

Front 143

TLRs or pathway involved in IRAK44 or MyD88 deficiency

Back 143

Recurrent infections with pyogenic bacteria
All TLRs

Front 144

PID with infectious and mycobacterial susceptibility ––> think ___

Back 144

NEMO

Front 145

Th9 cells:
induced by...
produce...
differentiation requires...

Back 145

induced by TGFb
produce IL9 +/– IL4
differentiation requires IRF4 and PU.1

Front 146

Th1 cells:
induced by...
produce...
TFs...
major function...

Back 146

induced by IL–12, IL–27, IL–18
produce IFNg, IL–2, TNF
TFs are Tbet, STAT4, STAT1
major function is intracellular defense

also, express CXCR3 and CCR5. Associated with type I DM, and MS

Front 147

Th2 cells:
induced by...
produce...
TFs...
major function...

Back 147

induced by IL–4, IL25, IL–33, TSLP
produce IL–4, IL–5, IL–13, IL–6, 10, 21, 25, 31, 33
TFs are GATA3, STAT6, STAT5
major function is humoral immunity, antiparasitic, allergy

Front 148

Th17 cells:
induced by...
produce...
TFs...
major function...

Back 148

induced by IL–6, IL–1, IL–21, IL–23, TGFb
produce IL–17, IL1, 6, 21, 22, TNFa, GMCSF
TFs are RORgT, STAT3
major function is extracellular defense, neut recruitment, autoimmunity

Express CCR6, involved in rA< IBD, MS, psoriasis

Front 149

Treg cells:
induced by...
produce...
TFs...
major function...

Back 149

induced by TGFb and retinoic acid
produce IL–10, TGFb
TFs are FOXp3, STAT5
major function is immunosuppression, autoimmunity

Front 150

Tfh cells:
produce...
TFs...
major function...

Back 150

produce IL–21
TF: BCL–6 (causes downreg CCR7 and upreg CXCR5)
major funcion is helping B cells make abs in germinal ctr follicles

Front 151

CTL cells:
produce:
TF:
major function

Back 151

produce IFNg, TNF, lymphotoxin
TF is EOMES (eomesodermin homologs)
major function: kill virally infected and tumor cells using perforin and granzyme

Front 152

gd T cells:
produce:
function

Back 152

produce IFNg and TNF
function is to bind lipids and heat shock proteins

Front 153

Natural T regs v. Induced T regs
Derived:
Expression:
Other features:

Back 153

N: thymically in response to autologus Ag
I: peripherally in response to self and external Ag

N: consitutive IL–2Ra (CD25)
I: inducible IL2Ra (CD25)

N: FOXP3+, mediates self tolerance
I: types Tr1 (make IL–10 and ! in immunotherapy). Th3 (make TGFb, ! for IgA production)

Front 154

Markers of NK cells

Back 154

CD16 (FCgRIII)
CD56 (NCAM)
natural cytotoxicity receptors (NCRs)
killer inhibitory receptors (KIRS)
NKs don't epxress CD3

Front 155

Markers of NK T cells
function
produce...

Back 155

CD3+
CD16+
CD56+
usually CD4+

Function: recognize glycolipid in context of CD1
Produce IFNg and iL–13

Front 156

Innate lymphoid cells
aka...
proliferate in response to...
produce...
function

Back 156

aka ILC2 or nuocytes
proliferate in response to IL25, IL33
produce IL5, IL9, IL13
function: central role in type 2 mediated immunity

Front 157

NK cell activating receptors (and ligands)

Back 157

2B4 (binds CD48 on EBV infected cell)
NKG2D (binds MICA/B & ULBP on stressed cell)
NKp44/46 (binds viral hemagllutinin)
NKG2C (binds HLA–E on NK cell)
FCgRIIIA (binds IgG on target cell)

Front 158

Inhibitory receptors

Back 158

KIR (binds MHC class I)
NKG2A/B (binds HLA–E)

Front 159

Where do B cells and T cells stay in the lymph node
What do they express to get there and what does that bind?

Back 159

T cells in parafollicular zone, B cells in follicles

T express CCR7 which binds CCL19/21
B express CXCR5 which binds CXCL13

Front 160

Early maturation of B and T cells requires this cytokine and if missing leads to this.

Back 160

IL–7

SCID

Front 161

VDJ recominbation occurs by recognition of ______ but only following _____ rule

Back 161

recombination signal sequences (RSS)

12/23 rule (one segment flanked by 12 nucleotide spacer and the other by 23)

Front 162

Enzymes involved in VDJ recombination and function

Back 162

RAG 1/2 (cleaves dsDNA btwn coding and RSS)
Ku (binds DNA ends or makes hairpin)
DNA–PK and Artemis (open hairpin randomly)
TdT (terminal deoxynucleotidyl transferase, adds nucleotides for junctional diversity)
Endonuclease (removes nucleotides for diversity)
DNA ligase IV & XRCC4: ligates DNA

Front 163

B cell maturation order

Back 163

Pro B cell
Pre B cell
Immature Naive B cell
Mature Naive B cell
Memory B cell or Plasma cell

Front 164

Pro B cell markers and major event

Back 164

CD19, CD20
heavy chain DJ and VDJ rearrangement

Front 165

Pre B cell markers and major event

Back 165

cytoplasmic mu chain
signaling through preB cell receptor
light chain VJ rearrangement

Front 166

Immature Naive B cell markers and major event

Back 166

IgM
Kappa/lambda binds mu heavy making igM
Receptor editing

Front 167

Mature B cell markers and major event

Back 167

IgM and IgD
Alternative splicing to express IgM and IgD

Front 168

Memory B cell markers and major event

Back 168

Isotype switching
Somatic hypermutation

Front 169

Plasma B cell markers and major event

Back 169

Alternative splicing to get Ig isotypes

Front 170

Enzymes needed for class switching

Back 170

AID
UNG
CD40
CD40L

Front 171

TFs associated with B cell differentiation

Back 171

PU.1
IKAROS
E2A
EBF
PAX5
IRF8

Front 172

Peripheral B cell survival signals and the receptors

Back 172

BLYSS
BAFF
APRIL

bind receptors on B cells
early: BR3 and TACI
late: BCMA

Front 173

Mature B cell types

Back 173

B1 cells (innate, similar to gamma–delta T, make natural abs for microbes and lipids, found in peritoneum & fetus, T indpdt)

Marginal zone B cells (present by 2 years, first responders esp polysaccharides, T indpdt)

B2 cells (memory and plasma, T dpdt)

Front 174

T cell maturation

Back 174

Immature DN T cells:
DN1, DN2 (DJ/VDJ recomb), DN3 (preTCR signaling), DN4 (prolif)
DP T cells (+ selection (cortex), – selection (medulla))
SP T cells
Leave lymphoid organs (S1P receptor)
Central memory T cells
Effector memory T cells

Front 175

function of notch

Back 175

commits T cells to develop

Front 176

Central and Effector memory T cell markers

Back 176

Central: CD45 RA–, CD27 +, CCR7+, CD62L+

Effector: CD45RA–, CD27–, CCR7–, CD62L–

Front 177

Two types of lymphocyte apoptosis and associated molecules

Back 177

Passive/Intrinsic Pathway:
– d/t neglect, Caspase 9
– BCL2 and bCL–XL are antiapoptotic
– BID/BIM are proapoptotic

Active/Extrinsic pathway:
– d/t repeated lymphocyte activation, Caspase 8
– fAS (cD95)/FasL(CD178) ––> FADD (fas assoc protein c death domain)

Front 178

Monocyte markers

Back 178

CD14, CD16

Front 179

Macrophage
markers
growth factors
activated by
produce

Back 179

Markers: CD14, CD11b/CD18 (Mac1), CD36

Growth factors: GM–CSF, M–CSF

Activated by: IFNg, LPS binding CD14

Produce: TNFa, IL12/18/1/6

Front 180

Macrophage subtypes by location

Back 180

Kupffer cells in liver
histiocytes in tissue
osteoclasts in bone
mesangial cells in kidney
alveolar macrophages in lung

Front 181

Macrophages associated with... (diseases)

Back 181

Granuloma formation in sarcoid, TB (promoted by TNFa)

Uncontrolled activation in HLH (common in boys with XLP and EBV infection)

Front 182

XLP is due to ___ mutations

Back 182

SH2D1A gene (encodes SAP protein)

Front 183

HLH diagnosis

Back 183

5 of 8 criteria:
Fever
splenomegaly
cytopenia with 2+ cell lines
hyperTGs or hypofibrinogenemia
Hemophagocytosis on BM bx
Hepatitis
Low/absent NK
Ferritin>500
CD25 (soluble Il–2R) >2400

Front 184

Dendritic Cell subsets

What stimulates development

Back 184

DC1 (myeloid/conventional)
DC2 (plasmacytoid)
Langerhans
Interstitial

GM–CSF, IL4

Front 185

DC1
markers
precursor
function

Back 185

Markers: CD1, CD11b/c, CD13, CD14
Precursor: Myeloid
Function: Phagocytosis and Antigen presentation

Front 186

DC2
markers
precursor
function

Back 186

Markers: CD1, CD11b/c, CD13, CD14
Precursor: Lymphoid
Function: Secretion of IFNa, assoc c viral infections

Front 187

Langerhans
markers
precursor
function

Back 187

Markers: CD11c, CD207, Birbeck granules (tennis racket shaped)
Precursor: Myeloid (CLA+)
Function:Prime CD8 T cells

Front 188

Interstitial
markers
precursor
function

Back 188

Markers: CD2, CD9, CD68
Precursor: Myeloid (CLA–)
Function: Activate B cells

Front 189

Mast cells
derived from...
mature in...
types...

Back 189

derived from pluripotent kit+ (CD117+) CD34+ stem cells

mature in the tissue (unlike baso/eos)

Types: MCt, MCtc, MCc

Front 190

MCt mast cells
mediators:
location:
other features

Back 190

Mediators: tryptase
Location: respiratory tract, intestinal mucosa
Other features: don't express C5aR (CD88), scroll like appearance, development is T dpdt, don't respond to opiates, C5a, C3a, vancomycin

Front 191

MCtc mast cells:
Mediators:
Location:
Otherfeatures:

Back 191

Mediators: Tryptase, Chymase, carboxypeptidase, cathepsin G
Location: skin, blood vessels, eyes, synovium, intestinal/resp submucoas
Other: Do express C5aR (cD88), whorled appearance, T cell indpendent development, respond to opiates, C5a, C3a, vanc

Front 192

MCc mast cells
Mediators:
Location:

Back 192

Chymase
Location: lymph nodes, intestinal submucosa, salivary glands

Front 193

High Affinity IgE receptor
(name of receptor, structure, expressed on which cells, binding site for IgE)

Back 193

Fc–episilon–RI
1 alpha chain (c Ig domains binding IgE), 1 beta chain (4 transmembrane domains, ITAM), 2 gamma chains (ITAMS, main signaling)
Found on mast cells, basophils, and in trimeric form (alpha and gamm only) on DCs/monos/eos
IgE binds alpha and signals via Lyn/Fyn/Syk.

Front 194

Low Affinity IgE receptor
(name of receptor, structure, expressed on which cells, What cleaves from the cell surface)

Back 194

Fc episilon RII (CD23)
C type lectin
On mature B cells, activated macs, eos, DC, plt
Der–p–! cleaves CD23 from the surface, increasing the production of allergen specific IgE

Front 195

Mast cell activation methods (9)

Back 195

IgE binding high affinity IgE receptor
IgG binding Fcgamma RI
bacterial antigens binding TLR 2/6 or 4
C3a/C5a anaphylotoxins (MCtc only)
cytokines
neuropeptides
physical stimuli (heat pressure)
substance P
drugs (contrast, opiods, muscle relaxants)

Front 196

Mast cell response to stimulation (timeframe, mediators and cytokines

Back 196

<15 min: preformed release (histamine, tryptase, chymase, TNF, heparin)
10–30min: lipid derived mediators ( PGD2, LTC4, LTB4, PAF)
hrs–days: cytokine/chemokine release (IL3,4,5,6,8,10,13, GMCSF, TNFa, MCP–1, MIP1a, RANTES (CCL–5))

Front 197

List function for histamine

Back 197

smooth muscle contraction
mucus production
vasodilation
gastric acid secretion
wakefulness

Front 198

List function for tryptase

Back 198

serine protease endopetidase

Front 199

List function for Carboxypeptidase

Back 199

peptidase for C terminal end of peptide

Front 200

List function for chymase

Back 200

serine (protease) endopeptidase

Front 201

List function for Prostaglandin D2

Back 201

increases vascular permeability
bronchoconstriction
platelet aggregation
chemoattraction

Front 202

List function for LTC4 LTB4

Back 202

increase vascular permeability
bronchoconstriction

Front 203

Platelet activating factor

Back 203

bronchoconstriction
vasodilation
platelet aggregation

Front 204

Bsophil Growth
– where do they mature
– where do they end up
Key cytokine for differentiation

Back 204

Mature in bone marrow
Found in blood and BAL
CD123 (IL–3 receptor) and IL3

Front 205

Mast cell mediator that is both preformed and found in late phase of reaction

Back 205

TNF

Front 206

Basophil response to stimulation (timeframe, mediators and cytokines

Back 206

<15 min: preformed release (histamine, chondroitin, MBP, charcot–leyden protein)
10–30min:lipid dervied mediators (LTC4)
min–days: cytokines (IL 3, 4, 5, 6, 8, 10, 13, GMCSF, TNFa, MCP1, MIP1a, RANTES, PAF)

Front 207

Differences between mast cells and basophils (8)

Back 207

Location: Mast tissues, Baso blood
Nucleus: Mast unsegmented, Baso bilobed
Granules: Mast more/small, Baso less/large
Tryptase: Mast has more
Chymase/Carboxypeptidase: only in Mast
LTB4/PGD2: only in mast
IL3 receptor: only in baso
C5a receptor: only in mast

Front 208

Eosinophil granules and contents

Back 208

Primary granules: Charcot–Leyden crystals
Specific/2ndary granules: preformed mediators – major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase, eosinophil derived neurotoxin

Front 209

Eosinophil receptors

Back 209

Fc receptors for immunoglobulins
Beta–2 integrins (CD11a–cCD18)
Beta–1 integrin (VLA–4)
Beta–4 integrin (alpha4beta7)
PSG1–1

Front 210

Eosinophil growth/differentiation
– cytokines
– where it matures
–migration chemokines
– where they reside
–half life

Back 210

differentiation/activation cytokines: GM–CSF, IL3, IL5
Matures in bone marrow (GATA1 TF !)
Migrate to tissue in response to RANTES (CCL–5), eotaxins (eostaxin–1, CCL–11, eotaxin–2, CCL24)
Resides in the tissue (lower GI, mammary gland, female reproductive tract, lymph tissue, 1–2% in blood)
Half life– 18hrs

Front 211

Eosinophil functions (6)

Back 211

Modulate immune response:
– release toxic granule proteins
– release reactive oxygen species
– release leukotrienes and prostglandins
– rleease cytokines (IL1,2,4,5,6,8,13,TNF)
Mammary gland development
Wound repair and tissue remodeling

Front 212

Disorders associated with hypereosinophilia

Back 212

Allergic disease/asthma
Rheum: Collagen vascular disorders, Kimura's dz, Churg–strauss vasculitis, Adrenal insufficiency (ADdison's dz)
Skin: Eczema, Pemphigoid
Resp: ABPA, eosinophilic pneumonia, LOeffler's syndrome,
GI: EoE
ID: HIV, parasites, Protozoa (isospora belli, sarcocystis) TB
Onc: Neoplasm (Hodgkin's lymphoma)
Other: Drug rxn,
Heme: Hypereosinophilic syndrome, mastocytosis,

Front 213

Neutrophils:
Ig surface receptors
Cytokines for suvival/maturation
Chemokines:

Back 213

Ig surface receptors IgG and IgA
Survival cytokines: IL–3, GMCSF, G CSF
Chemokines: IL8 (CXCL8)
Also, IFNg, fMLP, MIP–1, LTB4, C5a, Sialyl–lewix X, E/P selectins, LFA1/ICAM1

Front 214

Neutrophil granules

Back 214

Primary granules (azurophilic) – myeloperoxidase, defensins, elastase, lysozyme, cathepsin
Specific granules (secondary) – lactoferrin, cathelicidin, fMLP, CD11b
Gelatinase – fMLP, CD11b, lysoszyme, gelatinase
Secretory – fMLP, CD11b, alkaline phosphatase

Front 215

Platelet:
surface receptors

Back 215

Surface receptors for IgG and CD23

Front 216

Thrombus formation

Back 216

Endothelial damage ––> exposed collagen and vWF activate plts ––> plts release granules (contain ADP/ATP, Ca, serotonin, TGFb, plt factor 4, PDGF, vWF, fibrinogen) ––> arachidonic acid pathway initiated producing thromboxane A2 (activates more plts) ––> Plts clump with fibrinogen and vWF binding GP2b/3a receptor ––> cytokine release

Front 217

Thrombocytopenia and associated diseases

Back 217

Aplastic anemia
Bernard–soulier syndrome
Drug induced thrombocytopenia
Gaucher's disease
Glanzmann's thrombasthenia
HELLP
Hemophilia
Hermansky–Pudlak
Wiskott–Aldrich
ITP (abs to GP2b3a)
TTP (abs to ADAMTS13)
von willebrand's disease
HIT (abs to PF4)

Front 218

Epidermal layers:

Back 218

Before Signing Get Legal Counsel

Stratum Basale
Stratum Spinosum
Stratum Granulosum
Stratum Lucidum
Stratum Corneum

Front 219

Protein among the keratinized epithelial layers of skin

Back 219

Transglutaminase

Front 220

Skin adhesion moecules

Back 220

e cadherins in desmosomes
integrins in hemidesmosomes

Front 221

Pathogens that use epithelial receptors for infection

Back 221

Rhinovirus ––> ICAM–1
Influenza ––> glycans
Adenovirus ––> integrins and CD80/86

Front 222

How T cells home to the skin?

Back 222

T cells express cutaneous lymphocyte angiten (CLA) and CCR4 and CCR10.
Binds CCL17 (TARC) and CCL22 (MDC) on keratinocytes

Front 223

Airway epithelial cells make ______ in response to _____, which attacts monocytes and immature DCs to the lung

Back 223

CCL2, CCL20

house dust mite inhalation

Front 224

Epithelial cells produce ____ which activate DC's

Back 224

TSLP, GMCSF, IL–25, IL33

Front 225

Bronchial epithelial cells release ____ cytokines in response to allergen cells

Back 225

IL–33 and other IL–1 family (Il1a, Il1b, IL36g)

Front 226

In atopic dermatitis expression of ___ cytokines suppresses ____

Back 226

IL–4, IL13
beta defensins and cathelicidin

Front 227

In pemphigus vulgaris
direct IF shows ___
target antigen is ____
location is ____

Back 227

Intercellular IgG and IgM (epidermal IgG/C3)
Desmoglein3
Desmosome

Front 228

In pemphigus follacious
direct IF shows ___
target antigen is ____
location is ____

Back 228

Intercellular IgG (epidermal igG/C3)
Desmoglein 1
Desmosome

Front 229

In bullous pemphigoid
direct IF shows ___
target antigen is ____
location is ____

Back 229

Linear IgG/C3 at BMZ
BP230 (BP Ag 1) or BP180 (BPAg2)
Hemidesmosome

Front 230

In pemphigoid gestationis
direct IF shows ___
target antigen is ____
location is ____

Back 230

Linear IgG at BMZ
BP230 (BP Ag 1) or BP180 (BPAg2)
Hemidesmosome

Front 231

In dermatitis herpetiformis
direct IF shows ___
target antigen is ____
location is ____

Back 231

Granular IgA in dermis
Transglutaminase
Subepidermal

Front 232

In linear igA dermatosis
direct IF shows ___
target antigen is ____
location is ____

Back 232

Linear IgA at BMZ
BP 180 (BPAg2)
Hemidesmosome

Front 233

Autoantibody involved in typeI autoimmune hepatitis

Back 233

IgG anti–SMA (smooth muscle antibody)

Front 234

E–selectin
adhesion molecule location
ligand
ligand location

Back 234

endothelium
Sialyl–Lewis X
Leukocytes

Front 235

P–selectin
adhesion molecule location
ligand
ligand location

Back 235

endothelium
sialyl–Lewis X
Leukocytes (preformed in platelets)

Front 236

L–selectin
adhesion molecule location
ligand
ligand location

Back 236

Leukocytes
Sialyl Lewis X on GlyCAM1 and MadCAM1
High endothelial venules

Front 237

Integrins
adhesion molecule location
ligand
ligand location

Back 237

Leukocytes
ICAM and VCAM
Endothelium

Front 238

Hypersensitivity Reaction Type I
Key players, antigen, examples, main cytokines

Back 238

Mast cells, basos, IgE
Soluble antigen
Ex: allergic asthma, rhinitis, anaphylaxis, food allergy
IL–4, IL13, sIgE

Front 239

Hypersensitivity Reaction Type II
Key players, antigen, examples, what does it involve

Back 239

IgG, IgM, complement, phagocytes
Cell/matrix associated
Ex: hemolytic anemia, goodpasture's disease, Grave's disease, myasthenia gravis
Antibody binding antigens on a target cell causing damage by cellular neutralization/blocking (MG), cytotoxicity (hem anemia), cellular stimulation (Grave's)

Front 240

Hypersensitivity Reaction Type III
Key players, antigen, examples

Back 240

Complement, IgG (Immune complexes)
Antigen soluble
Ex: SLE, glomerulonephritis, vasculitis, serum sickness

Front 241

Hypersensitivity Reaction Type IV
Key players, antigen, examples

Back 241

T cells
–
Ex: contact derm, psoriasis, celiac

Front 242

Mediators in Type I hypersensitivity reaction and their roles

Back 242

Kalleikrein ––> contact system (bradykinin?)
Tryptase ––> kallikrein activity activates contact/complement/clotting cascades
Platelet activating factor ––> clotting and DIC and mast cell activation
Heparin ––> inhibits clotting
Chymase ––> converts angiotensin I to II modulating hypotension

Front 243

What is FcgRI (aka, function, ligand)

Back 243

aka CD64
high–affinity phagocyte receptor
Binds IgG1 IgG3 (most efficient opsonins)

Front 244

C3b receptors on phagocytes

Back 244

CR1 (CD35)

Front 245

What is antibody dependent cell mediated cytotoxicity

Back 245

NK cells bind to microbes coated with clustered igG
Binds via FcgammaRIII (low–affinity Fc receptor)
Nk cell secretes cytokines like IFNg, discharges its granules into a lytic synapse, and kills the cell

Front 246

Isotype switching to IgA occurs where most efficiently and d/t which cytokines

Back 246

most efficiently in mucosal lymphoid tissue
stim by TGFb and IL–5

Front 247

How is IgG transported across teh placenta and infant gut lumen?

Back 247

IgG specific Fc receptor (neonatal FC receptor FcRn)
resembles MHCI

Front 248

Immune complexes formed at ______ form a lattice and are rapidly removed by ______

Back 248

equivalence (ag=Ab)
mononculear phagocytes like Kupffer cells

Front 249

Most pathogenic state for Type III hypersensitivity occurs in a state of ______ (Ag or Ab) excess

Back 249

Moderate Antigen excess

Front 250

Positively charged immune complexes tend to deposit ______

Back 250

negatively charged basement membrane of skin and kidneys

Front 251

Immune complex injury is associated with the release of _____ cytokines

Back 251

Il1b, TNF, IL–2, IFN–g

Front 252

What is an arthus reaction

Back 252

Ag injected into skin/tissue ––>
local edema, neutrophil migration, hemorrhage, necrosis with peak intensity at 4–10 hrs (local type III affecting dermal blood vessels)

Front 253

SLE – immune complex deposition in ____
associated with _____.

Back 253

deposition in blood vessel walls and kidney glomeruli

low complement levles, hypergammaglobulinemia, presence of circulating ICs, autoantibody production

Front 254

Subtypes of Type IV hypersensitivity: IVa
T cell involved
cytokines
other cells
target organs
ex:

Back 254

T cell involved: CD4+ Th1
cytokines: IFNg, TNFa, IL2
other cells: macs, NK
target organs: skin, lung, GI
ex: contact derm, TB

Front 255

Subtypes of Type IV hypersensitivity: IVb
T cell involved
cytokines
other cells
target organs
ex:

Back 255

T cell involved: CD4+ Th2
cytokines: IL4, 5, 13
other cells: eos, B cells
target organs: skin, lung, GI
ex: chronic allergic disease

Front 256

Subtypes of Type IV hypersensitivity: IVc
T cell involved
cytokines
other cells
target organs
ex:

Back 256

T cell involved: CD4+ Th17
cytokines: IL17, 21, 22
other cells: neut
target organs: skin, lung, GI
ex: psoriasis

Front 257

Subtypes of Type IV hypersensitivity: IVd
T cell involved
cytokines
other cells
target organs
ex:

Back 257

T cell involved: CD8+
cytokines: –
other cells: –
target organs: skin, systemic
ex: contact derm

Front 258

Typical agents causing contact derm (5)

Back 258

nickel
quaternium–15 (cosmetics)
bacitracin
poison ivy (urushiol a hapten)
resin

Front 259

Serum sickness usually presents ____ after exposure to drug

Back 259

4–10 days (time to class–switch)

Front 260

What is nephelometry

Back 260

detection of Ig where turbidity is measured by pattern of scattered light.
works best in ag–ab equivalence
More sensitive than radial immunodefusion and works for 1–10 mcg/ml

Front 261

What is radial immunodiffusion?

Back 261

Antiserum mixed into a warm gel matrix, poored into flat plate. Ad antigen and watch for diffusion (precipitin line seen at zone of equivalence)
Can measure <10 mcg/mL

Front 262

What is the Laurell Rocket method

Back 262

Add sample to gel plates with antiserum, apply voltage. precipitin line occurs in rocket shape.
Quantitative/qualitative

Front 263

If antibody excess _____
equivalence______
antigen excess______
(best tests)

Back 263

ab excess: immunoblotting, ELISA
equivalence: radial immunodiffusion, double immunodiffusion, nephelometry
ag excess: radioimmunoassay, eLISA

Front 264

What is double immunodiffusion?

Back 264

aka ouchterlony method

holes in agarose gel, antigen in wells and serum in adjacent wells and look for precipitin line

Front 265

What is ELISA

Back 265

identify bound protein by an antibody, which is conjugated to a label. good in ab or ag excess.
detect signal using spectrophotometer, fluorometer, luminometer

direct assay: ag, primary ab conjugate
indirect assay: ag, primary ab, 2ndary ab conjugate
capture assay: capture ab, ag, ab, 2ndary ab

Front 266

What is Western blot?

Back 266

antibody excess assy for recognizing proteins through sds page gel, transfer to nitrocellulose membrane, add specific ab and secondary ab, and enzyme to get band

useful for: borrelia burgdorferi, HHV6/7, HIV, HTLV, prion, rsv, SARS, VZV, hepB, lyme

Front 267

What is immunofixation electrophoresis

Back 267

IFE measures immunodiffusion against an antiserum. through a gel

Good to confirm monoclonal gammothy (heavy/light chain class)

Front 268

What is Immunocap method?

Back 268

SAndwhich eLISA technique with fluorescent tag

Front 269

Flow cytometry: HLA–DR is a marker of ....

Back 269

CD4 or CD8 activation

Front 270

Flow cytometry: CD25 is a marker of ....

Back 270

activated T cells (regular expression)
T regs (high expression)

Front 271

These mitogens in proliferation assay test cell surface signaling

Back 271

PHA, PWM, ConA, anti–CD3 ab

Front 272

These mitogens in proliferation assay bypass proximal signaling

Back 272

phorbol ester (PMA)
calcium ionophore (ionomycin)

Front 273

This mitogen has b cell proliferation activity along with T cell proliferaation

Back 273

Pokeweed mitogen

Front 274

What is DTH testing

Back 274

Test for invivo T cell fxn using previously exposed antigen.
Candida, trichophyton, tetanus, mumps

Front 275

Flow cytometry: CD19 is a marker of...

Back 275

B cells (early–plasmablasts, not on plasma cells)

Front 276

Flow cytometry: CD20 is a marker of...

Back 276

pre–B cells and B cell blasts

Front 277

Lack of switched and unswitched memory B cells.
markers?
disease?

Back 277

unswitched (IgD+ CD27+)
switched (IgD–, CD27+)

CVID

Front 278

Mitogens for B cell proliferation

Back 278

Pokeweed mitogen, tetanus toxoid, SAC (staph aureus Cowan I)

Front 279

Measuring NK function

Back 279

perforin and granzyme B expression (defective in HLH)
expression of CD107a (marker of degranulation)

Front 280

Chediak Higashi
sx
dx

Back 280

Sx: neutropenia, recurrent skin/sinus/pulm infxn, oculocutaneous albinism, mitral regurg, neuropathy
Dx: giant granules on smear, mutations in LYST1q42

Front 281

LAD1
sx
dx

Back 281

Sx: recurrent infxn lung/GI/skin, poor wound healing, delayed umbilical cord separation, cigarette paper scarring

Dx: missing CD18 on flow (poor chemotaxis and leukocyte adhesion)

Front 282

Rac2 deficiency
sx
genetic transmission
function

Back 282

Ras–related C3 botulinum toxin substrate deficiency

Sx: simialr to LAD1 (infxn lung/GI/skin, poor wound heal, delay cord sep, cig paper scarring)
autosomal dominant
adhesion problems d/t RAC involvement in actin cytoskeleton regulation

Front 283

What is the basophil activation test

Back 283

Use IL–3 primed basophils, stim with allergens in vitro, measure LTC4, LTD4, LTE4 by ELISA

Front 284

What is the cellular allergen stimulation test (CAST)

Back 284

Quantitative measure of leukotriene release.
High sensitivity but low specificity for allergy to inhalants.

Front 285

What is the flow cytometric basophil activation test (FAST)

Back 285

Detects CD63 expression of basophils after allergen stimulation

Front 286

This has high diagnositic efficiency for detecting stinging insect allergy

Back 286

CAST and FAST

Front 287

how do you measure interleukins and TNF

Back 287

sandwich ELISA

Front 288

how do you measure prostaglandins?

Back 288

radioimmunoassay (RIA)

Front 289

How do you measure TLR?

Back 289

RT PCR on RNA samples
Flow cytometry
Functional study to test TLR1–9 production by RT–PCR, ELISA and flow

Front 290

how do you measure Fas (CD95, or Apo1)

Back 290

Flow cytometry for surface expression of Fas and FasL
ELISA for sFAS and sFASL
TUNEL reaction to measure apoptosis (labels tdt breaks)

Front 291

how do you measure bradykinin

Back 291

RIA

Front 292

CD1
– aka
– expressed on
– structure
– function

Back 292

(five subsets CD1a–e
CD1a aka Leu6

APCs

Ig superfamily (binds B2 microglobulin)

Presents lipid Ag to T cells

Front 293

CD2
– aka
– expressed on
– structure
– function

Back 293

LFA2, e rosette receptor

early T and NK cells

Ig superfamily

Binds LFA3 (CD58) on APC, activates T's, cytokine, T & APC adhesion, blocks apoptosis of activated T's

Front 294

CD3
– aka
– expressed on
– structure
– function

Back 294

aka –

T cells, plasma cells, macs (NOT ON NK)

Ig superfamily, delta, epsilon, g, z, chains

required for TCR expression/signal transduction

Front 295

CD14
– aka
– expressed on
– structure
– function

Back 295

aka LPS receptor

Macs and monos

pattern recognition receptor

Detects lipotechoic acid (gram +), LPS (gram – , mycobac, fungi), IL–12 & IFNg produxn

Front 296

CD16 (A)
– aka
– expressed on
– structure
– function

Back 296

aka FcgR3A, low affinity IgGR

NK, granulocytes, macs

–

ADCC

Front 297

CD16 (B)
– aka
– expressed on
– structure
– function

Back 297

aka FcgR3B, low affinity IgGR

Neutrophils

Most common IgG FcR

Phagocytosis

Front 298

CD18
– aka
– expressed on
– structure
– function

Back 298

aka Beta2 chain

neut, mac, monos, NK

combines with alphaL(in LFA1/CD11aCD18), alphaM (in MAC1 &CR3/CD11bCD18), alphaX (in p150,95 & CR4/CD11c/CD18)

adhesion/signaling. defect ––> LAD1

Front 299

CD19
– aka
– expressed on
– structure
– function

Back 299

aka –

preB cells, B cells, follicular DCs

co receptor with CD21

B cell ontogeny and activation

Front 300

CD20
– aka
– expressed on
– structure
– function

Back 300

aka L26, MS4A1

B cells (after CD19 expr), follicular DCs

transmembrane phosphoprotein (like Ca influx channel protein)

B cell activation/signaling

Front 301

CD21
– aka
– expressed on
– structure
– function

Back 301

aka CR2, C3d receptor, EBV receptor

Mature B cells and follicular DCs

–

Binds EBV, HHV8, C3d, CD23. CD21loBcells associated c CVID class Ia

Front 302

CD22
– aka
– expressed on
– structure
– function

Back 302

aka Bcell adhesion molecul (BL–CAM)

B cells

–

Blocks B cells

Front 303

CD23
– aka
– expressed on
– structure
– function

Back 303

aka low affinity IgE receptor (FceR2)

activated mature B cells, follicular DCs

type C lectin

Bcell ontogeny & activation

Front 304

CD25
– aka
– expressed on
– structure
– function

Back 304

aka IL2 Ralpha chain

activated B's and T's

–

Suppress self reactive T's & NKs, prevent CTL, cytolysis, elevated in HLH

Front 305

CD27
– aka
– expressed on
– structure
– function

Back 305

aka TNFRSF7

memory B's

TNF receptor superfamily

Bcell activation/Ig prodxn

Front 306

CD31
– aka
– expressed on
– structure
– function

Back 306

aka PECAM–1

endothelial cells, plt, monos, macs

Ig superfamily

cell adhesion and binds CD38

Front 307

CD32
– aka
– expressed on
– structure
– function

Back 307

aka FcgR2 (types a, b, c,)

WBCs

–

Binds Fc of IgG to remove foreign antigens. binds IVIG

Front 308

CD34
– aka
– expressed on
– structure
– function

Back 308

–

adult hematopoietic stem cells

–

adhesion moelcul and binds CD62L

Front 309

CD35
– aka
– expressed on
– structure
– function

Back 309

aka CR1, C3b and C4b receptor

WBCs

–

Binds immune complexes coated with C3b, C4b. Cofactor for factor I mediated cleavage

Front 310

CD40
– aka
– expressed on
– structure
– function

Back 310

aka TNFRSF

APCs

–

T cell dpdt Ig switching, B cells, defective in HIGM3

Front 311

CD44
– aka
– expressed on
– structure
– function

Back 311

–

activated B's and T's

surface glycoprotein

cell adhesion

Front 312

CD45
– aka
– expressed on
– structure
– function

Back 312

aka leukocyte common antigen (LCA)

naive T's (RA) and memory/activated Ts (RO)

protein tyrosine phosphatase

defective in SCID

Front 313

CD46
– aka
– expressed on
– structure
– function

Back 313

aka membrane cofactor protein (MCP)

all cells (no RBCs)

–

cofactor for factor I–mediated cleavage, adenovirus receptor

Front 314

CD49
– aka
– expressed on
– structure
– function

Back 314

aka very late antigen (VLA a–f)

WBCs

–

receptor for fibronectin, VCAM, other cell adhesion

Front 315

CD52
– aka
– expressed on
– structure
– function

Back 315

aka CAMPATH1 antigen

mature lymphs

–

target for Campath (alemtuzumab) used for CLL

Front 316

CD54
– aka
– expressed on
– structure
– function

Back 316

aka DAF (decay accelerating factor)

Hematopoeitic cells, epithelial cells, cell matrix

–

Binds C3bBb & C4b2a to accelerate C3 convertase decay. Deficient in PNH

Front 317

CD58
– aka
– expressed on
– structure
– function

Back 317

aka LFA3

WBCs

–

Binds CD2 and adhesion

Front 318

CD59
– aka
– expressed on
– structure
– function

Back 318

aka protecting, complement regulatory molecule

all cells

–

binds C8 or C9 and blocks MAC formation

Front 319

CD62 (E)
– aka
– expressed on
– structure
– function

Back 319

aka E selectin, ELAM1, SELE

endothelium

–

ligand for CD15s, CD44, CD162. leukocyte rolling. defect ––> LAD2

Front 320

CD62L
– aka
– expressed on
– structure
– function

Back 320

aka LECAM1, SELL, L selectin

T, B, Nk

Lymphocyte homing to HEV of lymphnode. cinbds CD34, CD15s, MAdCAM–1

Front 321

CD62P
– aka
– expressed on
– structure
– function

Back 321

aka PADGEM, SELP, P selectin

plts, activated endothelial cells (membranes of weibel–palade bodies)
–

binds CD162, rolling on activated endothelial cells. Defect ––> LAD2

Front 322

CD64
– aka
– expressed on
– structure
– function

Back 322

aka FCgR1, high affinity IgG receptor

APC (macs, neut, eos)

–

ADCC

Front 323

CD95
– aka
– expressed on
– structure
– function

Back 323

aka Fas, Apo–1, TNFRSF6

activated B's and T's

–

apoptosis when ligated by FasL. Defect––>ALPS

Front 324

CD106
– aka
– expressed on
– structure
– function

Back 324

aka VCAM1

expressed on endothelium, fibroblasts, resp epithelium
–

cell adhesion molecule for VLA–4 (a4b1), a4b7 (act–1, LPAM–1)

Front 325

CD154
– aka
– expressed on
– structure
– function

Back 325

aka CD40L, TRAP

T cells

–

REgulate B cell fxn, Defect ––> XHIGM

Front 326

CD158
– aka
– expressed on
– structure
– function

Back 326

aka KIR, (KIR2DL, NKG2A)

NK & T

–
Binds HLA class I, inhibits Nk or T cytotoxicity

Front 327

CD159
– aka
– expressed on
– structure
– function

Back 327

aka NKG2a

NK

–
modulates NK killing

Front 328

What is OKT3

Back 328

monoclonal antibody clone
recognizes human CD3 in treatment of solid organ transplant rejection and T cell ALL.
Induces activation then apoptosis of T cells causing immunosuppression

Front 329

CD162
– aka
– expressed on
– structure
– function

Back 329

aka P–selectin glycoprotein ligand–1 (PSGL–1)

myeloid cells, activated T cells

–

adhesion with endothelial cells

Front 330

CD178
– aka
– expressed on
– structure
– function

Back 330

aka cd95 ligand, FASL

activated CTLs

–

apoptosis fas–expressing cells

Front 331

Types of receptors required by phagocytic cells

Back 331

mannose receptors
scavenger receptors
toll–like receptors
opsonin receptors

Front 332

Molecules missing in LAD

Back 332

CD18, part of...
– CD11a/CD18 (LFA–1)
– CD11b/CD18 (Mac–1)
– CD11c/CD18 (p150/95)

Front 333

Respiratory burst: Contents of NADPH oxidase system

Back 333

p22 phox
p40 phox
p47 phox
p67 phox
gp91 phox
rac

Front 334

Describe respiratory burst

Back 334

NADPH oxidase converts O2 to superoxide ion ––> superoxide dismutase converts superoxide ion to hydrogen peroxide (H2O2)
1. MPO uses h2o2 to turn CL– and Br– into hypochloraite and hypobromite to kill bacteria
2. iNOS uses NO + h2o2 –> perioxynitrite radicals
3. Perioxidase uses h202+Fe––> hydroxyl radicals

Front 335

CGD is due to _____ which results in infections with __________ organisms (ex: ______).

Back 335

Mutations in NADPH genes

Catalase–positive organisms

Staph aureus, serratia marcescens, Pseudomonas, Salmonella

Front 336

Old test for CGD

Back 336

Nitro blue tetrazolium (NBT) reduction test
– qualitative
– mix neuts with NBT and stim with phorbol myristate acetate
– normal neuts reduce NBT and change color from yellow to blue

Front 337

New test for CGD

Back 337

Dihydrorhodamine 123 (DHR) oxidation test
–quantitative and distinguishes X–linked and autosomal and carriers
– DHR uptake by phagocytes and oxidized to green fluorescent compound by NADPH
– measure fluroescence with flow

Front 338

Another test for CGD (but not main)

Back 338

chemiluminescence assay
– uses scintillation counter to detect light from interaction of ROS with ingested microorganisms
– more sensitive than NBT
–can't distinguish different types
– if pts have CD11/CD18 deficiency ––> normal chemiluminescence with soluble stimulators but delayed after opsonized particles

Front 339

X linked CGD is due to mutation in ______

Back 339

gp91 phox

Front 340

Autosomal recessive CGD is due to a mutation in ____

Back 340

gp47 phox

Front 341

What is a hybridoma?

Back 341

Cell fusion of antibody producing B cell and myeloma cel ––> used to make monoclonal antibodies
– myeloma cells must lack Ab prodxn and hypoxanthine–guaninephosphoribosyl transferase (HGPRT) so that can stop growth in HAT medium

Front 342

How are hybridomas made

Back 342

Immunize mouse with antigen, remove spleen cells making ab ––> use PEG to fuse (spleen cells that have HGPRT gene but don't express) with myeloma cells (lacking Ab and HGPRT gene) ––> take misture o hybrid cells, unfused myeloma and unfused spleen ––> transfer to HAT where only hybridomas survive ––> select hybridoma that makes AB to Ag and clone it.

Front 343

Monoclonals antibodies that end in –omab:
mouse v. human type
means of synthesis

Back 343

– 100% mouse

– completely made in mouse with murine variable and constant regions

mOuse

Front 344

Monoclonals antibodies that end in –ximab:
mouse v. human type
means of synthesis

Back 344

– Chimera. 30–35% mouse

– Combines murine variable with human constant region to avoid production of human antimouse antibodies

miXing human and mouse

Front 345

Monoclonals antibodies that end in –zumab:
mouse v. human type
means of synthesis

Back 345

– Humanized (<10% mouse)

– murine hypervariable or CD regions with rest human Abs

humans at the Zoo are humaniZed

Front 346

Monoclonals antibodies that end in –umab:
mouse v. human type
means of synthesis

Back 346

– Human (no mouse)

– clone human variable regions into bacteriophage, expressed as a fusion protein on vell surface, multiplied in bacteria and select phage with desired Ag spcificity

hUman

Front 347

What does –cept indicate?

Back 347

Fusion proteins created by joining 2+ genes that were originally coded for separate antibodies

Front 348

What does –mab indicate?

Back 348

monoclonal antibody

Front 349

Nomenclature of product source identifiers:

a, e, i, o, u,
xi
axo
xizu

Back 349

rat, hamster, primate, mouse, human
chimera
rat/mouse
humanized and chimeric

Front 350

Abciximab
– target antigen molecule
– application

Back 350

Integrin alpha2beta3

cardiac ischemic complications

Front 351

Adalimumab
– aka
– target antigen molecule
– application
– AE
– testing after taking

Back 351

Humira
TNFalpha
RA, ankspond, Crohn's, psor arthr, psor, JIA
Injxn rxn, URI, TB, malig, hepB, demyelinating dz, cytopenias, heart failure, lupus
TB annually, watch for heart failure, LFT, no live vaccines

Front 352

Alemtuzumab (Campath)
– target antigen molecule
– application

Back 352

CD52

CLL

Front 353

Basiliximab
– target antigen molecule
– application
– AEs

Back 353

IL2 receptor alpha chain (CD25)

transplant rejection

N/abdpain, constipation, UTI/URI

Front 354

Belimumab
– target antigen molecule
– application

Back 354

B cell activating factor

SLE

Front 355

Bevacizumab
– target antigen molecule
– application

Back 355

Vascular endothelial growth factor (VEGF)

colorectal cancer

Front 356

Brentuximab vedotin
– target antigen molecule
– application

Back 356

CD30

anaplastic large cell ymphoma (ALCL), Hodgkin's lymphoma

Front 357

Canakinumab (ILaris)
– target antigen molecule
– application
– AE s
– precautions

Back 357

IL–1beta

Cyropyrin associated periodic syndrome (CAPS)
injection site reaction, incr infection, TB reactivation, malignancies
eval for latent TB, avoid live vaccines, watch lipids

Front 358

Cetuximab (ERbitux)
– target antigen molecule
– application

Back 358

Epidermal growth factor receptor

Colorectal cancer, head and neck cancer

Front 359

Certolizumab pegol
– target antigen molecule
– application
– AE
– testing after taking

Back 359

TNF alpha
Crohn's disease, RA
serious infxn, malignancie, CHF
TB annually, watch for heart failure, LFT, no live vaccines

Front 360

Daclizumab
– target antigen molecule
– application
– AEs

Back 360

IL–2 receptor alpha chain (CD25)

transplant rejection

Front 361

Denosumab
– target antigen molecule
– application

Back 361

RANK ligand

postmenopausal osteoperosis, osolid tumor bony mets

Front 362

Eculizumab (Solairis)
– target antigen molecule
– application

Back 362

Complement system protein C5

Paroxysmal nocturnal hemoglobinuria (PNH)

Front 363

Efalizumab (Raptiva)
– target antigen molecule
– application

Back 363

CD11a

Psoriasis

Front 364

Gemtuzumab
– target antigen molecule
– application

Back 364

CD33

AML

Front 365

Golimumab
– target antigen molecule
– application
– AE
– testing after taking

Back 365

TNF–alpha

Rheum arthritis, psoriatic arthritis, ankylosing spondylitis
URI, serious infxn, TB, fungal, hep B reactivation, lymphoma, CHF, demyelinating dz, cytopenia
TB annually, watch for heart failure, LFT, no live vaccines

Front 366

Ibritumomab tiuxetan
– target antigen molecule
– application

Back 366

CD20

Non hodgkin's lymphoma

Front 367

Infliximab
– aka
– target antigen molecule
– application
–AEs
– testing while taking

Back 367

Remicade
TNF alpha
RA, Ankspond, Crohn's/UC, Psor arthritis, psorsis
acute rxns, infxns, TB, sepsis, T cell lymphoma
TB annually, watch for heart failure, LFT, no live vaccines

Front 368

Ipilimumab (MDX–101)
– target antigen molecule
– application

Back 368

CTLA–4

Melanoma

Front 369

Keliximab
– target antigen molecule
– application

Back 369

CD4

Multiple sclerosis

Front 370

Mepolizumab
– target antigen molecule
– application

Back 370

IL–5

Hypereosinophilic syndrome

Front 371

Murmonab–CD3 (OKT3)
– target antigen molecule
– application

Back 371

T cell CD3 receptor

transplant rejection

Front 372

Natalizumab
– target antigen molecule
– application

Back 372

alpha 4 chain of integrin molecule

multiple sclerosis

Front 373

Ofatumumab
– target antigen molecule
– application

Back 373

CD20

CLL

Front 374

Omalizumab
– target antigen molecule
– application

Back 374

FceR1

Asthma

Front 375

Palivizumab (Syangis)
– target antigen molecule
– application

Back 375

RSV F protein

infants with BPD

Front 376

Panitumumab
– target antigen molecule
– application

Back 376

epidermal growth factor receptor (EGFr)

colorectal cancer

Front 377

Ranibizumab
– target antigen molecule
– application

Back 377

vascular endothelial growth factor (VEGF–A)

macular degeneration

Front 378

Rituximab
– target antigen molecule
– application

Back 378

CD20

autoimmune diseases, B cell lymphomas

Front 379

Tocilizumab
– target antigen molecule
– application

Back 379

anti–IL6R

Rheumatoid arthritis

Front 380

Tositumomab
– target antigen molecule
– application

Back 380

CD20

Non–hodkin's lymphoma

Front 381

Trastuzumab
– target antigen molecule
– application

Back 381

ERbB2

Breast cancer

Front 382

Etanercept
– aka
– target antigen molecule
– application
– AEs
– testing after taking

Back 382

– aka enbrel
–TNF alpha antagonist (and TNF beta)
–Fusion of TNFreceptor with IgG1 Fc segment (adds stability and deliverability)
–RA, psoriatic arthritis, ank spond, plaque psoriasis, juvenile idiopathic arthritis
– mild inject rxn, infection, sepsis, neuro/heme/malig
–TB annually, watch for heart failure, LFT, no live vaccines

Front 383

How do normal host cells prevent immune complex activation?

Back 383

factor H and I inactivate C3b to iC3b inhibiting IC formation

Front 384

How are ICs eliminated

Back 384

After IC formation, C3b binds ICs, and then binds CR1 on RBCs. RBCs go to the liver and spleen ––> Macs eliminate the ICs

Front 385

IC Mediated diseases

Back 385

SLE (DNA, nucleooproteins, others)
serum sickness (various ag)
post–strep glomerulonephritis (strep cell wall ag)
polyarteritis nodosa (HBV surface ag)
cryoglobulinemia (Hep C virus, RF)

Front 386

Laboratory testing for circulating ICs

Back 386

–C1q, C4b, C3b
–Conglutinin (binds iC3b)
–Raji cell (Burkitt's cell line with receptors for C1q, C3b, C3bi, C3d, and ICs bind to RAJI cells which can be detected by antihuman IgG)
–C1q binding assay (radiolabeled C1q binds cicurlating ICs)

Front 387

Most common cause for low complement

Back 387

Poorly handled specimen, repeat the test

Front 388

How is AH50 tested?

Back 388

Measure lysis of unsenitized rabbit RBCs

Front 389

How is CH50 tested?

Back 389

Measure lysis of sheep RBCs, sensitized with rabbit IgM

Front 390

How is MBL pathway function tested?

Back 390

Measured by ELISA. Coat wells with mannan and incubate with patient serum. Measure activation by prodxn of C4b and C4d

Front 391

Difference between acquired v. hereditary complement defects

Back 391

Acquired has low complement and hereditary has absent complement.

Acquired usually has multiple low components, while hereditary usually only has one.

Front 392

Component split product testing
– purpose
– types

Back 392

Purpose: to detect if activation has occurred (which may be masked by decreases in complement components from consumption)
–C4a/d ––> classical or lectin
–Bb ––> alternative pathway
– C3a, iC3b, Ca, soluble Cb–9 ––> terminal pathway activation

Front 393

Predictor of severe disease and poor outcome in lupus nephritis

Back 393

C3 and C4

Front 394

Total deficiency of C3 associated with _____

Back 394

membranoproliferative glomerulonephritis

Front 395

Difference between HAE and Acquired AE

Back 395

HAE has low C1 inh level and/or function (except type 3) but normal C1q

AAE has low inhibitor, function, and low C1q.

Both have low C4, which can be used as a screening test.

Front 396

C1q autoantibody associated with ____

Back 396

Hypocomplementemic vasculitis

Front 397

C1 inhibitor autoantibody associated with ____

Back 397

Some patients with acquired angioedema

Front 398

C3 nephritic factor associated with

Back 398

SLE (some pts)
Dense deposit disease (MPGN type 2)
partial lipodystrophy

Front 399

Low TRECS seen in

Back 399

SCID
22q11 deficiency
down syndrome (in newborns)
HIV infection

Front 400

RT PCR can be used to diagnosis____

Back 400

genetic diseases
studying RNA viruses (influenza A and HIV)

Front 401

In situ hybridization used for diagnosis of...

Back 401

ALL
DiGeorge
Down's

Front 402

B cells originate in _____

Back 402

Mostly bone marrow
Also fetal liver and neonatal spleen

Front 403

Growth factor produced by stromal cells in bone marrow and thymus, required for B and T cell development

Back 403

IL–7

Front 404

After negative selection, where do B cells go

Back 404

Migrate from bone periphery, to central sinusoid along reticulum processes. Enter the central sinus and blood vessels to get to secondary lymphoid tissues

Front 405

Thymus is formed from _____

Back 405

endoderm and mesoderm of 3rd and 4th pharyngeal pouche

Front 406

Thymic zones

Back 406

Sub capsular zone
Cortex
Medulla

Front 407

What does the subcapsular zone contain

Back 407

most primitive lymphocyte progenitors

Front 408

What does the cortex of the thymus contain

Back 408

small lymphocytes undergoing division, expression, and selection of T cell receptors

Front 409

What does the medulla of the thymus contain

Back 409

lymphocytes undergoing final stages of selection/maturation
Hassall's corpuscles (granular cells surrounded by epithelial cells)

Front 410

Most T cells go to the thymus for maturation, but some migrate to ____.

Back 410

cryptopatches, tiny mucosal lymphoid aggregates under the intestinal epithelium to form specialized T cell populations

Front 411

Anatomy of the lymph node

Back 411

Afferent and efferent lymphatic vessels
Capsule (outermost layer)
Subcapsular or marginal sinus (where afferent lymphatics drain)
Cortex (contains B cell rich follicles and T–cell parafollicular areas)
Medulla (less dense, lymphs, macs, plasma cells, granulocytes)
HIgh endothelial venules

Front 412

Spleen contains ______ of total blood lymphocytes and is mostly ______ pulp (___%)

Back 412

25%

red pulp (80%)

Front 413

Spleen has no afferent/efferent lymphatic supply

Back 413

No afferent.
Lymphocytes come in through splenic artery vasculature and out through efferent lymphatic vessels

Front 414

Splenic anatomy

Back 414

Periarteriolar lymphid sheath (inner region of white pulp with T cels)

B cell corona (surrounds PALS and B cell follicles)

Splenic artery, (branches along trabeculae of capsule)

Front 415

Sinuses and their drainage

Back 415

sinuses listen to the following radio channels
FM AM PS SS

Frontal sinus, Maxillary sinus, Anterior ethmoids drain into the Middle Meatus

Posterior ethmoids, Sphenoid sinus drain into Sphenoethmoidal recess above the Superior turbinate

Front 416

Paranasal sinus absent at birth

Back 416

Frontal sinus

Front 417

From a coronal view:
sinus at the top
fleshy part in middle
fleshy part in bottom
sinus at the bottom

Back 417

Ethmoid sinus
Concha bullosa
Inferior turbinate
Maxillary sinus

Front 418

From a sagittal view
sinus in hte middle
sinus in the back

Back 418

posterior ethmoid sinus
Sphenoid sinus

Front 419

Infections to middle ear travel from nasopharynx via ____

Back 419

pharyngeal ostium of eustachian tube

Front 420

tympanic membrane is innervated by ____ which only perceives ______

Back 420

auriculotemporal nerve

pain

Front 421

Asthmatic sputum contains...

Back 421

Curschmann's spirals (mucus corkscrews)
Creola bodies (epithelial cell clusters)
Charcot–Leyden crystals: eos and granule membrane lysophospholipase
Eos
Metachromatic cells

Front 422

Asthma v. COPD
– surface epithelium
– reticular basement membrane
– bronchial mucous cells
– bronchial smooth muscle
– mucus histochemistry
– cellular infilatrate
– cytokines

Back 422

A: Fragile; C: not fragile
A: thickened/hyaline; C: normal
A: poss metaplasia; C: Meta/hyperplasia
A: enlarged in large airways; C: small airways
A: no change; C: Incr acidic glycoprotein
A: CD3/4/25+, marked eos/mast; C: CD3/8/ 68/25+; VLA–1+ HLADR+, mild eo, incr mast
A: hyperinflation, airwayplug; C: mucus, small airway involvement, prominent emphysema

Front 423

Epidermal cells

Back 423

Keratinocytes
Melanocytes
Langerhan's cells
epidermal lymphocytes (mostly CD8+)

Front 424

Cytokines and receptors produced by keratinocytes

Back 424

MHCII proteins
IL–1
antimicrobial peptides
TSLP
RANKL

Front 425

Langerhans' cell histiocytosis
pathophys:
sx:

Back 425

clonal proliferation of langerhans' cells (immature DCs)

fever, lethargy, wt loss, multifocal orga involvement (bone, skin, BM, LN, endocrine, lungs)

Front 426

Layers of the basement membrane (dermoepidermal junction)

Back 426

Lamina lucida (extracellular part o hemidesmosomes)
Lamina densa (collagen IV and laminin network)
Sublamina densa (anchoring fibrils, collagen VII)

Front 427

Cells in Dermis

Back 427

Fibroblastas
Mast cells
Macrophages
Dermal dendritic cells
Dermal T cells

Front 428

Fibroblasats secrete

Back 428

eotaxin (if stim by IL–4)
IL–1
IL–6

Front 429

Dermal dendritic cells
–labeled by
express

Back 429

labeled by factor XIIIa
express DC–SIGN/CD209+, CD1b, CD1c, CD11c

Front 430

Dermal T cells express a carbohydrate epitope called _____ involved in _______.

Back 430

CLA–1 (cutaneous lymphocyte antigen)

homing to the skin

Front 431

Pemphigus Vulgaris
– presentation
– serum abs
– tissue immunofluorescence

Back 431

Flaccid>tense bullae, crusting, Nikolsky's sign (scalp, chest, intertriginous areas, oral mucosa)

IgG autoAbs to desmoglein 1 and 3

Epidermal IgG and C3 cell surface staining of suprabasal layers

Front 432

Pemphigus foliaceous
– presentation
– serum abs
– tissue immunofluorescence

Back 432

Superficial bullae, erosions, scale with crusting, Nikolsky's

IgG autoAbs to desmoglein 1

Epidermal igG and C3 cell surface staining of granular layer

Front 433

Paraneoplastic pemphigus
– presentation
– serum abs
– tissue immunofluorescence

Back 433

flaccid bullae, lichenoid/EMultiforme like lesions, affects mucosa, Nikolsky's

IgG autoAbs to plakin proteins, desmoglein 1, 3

Epidermal igG and C3 cell surface and basement membrane zone staining

Front 434

IgA pemphigus
– presentation
– serum abs
– tissue immunofluorescence

Back 434

pustules, erythema, flaccid lakes of pus

IgA autoAbs to desmoglein 3, desmocollin 1

Epidermal IgA cell surface staining

Front 435

Bullous Pemphigoid
– presentation
– serum abs
– tissue immunofluorescence

Back 435

tense>flaccid bullae, pruritus, Nikolsky's (10%)

IgG autoAbs to BP180, BP230

Linear basement membrane zone IgG and C3

Front 436

Cicatricial pemphigoid
– presentation
– serum abs
– tissue immunofluorescence

Back 436

Erosions, rare vesicles or bullae, scarring sequelae

IgG autoabs to integrins, BP180, laminins

Linear basement membrane zone IgG and C3

Front 437

Herpes gestationis
– presentation
– serum abs
– tissue immunofluorescence

Back 437

tense bullae, 2nd tri pregnancy, pruritis

complement fixing, basement membrane zone and epidermal. AutoAb to BP180

Linear basement membrane zone C3

Front 438

Epidermolysis bullosa acquisita
– presentation
– serum abs
– tissue immunofluorescence

Back 438

Tense bullae, erosions, scarring (often at sites of trauma or oral mucosa)

IgG autoAb to collagen VII

Linear basement membrane zone C3 and IgG

Front 439

Linear IgA bullous dermatosis
– presentation
– serum abs
– tissue immunofluorescence

Back 439

tense bullae, oral involvement

IgA autoab, LABD97, LAD–1

LInear basement membrane zone IgA

Front 440

If suspected immunobullous disease always get _______

Back 440

2 biopsies
one shave bx of intact vesicle/bulla for H&E
one perilesional tissue for Immunofluorescence

Front 441

Dermatitis herpetiformis
– presentation
– serum abs
– tissue immunofluorescence

Back 441

small bullae on elbows/knees, pruritic, assoc with celiac

IgA autoAb to epidermal transglutaminase

Granular basement membrane zone IgA with stippling in dermal papillae

Front 442

Bullous lupus erythematosus
– presentation
– serum abs
– tissue immunofluorescence

Back 442

Tense bullae, photo distributed

IgG autoAb to collagen VII

Linear basement membrane zone IgG; may show granular IgM and c3 basement membrane zone

Front 443

Which condition (pemphigus vulgaris, bullous pemphigoid, or dermatitis herpetiformis) is the most likely to show a positive Nikolsky's sign?

Back 443

pemphigus vulgaris

Front 444

Which condition(s) (pemphigus vulgaris, bullous pemphigoid, or dermatitis herpetiformis) are extremely pruritic

Back 444

bullous pemphigoid, dermatitis herpetiformis

Front 445

In pemphigus vulgaris and bullous pemphigoid, what two molecules react with antigens in the basement membrane zone?

Back 445

Immunoglobulin G and C3 complement

Front 446

Autoimmune skin disease: SLE
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 446

peripheral, homogenous, nucleolar, speckled

nDNA/dsDNA, ssDNA, histones, nucleolar RNA, ribonucleoproteins, cardiolipin, Sm (smith), U1–snRNP, HMG–17

2+ granular Ig/complement deposits at basement membrane zone (IgG, M, and/or A with c3) in involved & uninvolved skin.

Front 447

Autoimmune skin disease: Discoid lupus
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 447

No abs circulating

non detected

2+ granular Ig/complement deposits at basement membrane zone (IgG, M, and/or A with c3) in involved

Front 448

Autoimmune skin disease: Subacute cutaneous lupus erythematosus
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 448

Speckled

SS–A (Ro) and SS–B (La)

particulate intercellular staining with/without granular immune deposits at basement membrane zone

Front 449

Autoimmune skin disease: Neonatal lupus
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 449

Speckled

SS–A (Ro) and SS–B (La)

Granular igG (transplacental) at basement membrane zone

Front 450

Autoimmune skin disease: Drug induced lupus
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 450

peripheral homogenous

Histones

granular immune deposits at basement membrane zone

Front 451

Autoimmune skin disease: Cutaneous scleroderma
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 451

Peripheral

SCL–70, SS–A(Ro), SS–B(La)

no characteristic changes (occ vascular staining)

Front 452

Autoimmune skin disease: Limited Scleroderma (CREST)
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 452

Centromere

centromere, SCL–70, U1–snRNP, HMG17


no characteristic changes (occ vascular staining)

Front 453

Autoimmune skin disease: Progressive systemic sclerosis
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 453

Nucleolar speckeled

SCL–70, U1 and U3–snRNP, fibrillarin, RNA pol I, II, III

no characteristic changes (occ vascular staining)

Front 454

Autoimmune skin disease: Dermatomyositis, polymyositis
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 454

Speckled, nucleolar

Jo–1, PM–SCL, MI–2, U1–snRNP, SS–a (Ro)

no characteristic changes (occ vascular staining and lichenoid features)

Front 455

Autoimmune skin disease: SJogren's
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 455

fine speckled, nucleolar

Ss–A (Ro), SS–B (La), histones, and U1–snRNP

no characteristic changes (occ vascular staining)

Front 456

Autoimmune skin disease: Mixed connective tissue disease
– indirect immunofluorescence pattern
– Autoabs a/which nuclear antigens
– direct IF of tissue

Back 456

speckled

U1–snRNP and PM–scl

no characteristic changes (occ vascular staining, granular deposits at BMZ, lichenoid features)

Front 457

What are defensins?
– cytokines that stimulate synthesis

Back 457

antimicrobial peptides in the skin, abundant in neutrophil granules, that kill bacteria and fungi

IL–1 and TNF stimulate increased synthesis

Front 458

What do M cells in the GALT do?

Back 458

Microfold cells have microvilli that help in antigen sampling

Front 459

How do lymphocytes reach and leave the GALT

Back 459

reach via high endothelial venules (HEV)

leave via efferent lymphatics

Front 460

Which cytokines are implicated in the pathogenesis of EoE

Back 460

IL–5 and Eotaxin 3

Front 461

Endoscopy findings associated with EoE

Back 461

greater than 15 eos/hpf while on PPI x 4–8 weeks
linear furrows
white papules/plaques
concentric rings

Front 462

How to screen for celiac?

Back 462

tTG IgA level and serum IgA

Front 463

Celiac is due to sensitivity to_____.

Back 463

gliadin (alcohol soluble portion of fluten)

Front 464

CEliac disease causes the following histopathologic findings.

Back 464

Loss of intestinal villi
crypt hyperplasia
llymphocytic infiltrate

Front 465

CEliac disease symptoms

Back 465

malabsorption, chronic diarrhea, steatorrhea, abdominal distension, flatulance, weight loss, failure to thrive,
In absence of GI sx: oral ulcers, dermatitis herpetiformis

Front 466

What is Type I error?

Back 466

When you falsely reject the null hypothesis (think something is significant when it is not), alpha

Front 467

What is Type II error?

Back 467

When you fail to reject the null hypothesis, when it is actually false (think there's no difference when there actually is) (beta)

Front 468

What is the odds ratio?

Back 468

Odds that you were exposed give you have the disease/ odds that you were not exposed given that you don't have the disease

Front 469

What is the relative risk

Back 469

Ratio of the risk of disease among people who are exposed / risk among people who are not exposed

Front 470

What is sensitivity?

Back 470

Likelihood of testing positive if you have the disease

Front 471

What is specificity

Back 471

Likelihood of testing negative if you do not have the disease

Front 472

Clinical Evidence Ratings (I, II–1, II–2, II–3, III)

Back 472

I: 1+ good RCT
II–1: 1+ good controlled trial (no randomization)
II–2: cohort/case–ctrl
II–3: time series
III: opinion, descriptive studies, expert committee reports

Front 473

Clinical recommendations (A, B, C, D)

Back 473

A: good scientific evidence, benefits> risks
B: fair scientific evidence, benefits > risks
C: fair scientific evidence, benefits = risks
D: fair scientific evidence, risk > benefits
I: lacking evidence, cannot assess risk/benefit

Front 474

Belmont report principles

Back 474

respect for persons (autonomy)
beneficience
justice

Front 475

Elements of informed consent

Back 475

competence
disclosure
understanding
voluntariness
consent

Front 476

What symptoms of allergic rhinitis are caused by these mediators?
histamine:
PGD2:
leukotrienes:
kinins:

Back 476

histamine: itch, sneeze, rhinorrhea
PGD2: nasal congestion
leukotrienes: nasal congestion
kinins: nasal congestion and/or blockage

Front 477

Immediate allergic response in AR due to _____ cells and ______ mediators

Back 477

Mast cells
preformed mediators (histamine, tryptase, kinins like kallidin and bradykinin)
newly formed mediators (PGD2, LTC4, D4, E4)

Front 478

Late allergic response in AR due to ______ and ____ mediators

Back 478

BAsophils, eosinphils, infiltrating lymphocytes (esp Th2 CD4+)

Il3, IL4, IL–13, GMCSF, stem cell factor, eotaxin, RANTES (CCL5)

Front 479

Differential for non allergic rhinitis

Back 479

NARES
Vasomotor
Meds
Atrophic
Hormonal
Infectious (cold)
Occupational (flour in bakers, latex HCWs, pet dander)
Misc (anatomic, tumor, systemic dz, CSF rhinorrhea)

Front 480

Vasomotor rhinitis
triggers:
treatment:

Back 480

triggers: irritant, gustatory, cold, temp, strong scents (tobacco, perfume, cleaners)
treatment: intranasal ipratropium

Front 481

NARES
sx:
tx:

Back 481

stands for nonallergic rhinitis with eosinophilic syndrome

Sx: AR sx, eosinophilia on nasal smear in absence of incr IgE, middle aged adults, nasal polyps (may be prodrome to AERD)

Tx: intranasal steroids

Front 482

Atrophic Rhinitis
– features
– tx

Back 482

Non inflammatory usu in middle–aged and elderly, but also females at onset of puberty
Sx: nasal congestion, nasal pain from dryness, nasal crusting, foul smell
Tx: nasal saline irrigation, topical abx

Front 483

Medication induced rhinitis – common meds

Back 483

ASA, NSAIDS,
decongestants (rebound)
alphablockers,
beta blockers, anti–HTN
ACEIs
OCPs
sildenafil
intranasal cocaine or methamphetamine

Front 484

Hormone induced rhinitis
– typical situations
– tx

Back 484

OCP, pregnancy, menstrual, hypothyroid

steroids don't help rhinitis of pregnancy

Front 485

For CSF rhinorrhea, usually have history of ______ and you should check _____.

Back 485

Trauma

Beta2–transferrin

Front 486

How does nasal congestion or rhinorrhea develop in hypothyroidism?

Back 486

TSH increases edema in turbinates

Front 487

Common pathogens for acute bacterial sinusitis (and less frequent pathogens).

Back 487

Common: strep pneumo, Moraxella catarrhalis (100% beta lactamase positive), Haemophilus influenzae (50% beta lactamase positive) ––> need b–lactamase inhibitor

Less common: Staph aureus, group A strep, anaerobes

Front 488

Diagnosis of Acute Rhinosinusitis

Back 488

2 Major or 1 major and 2 minor

Major: purulent rhinorrhea, nasal congestion/obstruction, facial congestion, facial pain, fever, hyosmia/anosmia

Minor: headache, ear pain/pressure, bad breath, dental pain, fatigue, cough

Front 489

Gravity cannot drain this sinus

Back 489

Maxillary sinus

Front 490

Treatment of acute bacterial rhinosinusitis

Back 490

1. Augmentin x 10–14 d peds (5–7 d adult)
2. PCN allergic: Fluoroquinolone or doxy

high resistance to macrolides and bactrim

Front 491

Definition of recurrent sinusitis

Back 491

>=4 episodes in 1 year ––> eval for underlying inflammation, allergy, immunodeficiency, or anatomic abnormalities

Front 492

Chronic rhinosinusitis
– duration
– diagnosis

Back 492

>8–12 weeks
>=2 symptoms (nasal obstruction/congestion, facial pain/pressure/fullness, purulent anterior/posterior rhinorrhea, hyposmia/anosmia) for >12 weeks + documented inflammation (purulence/edema in middle meatus, polyps, imaging)

Front 493

Chronic rhinosinusitis
– workup

Back 493

quantitative immunoglobulin and pneumococcal titers
ciliary function tests
sweat test
HIV
sinus puncture with cultures

Front 494

Inflammatory mediators in chronic rhinosinusitis

Back 494

IL–1beta, Il–6, IL–8

Front 495

_______ is a risk factor for chronic rhinosinusitis

Back 495

Haller cell (a pneumatized ethmoid cell that blocks the ostiomeatal complex)

Front 496

Treatment for chronic rhinosinusitis

Back 496

ABx if acute
Treat underlying conditions (AR, GERD, AERD, CF)
Topical nasal steroids
Surgery if complications or medical tx failure

Front 497

Complications of sinusitis

Back 497

orbital cellulitis
subperiosteal abscess
cavernus sinus thrombosis
meningitis
subdural/epidural brain abscess
osteomyelitis
mucocele

Front 498

CRS with nasal polyps
– differences from CRS without

Back 498

Increased incidence of ...
anosmia
dustmite sensitization
eosinophils on biopsy
asthma
AERD
allergic fungal rhinosinusitis
LESS facial pain

Front 499

Inflammatory mediators in CRS with and without polyps

Back 499

CRS without NP: IL–3, GM–CSF, PGE2

CRS with NP:Il–5, IgE, eotaxin

Both: Eosinophil cationic protein, LTC4/D4/E4/B4, Lipoxin A4

Front 500

Recurrent acute otitis media is defined as...

Back 500

>=3 episodes in 6 months OR
>=4 episodes within 1 year (with 1 in last 6 months)

Front 501

Otitis media with effusion can result in

Back 501

– hearing loss (leading cause, usu 25 dB)
– language delay

Front 502

Treatment of otitis media with effusion

Back 502

3–month exams with baseline hearing test, until resolution or hearing loss documented

If structural damage, recurrent OME, or hearing loss ––> surgery (myrigotomy +/– tubes, adenoidectomy)

Front 503

Extracranial complications of otitis media

Back 503

TM perforation
Chronic acute otitis media
Labyrinthitis or vestibular disturbance
Mastoiditis
Facial paralysis
Subperiosteal abscess

Front 504

Intracranial complications of otitis media

Back 504

Meningitis
Brain abscess
Sinus thrombosis
Epidural abscess
Subdural empyema

Front 505

Complications of otitis media with effusion

Back 505

Hearing loss
TM retraction
Cholesteatoma

Front 506

Allergic conjunctivitis is marked by ______ of the conjunctiva

Back 506

limbal sparing

Front 507

Best treatments for allergic conjunctivitis

Back 507

H1 receptor antagonists and mast cell stabilizers (olopatadine, ketotifen, azelastine)

Front 508

Vernal keratoconjunctivitis
– features
– epidemiology
– Tx

Back 508

– sight threatening, bilateral chronic conjunctival inflammation, severe photophobia, intense itching, papillary hypertrophy, ptosis, thick/ropey discharge, HornerTrantas dots
– young atopic males living in warm/dry climate
– Allergen avoidance (occlusive eye tx), high dose pulse topical steroids, mast cell stabilizers (cromolyn), oral antiH, abx/steroid ointments

Front 509

Atopic keratoconjunctivitis
– features
– epidemiology
– treatment

Back 509

– sight threatening bilateral chronic conjunctival/eyelid inflammation, with chronic pruritus and burning. loss of vision from keratitis, coneal infiltrates, scar, keratoconus, cataracts
– teenagers/young adults with hx atopic derm
– allergen avoidance, transient topical corticoseteroid, cromolyn or dual acting meds (h1 blocker and mast cell stabilizer)

Front 510

Gian papillar conjnctivitis
– features
– epidemiology
– treatment

Back 510

– chronic bilateral inflammation with foreign body intolerance. Ocular itching after lens removal, AM mucus, photophobia, lens intolerance
– affects 20% of contact lens wearers, many with allergy
– reduce contact lense wearing

Front 511

Sight threatening conditions

Back 511

acute glaucoma
scleritis
iritis
uveitis
herpes simplex keratitis

Front 512

Red eye danger signs (concerning for sight loss)

Back 512

photophobia
blurry vision
severe pain
colored halos
abornmal pupil size
ciliary flush

Front 513

New onset dermatitis in adult with no history of childhood eczema, asthma, allergic rhinitis ––> consider ______

Back 513

cutaneous T cell lymphoma (requires a skin biopsy)

Front 514

_____ % of patients with atopic dermatitis will develop asthma.

Back 514

>50%

Front 515

Atopic dermatitis has two types of Ag presenting dendritic cells

Back 515

Langerhans cells
inflammatory dendritic epidermal cells (IDECs0

Front 516

These chemokines are specific for Atopic dermatitis (3)

Back 516

Cutaneous T cell attacting kemochine (cTACK) and CCL27 and thymus and activation regulated chemokine (TARC)

Front 517

Deficienciy in ____ expression in the setting of atopic dermatitis, results in impaired killing of _____.

Back 517

hBD–3 (defensin)
S. Aureus

Front 518

a ________ polymorphisms that results in impaired expression has been associated with severe atopic dermatitis with frequen bacterial infections

Back 518

TLR2–gene

Front 519

Loss of function variants of filaggrin results in atopic dermatitis that is

Back 519

earlier onset
more severe
persistent
increased risk of assthma

Front 520

Cytokines involved in early acute atopic dermatitis

Back 520

IL–4, IL–13

Front 521

Cytokines involved in chronic atopic dermatitis

Back 521

IL–5, IL–12, IFN gamma

Front 522

Cells involved in atopic dermatitis

Back 522

T cells (CD3+, cd$+, CD45RO, CD25+, HLADR+)
Langrehans cells
Inflammatory dendritic epidermal cells
Eosinophils

Front 523

Langerhans cells that express Fc epislon RI lack _____ and cotain ______ granules

Back 523

beta chain

Birbeck

Front 524

IDECs, once activated by FcepisilonRI, stimulate _____ to produce ____, leading to a switch from ____ to _______.

Back 524

naive T cells

IFN–gamma

Th1

H2

Front 525

Filaggren is expressed _______ (in the nose and lungs)

Back 525

In the anterior vestibulum of the nose

Front 526

Which has more FceRI expression: Langerhans cells or IDECs

Back 526

IDECS

Front 527

Extrinsic v Intrinsic atopic dermatitis
– aka
– differences
– similarities

Back 527

– aka Atopic eczema (70–80%) v. Nonatopic
–Diff: Atopic has IgE mediated sensitization, incr production of IL–4, 13, 5
– Same: eosinophilia, IL–10 plays immune modulating role

Front 528

Anterior cataracts are associated with _____, Posterior cataracts are associated with ____.

Back 528

atopic keratoconjunctivitis
Prednisone

Front 529

Common organisms of infections in the setting of atopic dermatitis

Back 529

S aureus
HSV
molluscum contagiosum
Pityrosporum orbiculare (aka malassezia furfur)
Pityrosporum ovale

Front 530

Diff'l Diagnosis of atopic dermatitis:
Chronic dermatoses (5)

Back 530

Netherton syndrome (congenitally acquired scaly dermatitis with short brittle bamboo hair)
Seborrheic dermatitis (areas with sebaceous glands)
Contact dermatitis
Nummular eczema (demarcated edges, limb)
Lichen simplex chronicus (response to Incr rubbing)

Front 531

Diff' Diagnosis of stopic dermatitis:
Other categories

Back 531

Infxn: Scabies, HIV associated
Malignancy: Cutaneous T cell lymphoma (adult)
Immune deficiency: Wiskott Aldrich, SCID, Hyper–IgE, IPEX, Dock8
Metabolic: Zinc, Pyridoxine (VitB6 & niacin), Multiple carboxylase, PKU deficiency
Proliferative – Letterer–Siwe disease

Front 532

eDescribe Zinc deficiency

Back 532

aka acrodermatitis enteropathica
perioral rash
necrotic areas around nose
infant with eczema who doesn't respond to steroids

Front 533

Describe pyridoxine deficiency

Back 533

aka Vit B 6 and niacin deficiency
seizures
irritability
cheilitis

Front 534

Describe multiple carboxylase deficiency

Back 534

infant with skin rash
alopecia
lethargy

Front 535

Describe phenylketonuria

Back 535

pale pigmentation
blue eyes
scleroderma
if untreated ––> mental retardation

Front 536

Describe letterer–Siwe disease

Back 536

Infants with anemia
thrombocytopenia
lymphadenopathy
histiocytic infiltration of liver, spleen, lymph nodes

Front 537

What is eczema vaccinatum and what deficiency can contribute to it?

Back 537

Eczema in the setting of smallpox vaccination.

Deficiency of LL–37 antimicrobial peptide

Front 538

Hallmark of fatal asthma

Back 538

neutrophilic accumulation

Front 539

Proinflammatory processes in asthma

Back 539

upregulation of adhesion molecules
arachidonic acid metabolite production (LTB4)
Chemokine synthesis (IL–8, MCP1, RANTES)
Cytokine secretion (IL–1b, 4,5,9,10,13,16, TNFa, IL–6, GMCSF, TGFb)

Front 540

oral vitamin D induces the production of this peptide in atopic invidiuals

Back 540

Cathelicidin

Front 541

Genetic factors associated with asthm

Back 541

Chromosome 5q, IL–4 gene cluster (polymorphism ––> incr IL–4 transcription, Beta2 gene polymorphisms)
Cd14 (polymorphism ––> high CD14, incr recognition of LPS)
Chromosome 20p13 (locus for ADAM33 ––> role in smooth muscle hyperreactivity)
Chitinase like proteins

Front 542

Differential for asthma

Back 542

COPD
CHF
PE
mechanical obstruction (tumor)
GERD
Bronchiectasis
Lower resp tract infection
VCD

Front 543

Asthma Predictive Index

Back 543

One of major:
– parental asthma
– MD dx atopic dermatitis
– sensitization to aeroallergens

2+ minor:
– food sensitizaiton
– >4% eos
– Non URI wheezing

Front 544

For children <4 years old, use long–term control therapy for asthma if...

Back 544

4+ wheezing (>1 d and affected sleep) with + asthma predictive index
Pts needing sx treatment >2d/week x >4weeks
Pts requiring oral steroids 2/6months
Periods of incr risk (URI season, pollen)

Front 545

Asthma terms:
Impairment
Risk
SEverity
Control

Back 545

Impairment = freq/intensity of sx and fxnal limitation of patient
Risk = likelihood of exacerbation
Severity = intesity of disease (assessed prior to longterm control meds)
Control = exten to which asthma is ctrled by tx

Front 546

% of astmatics with GERD

Back 546

45–65%

Front 547

Samter's triad

Back 547

asthma
nasal polyps
aspirin sensitivity 91–2 hours after ingestion)

Front 548

Diagnosing exercised induced bronchospasm

Back 548

>15% decrease in FEV1 after exercise challenge test

Front 549

Asthma in pregnancy

Back 549

1/3 worsen, 1/3 improve, 1/3 stay the same
preferred SABA albuterol, preferred ICS budesonide

Front 550

Assessing Asthma Severity: Risk
0–4y
5–11y
12+

Back 550

Exacerbations requiring oral steroids:
0–4y: intermittent = 0–1/year, rest=2+/6 mo or 4/1 year + risk factors for persistent asthma
5–11y: int/mild=0–1/y; mod/sev=2+/y
12+y: int/mild=0–1/y; mod/sev=2+/y

Front 551

Assessing Asthma Control: Risk
0–4y
5–11y
12+y

Back 551

exacerbations requiring steroids:
Well ctrl: 0–1/year
Not well ctrl: 2–3/year
Poorly ctrl: 3+/y (2+ for 12y+)

Should consider:
Tx related AEs
Progressive loss of lung function

Front 552

Assessing Asthma Severity: Impairment – Symptoms and SABA use (same for both)
0–4y
5–11y
12+y

Back 552

Int | Mild | Mod | Sev
0–4: 0–2d/w | 2+ d/w | daily | 2+/day
5–11: same
12+: same

Front 553

Assessing Asthma Severity: Impairment – Nighttime awakenings
0–4y
5–11y
12+y

Back 553

Int | Mild | Mod | Sev
0–4: 0 d/m | 1–2 d/m | 3–4 d/m | 1+/w
5–11: 0–2d/m | 3–4 d/m | 1+/wk | daily
12+: same

Front 554

Assessing Asthma Severity: Impairment – lung fxn
0–4y
5–11y
12+y

Back 554

Int | Mild | Mod | Sev
(listed FEV1, FEV1/FVC)
0–4: N/A
5–11: >80,>85 | >80,>80 | 60–80, 75–80 | <60,<75
12+: >80, nl | >80, nl | 60–80, –5% | <60, >–5%
must know normal ratio for age:
8–19: 85%; 20–39: 80%; 40–59: 75%; 60–80: 70%

Front 555

Assessing Asthma Severity: Impairment – inerference with normal activity
0–4y
5–11y
12+y

Back 555

Int | Mild | Mod | Sev
0–4: none | minor | some| extreme ltd
5–11: same
12+: same

Front 556

Assessing Asthma Severity: Treatment
0–4y
5–11y
12+ y

Back 556

Int | Mild | Mod | Sev
0–4: 1 | 2 | 3 +/– steroids| 4 +/–steroids
5–11: 1 | 2 | 3 +/– steroids| 3/4 +/–steroids
12+: 1 | 2 | 3 +/– steroids| 4/5 +/–steroids

Front 557

Asessessing Asthma Control: Impairment Sx and SABA
0–4y
5–11y
12+y

Back 557

Well Ctrl | Not well ctrl | Poorly ctrl
0–4: 0–2 d/w | >2d/w | 2+/d
5–11: same
12+: same

Front 558

Asessessing Asthma Control: Lung Function
0–4y
5–11y
12+y

Back 558

Well Ctrl | Not well ctrl | Poorly ctrl
0–4: N/A
5–11: >80, >80 | 60–80, 75–80 | <60, <75
12+: FEV1 only: same #s

Front 559

Asessessing Asthma Control: Impairment Nighttime awakening
0–4y
5–11y
12+y

Back 559

Well Ctrl | Not well ctrl | Poorly ctrl
0–4: 0–1/m | >1/m | >1/w
5–11: same
12+: 0–2/m | 1–3/w | 4+/week

Front 560

Asessessing Asthma Control: Impairment: Activity interference
0–4y
5–11y
12+y

Back 560

Well Ctrl | Not well ctrl | Poorly ctrl
0–4: none | some | extremely
5–11: same
12+: same

Front 561

Asessessing Asthma Control: Treatment
0–4y
5–11y
12+y

Back 561

Well Ctrl | Not well ctrl | Poorly ctrl
0–4: maintain/stepdown if >3m | step up 1 | 1–2 +/– steroids
5–11: same
12+: same

Front 562

ASsessing Asthma Control: Questionnaires

Back 562

Only for 12+ y:

ATAQ: 0 | 1–2 | 3–4
ACQ: <0.75 | >=1.5 | N/A
ACT: >=20 | 16–19 | <=15

Front 563

Testing for occupational asthma?

Back 563

Methacholine challenge (decrease in 50% of the amount of methacholine required to drop FEV1 by 20%)

Front 564

Time to sensitization for laboratory workers

Back 564

2 years (longer for flour workers)

Front 565

Allergic rhinitis precedes occupational asthma for ____ agents

Back 565

HMW (protein/polysaccharide agents) not LMW (chemical agents)

Front 566

Occupational asthma: Plicatic acid

Back 566

LMW
Western red cedar mill, carpenters, woodworkers

Front 567

Occupational asthma: Isocyanates

Back 567

LMW
Body shop, spray paint, insulation, roofers, auto industry

Front 568

Occupational asthma: acrylates

Back 568

LMW
nail salon workers

Front 569

Occupational asthma: Platinum salts

Back 569

LMW
Welder, metal/chemical workers

Front 570

Occupational asthma: potassium dichromate

Back 570

LMW
Welder, metal/chemical workers

Front 571

Occupational asthma: ammonium persulfate

Back 571

LMW
Hairdressers

Front 572

Occupational asthma: phthalic anhydride

Back 572

LMW
adhesives, epoxy resin, paint, plastics

Front 573

Occupational asthma: trimellitic anhydride

Back 573

LMW
plastics, paint

Front 574

Occupational asthma: Amines

Back 574

LMW
Shellac, Lacquer, plastics, Cleaners

Front 575

Occupational asthma: formaldehyde

Back 575

LMW
Hospital workers, laboratories

Front 576

Occupational asthma: beta–lactam agents

Back 576

LMW
Drug industry workers

Front 577

Occupational asthma: animal proteins

Back 577

HMW
lab workers, vets

Front 578

Occupational asthma: crab/lobster

Back 578

HMW
seafood handlers

Front 579

Occupational asthma: flour (wheat, soy dust)

Back 579

HMW
Baker

Front 580

Occupational asthma: Wheat, coffee, tobacco dust, psyllium, latex

Back 580

HMW
Baker/textiles

Front 581

Occupational asthma: enzymes (amylase, lipase, pectinase)

Back 581

HMW
Baker/pharmaceuticals

Front 582

Increases the risk of TDI OA

Back 582

HLA DQB1*0503/0201/0301

Front 583

Increases the risk of occupational asthma in general

Back 583

HLA DR3, DR7

Front 584

Increases the risk of diisocyanate occupational asthma

Back 584

Glutamine S transferase (GSTP1) enzyme defects

Front 585

Most common causes of occupational asthma

Back 585

Plicatic acid, isocyanates, wheat flour, latex

Front 586

Smoking is a risk factor for sensitization to____

Back 586

Platinum

Front 587

Complement is activated by this occupational asthma trigger

Back 587

plicatic acid

Front 588

What is reactive airway dysfunction syndrome (rADS)

Back 588

aka irritant induced asthma
nonimmunologic process 2/2 high dose single exposure to irritant agent
sx immediate and last a long time

Front 589

Diagnosis of VCD

Back 589

Inspiratory wheezing over larynx
Bronchodilators worsen
Redeced FEV1 and FVC with preserved ratio and blunted inspiratory loop
Dx confirmed by fiberoptic laryngoscopy while patient is symptomatic

Front 590

Treatment of VCD

Back 590

Short term: heliox inhlation, topical lidocaine, intermittent positive pressure ventilation

Long term: panting, speech therapy, botox into vocal cords

Front 591

Immune response to aspergillus

Back 591

Dectin 1 receptor on alveolar macrophages binds Beta–1,3 glucan on Aspergillus cell walls
Production of TNFa, Il1b, Il1a, IL–6, IL10, IFNg ––> Th1 response

Front 592

Clinical Features of ABPA

Back 592

Asthmatics
– worsening asthma sx, brown/tan sputum, fever/malaise
– X–ray: pulm infiltrates in mid/upper lung fields (tram line, parallel lines, hilar adenopathy)
– CT: central/upper lobe bronchiectasis, pulm nodules, air trapping
CF: similar sx to primary disease