Chapter 14

Question 1

Tolerance

Answer 1

Unresponsiveness to an antigen that is induced by previous exposure to that antigen

Question 2

Tolerogens

Answer 2

tolerogenic antigen

antigens that result in tolerance

Question 3

Immunogens

Answer 3

immunogenic antigen

antigens that result in immunity

Question 4

Can the same antigen be either tolerogenic or immunogenic?

What does this depend on?

Answer 4

yes

depends on how the naive cell first encounters the antigen

Question 5

What are the fates of lymphocytes after antigen encounter?

Answer 5

1. normal immune response –> proliferation and differentiation
2. Self-tolerance –> anergy, deletion, or receptor editing

Question 6

What is the result of failure of self/nonself discrimination?

Answer 6

autoimmune disease

Question 7

Can foreign antigens be presented in a way to promote tolerance?

Answer 7

yes

Question 8

Central tolerance

Answer 8

Involves immature lymphocytes

Occurs in generative organs

Question 9

Peripheral tolerance

Answer 9

involves mature lymphocytes

Occurs in peripheral tissues

Question 10

Is negative selection an example of central or peripheral tolerance?

Answer 10

central

Question 11

Mechanisms of tolerance

Answer 11

1. apoptotic cell death - main mechanism for central tolerance
2. anergy
3. suppresion by regulatory lymphocytes

all 3 function in peripheral tolerance

Question 12

clonal ignorance

Answer 12

some antigens are completely ignored by the immune system so when a lymphocyte encounters this antigen it fails to respond in any detectable way but it remains viable and functional

Question 13

What are the fates of a self-reactive T cell in the thymus?

Answer 13

Negative selection or development of regulatory T cell

Question 14

Normal T cell response

Answer 14

T cell engages TCR
B7 engages costimulatory molecule (CD28

T cell becomes activated

Question 15

Mechanism of anergy for T cell

Answer 15

B7 is not engaged or interacts with CTLA4

T cell becomes anergized

Question 16

CTLA-4

Answer 16

inhibitory receptor for B7

results in anergy by delivering an inhibitory signal to the T cell

Question 17

What happens to CTLA-4 deficient mice?

Answer 17

uncontrolled lymphocyte activation
fatal multi-organ lyphocytic infiltrates

blocking CTLA-4 enhances autoiimmune disease

T cell lacking CTLA-4 are resistant to the induction of anergy

Question 18

Do anergized T cells produce their own IL-2 or proliferate when stimulated with antigen a second time?

Answer 18

No, turned off permanently

Question 19

How is CTLA-4 overcome for a normal response?

Answer 19

Naive cells express lots of CD28 –> favors activation

Mature/activated T cells express less CD28 so the body can return to homeostasis

Question 20

How is it ensured that most self reactive T cells will be anergized and not activated?

Answer 20

Weakly activated or non-activated APCs express low levels of B7

CTLA-4 will bind preferentially because it has higher affinity than CD28

Question 21

Regulatory T cells

Answer 21

CD4 T cells expressing FOXP3

Question 22

How can regulatory T cells suppress t cell responses?

Answer 22

1. inhibit T cell activation by acting on naive T cells - contact dependent
2. inhibit effector functions of activated T cells - cytokine mediated through IL-10 and TGF-beta

Question 23

IL-10

Answer 23

inhibits APC function and macrophage activation

Question 24

TGF-beta

Answer 24

tissue growth factor

inhibits T cell proliferation and macrophage activation

Question 25

anti-apoptotic proteins

Answer 25

produced by activated T cells which have received co-stimulation

Question 26

pro-apoptotic proteins

Answer 26

produced by T cells which don't receive costimulation

Question 27

Fas and FasL

Answer 27

upregulated by T cells which don't receive costimulation --> cell death

Question 28

What are the two mechanisims used to kill T cells which don't receive costimulation?

Answer 28

upregulation of pro-apoptotic proteins or Fas and FasL

Question 29

What are the 2 pathways of T cell apoptosis?

Answer 29

Passive cell death/death by neglect (lack of survival signals) Activation induced cell death via Fas (receptor) and FasL (signal) b/c of overstimulation

Question 30

6 Factors that favor tolerance

Answer 30

High doses prolonged stimulation IV or oral entry presence in generative organs No adjuvants low levels of costimulators and cytokines

Question 31

6 Factors that favor immune responses

Answer 31

``` optimal doses (varies by antigen) short lived stimulation ``` subQ, intradermal entry Absence from generative organs adjuvants present high levels of costimulators

Question 32

Follicular exclusion

Answer 32

Mechanism of peripheral tolerance for B cells B cell kept out of follicle so it can only become a short lived plasma cell and not a memory cell

Question 33

How does Central tolerance begin?

Answer 33

an immature B cell encounters self-antigen in the bone marrow during development

Question 34

What are the possible outcomes for self reactive B cells during central tolerance?

Answer 34

1. death by apoptosis 2. receptor editing 3. exit marrow with less B cell receptor on surface

Question 35

Receptor editing

Answer 35

self-reactive B cells reactivate Rag genes to express new light chain

Question 36

How does peripheral tolerance begin?

Answer 36

mature B cell recognizes antigen in the periphery but doesn't get help from CD4 cells

Question 37

possible outcomes of a self-reactive B cell from peripheral tolerance

Answer 37

1. a block in antigen receptor induced signals (anergy) | 2. exclusion of B cell from lymphoid follicles

Question 38

Principal site of tolerance induction for T cells

Answer 38

thymus and periphery

Question 39

principal sites of tolerance induction in B lymphocytes

Answer 39

bone marrow and periphery

Question 40

Tolerance sensitive stage of maturation for T cells

Answer 40

CD4+CD8+ T cell

Question 41

tolerance sensitive stage for B cells

Answer 41

immature lymphocytes

Question 42

stimuli for peripheral tolerance in T cells

Answer 42

antigen presentation by APCs lacking costimulators repeated stimulation by self antigen

Question 43

stimuli for peripheral tolerance induction in B cells

Answer 43

antigen recognition without T cell help

Question 44

Stimulus for central tolerance induction in both T and B cells

Answer 44

high-avidity recognition of antigen in generative organ

Question 45

principal mechanisms of central tolerance for T cells

Answer 45

clonal deletion (apoptosis)

Question 46

principal mechanism of peripheral tolerance for T cell

Answer 46

anergy, activation-induced cell death, suppression

Question 47

principal mechanism for central tolerance in B cell

Answer 47

clonal deletion (apoptosis), receptor editing

Question 48

principal mechanisms of peripheral tolerance for B cell

Answer 48

block signal transduction (anergy), failure to enter lymphoid follicles

Question 49

What is the principal mechanism for the return to homeostasis after an immune response?

Answer 49

apoptosis