Contraction of the Immune Response Notes

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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
Figure 46.3 Clonal deletion. T cells express Fas → bind to Fas ligand on CD8+ T cell/NK cell → caspases activated → apoptosis. B & T CELL MEMORY osms.it/B-and-T-cell-memory ▪ Ability of B, T cells to “remember” particular antigen ▫ B, T cells multiply when receptors detect particular antigen ▫ After immune response mounted, excess cells undergo apoptosis ▫ Memory B, T cells contain same receptors after immune response ▪ Immunologic memory → secondary (anamnestic) response ▫ Primary response: naive B, T cells require activation before response to pathogen → high pathogen burden (response can take days, weeks) ▫ Secondary response: memory B, T cells, antibodies needed to respond to pathogen already exist → low pathogen burden (response occurs right away) 396 OSMOSIS.ORG MEMORY B CELLS ▪ Only B cells that have undergone class switching become memory B cells ▫ Memory response limited to peptide antigens (not lipids/carbohydrates)— follicular T helper cells needed for class-switching only respond to peptide antigens ▫ Memory B cells don’t produce IgM/IgD ▪ Live up to 10 years in lymph nodes ▪ Often differentiate into IgG-producing plasma cells when reactivated ▪ Due to somatic hypermutation, IgG created late in immune response typically has higher affinity than IgM created early in immune response → IgG binds to Fc gamma receptor II on IgM-producing B cells, prevents differentiation into plasma cells → ↓ IgM production, ↑ IgG production
Chapter 46 Immunology: Contraction of the Immune Response Figure 46.4 B cells are activated through interactions with other immune cells. Step 1a: follicular dendritic cell traps antigens and 1b: sends out stimulatory cytokines. Step 2: the B cell presents the antigen to a follicular T helper cell. Step 3a: the follicular T helper cell expresses CD40L on its surface and produces IL-21. 3b: together, they induce the B cell to undergo class switching (shift from expressing a B cell receptor with IgM and IgD to expressing IgG, IgE, or IgA. 3c: some of these B cells become memory B cells. OSMOSIS.ORG 397
Figure 46.5 Process by which higher affinity IgG production is favored over lower affinity IgM production. Memory B cells differentiate into high affinity IgG-producing plasma cells. IgG binds to Fc gamma receptor II on newly activated B cells, which produce low affinity IgM. This prevents them from differentiating into low affinity IgM-producing plasma cells, allowing the proportion of high affinity IgG in the response to be greater. MEMORY T CELLS cytotoxic cells, binding to, destroying target cells) ▪ IL-7 receptors replaced with IL-2 receptors during activation → cells die shortly after immune response Effector memory T cells ▪ Move around body looking for pathogens ▪ Respond as primary response (for CD4+ helper cells, secreting cytokines; for CD8+ Central memory T cells ▪ Live up to 25 years ▪ Remain in lymphoid tissues ▪ High levels of IL-7 receptors maintained → cells live on after immune response ▪ Cell surface ligand CD45 used to identify T cells ▫ Naive T cells express CD45A ▫ Memory T cells express CD45O 398 OSMOSIS.ORG
Chapter 46 Immunology: Contraction of the Immune Response Figure 46.6 The two types of memory T cells (effector memory T cells and central memory T cells) and their functions. CONTRACTING THE IMMUNE RESPONSE osms.it/contracting-immune-response ▪ Immune response termination ▪ Peripheral tolerance to self antigens limits immune response (preventing autoimmune disease) ▪ Mechanisms directed primarily at T cells; includes use of T regulatory cells, clonal anergy, exhaustion, deletion B CELLS ▪ Similar mechanisms to T cells ▪ Later in immune response, reduced presence of antigens, T cells prevent B cell activation → anergy ▪ Surplus IgG binds to Fcγr II on B cells → prevent differentiation into plasma cells T REGULATORY CELLS ▪ Inhibit antigen-presenting cells by releasing specific molecules (e.g. indoleamine 2,3 dioxygenase) ▪ Release cytokines (e.g. IL-10, TGF-beta) → antigen-presenting cells express inhibitory ligand (e.g. PD-L1) ▪ Express high levels of IL-2, adenosine receptors (competing with other T cells) OSMOSIS.ORG 399

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Contraction of the Immune Response essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Contraction of the Immune Response by visiting the associated Learn Page.