Resistance and the Immune System: Adaptive Immunity Chapter 21 Resistance and the Immune System: Adaptive Immunity

Figure 21.02A: The various antigens possible on a bacterial cell. 21.1 The Adaptive Immune Response Targets the Specific Invading Pathogen The ability to eliminate pathogens requires a multifaceted approach. Antigens are microbes or microbe parts that provoke an immune response. The immune system recognizes unique antigenic determinants (epitopes). Figure 21.02A: The various antigens possible on a bacterial cell.

Figure 21.01: Uninfected and HIV-Infected T Lymphocytes. Immune deficiency is the loss of the body’s ability to respond to antigens and epitopes. Regulatory T cells prevent other T cells from attacking “self” cells. Autoimmune diseases occur when self-tolerance breaks down. If nonimmunogenic molecules (haptens) are linked to proteins, they may not be recognized as “self.” Thus they might provoke an immune response (allergies). © Dr. Klaus Boller/Photo Researchers, Inc. © NIBSC/Photo Researchers, Inc. Figure 21.01: Uninfected and HIV-Infected T Lymphocytes.

Immunological memory is the ability to “remember” past pathogen exposures. The body fights off any subsequent infections. Adaptive immunity generates two complementary responses to most pathogens. B lymphocytes (B cells) are involved in producing antibodies against epitopes. T lymphocytes (T cells) provide resistance through lysis of infected or abnormal cells.

Figure MI21: Mucosal lining of the intestine. The humoral immune response involves: activation of B cells. production of antibodies against the identified antigen. If the microbes enter cells, antibodies are useless. Then the cell mediated immune response is activated to eliminate “nonself” cells. T cells control and regulate these activities. Figure MI21: Mucosal lining of the intestine. Adapted from Wells, Jerry, M. and Mercenier, Annick, Nat Rev Microbiol. 6 (2008): 349-362.

Lymphoid Progenitors Differentiate Into Several Types of Lymphocytes In the fetus, lymphocytes arise from hematopoietic stem cells in the yolk sac and bone marrow. Myeloid progenitors, which become: red blood cells. most white blood cells. Lymphoid progenitors, which become lymphocytes. T cells mature in the thymus B cells mature in the bone marrow Figure 21.03: The Fate of Lymphoid Progenitors.

Clonal selection activates the appropriate B and T cells. Antigen exposure activates only T and B cells with receptors that recognize specific epitopes on that antigen. B and T cell clones contain lymphocytes that develop into: effector cells that target pathogens. memory cells are long-lived B and T cells that provide long term immunity Figure 21.04: Clonal Selection of B Cells.

Figure 21.05A: Structure of an Antibody. 21.2 Humoral Immunity Is an Antibody Response to Pathogens in Body Fluids Antibodies are proteins called immunoglobulins. Epitope recognition requires antibodies to have a special structure of: 2 identical heavy (H) chains. 2 identical light (L) chains. Each light and heavy chain have: A constant region (Fc), which determines the location and functional class of the antibody. A variable region (Fab), which contains different amino acids for the many antibodies produced. Figure 21.05A: Structure of an Antibody.

Figure 21.05B: Structure of an Antibody. The variability allows formation of the specific antigen binding site. The Fab fragment of an antibody combines with the Epitope. The Fc fragment performs functions in: opsonization. activation of the complement system. allergic reactions. Figure 21.05B: Structure of an Antibody. Genetics Home Reference. [Internet] Bethesda (MD): National Library of Medicine (US); 2003- [updated 2004 Aug 4; cited 2006 Aug 08] Immunoglobulin G (IgG) Available from http://ghr.nlm.nih.gov/handbook/illustrations/igg

There are five immunoglobulin (Ig) classes. IgG (gamma globulin) is the major circulating antibody. It provides immunity to the fetus and newborn. IgM is the first (but short-lived) Ig to appear in circulation after B cell stimulation. IgA provides resistance in the respiratory and gastrointestinal tracts (mucosal immunity). It is found in colostrum. IgE plays a role in allergic reactions. IgD is a cell surface receptor on B cells and activates them.

Figure 21.06: The primary and secondary antibody responses. Antibody responses to pathogens are of two types. A primary antibody response occurs the first time the body encounters a pathogen. A secondary antibody response is more powerful and sustained . It occurs with a subsequent infection by the same pathogen. Figure 21.06: The primary and secondary antibody responses.

Figure 21.07: The source of antibody diversity. Antibody diversity is a result of gene rearrangements. Somatic recombination is a random mix and match of gene segments. This accounts for the large number of unique antibodies encoded by immune system genes. Figure 21.07: The source of antibody diversity.

Figure 21.08: Mechanisms of Antigen Clearance. Antibody interactions mediate the disposal of antigens (pathogens). Formation of antigen-antibody complexes result in: Inhibition Neutralization Opsonization Agglutination Precipitation Phagocytosis Figure 21.08: Mechanisms of Antigen Clearance.

Figure 21.09: T-Cell Receptors. 21.3 Cell-Mediated Immunity Detects and Eliminates Intracellular Pathogens Cellular immunity relies on T-lymphocyte receptors and recognition. Cytotoxic T cells have T-cell receptors (TCRs) and CD8 coreceptor proteins. Helper T (TH) cells have TCRs and CD4 coreceptor proteins.. HIV attaches to the CD4 receptor and infects the cell. Figure 21.09: T-Cell Receptors.

Figure 21.13A: Normal binding between APC and T cell. TCRs and coreceptors allow T cells to recognize and bind to the major histocompatibility complex (MHC). MHC proteins are unique for nearly all individuals. They mark the body’s cells as “self.” Class II MHC proteins on the surface of immune cells present antigen fragments to Helper T cells. They are called antigen-presenting cells (APCs). Class I MHC proteins are found on the surface of nearly all the body’s cells. Figure 21.13A: Normal binding between APC and T cell.

Helper T cells can help with both humoral and cell mediated immunity TH1 cells control cell-mediated processes CTL Macrophage Neutrophil NK cell activation TH2 cells activate B cells in humoral immune response Figure 21.10: Cell-Mediated Immunity: Helper T Cell activation and Effector Activity.

Cytotoxic T cells recognize MHC-1 peptide complexes. Host cells infected by viruses can: degrade viral antigens. present peptide fragments with MHC-1 proteins on the cell surface. Activated cytotoxic T cells recognize and bind to the MHC-1/peptide complex on infected cells. They release toxic substances such as perforin and granzymes to: cause cell death. expose pathogens to antibodies. T cells can also recognize and kill tumor cells. Figure 21.12: A "Lethal Hit”. © Steve Gschmeissner/Photo Researchers, Inc.

Some Antigens are T-Cell Independent T-cell independent: Some antigens (bacterial capsules and flagella) do not require the help of T cells Bind directly with receptors on B cells Superantigens (viral proteins and bacterial exotoxins) crosslink MHC and TCRs already bound to a peptide fragment Cytokine storm (over-reacts) can lead to shock and death Figure 21.13B: Superantigen Binding.

Figure 21.14: A concept map Summarizing the Adaptive Immunity.