Immunology - Exam 2 - Part 1

Front 1

Definition of
TOLERANCE

Back 1

lack of response to certain antigens

induced by exposure of lymphocytes to those antigens

Front 2

CENTRAL TOLERANCE

Back 2

developing T/B cells see self-antigens in primary lymphoid organs and develop tolerance to them

Front 3

PERIPHERAL TOLERANCE

Back 3

mature B/T cells see self antigens in secondary lymphoid tissues and develop tolerance to them

Front 4

What proportion of the population has an autoimmune disease?

Back 4

1-2%

Front 5

2 main factors in development of autoimmune disease

Back 5

inheritance of susceptibility genes
--> failure of self-tolerance

environmental triggers
--> self-reacting B/T cells

Front 6

What type of lymphocyte controls almost all immune response to protein antigens?

Back 6

CD4+ T cells

Front 7

principal mechanism of central tolerance

Back 7

negative selection

Front 8

Autoimmune regulator (acronym)

Back 8

AIRE

Front 9

What is responsible for thymic expression of many self-protein antigens?

Back 9

AIRE

Front 10

APECED stands for...

Back 10

Autoimmune polyendocrinopathy with candidiasis & ectodermal dysplasia

Front 11

Etiology of APECED

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mutations in aire gene

Front 12

Development of Tregs

Back 12

some immature T cells that recognize self-antigens in thymus develop into Tregs and enter peripheral tissues

Front 13

Defective central tolerance development can lead to...

Back 13

autoimmunity

Front 14

2 mechanisms of peripheral T cell tolerance

Back 14

mature T cells recognize self-antigens in peripheral tissues, --> anergy (functional inactivation) or death

self-reactive T cells suppressed by Tregs

Front 15

ANERGY

Back 15

functional inactivation of T cells

Front 16

When does anergy occur?

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when T cells recognize antigens without adequate levels of costimulators

Front 17

What molecule do T cells express when they recognize self antigens?

Back 17

CTLA-4

Front 18

What kind of molecule is CTLA-4?

Back 18

high affinity receptor for B7

Front 19

What happens when T cell expressing CTLA-4 encounters self-antigen on APC?

Back 19

CTLA-4 engages B7, which inactivates T cell

Front 20

What is the ACTIVATING coreceptor on T cells?

Back 20

CD28

Front 21

What is the INACTIVATING coreceptor on T cells?

Back 21

CTLA-4

Front 22

ACTIVATION-INDUCED CELL DEATH

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self-reactive T/B cells are deleted after repeated activation by self-antigen

or recognition of antigens without second signals

Front 23

2 mechanisms of activation-induced cell death

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(1) CD4+ T cells: repeated activataion leads to coexpression of Fas and FasL

(2) antigen recognition --> proapoptotic proteins in T cells, but only microbial antigens --> ANTIapoptotic proteins. Therefore, self-reactive T cells die.

Front 24

Which cytokine potentiates Fas-mediated apoptosis?

Back 24

IL-2

Front 25

Function of Tregs

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immunosuppression

Front 26

Where do Tregs develop?

Back 26

primary or secondary lymphoid tissues

Front 27

usual combination of coreceptors on Tregs

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CD25+ CD4+ T cells

Front 28

?What is CD25

Back 28

alpha chain on IL-2R

Front 29

cytokines released by Tregs

Back 29

TNF-beta

IL-10

Front 30

Function of TGF-beta and IL-10

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immunosuppressive:

block ativation of T/B cells and Mphages

Front 31

Generation and functino of Tregs depend on what genetic factor

Back 31

TF: FoxP3

Front 32

Mutation in FoxP3 --> ?

Back 32

autoimmune disease

Front 33

2 options for immature B cells that interact strongly with self antigens in bone marrow

Back 33

negative selection (--> death)

change receptor specificity (express new Ig light chain)

Front 34

What happens to mature B cells that encounter high concentrations of self-antigens in peripheral tissue?

Back 34

--> anergic and not respond to that self-antigen

follicle exclusion

Front 35

Diseases associated with auto-antibodies (SLE, etc.) are caused by...

Back 35

a defect in tolerance mechanisms of B cells and T-helper cells

Front 36

Most important of multiple genes predisposing individual to autoimmune disease

Back 36

MHC genes

Front 37

HLA allele can _____ of disease, but does not _____ the disease

Back 37

HLA allele can increase the RR of the disease, but it does NOT CAUSE the disease

Front 38

Do most patients that inherit a disease-related allele develop the disease?

Back 38

NO

Front 39

2 reasons an HLA allele may be "bad"

Back 39

ineffective at displaying self antigen (--> defect in negative selection)

peptide antigens presented fail to stimulate Tregs

Front 40

General role of infection in development of autoimmune disease

Back 40

infections may activate self-reactive T/B cells

Front 41

infectious prodromes often precede what?

Back 41

development of autoimmune disease

Front 42

Mechanism by which infection stimulates development of autoimmune disease

Back 42

infection in a tissue --> local, innate immune response --> increased expression of costimulators and cytokines by local APCs

activated tissue APCs stimulate self-reactive T cells that econcounter self-antigens

Front 43

Short version of infection --> autoimmunity mechanism

Back 43

infection can "break" T cell anergy and promote survival and proliferation of self-reactive T cells

Front 44

MOLECULAR MIMICRY

Back 44

some microbes produce peptide antigens that cross-react with self-antigens

s.t. immune responses against microbial peptides also attack self

Front 45

Alternative mechanism by which infection triggers autoimmunity

Back 45

infections may trigger release of antigens no usually seen by immune system

release may stimulate autoimmune reaction against the tissue from which they were released

Front 46

IMMUNE SURVEILANCE

Back 46

adaptive immune system prevents the outgrowth of transformed cells

or destory them before they become tumors

Front 47

How may malignant cells signal immune system

Back 47

molecules recognized as foreign antigens

normal proteins overexpressed or dysregulated

Front 48

Example of a self protein that, expressed on a malignant cell, may trigger immune response

Back 48

protein found in embryonic but not adult tissue may not induce tolerance

Front 49

principal immune mechanism against tumors

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CTLS specific for tumor antigens

Front 50

most tumor antigens are...

Back 50

endogenously synthesized, cytosolic proteins

Front 51

How are tumor antigens displayed to CTLs

Back 51

by MHC I on APCs

Front 52

From which types of cells can tumors arise?

Back 52

any nucleated cell type

Front 53

CROSS-PRESENTATION allows...

Back 53

cells that don't express costimulators or MHC II to activate CD8+ T cells

Front 54

CROSS-PRESENTATION mechanism

Back 54

tumor cells ingested by APCs

APCs provide 2nd signals (costimulators) to activate T cells

Front 55

Definition of CROSS PRESENTATION

Back 55

One cell type presents antigens of another cell type

and primes T cells for 2nd cell type

Front 56

After differentiation, CTLs can kill tumor cells with _____, but without...

Back 56

with relevant antigens

without costimulators or T-helper cells

Front 57

2 passive evasion mechanisms of tumors

Back 57

growth can outstrip immune defenses

many tumor antigens are only weakly immunogenic because they differ so slightly from self-antigens

Front 58

2 active evasion mechanisms of tumors

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tumors stop expressing antigens that are the targests of immune attack

tumors stop expressing MHC I

Front 59

Antigen-loss variants

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tumors that stop expressing the antigens that are the targets of immune attack

Front 60

Consequences of tumor stopping expression of MHC I

Back 60

stop CD8+ T cell activation, but may be attacked by NK cells

Front 61

3 main immuno-based anti-tumor strategies

Back 61

provide anti-tumor effectors (Ig's and T cells)

actively immunize patients against tumors

stimulate patients own anti-tumor immune responses

Front 62

HER2/neu

Back 62

antigen overexpressed in patients with certain types of BRCA

Front 63

immunological treatment for B-cell malignancies

Back 63

mAb against CD20, expressed by B cells

CD20 not expressed by hematopoietic stem cells, so normal B cells replenished after treatment stopped

Front 64

adoptic cellular immunotherapy

Back 64

T cells isolated from blood/tumor infiltrates of patient

expanded w/ GFs in vitro

injected back into patient

Front 65

3 means of increasing host's own anti-tumor responses

Back 65

(1) vaccinate patients with own tumor cells/antigens - recominant proteins with adjuvants

(2) grow DCs & expose them them to tumor cells/antigens = "tumor pulsing" --> vaccine mimicking normal cross-presentation pathway

(3) vaccinate with plasmid of cDNA encoding tumor Ag - host cells, including APCs take up plasmid, express Ag, elicit specfic T cell response

Front 66

Aim of anti-tumor treatment with cytokines, e.g.: IL-2

Back 66

let patients generate own anti-tumor responses

Front 67

limitations of IL-2 treatment for tumors

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serious toxic effects

Front 68

syngeneic

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animals that are genetically identical (MHC alleles)

Front 69

allogenic

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animals that are not genetically identical (MHC alleles)

Front 70

xenogenic

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animals from different species

Front 71

allografts and xenografts are always....

Back 71

rejected

Front 72

clinically, most transplants are...
(syngeneic/allogenic/xenogenic)

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allogenic

Front 73

all ____ molecules are potential targets for rejection

Back 73

MHC

Front 74

why do MHC molecules from another individual's cells elicit such a strong immune response?

Back 74

cross-reaction:
allogenic MHC with allogenic-peptides look like self-MHC molecules with bound foreign peptides

Front 75

minor histocompatibility antigens

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non-MHC antigens that elicit graft rejection

Front 76

minor histocompatability antigens usually take the form of...

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allelic forms of normal cell proteins that differ between donor and host

Front 77

which 2 transplant types are most affected by MINOR histocompatibility antigens?

Back 77

blood transfusion

BM transplant

Front 78

direct allorecognition

Back 78

host T cell recognize unprocessed allogenic MHC molecules on graft APCs

Front 79

indirect allorecognition

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host T cell recognizes a processed peptide of allogenic MHC bound to self MHC on host APC

Front 80

MLC

Back 80

mixed lymphocyte reaction

Front 81

definition of MLC

Back 81

in vitro model of T cell recognition of alloantigens

T cells from 2 individuals cultured together

level of T cell response assayed is propotional to the extent of MHC differences

Front 82

3 classifications of graft rejection

Back 82

hyperacute

acute

chronic

Front 83

timeframe for hyperacute rejection

Back 83

within minutes

Front 84

physiologic effects of hyperacute rejection

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thrombosis of graft vessels

ischaemic necrosis of graft tissue

Front 85

hyperacute rejection is mediated by...

Back 85

circulating antibodies, specific for antigens on graft endothelium

these antibodies are present pre-transplant, possibly b/c of previous transfusions and reactions against alloantigens in transfused blood cells

Front 86

pathways activated by circulating antibodies in hyperacute rejection

Back 86

complement

inflammation

thrombosis

Front 87

why is hyperacute rejection fairly uncommon?

Back 87

clinical practice of cross-matching

Front 88

time frame for acute rejection

Back 88

days/weeks

Front 89

principal cause of early graft failure

Back 89

acute rejection

Front 90

acute rejection is primarily mediated by which cell type?

Back 90

CD8+ T cells

Front 91

Effects of Ig's in acute rejection

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contribute primary to vascular damage:

parenchymal cell damage

insterstitial inflammation

endothelialitis

Front 92

time frame for chronic rejection

Back 92

months to years

Front 93

definition of chronic rejection

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progressive loss of graft function

Front 94

physiologic effects of chronic rejection

Back 94

fibrosis of graft

gradual narrowing of vessels (graft atherosclerosis)

Front 95

Effect of T cells in chronic rejection

Back 95

secrete cytokines

stimulate fibroblasts and vascular smooth muscle cells in graft

Front 96

mainstay of prevention/treatment of graft rejection

Back 96

immunosuppression

designed to inhibit T cell activation & effector function

Front 97

most useful drug for prevention of graft rejection

Back 97

cyclosporine

Front 98

mechanism of cyclosporine

Back 98

blocks T cell phosphatase required to activate NFAT

thereby inhibiting cytokine genes in T cells

Front 99

types of transplants allowed by cyclosporine

Back 99

heart, liver, lung

Front 100

problem with all transplant drugs

Back 100

non-specific immunosuppression

Front 101

transplant drugs increase the incidence of which 2 things?

Back 101

infections

cancer

Front 102

Is HLA matching always necessary?

Back 102

No - b/c of cyclosporine

Front 103

xenotransplantation elicits...

Back 103

hyperacute rejection

Front 104

describe antibodies that mediate hyperacute rejection in cases of xenotransplanation

Back 104

not require previous exposure

may be produced against bacteria that normally inhabit gut & cross react with cells of other species

Front 105

blood group antigens are which type of macromolecule?

which means they elicit which type of immune response

Back 105

sugar

T cell response

Front 106

Why does BM transplant in particular weaken the immune system

Back 106

before transplant, part of host BM is destroyed to make room for graft

Front 107

GVHD

Back 107

graft-versus-host disease

Front 108

etiology of GVHD

Back 108

If mature T cells are transplanted with BM cells, can attack host tissues