Contraction of the Immune Response Notes

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