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Micro/Immuno Part 2 > Regulation of Immune Response > Flashcards

Regulation of Immune Response Flashcards

1
Q

Immunological tolerance

A
  • lack of response to a specific antigen-reaction to self

- we cannot allow reactivity to self antigen or we will have autoimmune disease

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2
Q

achievement of immune tolerance

A
  • elimination of cell populations reactive to self antigen
  • neutralization of reactive cell populations
  • generation of unique cell populations that produce antigen specific tolerance
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3
Q

tolerance

A
  • can be induced in B cells and T cells
  • learned/self acquired
  • more easily induced in young animals/humans (but occurs throughout the life of an organism
  • found in the 1920s when a large dose of diptheria toxoid suppressed immunity normally elicited by smaller doses
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4
Q

two major mechanisms of tolerance induction

A
  • deletion of reactive cells

- inactivation of reactive cells-anergy

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5
Q

clonal deletion

A
  • immature or developing T cells are deleted
  • apoptosis
  • major mechanism for deleting autoreactive T cells as the develop in the thymus
  • caused by tight association of autoreactive TCR to MHC and self antigen
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6
Q

clonal anergy

A

-some peptides aren’t presented in thymus
-immature cells can be functionally eliminated if they don’t get co stimulatory signal
-still express receptor but are basically dead
-can’t get 2 signals in the future and be reactivated
(normally gets two signals and becomes activated then kills other cells it recognizes)
-can’t recognize pathogen after anergic from self

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7
Q

functional deletion

A
  • loss of T cell help by CTL or B cells
  • bias toward inappropriate TH1 or TH2 response
  • delete antigen specific helper cells and loost CD8 toxicity or B cell antibody formation
  • block helper T cells with IL10 bias toward TH2 respons
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8
Q

leprosy

A
  • need TH1 response-tuberculoid

- TH2 response is lepromatous

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9
Q

Generation of regulatory T cells

A

-suppress autoreactive T cells interacting with same APC

-

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10
Q

blocking of presentation or activation

A
  • directed at co receptors or at MHC
  • reduces effected presentation
  • CTLA4 competes for CD28 binding (with B7)
  • drugs can block presentation
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11
Q

clonal deletion in B cells

A
  • in some cases in immature cells in the bone marrow
  • bone marrow doesn’t educate like thymus does
  • is given a chance to try again
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12
Q

clonal abortion/anergy

A
  • elimination of reactive clones when they are immature
  • particularly efficacious in young animal and when used in a putatively virgin response
  • immature cell has IgM-exposed to polyclonal IgM or tolerizing antigen exposure, its capped and internalized
  • in mature B cells reexpression is in 24-48 hours
  • immature cells don’t re-express
  • could also express antigen but not react
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13
Q

functional deletion in B cells

A

-unavailability of T cell help of presentation to B cell in a non-crosslinking form

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14
Q

inducing and maintaining tolerance

A
  • maturity of immunized host
  • inherent immunogenicity of a substance
  • antigen dose
  • form of antigen
  • immunosuppression
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15
Q

maturity

A
  • immune response in older and immunologically mature

- tolerance in newborn and immunogically immature

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16
Q

form of antigen

A
  • immune response in large, aggregated complex molecules

- tolerance in soluble, aggregate free, smaller, less complex molecules not processed by APC

17
Q

route of administration

A
  • immune response in subQ or intramuscular

- tolerance in oral or IV

18
Q

dose of antigen

A
  • immune response in optimal dose

- tolerance in very large or maybe very small dose

19
Q

differentiation state of cell

A
  • immune response in fully differentiated cells; memory T and memory B cells
  • tolerance in relatively undifferentiated: B cells with only IgM, thymocytes
20
Q

Generation of self tolerance

A
  • education in the thymus

- Goldilocks theory

21
Q

necessity for regulation

A
  • prevent uncontrolled proliferation of individual B or T cell clones
  • prevent an indefinite response to one challenge
  • conserve resources by fine tuning the response
22
Q

regulatory T cells

A
  • FoxP3, CD25, CD4
  • thymectomized mice develop AI disease-transfer of CD25 T cells from adult mice prevented autoimmunity
  • selected positively in thymus on MHC class II
  • suppress pathological and physiological immune responses
  • control colitis, diabetes, EAE, SLE, graft versus host disease, graft rejection
23
Q

deletional tolerance (recessive)

A
  • self reactive T cells deleted in the thymus, may escape

- in the periphery cause tissue damage

24
Q

regulatory tolerance

A
  • T cell specific for self antigen becomes a Treg

- cytokines IL10 and TGFB produced by Treg inhibit other self reactive T cells

25
Q

antigen can regulate the immune response

A
  • chemical nature of the antigen
  • amount of antigen
  • portal entry of antigen
  • packaging of antigen
  • presentation of antigen is affected by genetic background
26
Q

chemical nature of antigen

A
  • protein antigen for CMI and humoral immunity
  • polysaccharides/lipids for humoral immunity (can’t be presented to T cells)

-leads to short lived immunity for bacterial whose capsules are polysaccharides

27
Q

amount of antigen

A
  • very large or frequent small doses can be inhibitory

- dose has optima

28
Q

portal of entry of antigen

A
  • subQ and intradermal is immunogenic

- large doses IV or orally often tolerizes

29
Q

packaging of antigen

A

-adjuvents

30
Q

increased immunogenicity

A
  • large size
  • intermediate dose
  • subQ IM
  • complex antigen
  • particulate or denatured
  • very different from self
  • slow release of adjuvents
  • bacterial adjuvents
  • effective interaction with MHC
31
Q

double cross linking

A

-turns off response/B cell

Micro/Immuno Part 2 (17 decks)

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