Regulation of the Immune Response Flashcards
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?
- clonal deletion
- clonal anergy
- functional deletion
- regulatory T cells
- blocking of presentation or activation
What are the 3 mechanisms of tolerance in B cells?
- clonal deletion
- clonal anergy
- 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
