Chapter 17: Adaptive (specific) Immunity

1 Adaptive Immunity Host defenses that are specific to a Chapter 17: particular infectious agent Can be innate or genetic for humans as a Adaptive ( specific ) Immunity group: most microbes can only infect certain species Most specific immune responses improve Bio 139 with repeated exposures to the infectious Dr. Amy Rogers agent or antigen Adaptive Immunity : 2 kinds Humoral Immunity Humoral & Cell-mediated B cells Humoral Immunity : mediated by are lymphocytes (leukocytes of the antibodies circulating in the blood. lymphoid lineage). B cells are produced & differentiate in (human). bone marrow Cell-mediated Immunity : Subsequently, they circulate/reside in blood &. T cells various lymphoid tissues produce antibodies Antibodies Antigens Are substances that trigger an immune are proteins response, including (but not only) antibody have highly specific binding sites for production by B cells antigen The best antigens (that provoke the Each individual antibody is specific for ONE.)

2 Strongest, most specific immune antigen responses) are large proteins Each B cell produces ONLY antibodies with that one specificity Other molecules can also be antigens (polysaccharides, peptides). Antibodies bind to antigens 1. Antigens Chemically complex antigens may have more than one specific target / binding site for antibodies / antigenic determinant called epitopes In the case of invading microorganisms, each one may present many antigens to the immune system, prompting B cells to make many kinds of antibodies What do antibodies look like? Immunoglobulin (Ig). proper name for the antibody protein Ig structure: Y-shaped Variable region with two antigen binding sites at tips of Y. Constant region stem . Immunoglobulin classes: IgG Immunoglobulin classes: IgM.

3 Ig classes differ in structure of constant region IgM: Each Ig class has a different function Secreted as a pentamer (5 Y units All Ig's bind specific antigens connected together; ten antigen binding sites). IgG: First class of antibody secreted, especially during primary immune Prominent in blood responses; high levels indicate recent Main antibody of memory (secondary) immune responses exposure to antigen Acts as an opsonin Activates complement Activates complement (classical pathway) Causes very strong agglutination Crosses the placenta from mother to fetus reactions (clumping microbes helps to Is found in milk eliminate them) Others: IgE, IgA, IgD. 2. What do antibodies do? Neutralize: antibody binding to antigen can render it harmless Toxins: antibodies can block toxin's active site, or agglutinate toxin molecules Bacteria & viruses: antibodies can agglutinate them, prevent them from adhering to cell surfaces Opsonize: antibody binding enhances phagocytosis of the antigen (including whole bacteria or viruses).

4 Lyse: antibodies that activate complement can trigger formation of membrane attack complexes Getting antibodies Getting antibodies Active immunization: Passive immunization: Natural exposure to infectious agent Antibodies NOT produced by your own B cells stimulates your own B cells to produce Maternal antibodies (IgG). antigen- specific antibodies can cross the placenta to protect the fetus;. Colostrum, the milk produced during the first days Artificial immunization (vaccination) with key after birth, contains large quantities of maternal antigens or epitopes from an infectious agent antibodies does the same thing Under certain circumstances, antibodies can be (artificially) injected into a person recently Active immunization results in immunologic exposed to a toxin or microbe memory (more vigorous response next time) antiserum produced in animals.

5 Monoclonal Passive immunization (next slide) does NOT antibodies made in a lab Active Immunization, or How B lymphocytes make antibodies B cells (B lymphocytes) are born in the bone marrow Lymphoid stem cell precursor differentiates into pre-B cell Young B cells express membrane-bound antibodies on their surface Each B cell makes a different antibody ( , an antibody with a different variable region that can specifically bind to a different antigen). 3. Active Immunization, or Active Immunization, or How B lymphocytes make antibodies How B lymphocytes make antibodies Antibody on the surface of a B cell Antigen stimulation leads to: encounters the antigen it is specific for 1. Clonal expansion: The antigen binds to the membrane-bound The one B cell that produces the correct antibody antibody multiplies into many identical B.

6 Cells, all producing the right antibody The B cell is activated Active Immunization, or How B lymphocytes make antibodies Expanded B cell clones then will either: Bone marrow 1. Differentiate into Plasma Cells Plasma cells are mature B lymphocytes which synthesize and secrete massive quantities of the needed antibody or, with the help of TH (T helper) lymphocytes, 2. Become B memory cells Note membrane-bound Memory cells are long-lived. If these cells encounter the (surface) antibody antigen again in the future, the humoral immune response is faster & more vigorous (secondary or anamnestic response). Primary antibody responses (first time the antigen or infection is encountered). Initial B cell clonal expansion Response is dominated by IgM. Memory cells are generated 4.

7 Secondary Generation of Antibody Diversity (anamnestic) antibody responses How does a B cell know what antibody to produce? B Memory cell Immunoglobulins (antibodies) are proteins. population is activated Each Ig must be coded for by a gene. IgG appears faster and The human immune system can recognize more in greater quantity than 10,000,000 different antigens This means if we had one gene for each antibody, we More memory cells are would need 107 genes for Ig production alone! generated (The entire human genome actually codes for only about 30,000 structural genes.). Generation of antibody Generation of Antibody Diversity diversity Antibody genes are constructed individually in each B cell by recombination of gene parts B lymphocytes break the rule that every cell in your Gene bits for the variable region are randomly body has exactly mixed and intentionally mutated to generate a the same DNA.

8 Spectacular number of genetically unique B cell clones The antibody- encoding gene in each B cell is unique to that cell Generation of Antibody Diversity Self-tolerance Antibody diversity is randomly generated before antigen exposure Q: If antibody sequences are generated randomly to include all possible antigens, When antigen enters the body, appropriate why don't B cells produce antibodies that antibodies are selected from the pool of react with normal proteins or cells in our B cells with membrane-bound antibody on bodies (self)? their surface See fig. Selected B cells proliferate, differentiate 5. Self-tolerance This happens with immature lymphocytes Anti-self antibody genes are (randomly). generated all the time B cells: bone marrow;. but receptor is membrane- bound Ig B (and T) lymphocyte clones with anti-self T cells: specificity are deleted during lymphocyte thymus.

9 Receptor is maturation the T cell receptor Clonal deletion & Self-tolerance Cell-mediated Immunity Humoral Immunity : B lymphocytes &. Lymphocytes that could potentially react antibodies against self are killed ( deleted ) early in particularly important for bacteria & extracellular their development toxins This mechanism sometimes fails, and Cell-mediated Immunity : T lymphocytes &. autoimmune disease results NK (natural killer) cells Lupus, myasthenia gravis, rheumatoid arthritis, etc. particularly important for viruses & other intracellular pathogens also acts on tumors & transplants T cells What do T cells do? are lymphocytes (leukocytes of the More than you can imagine! lymphoid lineage) Multiple types exist including are produced from stem cells in the bone TH (helper): CD4+, activated by MHC II.

10 Tc (cytotoxic or killer): CD8+, activated by MHC I. marrow but mature in the thymus T cells secrete a large number of immunologically do NOT produce antibodies important molecules called lymphokines or have clonally unique surface proteins cytokines called T cell receptors (TCR) Interleukins (especially IL-2). Interferon gamma 6. Helper T cells (CD4) Cytotoxic T cells (CD8). CD molecules are a large group of unrelated cell Tc cells attack virus-infected cells surface markers CD4 is a marker of TH cells; CD8 of Tc cells Tc cells produce perforin Like C9 membrane attack complex, perforin bores holes in target cell membranes Main functions of Helper T cells: Occasionally, the action of cytotoxic T cells is more Assist with cellular Immunity damaging than the actual infection!