Chapter 37 Immunity Sections 7-12 Albia Dugger • Miami Dade College 37.7 Overview of Adaptive Immunity • Vertebrate adaptive immunity adapts to different antigens an individual encounters during its lifetime • Lymphocytes and phagocytes interact to effect four defining characteristics: self/nonself recognition, specificity, diversity, and memory 4 Characteristics of Adaptive Immune Responses 1. Self/Nonself recognition is based on the ability of T cell receptors to recognize self (MHC) markers; TCRs and other antigen receptors recognize nonself, in the form of antigen 2. Specificity means the adaptive immune response can be tailored to combat specific antigens 4 Characteristics of Adaptive Immune Responses 3. Diversity refers to the billions of different antigen receptors that a person’s B and T cells can make 4. Memory refers to the capacity of the adaptive immune system to “remember” an antigen – the second time an antigen shows up, the response is faster and stronger Two Arms of Adaptive Immunity • Antibody-mediated immune response • B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid • Cell-mediated immune response • Cytotoxic T cells and NK cells detect and destroy infected or altered body cells Antigen Processing • Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis • All descendent cells recognize the same antigen • T cells do not recognize an antigen unless it is presented by an antigen-presenting cell • Macrophages, B cells, and dendritic cells digest particles and display antigen-MHC complexes Antigen Processing 1 7 2 6 lysosome 5 3 MHC molecule 4 Intercepting Antigen • A dendritic cell or macrophage migrates to a lymph node, where it presents antigen to T cells • The T cell secretes cytokines, which signal other B or T cells with the same antigen receptor to divide and differentiate • Effector cells are differentiated B and T cells that act at once to fight infection • Memory cells are long-lived B and T cells reserved for future encounters with the same antigen Clearing Out Antigen • Effector cells destroy most antigen-bearing agents • Antibody–antigen complexes form large clumps that are quickly cleared from the blood by the liver and spleen • Complement proteins assist in the cleanup memory cells memory cells B or T cell effector cells effector cells primary secondary immune response immune response first exposure second exposure Figure 37-15 p661 Take-Home Message: What is the adaptive immune system? • Phagocytes and lymphocytes interact to bring about vertebrate adaptive immunity, which has four defining characteristics: self/nonself recognition, specificity, diversity, and memory. • The two arms of adaptive immunity work together. Antibodymediated responses target antigen in blood or interstitial fluid; cell-mediated responses target altered body cells. 37.8 The Antibody-Mediated Immune Response • Antibody-mediated immune response • Antigen activates naïve B cells and dendritic cells • Naïve T cell binds to APC and differentiates into effector and memory helper T cells • Helper T cells bind antigen-MHC complexes on activated B cell and secrete cytokines • B cell differentiates into effector B cells, which produce antibodies, and memory B cells 2 1 dendritic cell bacterium naive B cell complement antigenpresenting dendritic cell naive helper T cell 4 B cell cytokines 3 memory helper T cell effector helper T cell 5 memory B cell effector B cell 6 Stepped Art Figure 37-16a p662 Antibody Action • Circulating antibodies attach themselves to pathogens • An antibody coating prevents bacteria from attaching to body cells and brings them to the attention of phagocytic cells • Antibodies also cause agglutination of foreign cells – clumps are removed from the circulatory system by the spleen • Antibodies also initiate a complement cascade in innate immune responses Lymphocyte Activity in a Lymph Node Clonal Selection • Only B and T cells with receptors that bind antigen divide (clone) and differentiate into effector and memory cells • Primary response produces memory B and T cells; secondary response is stronger and faster antigen Antigen binds only to a matching B cell receptor. mitosis clonal population of effector B cells Many effector B cells secrete many antibodies. Figure 37-18 p663 Take-Home Message: What happens during an antibody-mediated immune response? • T cells, B cells, and antigen-presenting cells carry out an antibody-mediated immune response. • Effector B cells that form during an antibody-mediated immune response make and secrete antibodies that recognize and bind antigen-bearing particles in blood or tissue fluids. Antibody binding can neutralize a pathogen or toxin and facilitate its elimination from the body. • Memory cells also form, and these are reserved for a potential future encounter with the antigen. 37.9 The Cell-Mediated Response • Cell-mediated immune response • Dendritic cell ingests altered body cell, displays antigenMHC complexes, and migrates to lymph node • Naïve helper T and cytotoxic T cells bind to APC • Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells • Cytotoxic T cells circulate and touch-kill altered body cells dendritic cell 1 naive antigencytotoxic presenting T cell dendritic cell naive helper T cell 3 2 4 activated cytokines effector helper cytotoxic T cell T cell memory cytotoxic T cell effector cytotoxic T cell memory helper T cell 5 Stepped Art Figure 37-19a p664 APC and T Cell TCR Binding Antigen/TCR/ MHC Complex Cytotoxic T Cells • Cytotoxic T cells kill body cells displaying antigen-MHC markers – including cancer cells that display altered body proteins, and body cells infected with intracellular pathogens • T cell releases protein-digesting enzymes and perforins • Perforins assemble into complexes that insert themselves into a plasma membrane as a transmembrane channel; enzymes enter the cell and induce it to commit suicide Natural Killer Cells • Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division • Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers Take-Home Message: What happens during a cell-mediated immune response? • T cells, NK cells, and antigen-presenting cells carry out a cellmediated immune response. • Effector cytotoxic T cells and NK cells that form during a cellmediated immune response kill infected body cells or those that have been altered by cancer. • Memory cells also form, and these are reserved for a potential future encounter with the antigen. 37.10 When Immunity Goes Wrong • An allergy is an immune response to something that is ordinarily harmless to most people • Autoimmune disorders occur when an immune response is misdirected against a person’s own healthy body cells • In immunodeficiency, the immune response is insufficient to protect a person from disease Allergies • Allergy • An immune response to a typically harmless substance (allergen) • First exposure stimulates production of IgE, which becomes anchored to mast cells and basophils • Later exposure stimulates secretion of histamine and cytokines that initiate inflammation Allergies: Hives Allergies: Hay Fever Overly Vigorous Responses • Acute illnesses arise when mechanisms that limit immune responses fail • Severe episodes of asthma or septic shock occur when too many neutrophils degranulate at once • Anaphylactic shock is a severe and potentially fatal allergic reaction Anaphylactic Shock Autoimmune Disorders • Sometimes lymphocytes and antibodies fail to discriminate between self and nonself • Autoimmune response is an immune response that is misdirected against the person’s own tissues • Autoimmune diseases include rheumatoid arthritis, Graves’ disease, and multiple sclerosis Table 37-4 p667 Immunodeficiency • In immunodeficiency, the immune response is insufficient to protect a person from disease • Primary immune deficiencies such as SCIDs and ADA are present at birth • Secondary immune deficiency such as AIDS results from exposure to an outside agent, such as a virus Take-Home Message: What happens when the immune system does not function properly? • Normally harmless substances may induce an immune response in some people. Sensitivity to such allergens is called an allergy. • Misdirected or compromised immunity, which sometimes occurs as a result of mutation or environmental factors, can have severe or lethal outcomes. 37.11 HIV and AIDS • Acquired immune deficiency syndrome (AIDS) • A group of disorders resulting from a failure of the immune system due to HIV infection • Includes rare cancers and infections caused by normally harmless microorganisms • Human immunodeficiency virus (HIV) • A retrovirus that attacks specific cells of the immune system, including helper T cells Table 37-5 p669 Symptoms • Early symptoms include fever, enlarged lymph nodes, chronic fatigue and weight loss, and drenching night sweats • AIDS results in infections caused by normally harmless microorganisms, and cancers such as Kaposi’s sarcoma Transmission of HIV through Mother’s Milk Kaposi’s Sarcoma HIV Revisited • HIV is a retrovirus with a lipid envelope consisting of a small piece of the host’s plasma membrane • Viral proteins enclose two RNA strands and reverse transcriptase enzymes • Reverse transcriptase copies viral RNA into DNA, which becomes integrated into the host cell’s DNA • The host then begins to produce viral proteins Cellular Struggle • HIV infects macrophages, dendritic cells, and helper T cells • For years or decades, IgG antibodies keep the level of HIV in the blood low, and cytotoxic T cells kill HIV-infected cells • Eventually the immune system becomes less effective at fighting the virus, and HIV demolishes the immune system • Secondary infections and tumors kill the patient Infected T Cell with Budding HIV Virus Transmission and Testing • Common modes of HIV transmission include unprotected sex, mother to child, and shared syringes • Most AIDS tests check blood, saliva, or urine for antibodies that bind to HIV antigens • One test can detect viral RNA at about eleven days after exposure • Home test kits are not reliable Treatments • Drugs • There is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress • Education • The best option for preventing the spread of HIV is teaching people how to avoid being infected Take-Home Message: What is AIDS? • AIDS is a secondary immune deficiency caused by HIV infection. • HIV infects lymphocytes and so cripples the human immune system. Video : Vaccinating Against Cancer 37.12 Vaccines • Immunization • The administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease • Vaccine (active immunization) • A preparation containing an antigen that elicits a primary immune response • Passive immunization • Administration of antibodies; no immune response The First Vaccine • Benjamin Jesty showed that people deliberately infected with cow pox became immune to the more deadly smallpox • In 1796, Edward Jenner used cowpox to created the first vaccine against smallpox • The vaccine has now eradicated smallpox A Case of Smallpox Table 37-6 p670 Progress on an HIV Vaccine • HIV vaccines are notoriously ineffective because the HIV virus has a very high mutation rate • One promising strategy involves reverse engineering HIV antibodies isolated from people with AIDS • Genes encoding effective antibodies are also being inserted into viral vectors for use in gene therapy Take-Home Message: How do vaccines work? • Immunity to many diseases can be elicited by administering antigen-bearing vaccines, a process called immunization Video: Restarting the Immune System