Adaptive Immunity Chapter 7 Elsevier items and derived

Adaptive Immunity Chapter 7 Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Characteristics of Adaptive Immunity Third line of defense (after surface barriers and inflammation) Compared to inflammation it is: Ø Slower, more specific, and longer lasting. Acquired after contact with antigens (so also called acquired immunity) Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Characteristics of Adaptive 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Components of Adaptive Immunity Antigen presenting cells (APCs, macrophages or other phagocytes) process invading pathogens. Ø Present portions of engulfed pathogens to lymphocytes in peripheral lymphoid tissue. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antigen Processing and Presentation Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Components of Adaptive Immunity Lymphocytes mediate adaptive immune response (primary cells responsible) Ø B lymphocytes - responsible for humoral immunity. Ø T lymphocytes - responsible for cellmediated immunity. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Humoral and Cell Mediate Immunity Humoral immunity - mediated by circulating antibodies made by B cells (plasma cells). Cell-mediated immunity - T cells kill targets directly or stimulate the activity of other leukocytes. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Overview of Immune Response Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Active and Passive Immunity Active immunity – immune response originated in the host after exposure to antigen Ø Natural exposure or through immunization Passive immunity – preformed antibodies or T cells are passed to host from a donor. Ø Mother to child across placenta or through milk, or injection of antisera containing immune globulins. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Activity Match the type of immunity to its description or characteristic. Choices: a. Innate immunity b. Adaptive immunity c. Humoral immunity d. Cell-mediated immunity e. Active immunity f. Passive immunity Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Activity 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antigens - molecules that react with components of the immune response, such as antibodies and receptors on B and T cells. Ø Most antigens then induce an immune response resulting in production of antibodies or activated T cells (thus they are also immunogens). Antigenic-determinant (or epitope) - precise chemical structure with which an antibody or B cell/T cell receptor reacts. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antigens Self-antigens - antigens on an individual's own cells or tissues (endogenous antigens). Ø The individual's immune system does not normally recognize self-antigens as immunogenic, a condition known as tolerance. Ø Autoimmunity – the immune system attacks the body’s own tissues as if they were foreign. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Humoral Immune Response The humoral immune response is provided by molecules (antibodies) produced by B cells. Antibodies (Immunoglobulins) Serum glycoproteins produced by mature B cells in response to an antigenic challenge. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Classification of Antibodies Classification - by chemical structure and biologic activity. a. Ig. G – most abundant, provide most protection (especially after initial exposure), found in near adult levels even in blood of newborn. b. Ig. A – found in body secretions and transferred from mother to infant in milk; acts as antigen receptors in mucosal membranes (prevents antigens from entering body). Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antibodies Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Classification of Antibodies c. Ig. M – first produced after exposure; made prenatally so respond to infections in womb. d. Ig. D – act as antigen receptors on the surface of early B cells. e. Ig. E – mediates allergic responses (including anaphylaxis) and protects against parasites. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Ig. E Function Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Molecular Structure of 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. Ø Complementary-determining regions (CDRs) – highly variable regions that determine the specificity of a given antibody (what it binds to). Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Molecular Structure of Antibodies b. Crystalline fragment (Fc) (1) – the base of the Y, responsible for most of the biological properties of antibodies. Ø Interacts with inflammatory cells Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antibodies Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Activity ACTIVITY: On the diagram of Ig. G, 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Function of Antibodies To protect against infection, either directly or indirectly. 1. Direct effects – can affect 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 Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Functions of Antibodies Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Function of Antibodies 2. Indirect effects - activation of inflammation through the Fc portion of the molecule. Causes: Opsonization – coats particle to increase phagocytosis Complement activation - killing the infectious agent through MAC formation. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Function of Antibodies 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 Ig. A) function in the secretions of mucous membranes. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Secretory (Mucosal) Immune System Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Monoclonal Antibodies Produced in the laboratory from one B cell that has been cloned, thus all the antibody is of the same class, specificity, and function. Used for sensitive laboratory tests (e. g. , pregnancy tests) and cancer therapies Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

T Cell Recognition of Target Cell 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

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 Ø Present on most cells. MHC Class II – required for presentation of antigen to T-helper cells (Th cells). Ø On APCs and B cells. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Antigen Presentation Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Superantigens (SAGs) Bind the variable portion of the TCR and the MHC class II molecules outside of their antigen-presentation sites Activates a large population of Tlymphocytes regardless of antigen specificity Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Superantigens (SAGs) (cont’d) SAGs induce an excessive production of cytokines Ø Causes fever, low blood pressure, and potentially shock Examples: Toxins produced by Staphylococcus aureus (toxic shock syndrome) Ø Streptococcus pyogenes (food poisoning). Ø Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

T Lymphocyte Function 1. Killing abnormal cells a. Cytotoxic T lymphocytes (Tc cells) - kill cells infected with viruses or cancer cells. Ø Kill targets by producing toxins and stimulating the cells to undergo apoptosis. Ø Tc cells have CD 8 molecules that bind to MHC class I on the target (so called CD 8 cells). Ø Activated by Th 1 cells (T-helper cells, type 1). Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

T Lymphocyte Function 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 Ig. G bound to their surface, so they can coordinate with other immune responses. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Cell-Killing Mechanisms Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

T Lymphocyte Function 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 CD 4 molecules that bind to MHC Class II antigens on macrophages and B cells. The AIDS virus specifically attacks CD 4 cells, including Th cells. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Phases of Immune Response A. Generation of clonal diversity Occurs before birth in the thymus (T cells) and bone marrow (B cells). 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Phases of Immune Response Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Phases of Immune Response 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 APC. This activates the lymphocyte, causing it to proliferate. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Phases of Immune Response 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. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

B Cell Clonal Selection Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Phases of Immune Response Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

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 Th 2 cells (T-helper cells, type 2). Ig. M is detected in blood first, followed by Ig. G. Memory B cells form. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Secondary Response Occurs each successive time that the body encounters this antigen. Memory B cells are rapidly activated and produce large amounts of Ig. G very quickly. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

ACTIVITY a. T cells b. B cells c. Both T and B 1. Undergo clonal selection after activation. 2. Produce cytokines. 3. Form helper and suppressor cells. 4. Produce antibodies. 5. Directly attack infected cells. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Pediatrics and Immune Function Mechanisms of self-defense are naturally somewhat deficient in the fetus and neonate. Ig. M production is adequate in the fetus and neonate, but Ig. G and Ig. A production develops slowly during the first 12 -16 months of life. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Pediatrics and Immune Function Maternal Ig. G antibodies are transported across the placenta into the fetal blood and protect the neonate for the first 6 months, after which they are replaced by the child's own antibodies. At 1 year an infant’s immune response is about 60% of the adult level. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Fetal and Neonatal Immunity Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Aging and Immune Function Thymus size reaches its maximum at puberty and declines after this. As a result cellmediated immunity also declines. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.

Aging and Immune Function Elderly persons have somewhat deficient T cell function and antibody production, so they are at greater risk for infections. Elderly individuals also tend to have increased levels of circulating autoantibodies (antibodies against self-antigens), so they have a greater incidence of autoimmune diseases and hypersensitivity reactions. Elsevier items and derived items © 2008 by Mosby, Inc. , an affiliate of Elsevier Inc. Some material was previously published.