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Immunological Tolerance
01/27/15 - Quiz Two Material
11
Pharmacology
Graduate
02/02/2015

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Term
Immunological Tolerance
Definition
Specific unresponsiveness to previously exposed antigen
- normal individuals are tolerant of their self-antigens
Term
Three Outcomes of Antigenic Encounter with lymphocyte
Definition
Immunogenic antigen: protective immune response, typical response to microbes
Tolerogenic: lymphocyte is functionally inactivated or killed, typical response to self antigens
Ignorance: lymphocyte ignores presence of antigen
Term
Negative Selection
(Central T cell Tolerance)
Definition
T cells that recognize self MHC+ peptide too strongly undergo apoptosis
Term
Positive Selection
(Central T cell Tolerance)
Definition
Selects T cells that recognize self MHC+ peptide
T cells that don't recognize self MHC die
Term
Peripheral T cell Tolerance
Definition
Prevents T cell responses to antigens not found in thymus
Provides backup for incomplete central tolerance
Two Mechanisms:
- Recognition of self antigens by mature T cells in periphery leads to functional inactivation (anergy) or death
- Self-reactive lymphocytes are suppressed by regulatory T cells (Tregs)
Term
T cell Anergy
Definition
If T cell recognizes antigen without strong costimulation
- t cell receptors may lose ability to deliver activating signals
- T cell may engage inhibitory receptors that block activation (CTLA cytotoxic T lymphocyte associated protein 4)
* First signal for T cells; exposure to antigen being expressed by MHC
* Signal 2: costimulatory molecules (like B7 and CD28 on APC)
Term
Tregs
Definition
Block activation of potentially harmful lymphocytes specific for self antigens.
- Most are CD4+ and express high levels of CD25 (alpha cahin of IL-2 receptor)
- Development and function require FoxP3 (transcription factor)
Term
Negative selection of B cells
Definition
occurs in bone marrow or secondary lymphoid tissue
CHANGE OR DIE
Term
Peripheral B cell Tolerance
Definition
Mature B cells that encounter self antigens in peripheral lymphoid tissues become incapable of responding to that antigen
- Lack of T cell help
* anergy
* apoptosis
* suppression by inhibitory receptors
Term
Autoimmunity
Definition
Major factors contributing to development of autoimmunity.
- Genetic susceptibility
- Environment triggers
* infections
Term
Microbes can induce autoimmunity
Definition
Activated APC's to express costimulators
- when APC's present self-antigens specific T cells are activated, rather than being rendered toelrant.
* Mimicry
- Some microbial antigens cross-react with self antigens
- Immune responses initiated by microbes directed at self cells and tissues
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