Rishi Desai, MD, MPH

Anergy, exhaustion, and clonal deletion

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NOTES NOTES  CONTRACTION OF THE IMMUNE RESPONSE  ANERGY, EXHAUSTION, & CLONAL DELETION osms.it/contracting-immune-response CLONAL ANERGY  ▪ Functional unresponsiveness to self antigens ▪ Lymphocytes can bind to antigens, without costimulation ▪ T cells: costimulation involves CD28 binding to B7 on antigen-presenting cells (APCs) ▫ T regulatory cells reduce B7 expression on antigen presenting cells ▫ Later in immune response, T cells begin to express cytotoxic T-lymphocyte associated protein 4 (CTLA-4) → binds to B7 Figure 46.2 T cells express much more CTLA-4 later in immune response. B7 binds to CTLA-4 more strongly than it does to CD28 and inhibits T cell → T cell inactivation.  CLONAL EXHAUSTION  ▪ Later in immune response, T cells begin to express program death 1 (PD-1) ▪ Program death ligand 1 (PD-L1) on antigen-presenting cells bind to PD-1 → T cells shut down  CLONAL DELETION Figure 46.1 T regulatory cells reduce costimulation by releasing cytokines that reduce B7 expression on antigen-presenting cells (APCs).  ▪ Recognition of self antigens → T cell apoptosis (programmed cell death) ▪ Later in immune response, T cells express Fas ▪ Fas ligands on CD8+ T cells, NK cells bind to Fas → activate enzymes called caspases → apoptosis  OSMOSIS.ORG 395   

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Anergy, exhaustion, and clonal deletion

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