Path: Diseases Of Immunity

Front 1

DR3/4 HLA

Back 1

Diabetes

Front 2

B27 HLA

Back 2

Psoriasis, Ankylosing Spondylitis, IBD, Reiter's Syndrome

Front 3

Rheumatic fever caused by

Back 3

x-reacting antibody (molecular mimicry)

Front 4

autoimmune dz sperm and ocular antigens?

Back 4

release of sequestered antigens

Front 5

specific site on Ag recognized by Ab, BCR, or TCR

Back 5

Epitope

Front 6

Epitope spreading?

Back 6

immune response against initial "self" Ag
-damage reveals additional epitopic sites that are recognized

Front 7

Why does Lupus become so widespread

Back 7

it is an example of epitope spreading (also a Type III) inflammatory rxn.

Front 8

Do vaccinations predispose to Autoimmne DZ?

Back 8

No- dz's themselves, b/c of tissue damage, could lead to epitope spreading to cause autoimmune DZ

Front 9

Immune mediated inflammatory types are 3 basic types

Back 9

1. Ab or immune complex mediated (organ-specific or diffuse or systemic)
2. Primarily T-cell mediated (organ specific or systemic)
3. Chronic inflammatory (inflammation)

Front 10

What are the systemic AI dz's we really need to know for his lecture?

Back 10

Systemic Lupus Erythematosis (SLE)
Scleroderma: systemic sclerosis
Sjogren's Synrom
MCTD (mixed connective tissue dz)

Front 11

How many of 11 criteria need to dx lupus?
-arthritis
-unusual sensitivty to light
-butterfly or malar rash
-renal disorder
-neuro disorder
-oral ulcers
-discoid rash
-serositis (pericarditis/pleurits)
-hematoogic disorder (anemia, leukopenia)
-immunologic disorder (+LE, anti-dsDNA, etc_
-+ANA (antinuclear ab)

Back 11

4 of 11

Front 12

Is lupus febrile or afebrile

Back 12

chronic, remitting, relapsing, febrile

Front 13

What type of autoimmune DZ is lupus?

Back 13

Immune complex DZ
-Antigen-antibody (IgG) complexes activate complement and attract neutrophils
-neutrophils release lysosomal enzyme

Front 14

What antibody is virtually diagnostic for SLE?

Back 14

Anti-dsDNA or Smith Ag

Front 15

positive syphilis testing is someone who doesn't have syphilis may indicate?

Back 15

Antiphospholipid syndrome
-Lupus anticoagulant, induces PROTHROMBOTIC STATE
-miscarriages seen

Front 16

Clinically what might lead to thoughts of Antiphospholipid syndome?

Back 16

-miscarriages, positive syphilis, unexplained prolonged aPTT

Front 17

Drug induced lupus associated w/ what antibody?

Back 17

Anti-histone
**History? or drug use for anti-HISTOne antibodies
**he said this is commonly tested on board exam

Front 18

Lupus more common male of f/m?

Back 18

F:m - 9:1
-sex hormones may trigger flare up of dz

Front 19

How do you deetect anti-nucear antibodies (ANA)

Back 19

1. Take patient's serum
2. add to cultured cells
3. Add fluorescent ab
**if cell lights up, positive test for ANA in patient

Front 20

Is ANA a specific test?

Back 20

Very nonspecific b/c many types of nuclear antibodies

Front 21

The four types of ANAs provide greater specificity:
1. Anti-DNA
2. Anti-histone
3. Anti-non histone (anti-SSA, anti-SS-B, anti-U1-RNP)
4. Anti-nucleolar
*why importatn?

Back 21

ANA antibodies non-specific, so further testing needed to determine subtype DZ
1. Anti-DNA
-specific SLE
2. Anti-histone
-specific drug induced Lupus
3. Anti-non histone (anti-SSA, anti-SS-B, anti-U1-RNP)
-Sjogren's syndrome (anti-SSA/B)
-Mixed CT dz
4. Anti-nucleolar

Front 22

What can be found in blood that may be SUGGESTIVE of SLE?

Back 22

big puffy phagocyte (light purple) from having eaten denatured nucleus
**phagocytosis prompted by Anti-nuclear ab binding (opsonization)

Front 23

SLE Visceral lesions caused by?

Back 23

DNA-anti-DNA complex deposits

Front 24

Hight titer or anti-dsDNA may be indicative of?

Back 24

Nephritis

Front 25

Anti-SS-B antibody (usually associated w/ Sicca syndrome) indicates

Back 25

LOW risk nephritis

Front 26

What if anti-SS-B present w/ SLE?

Back 26

NEONATAL LUPUS (present n 90% of mothers of infants w/ neonatal lupus (heart block)
-SSB for Baby

Front 27

What is the key difference between Proliferative Nephritis types and Membranous Nephritis types of Lupus Nephritis?

Back 27

Proliferative involve hypercellular states (hence, proliferation of mesandial, endothelial, and leukocyte cells)
-Membranous is the ONE non-proliferative type

Front 28

In all types of Lupus Nephritis, what causes histological changes?

Back 28

deposition of immune complex DNA:anti-DNA in glomerulus

Front 29

How do you know if there is minimal mesangial nephritis (class I)

Back 29

can only detect immune complex deposits by ELECTRON microscopy, no visible changes LIGHT microscopy

Front 30

What is the difference between Mesangial Proliferative (class II) and Focal Proliferative (class III) lupus nephritis?

Back 30

Class III - has Mesangial AND Subendothelial or Subepithelial deposits while Class II DOES NOT!!!
-Class II mainly has some matrix expansion

Front 31

Big difference between Focal Proliferative (class III) and Diffuse Proliferative (Class IV)?

Back 31

involvement >50% glomeruli
-often progresses to end stage renal dz
-tons of protein loss

Front 32

"wire loops" may be seen histologically b/c?

Back 32

extensive deposition of immune complexes mesangial, subendo, subepithelial - wire loops are just buildup of IC deposits

Front 33

What observed histologically with Type V, Membranous?

Back 33

Subethial +/- mesagnial involvement
-scattered subendothelial IC deposits (if seen by light may also indicate involvement w/ proliferative)
- may see wire loops
-WILL NOT SEE HYPERPROLFERATIVE CELLS (no crescenting)
-marked protein loss

Front 34

Endothelial pattern vs Epithelial pattern

Back 34

Epithelial is membranous - injury to podocyte of BM - wall lesions with protein loss

Endothelial: leukocyte accumulation, may cells in capillary loops, capillary wall destruction (mostly seen chronic phase of lupus)

Front 35

Mesangial, Endocapillary profliferative pattern or membranous?
- microscopic hematuria and proteinuria, w/ well preserved GFR (glomerular filtration rate)

Back 35

Mesangial

Front 36

Mesangial, Endocapillary profliferative pattern or membranous?
-sig. proteinuria, often w/ nephrotic syndrome (>3.5g/day)
-limited inflammatory infiltrate, so glomerular structure maintained w/ preservation and more gradual reduction GFR

Back 36

Membranous pattern

Front 37

Mesangial, Endocapillary profliferative pattern or membranous?
-acute reduction GFR
-hematuria
-mild to moderate proteinuria

Back 37

Endocapillary proliferative pattern: focal and diffuse

Front 38

How are these two Type III autoimmune DZs different w/ regard to immunofluorescence?
SLE GN vs Post-streptococcal GN

Back 38

Post-streptococcal GN is grainy
-SLE GN is smoother

Front 39

W/ proliferative glomerulonephritis via lupus, what might observe relative to normal glomerulus

Back 39

expanded glomerulus due to cell proliferation
-areas of focal necrotizing lesions in expanded glomerulus

Front 40

What might crescents along edge of Bowman's capsule indicate?

Back 40

Proliferative GN
-capsule is proliferating parietal epithelial cells and infiltrating leukocytes
**occurs following immune/inflammatory injury

Front 41

What does "wire loop" thickening indicate w/ Glomerulonephritis?

Back 41

Extensive subendothelial deposits (thickening of the glomerular capillary basement membrane)

Front 42

What is big histogical diff. between membranous GN and Proliferative GN?

Back 42

normal cellularity for membranous GN (aka no proliferation), may still see start of formation membranous deposits)
*intergitiating spike formation

Front 43

What is Glomerular sclerosis?

Back 43

Entire bowman's capsule space is scarred over (very bad)

Front 44

What is Libman-Sacks endocarditis

Back 44

Lupus
-warty vegetations
-smaller than infectious endocarditis and larger than rheumatic fever lesions

Front 45

What type of lupus disorder affects skin only-erythematous scaly plaques
KEY: scar formation
-typically no systemic symptoms

Back 45

Discoid lupus
*may give "butterfly" malar rash

Front 46

Anti-S-A, abs and HLA-DR3 genotype common
-skin only, more widespread, NONSCARRING

Back 46

Subacute cutaneous lupus
+ stained nuclei in epidermis

Front 47

Buzzword for drug induced lupus? (drug causes + ANA but symptoms mild and remit w/ drug w/drawal?

Back 47

Anti-Histone-Abs
*HistOry of drug use
-also may have HLA-DR4 or Hydralazine-induced SLE

Front 48

People w/ cutaneous lupus need to take care to avoid?

Back 48

UV light
-IgG direct (IF) aka Lupus Band test

Front 49

DZ marked by progressive interstitial and perivascular fibrosis of skin and viscera?

Back 49

Scleroderma or "progressive" systemic sclerosis

Front 50

what kind of dizease is scleroderma?

Back 50

affects vasculature, so inevitably affects most tissue types
-proliferation intimal cells, endothelial cells, smooth muscle cells w/ perivascular fibrosis

Front 51

With scleroderma, what might seen perivascularly?

Back 51

Lymphocytic cuffing (CD4+ T-cells) induce repair, but overly robust repair system leads to scarring

Front 52

What autoantibodies found in scleroderma?

Back 52

Scl70 (10-20%) (scl for scleroderma)
-increased risk interstitial pulmonary fibrosis
RNA polymerase I,III
-increased risk renal dz, prob. cardiac dz too

Front 53

What do anticentromere antibodies indicate?

Back 53

(20-30%) increased risk for pulmonary hypertenstion and CREST

Front 54

what is CREST?

Back 54

C-calcinosis
R-raynaud phenomena
E-Esophageal dysmotility
S-Sclerodactyly
T-telangietasia
*limited cutaneuous involvement

Front 55

In sceroderma, Tcell activation leads to release of what key cytokine that is fibrogenic?

Back 55

TGFB
-recruits Fibroblast and fibroblast may be hypersensitive in mediating response and have abnormal collagen production

Front 56

What leads to esophageal dysmotility?

Back 56

Submucosal collagen deposition - can occur anywhere in GI tract, but most comon esophagus

Front 57

How does scleroderma cause hypertension and potential renal disease?

Back 57

hyperplastic arteriosclerosis
-intimal fibrosis leads to hypertension and vasculature issues

Front 58

anti-centromere ab can be seen in CREST scleroderma as well as in

Back 58

primary biliary cirrhosis

Front 59

What is Raynaud's phenomena?

Back 59

brief cold exposure: exaggerated microvessel response, white, blue, red

Front 60

What is big histologic diff. between SLE and scleroderma?

Back 60

Scleroderma has incrased dermal collagen and very few Inflammatory cells

Front 61

Is immunofluorescence helpful in dx scleroderma?

Back 61

No- it is w/ SLE though

Front 62

What can Systemic slerosis do to lung?

Back 62

Interstitial pulmonary fibrosis

Front 63

Key symptoms of this dz are keratoconjunctivitis and siccaxerostomia?

Back 63

Sjogren's (sicca) syndrome

Front 64

What antibodies are present for Sjogren's syndrome?

Back 64

anti-SS-A/anti-SS-B

Front 65

What is Mikulicz syndrome (found with sjogren's (sicca) syndrome?)

Back 65

lacrimal and salivary gland enlargement

Front 66

Sjogren's syndrome mostly affects?

Back 66

Glands
ie: salivary gland
-extraglandular involvement only 30%

Front 67

Sjogren's syndrome may predispose one to?

Back 67

B-cell marginal zone lymphomas
-approx 40X increased risk

Front 68

What antibodies present for Mixed Connective Tissue DZ?

Back 68

anti-snRNP
U1-RNP (ribonucleoprotein)

Front 69

How would you describe Mixed connective tissue dz?

Back 69

mixture of SLE, RA, scleroderma, and polymyositis

Front 70

What is polymyositis?

Back 70

inflammatory myopathy

Front 71

dsNDA (SLE)

Back 71

high titers = nephritis

Front 72

SLE, SS-B

Back 72

neg. association w/ nephritis

Front 73

anti-histone ab?

Back 73

drug-induced lupus

Front 74

SS-A/SS-B

Back 74

Sjogren's OR

SS-B neonatal lupus (heart block)

Front 75

ScI-70 centromere

Back 75

diffuse disease of scleroderma

Front 76

cetromere ab?

Back 76

CREST/prim bil. cirrhosis (Scleroderma)
**C in Centromere is for CREST for sCleroderma's

Front 77

If anti-dsDNA or -SmAG is present, regardless of other antibodies present, what is most likely DZ?

Back 77

SLE

Front 78

This defect may mimic HIV in that susceptible to viral infections such as Cytomegalovirus, Epstein-Barr, Varicella, and have chronic respiratory and enterovirus infections?

Back 78

T-cell defect

Front 79

What prob. T-cell defect have to worry about: bactera?

Back 79

bacterial sepsis

Front 80

What prob. T-cell defect have to worry about: fungi and parasites

Back 80

candida and pneumocystis

Front 81

B-cell defect typically leaves one susceptible to

Back 81

Bacteria
-esp. pyogenic bacteria like streptococci, staph, and haemophilus

Front 82

What prob. B-cell defect have to worry about: viruses?

Back 82

Enteroviral encephalitis

Front 83

What prob. B-cell defect have to worry about: fungia nd parasites?

Back 83

Severe intestinal giardiasis

Front 84

Special features of B-cell defect?

Back 84

-recurrent sinopulmonary infections
-sepsis
-chronic meningitis

Front 85

Bruton's Dz is of the

Back 85

B-cells
B is Bruton for B-cells
-also for Boys, X-linked

Front 86

What deficiency does Bruton's have? and what does it cause?

Back 86

Tyrosine kinase
-defect b-cell maturation and light chain rearrangement
-heavy chain produced but no light chain
-can't be activated by Ag

Front 87

w/ Bruton's aggamaglobulinemia, what kind of b-cells see and where are they?

Back 87

Immature B-cells may be seen in MB, but not blood
-have underdeveloped lymph node germinal centers

Front 88

When start to notice child has Bruton's?

Back 88

after about 6 mos age
-initally has mom's IgG and IgM, but then this will be lost over time
*note, high freq. autoimmune dz w/ bruton's

Front 89

Common variable immunodef prevalence?

Back 89

relatively common, sporadic and inherited
-males=f/ms

Front 90

Why are symptoms similar, yet often less severe for common variable immunodef vs brutons'

Back 90

infeffecient immunoglobulin synthesis: variable loss of Ig Classes, so still may have some Ig classes that are ok
*also has high freq. autoimmune dz and lymphoma

Front 91

What is the most common primary immunodeficiency dz?

Back 91

Isolated IgA def
(1:600 euro. descent)
-familial and acquired (post-viral syndrome)

Front 92

How is DVI sim. to isolated IgA

Back 92

both involve defect in B-cell maturation cells

Front 93

what kind of infections common in isolated IgA def?

Back 93

mucosal infections (sinopulmonary, GI, UTI), high rates of atopy (allergic bronchitis) and Autoimmune dz

Front 94

Common board question involving IgA deficiency and blood transfusions?

Back 94

IgA deficiency people often have anaphylactic rxn when receiving whole blood transfusions b/c plasma contains IgA

Front 95

Hyper-IgM syndrome involves?

Back 95

Defect in B-cell class switching and maturation

Front 96

What kind of infections susceptible to w/ Hyper IgM syndrome?

Back 96

pyogenic infections/pneumo from intracellular pathogen: pneumocystistis jiroveci

Front 97

How is Hyper IgM syndrome commonly inherited?

Back 97

-70% X-linked loss of CD40 ligand on T-cells

-others Autosomal recessive - mutations encoding CD40 or the enzyme activation-induced deaminase (rq'd for class switching)

Front 98

What deletion causes DiGeorge Syndrome: Thymic hypoplasia?

Back 98

22q11
-aplasia or hypoplasia of 3rd and 4th laryngeal pouches during embryogensis

Front 99

DiGeorge Syndrome: Thymic hypoplasia associated w/?

Back 99

abnormalities or aorta, congenital heart dz, facial abnormalities

Front 100

DiGeorge Syndrome: Thymic hypoplasia causes what problems since no thymus and no parathyroid?

Back 100

- failure t-cell maturation

-hypocalcemic seizure/tetany in newborn b/c no parathyroid

Front 101

SCID (severe combined immunodeficiency syndrome) is usually inherited how?

Back 101

X-linked (most common)
-genetic loss of common gamma-c chain for cytokine receptors, esp IL-7

Autosommal recessive
-adenosine deaminase, JAK3 (gamma-c chain signaling), IL-7 receptor, MHC class II def.

Front 102

why is IL-7 important?

Back 102

lymphoid progenitor proliferation, often impaired in SCID

Front 103

what is MHCII deficiency also known as?

Back 103

"bare lymphocyte syndrome"

Front 104

X-linked defect in ability to mount IgM response to CAPSULAR polysaccharides of bacteia
-assoc. w/ eleveated IgE and IgA levels, low IgM levels
**Triad of symptoms inludes recureent pyogenic Infections, thrombocytopenic Purpura, Eczema?

Back 104

Wiskott-Aldrich Syndrome (affects B-cells)
-WASP preotein

Front 105

Complement system defect:
-Alternative pathway: properdin, Factor D

Back 105

Pyogenic infections

Front 106

Complement system defect:
C2, C1, C4

Back 106

Autoimmune Dz's

Front 107

Complement system defect:
C3 (alternate and classical pathways)

Back 107

SEVERE pyogenic infections

Front 108

Deficiency of complement inhibitors:
C1

Back 108

-hereditary angioedema = elevated bradykinin
-prone to resp/mucosal edema

Front 109

Deficiency of complement inhibitors:
GPI (glycophosphatidyl inositol)

Back 109

CD59 and Decay accelarting factor!!!
--Paraxysmal nocturnal hemogolbinuria

Front 110

Acquired secondary immuno-def. syndromes present in?

Back 110

aids
cancer tx
aging: decreased T-cell prolif. response, blunted cytokine response

Front 111

How detect amyloid?

Back 111

CONGO RED STAINING!!! - congo red birefringence**note this was once a previous test question

Front 112

Amyloidosis is?

Back 112

one of the extracellular "hyaline"
-DISTINCT from IMMUNCE COMPLEX DZ or FIBRINOID RXN

Front 113

What structure is amyloid?

Back 113

B-pleated sheats aggregate as result of lambda light chains and b-amyloid protein

Front 114

Why can't get rid of b-pleated sheets?

Back 114

resistant to proteolytic degradation - amyloidosis

Front 115

What major neuro. dz is amyloid involved in?

Back 115

alzheimer's Dz = amyloid beta plaques form amyloid precursor protein

Front 116

Once again, what staining detects Amyloid?

Back 116

Congo RED staing
- plane polarized birefringence