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Chapter 18 Lecture Outline* The Immune System Eric P. Widmaier Boston University Hershel Raff Medical College of Wisconsin Kevin T. Strang University of Wisconsin - Madison *See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Cells Mediating Immune Defenses 2 Cytokines 3 Nonspecific Immune Defenses • These defenses recognize some general property marking the invader as foreign and they protect the body as the first line of defense. • The nonspecific defenses include: – Physical barriers – Inflammation – Interferons – Natural killer cells – Complement system 4 Defenses at Body Surfaces • The body’s first lines of defense against microbes are the barriers offered by surfaces exposed to the external environment and their various antimicrobial secretions. • Examples: skin and mucous membranes 5 Inflammation 6 Phagocytosis Fig. 18-2 7 Role of Phagocytosis Fig. 18-3 8 Oponization Fig. 18-4 9 Complement System • The complement system is composed of plasma proteins that lyse foreign cells, especially bacteria. • Approximately 30 proteins participate in the cascades that result in a Membrane Attack Complex (MAC) on the surface of the invading bacteria. • The MAC ruptures the bacterial membrane causing lysis of the bacteria and death of the organism. 10 Functions of Complement Fig. 18-5 11 Interferons Fig. 18-6 12 Specific Immune Defenses: Overview • Lymphocytes recognize specific foreign molecules called antigens. 13 Lymphoid Organs Fig. 18-714 Lymphoid Tissues • Primary Lymphoid organs: – Bone marrow – Thymus • Secondary Lymphoid Organs: – – – – – – Spleen Lymph nodes Tonsils Adenoids Appendix Peyer’s patches 15 Lymphocyte Origins Fig. 18-8 16 Functions of B Cells and T Cells Fig. 18-9 17 Lymphocyte Receptors (Antibodies) Two heavy chains Two light chains Constant region— same within a class of antibodies Variable region— differs for different antigens, gives specificity to antigen-binding site Two antigen-binding sites Fig. 18-10 18 Antibody Function in Humoral Immunity • The antibody functions to bind the specifc antigen. • This leads to inactivation and destruction of the foreign antigen. • There are 5 classes of antibodies: – IgG – IgM – IgE – IgD – IgA 19 Antibody Functions • Neutralization • Agglutination • Opsonization • Complement Activation • Enhanced Natural Killer Cell Activity 20 Major Histocompatibility Complex (MHC) Molecules • There are two classes of MHC molecules: – Class I MHC are expressed on the surface of all nucleated cells. – Class II MHC are expressed on the surface of macrophages, activated B cells, activated T cells, and thymus cells. • T cells have antigen receptors which recognize antigens only when they are associated with MHC molecules. This is part of the antigen presentation mechanisms. 21 MHC is the “Self” Recognition • MHC molecules are unique to each individual person and are also known as HLA (human leukocyte antigen). • These markers are important because they mark cells as “self” or belonging to that organism. • Cells that do not match the MHC are foreign and are responsible for tissue or organ rejection because they stimulate the immune response to foreign tissue. 22 Antigen Presentation to T Cells Fig. 18-11 23 Activation of Helper T Cells Fig. 18-12 24 Cytotoxic T Cells Fig. 18-13 25 NK Cells • NK cells are a class of lymphocytes similar to cytotoxic T cells, whose major targets are virus-infected cells and cancer cells; however, they are not antigen-specific. 26 Development of Immune Tolerance • Immune tolerance develops during fetal and early postnatal life due to clonal deletion or clonal inactivation. • Autoimmune diseases are caused by failure of self-tolerance. 27 Defenses Against Bacteria, Extracellular Viruses, and Toxins Fig. 18-14 28 Enhancement of Phagocytosis by Antibodies Fig. 18-15 29 Activation of Complement Fig. 18-16 30 Defenses Against Virus-Infected Cells and Cancer Cells Fig. 18-18 31 Role of IL-2 and Interferon-gamma Fig. 18-19 32 Memory • Primary immune response: (1st exposure) – Generally takes 10–17 days to occur after exposure – Symptoms of illness occurs during these days – Antigen-selected B and T cells proliferate and differentiate into effector cells • Secondary immune response: (all other exposures) – Takes 2–7 days to occur – Greater response – Occurs due to memory cells 33 Memory Fig. 18-17 34 Systemic Manifestations of Infection Fig. 18-20 35 Factors that Alter the Body’s Resistance to Infection • Factors include nutrition, pre-existing disease, stress, physical exercise, sleep deprivation, and genetic deficiency. 36 Immunity • Active immunity is an immune response to vaccine or pathogen in an individual and gives immunity because of the production of memory cells. • Vaccine is the introduction of a microorganism or its antigens in a form not expected to cause disease, which induces an immune response including production of memory cells 37 Immunity • Passive immunity comes from the administration of synthetically produced antibodies. • This results in no memory cell production, so there is no long-term memory and immunity. • Passive immunity can also come from mother to fetus or baby because antibodies pass in the placenta (IgG) and breast milk (IgA). 38 Harmful Immune Responses • Graft Rejection • Transfusion Reactions • Allergy (Hypersensitivity) • Autoimmune Disease • Excessive Inflammatory Responses 39 Tissue Grafts and Organ Transplantation • HLA molecules (MHC) stimulate rejection by inducing immune response, so there must be as close a match in the MHC between the donor and recipient as possible. • The recipient will have to suppress the immune system pharmacologically to prevent rejection. – Cyclosporin A – FK506 40 Transfusion Reactions • Transfusion reactions are the illness caused when erythrocytes are destroyed during blood transfusion. • It is caused by antibodies rather than cytotoxic T cells. • Erythrocytes do not have MHC proteins, but they do have plasma membrane proteins and carbohydrates that can function as antigens. • The ABO system of carbohydrates is the most important for transfusion reactions. • Another group of erythrocyte membrane antigens of medical importance is the Rh system of proteins. 41 Blood Typing 42 Immediate Hypersensitivity Allergic Response Fig. 18-21a 43 Anaphylactic Shock • Anaphylatic shock is a severe allergic reaction that results from a massive release of histamine from mast cells throughout the body. This causes a massive drop in systemic blood pressure and can cause circulatory collapse. 44 Autoimmune Diseases • The immune system treats a part of itself like an invading pathogen. • Examples: – Insulin-dependent diabetes mellitus (type I) – Lupus – Rheumatoid arthritis – Multiple sclerosis 45 Immunodeficiency Diseases • Immunodeficiency diseases result from weak or under-active immune systems. • Examples: – SCID = severe combined immunodeficiency disease – Hodgkin’s Disease = cancer of lymphatic system – AIDS = affects helper T cells 46 Acquired Immune Deficiency Syndrome (AIDS) • Human immunodeficiency virus (HIV) infects and kills helper T cells resulting in impairment of the immune response to other infectious organisms. 47