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Immunology > Chapter 14 > Flashcards

Chapter 14 Flashcards

1
Q

Tolerance

A

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

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2
Q

Tolerogens

A

tolerogenic antigen

antigens that result in tolerance

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3
Q

Immunogens

A

immunogenic antigen

antigens that result in immunity

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4
Q

Can the same antigen be either tolerogenic or immunogenic?

What does this depend on?

A

yes

depends on how the naive cell first encounters the antigen

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5
Q

What are the fates of lymphocytes after antigen encounter?

A
  1. normal immune response –> proliferation and differentiation
  2. Self-tolerance –> anergy, deletion, or receptor editing
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6
Q

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

A

autoimmune disease

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7
Q

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

A

yes

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8
Q

Central tolerance

A

Involves immature lymphocytes

Occurs in generative organs

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9
Q

Peripheral tolerance

A

involves mature lymphocytes

Occurs in peripheral tissues

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10
Q

Is negative selection an example of central or peripheral tolerance?

A

central

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11
Q

Mechanisms of tolerance

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

all 3 function in peripheral tolerance

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12
Q

clonal ignorance

A

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

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13
Q

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

A

Negative selection or development of regulatory T cell

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14
Q

Normal T cell response

A

T cell engages TCR
B7 engages costimulatory molecule (CD28

T cell becomes activated

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15
Q

Mechanism of anergy for T cell

A

B7 is not engaged or interacts with CTLA4

T cell becomes anergized

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16
Q

CTLA-4

A

inhibitory receptor for B7

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

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17
Q

What happens to CTLA-4 deficient mice?

A

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

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18
Q

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

A

No, turned off permanently

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19
Q

How is CTLA-4 overcome for a normal response?

A

Naive cells express lots of CD28 –> favors activation

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

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20
Q

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

A

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

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

21
Q

Regulatory T cells

A

CD4 T cells expressing FOXP3

22
Q

How can regulatory T cells suppress t cell responses?

A
  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
23
Q

IL-10

A

inhibits APC function and macrophage activation

24
Q

TGF-beta

A

tissue growth factor

inhibits T cell proliferation and macrophage activation

25
Q

anti-apoptotic proteins

A

produced by activated T cells which have received co-stimulation

26
Q

pro-apoptotic proteins

A

produced by T cells which don’t receive costimulation

27
Q

Fas and FasL

A

upregulated by T cells which don’t receive costimulation –> cell death

28
Q

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

A

upregulation of pro-apoptotic proteins or Fas and FasL

29
Q

What are the 2 pathways of T cell apoptosis?

A

Passive cell death/death by neglect (lack of survival signals)

Activation induced cell death via Fas (receptor) and FasL (signal) b/c of overstimulation

30
Q

6 Factors that favor tolerance

A

High doses
prolonged stimulation

IV or oral entry

presence in generative organs

No adjuvants

low levels of costimulators and cytokines

31
Q

6 Factors that favor immune responses

A 
optimal doses (varies by antigen)
short lived stimulation

subQ, intradermal entry

Absence from generative organs

adjuvants present

high levels of costimulators

32
Q

Follicular exclusion

A

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

33
Q

How does Central tolerance begin?

A

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

34
Q

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

A
  1. death by apoptosis
  2. receptor editing
  3. exit marrow with less B cell receptor on surface
35
Q

Receptor editing

A

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

36
Q

How does peripheral tolerance begin?

A

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

37
Q

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

A
  1. a block in antigen receptor induced signals (anergy)

2. exclusion of B cell from lymphoid follicles

38
Q

Principal site of tolerance induction for T cells

A

thymus and periphery

39
Q

principal sites of tolerance induction in B lymphocytes

A

bone marrow and periphery

40
Q

Tolerance sensitive stage of maturation for T cells

A

CD4+CD8+ T cell

41
Q

tolerance sensitive stage for B cells

A

immature lymphocytes

42
Q

stimuli for peripheral tolerance in T cells

A

antigen presentation by APCs lacking costimulators

repeated stimulation by self antigen

43
Q

stimuli for peripheral tolerance induction in B cells

A

antigen recognition without T cell help

44
Q

Stimulus for central tolerance induction in both T and B cells

A

high-avidity recognition of antigen in generative organ

45
Q

principal mechanisms of central tolerance for T cells

A

clonal deletion (apoptosis)

46
Q

principal mechanism of peripheral tolerance for T cell

A

anergy, activation-induced cell death, suppression

47
Q

principal mechanism for central tolerance in B cell

A

clonal deletion (apoptosis), receptor editing

48
Q

principal mechanisms of peripheral tolerance for B cell

A

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

49
Q

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

A

apoptosis

Immunology (9 decks)

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