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

Flashcards in Regulation of Immune Response Deck (31):

Immunological tolerance

-lack of response to a specific antigen-reaction to self
-we cannot allow reactivity to self antigen or we will have autoimmune disease


achievement of immune tolerance

-elimination of cell populations reactive to self antigen
-neutralization of reactive cell populations
-generation of unique cell populations that produce antigen specific tolerance



-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


two major mechanisms of tolerance induction

-deletion of reactive cells
-inactivation of reactive cells-anergy


clonal deletion

-immature or developing T cells are deleted
-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


clonal anergy

-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


functional deletion

-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



-need TH1 response-tuberculoid
-TH2 response is lepromatous


Generation of regulatory T cells

-suppress autoreactive T cells interacting with same APC


blocking of presentation or activation

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


clonal deletion in B cells

-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


clonal abortion/anergy

-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


functional deletion in B cells

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


inducing and maintaining tolerance

-maturity of immunized host
-inherent immunogenicity of a substance
-antigen dose
-form of antigen



-immune response in older and immunologically mature
-tolerance in newborn and immunogically immature


form of antigen

-immune response in large, aggregated complex molecules
-tolerance in soluble, aggregate free, smaller, less complex molecules not processed by APC


route of administration

-immune response in subQ or intramuscular
-tolerance in oral or IV


dose of antigen

-immune response in optimal dose
-tolerance in very large or maybe very small dose


differentiation state of cell

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


Generation of self tolerance

-education in the thymus
-Goldilocks theory


necessity for regulation

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


regulatory T cells

-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


deletional tolerance (recessive)

-self reactive T cells deleted in the thymus, may escape
-in the periphery cause tissue damage


regulatory tolerance

-T cell specific for self antigen becomes a Treg
-cytokines IL10 and TGFB produced by Treg inhibit other self reactive T cells


antigen can regulate the immune response

-chemical nature of the antigen
-amount of antigen
-portal entry of antigen
-packaging of antigen
-presentation of antigen is affected by genetic background


chemical nature of antigen

-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


amount of antigen

-very large or frequent small doses can be inhibitory
-dose has optima


portal of entry of antigen

-subQ and intradermal is immunogenic
-large doses IV or orally often tolerizes


packaging of antigen



increased immunogenicity

-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


double cross linking

-turns off response/B cell