PATHOPHYSIOLOGY Name Chapter 6: Adaptive Immunity I. Characteristics of Adaptive Immunity A. General Characteristics Third line of defense (after surface barriers and inflammation) Compared to inflammation it is: o Slower, more specific, and longer lasting. Acquired after contact with antigens (so also called acquired immunity) Adaptive response usually initiated by cells of innate system, primarily phagocytes. Recognizes specific antigens. Provides memory to fight pathogens when they are encountered again. B. Components 1. Antigen presenting cells (APCs, macrophages or other phagocytes) process invading pathogens. o Present portions of engulfed pathogens to lymphocytes in peripheral lymphoid tissue. 2. Lymphocytes mediate adaptive immune response (primary cells responsible) o B lymphocytes (B cells) - responsible for humoral immunity. o T lymphocytes (T cells) - responsible for cell-mediated immunity. C. Humoral and Cell-Mediated Immunity 1. Humoral immunity - mediated by circulating antibodies made by activated B cells (plasma cells). 2. Cell-mediated immunity - T cells kill targets directly or stimulate the activity of other leukocytes. D. Active and Passive Immunity 1. Active immunity – an immune response originated in the host after exposure to an antigen. o Natural exposure or through immunization 2. Passive immunity – pre-formed antibodies or T cells are passed to the host from a donor. o Mother to child across placenta or through milk, or injection of antiserum containing immune globulins. ACTIVITY 1: Match the type of immunity to its description or characteristic. a. Innate immunity c. Humoral immunity e. Active immunity b. Adaptive immunity d. Cell-mediated immunity f. Passive immunity 1. Immunity conferred on a host by transfer of antibodies from a donor. 2. Involves direct attack upon pathogens by T cells. 3. Includes the inflammatory response and other nonspecific protective mechanisms. 4. Immune mechanisms that are acquired after contact with a specific antigen. 5. Immune response that specifically involves antibodies and B cells. 6. The type of immunity produced by vaccinations. 2 E. Antigens 1. Antigens - molecules that react with components of the immune response, such as antibodies and receptors on B and T cells. o Most antigens then induce an immune response resulting in production of antibodies or activated T cells (thus they are also immunogens). 2. Antigenic-determinant (or epitope) - the precise chemical structure with which an antibody or a B or T cell receptor reacts. 3. Self-antigens - antigens on an individual's own cells or tissues (endogenous antigens). o The individual's immune system does not normally recognize self-antigens as immunogenic, a condition known as tolerance. o Autoimmunity – the immune system attacks the body’s own tissues as if they were foreign. II. Humoral Immune Response The humoral immune response is provided by molecules (antibodies) produced by B cells. A. Antibodies (Immunoglobulins) 1. Serum glycoproteins produced by mature B cells in response to an antigenic challenge. 2. Classification - by chemical structure and biologic activity. a. IgG – most abundant, provides most protection (especially after initial exposure), found in near adult levels even in blood of newborn. b. IgA – found in body secretions and transferred from mother to infant in milk; acts as antigen receptor in mucosal membranes (prevents them entering body). c. IgM – first type produced after exposure; made prenatally so responds to infections in womb. d. IgD – acts as antigen receptor on the surface of early B cells. e. IgE – mediates allergic responses (including anaphylaxis) and protects against parasites. 3. Molecular structure – antibodies are Y-shaped molecules consisting of four polypeptide chains. a. Antigen-binding fragments (Fab) (2) – the two arms of the Y; the end of each has the site that recognizes and binds to antigen. o Complementary-determining regions (CDRs) – highly variable regions that determine the specificity of a given antibody (what it binds to). b. Crystalline fragment (Fc) (1) – the base of the Y, responsible for most of the biological properties of antibodies; this portion interacts with inflammatory cells. ACTIVITY 2: On the diagram of IgG, label the following: a. Fab portion b. Fc portion c. CDR regions d. Put a star (*) at the points where the antibody interacts with antigen. 3 B. Function of antibodies To protect against infection, either directly or indirectly. 1. Direct effects – can act against infectious agent or their toxins by: Neutralization – prevents binding to receptors and entry into cells Agglutination – causes clumping of antigens with antibody, forming immune complexes Precipitation – takes a soluble antigen out of solution 2. Indirect effects - activation of inflammation through the Fc portion of the molecule. Causes: Opsonization – coats particle to increase phagocytosis Complement activation - kills the infectious agent through MAC formation. 3. Internal - antibodies of the systemic immune system function internally, in the bloodstream and tissues. 4. External - antibodies of the secretory, or mucosal, immune system (primarily secretory IgA) function in the secretions of mucous membranes. C. Monoclonal antibodies 1. Produced in the laboratory from one B cell that has been cloned, thus all the antibody is of the same class, specificity, and function. 2. Used for sensitive laboratory tests (for example, pregnancy tests) and cancer therapies. III. Cell-Mediated Immune Response Accomplished by T cells to protect against viruses, tumors, and pathogens resistant to phagocytosis. There are several types of mature T cells: cytotoxic T cells (Tc), regulatory T cells including T-helper (Th) and T-suppressor (Ts) cells, and memory cells. A. T Cell Recognition of Target 1. Process of Recognition T cells have antigen specific receptors (T cell receptor or TCR) that must “see” antigen. This requires presentation of antigen by molecules of the major histocompatibility complex. 2. Major Histocompatibility Complex (MHC) Molecules These are antigens on the surface of all body cells, except RBCs. Used to distinguish “self” from “nonself” MHC Class I – used to present fragments of antigen to most immune cells; present on most cells. MHC Class II – required for presentation of antigen to T-helper cells (Th cells); on APCs and B cells. 3. Superantigens (SAGs) Molecules that bind to the variable portion of the TCR and the MHC class II molecules outside of their antigen-presentation sites. Activates a large population of T-lymphocytes regardless of antigen specificity. SAGs induce an excessive production of cytokines. o Causes fever, low blood pressure, and potentially shock. Examples: Toxins produced by Staphylococcus aureus (toxic shock syndrome) and Streptococcus pyogenes (food poisoning). 4 B. T Lymphocyte Functions 1. Killing abnormal cells a. Cytotoxic T lymphocytes (Tc cells) - kill cells infected with viruses or cancer cells. Kill targets by producing toxins and stimulating the cells to undergo apoptosis. Tc cells have CD8 molecules that bind to MHC class I on the target (so called CD8 cells). Activated by Th1 cells (T-helper cells, type 1). b. Natural Killer (NK) Cells – similar to Tc cells, but they are less specific and can attack a wide range of cancerous or virus-infected cells. Antibody-dependent cellular cytotoxicity (ADCC) – allows NK cells to target any cells that have IgG bound to their surface, so they can coordinate with other immune responses. 2. Macrophage activation – during chronic inflammation, T cells release cytokines to activate macrophages. 3. Regulation of humoral and cell-mediated immunity – both require activity of T-helper cells. Th cells have CD4 molecules that bind to MHC Class II antigens on macrophages and B cells. The AIDS virus specifically attacks CD4 cells, including Th cells. IV. Phases of Immune Response A. Generation of clonal diversity Occurs before birth in the thymus (T cells) and bone marrow (B cells). The body produces millions of different T and B cells that each have receptors to recognize one specific antigen. Thus there should be a B or T cell that can recognize any antigen the body encounters. These are released into body and migrate to other lymphoid organs to await exposure to antigen. B. Induction of the Immune Response Also referred to as clonal selection Antigen presenting cells interact with B and T cells that recognize the antigen carried by an APC. This activates the lymphocyte, causing it to proliferate. B cells become plasma cells that secrete large amounts of antibody against the antigen. T cells become cytotoxic T cells capable of direct attack against cells carrying antigen. T-helper cells are needed to facilitate B and T cell activation. C. Primary Response Occurs the first time the body is exposed to a particular antigen. A latent period of 5-7 days occurs during which B cell clonal selection occurs. Activated by Th2 cells (T-helper cells, type 2). IgM is detected in blood first, followed by IgG. Memory B cells form. 5 D. Secondary Response Occurs each successive time that the body encounters this antigen. Memory B cells are rapidly activated and produce large amounts of IgG very quickly. ACTIVITY 3: Match the lymphocyte activity with the type of cells involved. a. T cells b. B cells c. Both T and B cells 1. Undergo clonal selection after activation. 2. Produce cytokines. 3. Form helper and suppressor cells. 4. Produce antibodies. 5. Directly attack infected