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The Immune System, Part II Medgar Evers College, CUNY Bio 261 Prof. Santos Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity – Is the body’s second major kind of defense – Involves the activity of lymphocytes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The nature of the antigen • An antigen is any foreign molecule – That is specifically recognized by lymphocytes and elicits a response from them • A lymphocyte actually recognizes and binds – To just a small, accessible portion of the antigen called an epitope Antigenbinding sites Antibody A Antigen Antibody B Antibody C Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Epitopes (antigenic determinants) Antigen Recognition by Lymphocytes • The vertebrate body is populated by two main types of lymphocytes – B lymphocytes (B cells) – T lymphocytes (T cells) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T Cells • Produced in the bone marrow • Mature in the thymus • Have T cell receptors that interact with a specific antigen • T cell receptors consist of 2 chains (Alpha and Beta) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The T cell receptor is always attached to the cell • The receptor only interacts with antigens presented to them. • A T cell will only recognize an antigen when complemented with an MHC protein Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T Cell Receptors for Antigens and the Role of the MHC • Each T cell receptor – Consists of two different polypeptide chains AntigenBinding site Variable regions Constant regions V V C C Transmembrane region Plasma membrane a chain b chain Disulfide bridge Cytoplasm of T cell (b) A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T cell • T cells bind to small fragments of antigens – That are bound to normal cell-surface proteins called MHC molecules • MHC molecules – Are encoded by a family of genes called the major histocompatibility complex Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings MHC system • Class I MHC molecules, found on almost all nucleated cells of the body – Display peptide antigens to cytotoxic T cells Infected cell Antigen fragment 1 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. Class I MHC molecule 2 T cell receptor (a) Cytotoxic T cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. • Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells – Display antigens to helper T cells Microbe 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. Antigenpresenting cell Antigen fragment 1 Class II MHC molecule 2 2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. (b) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T cell receptor Helper T cell Helper T Cells: A Response to Nearly All Antigens • Helper T cells produce CD4, a surface protein – That enhances their binding to class II MHC molecule–antigen complexes on antigenpresenting cells • Activation of the helper T cell then occurs Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Activated helper T cells – Secrete several different cytokines that stimulate other lymphocytes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells • Cytotoxic T cells make CD8 – A surface protein that greatly enhances the interaction between a target cell and a cytotoxic T cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Cytotoxic T cells – Bind to infected cells, cancer cells, and transplanted tissues • Binding to a class I MHC complex on an infected body cell – Activates a cytotoxic T cell and differentiates it into an active killer Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The activated cytotoxic T cell – Secretes proteins that destroy the infected target cell 2 1 A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. Cytotoxic T cell 3 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. Released cytotoxic T cell Perforin Cancer cell Granzymes 1 TCR Class I MHC molecule Target cell 3 CD8 2 Peptide antigen Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Apoptotic target cell Pore Cytotoxic T cell B cells • Are made in the bone marrow and mature in other secondary lymphoid organs such as peyer’s patches, spleen and lymph nodes. • Have receptors called B cell receptors. • 5 classes of B cells are immature, naïve, activated, effector (plasma), and memory B cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings B Cell Receptors for Antigens • B cell receptors – Bind to specific, intact antigens – Are often called membrane antibodies or membrane immunoglobulins Antigenbinding site Antigenbinding site Disulfide bridge Variable regions Light chain Constant regions C C Transmembrane region Plasma membrane Heavy chains B cell Cytoplasm of B cell (a) A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • B cell receptors allow B cells to bind to a specific antigens. • B cells become activated and differentiate into effector B cells that produce specific antibodies against the antigen. • 2 types of antigens are T cell dependent antigen and T cell independent antigen, Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T cell dependent B cell activation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T cell independent B cell activation • The B cell does not need the T cell to become activated! The antigens that can activate B cells in this manner are carbohydrates in nature. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antibody Classes • The five major classes of antibodies, or immunoglobulins – Differ in their distributions and functions within the body Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 5 classes of Antibodies • The five classes of immunoglobulins IgM (pentamer) First Ig class produced after initial exposure to antigen; then its concentration in the blood declines J chain IgG (monomer) Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19) Most abundant Ig class in blood; also present in tissue fluids Only Ig class that crosses placenta, thus conferring passive immunity on fetus Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than IgM (see Figure 43.19) Present in secretions such as tears, saliva, mucus, and breast milk IgA (dimer) Secretory component J chain Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19) Presence in breast milk confers passive immunity on nursing infant IgE (monomer) IgD (monomer) Transmembrane region Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20) Present primarily on surface of naive B cells that have not been exposed to antigens Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection) • The roles of the major participants in the acquired immune response Cell-mediated immune response Humoral immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Activate Activate B cell Gives rise to Plasma cells Memory B cells Helper T cell Gives rise to Active and memory helper T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Secreted cytokines activate Cytotoxic T cell Gives rise to Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Immunological Disorders 1- Hypersensitivities 2- auto-Immune disorders 3- Immune deficiencies Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Type I Hypersensitivity: Immediate Ig E mediated • Localized anaphylaxis: hives, hay fever and asthma • Generalized anaphylaxis: antigens enter the bloodstream and become widely spread Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Type II Hypersensitivity: cytotoxic • Cells are destroyed. • Examples: transfusion reactions and hemolytic disease of a newborn Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Type III Hypersensitivities: Immune complex mediated • An immune complex consists of an antigen and antibody bound together often with some complement components. • Example: Disseminated intravascular coagulation and serum sickness Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Type IV Hypersensitivities: Delayed cell mediated • Examples: tuberculin skin test, contact hypersensitivities Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Auto immune disorders • The immune system attacks its own cells • Example: lupus, Diabetes mellitus type I, Crohn’s disease, and rheumatoid arthritis • Treatment includes immuno-suppressants. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Immunodeficiency disorders 1- primary (genetic based) 2-secondary (caused by an environmental factor) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings