Immunology Notes

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Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

Immunology NotesNov 1512 Immunological tolerance Tolerance is nonresponsiveness to an antigen Selftolerance is nonresponsiveness to selfantigens Acquired induced tolerance is the suppression of a specific systemic immune response to foreign antigens induced by the specific actions of lymphocytes Examples of acquired tolerance are fetal tolerance and oral tolerance Fetal tolerance is the suppression of a specific systemic immune response to foreign antigens found within a developing fetus Oral tolerance is the suppression of a specific systemic immune response against antigens encountered via the enteric oral route like food or gut flora Types of selftolerance Central tolerance causes deletion and editing and occurs in the thymus and bone marrow Antigen segregation forms a physical barrier to selfantigen access to the lymphoid system and occurs in the peripheral organs thyroid pancreas Peripheral anergy causes cellular inactivation by weak signalling without costimulus and occurs in secondary lymphoid tissue Regulatory T cells cause suppression by cytokines and intercellular signals in secondary lymphoid tissue and sites of inflammation Functional deviation causes differentiation of regulatory T cells that limit inflammatory cytokine secretion and occurs in secondary lymphoid tissue and sites of inflammation Activationinduced cell death causes apoptosis and occurs in secondary lymphoid tissue and sites of inflammation Antigen segregation Most self antigens are retained outside of the lymphoid system by physical barriers cell membranes endothelium In the absence of tissue damage these antigens are not encountered by immune cells Immune privileged sites include the brain testes eyes and placenta and fetus This is a form of antigen segregation Immune privileged sites are sites capable of tolerating the introduction of an antigen or foreign tissue without eliciting a damaging immune response Tissue grafts into these tissues often can survive without immunosuppressive drugs Immune privileged sitesmechanismsRestricted entry of immune cells has vasculature that makes it hard for immune cells to enterExpression of class Ib MHC in preference to classical MHC I class Ib MHC doesnt present antigen so it does not activate T cells but it does activate NK cellsHigh expression of complement inhibitorsLocal production of TGFMinimalno draining lymphatics retains antigen to keep it away from immune system Constitutive expression of apoptosisinducing ligands such as FASL and TRAIL they activate proapoptotic receptors on lymphocytesTissuespecific immunomodulation The placenta expresses IDO which removes tryptophan preventing T cells from proliferating Tryptophan is an amino acid we dont synthesize so T cells cant make full proteins without this amino acid FASFASL Binding of FASL to FAS initiates the extrinsic pathway of apoptosis FASL is a trimer and it binds to FAS making it a trimer trimer is the active form of FAS The three death domains of the FAS trimer cluster together and bind to FADD via its death domain The death effector domains DED of FADD recruit and bind to DEDs of procaspase 8 Procaspase 8 becomes activated and caspase 8 which is the target of granzyme B is released from the receptor complex Immune privileged sitesconsequences They do not fight off infections well sometimes Damage to an immunologically privileged site can induce an autoimmune response Trauma or damage to one eye results in the release of sequestered protein antigens from this eye Released antigen is carried to
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