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Flashcards in Regulation of the Immune Response Deck (37):

What is immunological tolerance?

Lack of response to a specific Ag


What are the two major mechanisms of tolerance induction?

deletion of reactive cells, inactivation of reactive cells (anergy)


What is clonal deletion? Where does it occur?

elimination of autoreactive T cells in thymus caused by tight association of T cell to MHC-presented antigen


Why do antigens presented from self-cells induce anergy?

Most self-cells don't have B7-1 or B7-2 so Ag from them isn't costimulated, preventing self-Ag recognition.


What is functional deletion?

deletion of function of T helper cells, causing loss of cytotoxicity of CTL and B cell antibody formation that require help


What are some mechanisms of functional deletion?

deletion of T helper specificity during selection, bias for inappropriate Th1 or Th2 response from production of certain cytokines (i.e. block Th1 cells with IL-10)


How does a regulatory T cell bind APCs? How is it activated?

CD4+ T cell binds B7 receptor on APC with CTLA-4, which is activated by the crosslinking of CD28 molecules


What are the 5 mechanisms of tolerance n in T cells?

1. clonal deletion
2. clonal anergy
3. functional deletion
4. regulatory T cells
5. blocking of presentation or activation


What are the 3 mechanisms of tolerance in B cells?

1. clonal deletion
2. clonal anergy
3. functional deletion


How do B cells become anergic?

Immature B cells expressing IgM are capped when exposed to polyclonal IgM or tolerizing Ag and the IgM internalizes. In mature B cells, re-expression occurs within 1-2 days, but immature cells don't re-express surface Ig


How are B cells functionally deleted?

lack of T cell help for T-dependent B cells, presentation of TI-Ag in non-crosslinking form for TI Bcells


What affects whether an antigen induces maturity or tolerance?

form, amount or manner of presentation of the antigen


Is tolerance easier to induce in mature or immature cells?

Immature cells


How does the immunogenicity of an antigen affect induction of tolerance?

The stronger an immunogen the more stringent regime to induce tolerance


How does the dose affect immunogenecity of a substance?

need the optimal dose range, higher or lower doses usually induce tolerance


What is high dose tolerance?

very large quantity of immunogen can turn off response to it


What is more immunogenic: aggregated material or disaggregated material? Why?

aggregated material, clumps and aggregates stimulate APC to phagocytose the antigen


Tell whether each of the following routes of administration of antigen favors immune response or tolerance: subcutaneous, oral, IM, IV

immune respone: subcutaneous, IM
tolerance: oral, IV


What is cyclophosphamide? What lymphocytes does it work on?

immunosuppressive drug, acts on T and B cells


What cells mediate positive selection in the thymus? What is the cell transition at positive selection?

cortical epithelial cells, go from immature CD3- DN thymocytes to immature CD3+ DP thymocytes


What cells mediate negative selection in the thymus? What is the cell transition at negative selection?

dendritic cell, immature CD3+ DP thymocytes to mature CD3+ SP thymocytes


Why is immune regulation needed?

prevent uncontrolled proliferation of individual B or T cell clones, prevent indefinite response to one challenge to conserve resources for another


What is the expression pattern of Tregs?

FoxP3+ , CD25 +, CD4 +


What is regulatory tolerance?

T cell specific for self-Ag becomes regulatory, IL-10 and TGFb produced by Treg inhibitsother self-reactive T cells


What 6 diseases do Tregs have a role in controlling?

colitis, diabetes, MS, SLE, GVHD, graft rejection


What are mechanisms of regulation of Tregs?

direct contact with target cells, cytokine-mediated suppression of T cells


What type of immunity do proteins induce?

Humoral and CMI


Why can't polysaccharides and lipids induce CMI?

can't be presented by MHC molecules to T cells


What type of immune response do polysaccharides and lipds induce?

short-lived, IgM and some IgG response to capsule


What type of antigen can induce long-lived immunologic memory? How?

proteins/peptides via T cell activation


What is antigen blocking?

Ab sequesters Ag which prevents it from being recognized by other Ag-recognizing cells and thus from activating them


What does crosslinking of Ig and Fc receptors on the same B cell cause?

paralytic signal to the cell


What does crosslinking of two Igs on the same B cell cause?

proliferative signal


When do immune complexes augment B cell response? Which Ab type tends to enhance?

when they opsonize APCs, IgM


When do immune complexes inhibit B cell response? Which Ab type tends to inhibit?

when they crosslink on same B cell, IgG


How is Rh disease prevented?

prevent immune response by using high dose of antiRh Ab to prevent Rh+ from seeing mother's Rh- and forming immune reponse


What is a direct Coomb's test?

look to see if fetal RBC agglutinate when you add anti-human rabbit Ag--if yes, they are coated in maternal Ab
take maternal serum and add Rh+ RBCs and rabbit Ag---if agglutinates, if Rh+ Ab exist