Immunology Unit Iii

Front 1

Which cytokine is most strongly associated with septic shock?

Back 1

TNF(alpha)

Front 2

What is the function of CXCL8?

Back 2

Directs chemotaxis of neutrophils, basophils, and T cells

Front 3

What is the function of IL-12?

Back 3

Activates NK cells
Induces Th1 differentiation

Front 4

What are NSAIDs and how do they work?

Back 4

Non-steroidal anti-inflammatory drugs work by inhibiting the cyclogenase pathway, and thereby decreasing prostaglandin production (so decreasing vascular permeability and neutrophil chemotaxis)

Front 5

How do steroid anti-inflammatory drugs work?

Back 5

By mimicking hormones with immuno-suppressive effects

Front 6

What is the function of CTLA-4?

Back 6

An Ig protein expressed on activated T cells that interacts with B7 molecules to send inhibitory signal to T cell (associated with ITIM) to inhibit IL-2 and decrease sensitivity to APC stimulation

Front 7

What factors induce inflammatory response?

Back 7

-Complement cascade
-Cytokines
-Lipid inflammatory mediators
-Plasma enzyme activators

Front 8

What is the function of inflammation?

Back 8

-To control and contain infection through shuttling of immune cells to the site of infection and induce clotting
-To effect tissue repair

Front 9

What is the beneficial effect of vasodilation about the site of infection?

Back 9

-Total blood volume increases, so more cells to the region
-Local flow rate decreases, so increased likelihood of immune cells tethering to vasculature at site of infection and diffusing out

Front 10

What is the beneficial function of fever?

Back 10

-Increase in temperature makes harsh environment for bacteria
-Increases blood flow

Front 11

Which is the first immune cell to traffic to the site of infection after induction of inflammation?

Back 11

The neutrophil

Front 12

What are the types of lipid mediators?

Back 12

Arachidonic acid metabolites (prostaglandinss, leukotrienes)
Platelet activating factors

Front 13

What is the role of the lipid mediators?

Back 13

Increased vascular permeability
Chemoattractants
Increased mucous secretion
Increased smooth muscle contraction
Blood clot induction

Front 14

What is the function of prostaglandin?

Back 14

Vasodilation + increased vascular permeability
Chemoattraction

Front 15

What is the function of leukotriene?

Back 15

-Increased mucous secretion
-Increased bronchial smooth muscle constriction

Front 16

Which selectin(s) are expressed in the endothelium? Which in the cells?

Back 16

P and E selectin are found in the endothelum, whereas L-selectin is found in neutrophils/lymphocytes

Front 17

Expression of which cell-surface motif(s) will keep lyphocytes in the secondary lymphoid tissues?

Back 17

L-selectin

Front 18

Which cell types express integrins?

Back 18

Circulating cells: APCs, T cells, neutrophils

Front 19

Which cytokines are considered IFN-1s? What are the effects of up-regulation of IFN-1s?

Back 19

IFN-1 = IFN(alpha) and IFN(beta)

The up-regulation of these signals in an auto- and paracrine fashion the presence of a viral threat (so neighboring cells become more sensitive to viral presence, up-regulates MHC I, and activates NK cells)

Front 20

Where are mucin-like CAMs expressed?

Back 20

On the endothelium, as a signal for cells to exit the blood stream

Front 21

What part of cell recruitment is mediated by mucin-like CAM:selectin binding?

Back 21

Rolling and tethering

Front 22

What part of cell recruitment is mediated by ICAM:integrin binding?

Back 22

Arrest/adhesion

Front 23

What is the relationship between chemokines and interleukins?

Back 23

When chemokines were first discovered, they were termed interleukins, so all interleukins have some chemotaxic property

Front 24

How do interleukins (chemokines) perform their effector function?

Back 24

They alter the conformation of cellular integrins to allow adhesion to endothelial ICAMs, then creates a gradient (has net positive charge increasing in concentration toward the site of infection) through which the directed cells are guided

Front 25

By what mechanisms do neutrophils effect bacterial killing?

Back 25

-Phagocytosis
-Toxic chemical products (oxygen-derived radicals, reactive nitrogen species, etc.)
-Enzyme breakdown of pathogenic products (protease, phospholipase, collagenase, etc.) in lysozyme
-Opsonization through Fc receptor of bacteria marked with antibodies

Front 26

By what mechanism do the cytokines IL1, IL6, TNF(alpha) interact with the central nervous system?

Back 26

-Through the liver, by stimulating APR such that liver releases ACTH
-Directly on the hypothalamus to effect fever

Front 27

In what way is DTH (type IV hypersensitivity) similar to common allergy (type I hypersensitivity)?

Back 27

They both require a sensitization period and are both innocuous to small antigens

Front 28

Define: DTH

Back 28

Delayed-type (Type IV) hypersensitivity occurs when prolonged Th1 cell signaling results in tissue-damaging macrophage action, which in turn continue to present antigen to Th1 cells and to produce IFN(gamma), TNF(alpha)

Front 29

Which cytokines do activated macrophages produce to encourage inflammation?

Back 29

The APPs; TNF(alpha), IL-1, IL-6

Front 30

Which onco-antigens are considered "shared tumor antigens" and why?

Back 30

Overexpressed normal antigens and re-expressed fetal antigens because they're likely to be expressed in the widest variety of tumor types and indiviuals

Front 31

On which immune defense does tumor eradication more rely?

Back 31

On CTLs, NK cells

Front 32

In which classes of gene is mutation most likely to cause cancer?

Back 32

Proto-oncogenes (associated with growth)
Tumor-suppression genes (prevention of unwanted proliferation)

Front 33

What is the cause of lupus?

Back 33

Th1 response triggers CTL and IgG sensitivity to nucleoproteins

Front 34

What are the stages of immune cell extravasion?

Back 34

Rolling--selectin + mucin-like
Activation
Anchoring
Extravasion

Front 35

What proteins are produced by the liver during acute-phase reaction?

Back 35

Fibrinogen
C-reactive protein
Complement proteins

Front 36

Differentiate "chronic stress" from "chronic inflammation"

Back 36

-Chronic stress is a CNS complex that has as a symptom delocalized inflammation
-Chronic inflammation is a complication of prolonged adaptive immune response

Front 37

How do C-type lectins on DCs work?

Back 37

-Transmembrane: mediate internalization of glycosylated Ags
-Soluble: Ligate/opsonize microbes

Front 38

IN the case(s) of which exception(s) is CD4+ help unnecessary for CD8 T cell activation?

Back 38

At high density of B7 or of IL-12, IL18

Front 39

Wha are the determining properties of memory cells?

Back 39

-CD44+CD45RO+
-Down-regulation of L-selectin
-Increased sensitivity to antigen => a rapid and vigorous response induced by small amount of antigen

Front 40

Define: Lamina propia

Back 40

Layer of connective tissue under the mucosal epithelium throughout which there exist clusters of lymphoid tissue

Front 41

Define: isolated lymphoid follicle

Back 41

B cell cluster covered by M cell

Front 42

What combination of surface antigen homes naive T cells to Peyer's Patches?

Back 42

L-selectin + CCR7

Front 43

How is inflammation due to IgA binding avoided in the gut?

Back 43

Because IgA lacks the ability to activate complement

Front 44

How does IgA traffic to the mucosa?

Back 44

Picked up by Polymorphic Ig Receptors and transcytosed through the epithelial cells

Front 45

By what mechanism(s) does IgA eliminate threats to the mucosal immunity?

Back 45

-By directly neutralizing toxins through binding
-By enhancing endosomal formation (destruction in lysosome)
-By transcytosing pathogen from basal to lumenal side for expulsion

Front 46

How do comensal bacterial avoid detection?

Back 46

-No activation of complement from Abs or immune activation by TLRs
-Unable to infect
-Inhibition of inflammatory response

Front 47

Define: gp120

Back 47

One of two envelope proteins expressed by the HIV virus, gp120 is necessary for binding to host cells to infect and very difficult to defend against because its heavy glycosylation makes Ab binding difficult

Front 48

What proteins are encoded by the gag genes in the HIV virus?

Back 48

The nucleocapsid proteins p24,17

Front 49

what is the effector function of histamine?

Back 49

Vasodilation, release of enzymes for tissue destruction

Front 50

What is the ultimate MO of anti-allergens theophylline and pqinephrine

Back 50

Inhibition of mast cell degranulation

Front 51

Which immune cells are responsible for the production of the the tumor necrosis factor cytokines (TNF alpha, beta)?

Back 51

CD4 T cells

Front 52

What PAMP is recognized by TLR4?

Back 52

LPS

Front 53

What PAMP is recognized by TLR9

Back 53

Unmethylated CpG motifs on DNA

Front 54

Define: hapten

Back 54

A small, non-immunogenic particle that can, when coupled to a carrier protein, illicit an immune response

Front 55

What effector function do antibodies induce on bacterial toxins?

Back 55

Neutralization

Front 56

What effector function to antibodies induce on bacteria in the extracellular space?

Back 56

Macrophage-mediated opsonization

Front 57

What effector function do antibodies induce on bacteria in the plasma?

Back 57

Complement-mediated lysis/ingestion

Front 58

What property of binding is taken advantage of in opsonization?

Back 58

Affinity = Avidity * # binding sites

Front 59

Which proteins are associated specifically with the alternative pathway of complement?

Back 59

Factor B
Factor D
Properidin

Front 60

What do the subscripts "ab" and "c" mean in the context of antibody bits?

Back 60

"Antigen binding" and "crystallizable" respectively, corresponding to the fragments = "F"

Front 61

Distinguish isotype from allotype from idiotype

Back 61

Rel: Antibodies
-Isotype => same species, but not necessarily same Fc
-Allotype => same species, same Fc, different strains
-Idiotype => same species, same Fc, same strain, different variable region

Front 62

What is the aim of a radioimmune assay?

Back 62

To detect the concentration of soluble protein in a sample. Often used in hormone detection. Interchangeable with ELISA.

Front 63

What is the aim of enzyme-linked immunosorbent assay (ELISA)?

Back 63

To measure the amount of a soluble protein (usu. cytokine) in a sample. Often used in viral diagnostics. Interchangeable with RIA.

Front 64

What is the aim of Elispot?

Back 64

To measure the amount of secreting T cells in a sample (by binding cell using adhered Ab, then by measuring secretion Ab to cytokine of interest).

Front 65

What is the aim of immunopreciptiation?

Back 65

To determine the amount of protein in a sample

Front 66

What is the aim of flow cytometry/FACS?

Back 66

To identify/quantify relative populations of cells within a sample that express some surface protein that can be interrogated using monoclonal antibodies

Front 67

What are the mechanisms of B cell tolerance?

Back 67

-Ongoing recombination (of light chain)
-Clonal deletion (at the periphery)
-Anergy
-Ignorance (when [self proteins] insufficient to cause reaction)

Front 68

Which light chain locus is first rearranged? Upon failing a productive rearrangement, which light chain locus is tried?

Back 68

Kappa (each chromosome) then lambda.

Front 69

What are the mechanisms of introducing diversification in the development of lymphocytes?

Back 69

-Combinatorial diversity (VDJ recombination)
-Junctional diversity (addition/subtraction of nucleotides @ junction)
-Combinatorial diversity from heavy chain + light chain matching
-Somatic hypermutation

Front 70

Through what enzyme is post-activation diversification of antibodies induced?

Back 70

Through activation-induced cytidine deaminase (AID)

Front 71

Where and by what mechanism is B cell affinity maturation achieved?

Back 71

In the germinal centers of lymphoid tissue by competition for DC stilmulation

Front 72

What MHC loci correspond to Class I genes in humans? Class II?

Back 72

Class I: HLA-A,B,C
Class II: HLA-DP, DQ, DR

Front 73

What MHC loci correspond to Class I genes in mice? Class II?

Back 73

Class I: K, D, L
Class II: I-A, I-E

Front 74

Which loci are most important to match in human allograft?

Back 74

HLA-DR, A, B (Dr. Abs)

Front 75

How do the structures of MHCI and MHCII differ?

Back 75

MHC I: 3-Ig alpha chain (with transmembrane region) and beta-2 microglobulin

MHCII: 2-Ig transmembrane alpha chain + 2-Ig transmembrane beta chain

Front 76

What cellular machine is responsible for peptide trafficking from cytosol to ER for association with MHC I?

Back 76

TAP

Front 77

What is the value of using endo-H to study MHC development?

Back 77

MHC is only susceptible to endo-H before trafficking to the Golgi (for sugar addition), so susceptibility to endo-H is a marker of development stage

Front 78

What does an OT-I TCR transgene do?

Back 78

Make only TCRs that bind MHC I for OVA (except through endogenous rearrangement to produce low levels of MHCII-sensitive TCRs) due to expression of MHC I only at thymus while priming

Front 79

What does AND TCR transgene do?

Back 79

Shift toward MHC II allele present on I-Ek, with only low levels of TCR sensitive to MHC I --at mouse MHC type isn't K, then will have low to no development past dp stage, esp. w/ Rag -/-

Front 80

Through which receptor(s) does the T cell receive its secondary signal? Which ligand(s) bind it?

Back 80

-T cell receives 2ndary signal through CD28 (stimulatory), CTLA-4 (inhibitory)
-CD28, CTLA-4 bound by B7

Front 81

Which are the main transcription factors associated with each T cell lineage?

Back 81

Treg -- FoxP3
Th1 -- Tbet
Th2 -- Gata3
Th17 -- ROR(gama)t