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Lecture 9: Immunity, Disease, and Vaccines Objectives: •Understand how the body fights infections •Defense strategies •Components of the defense •Understand how pathogens fight the defense •Understand how a vaccine works Background Reading: Chapter 35 Three Lines of Defense Barriers at Body Surfaces • Physical barriers • Chemical barriers • Normal flora • Disposable surfaces Nonspecific Responses (Innate Immunity) • Inflammation – – – Fast acting cell types (self vs. non-self) Cells that remove debris Proteins: hole plugging, hole making, and cutting tools Specific Immune Responses (Cellular Immunity) • B and T cells • Communication • Antibodies and perforins Barriers at Body Surface • • • • Intact skin and mucous membranes Lysozyme Normal bacterial flora Flushing and Sheading Three Lines of Defense Barriers at Body Surfaces Nonspecific Responses (Innate Immunity) • Inflammation – – – Fast acting cell types (self vs. non-self) Cells that remove debris Proteins: hole plugging, hole making, and cutting tools Specific Immune Responses (Cellular Immunity) Nonspecific Responses • Lymph nodes trap and kill pathogens • Natural killer cells attack a range of targets • Inflammation Inflammation Fast acting cell types (self vs. non-self) Cells that remove debris Proteins: hole plugging, hole making, and cutting tools Complement System • Plasma proteins that take part in both specific and nonspecific response • Activation of one triggers cascade of reactions that activate others CASCADE REACTION FORMATION OF ATTACK COMPLEXES LYSIS OF TARGET Acute Inflammation • Nonspecific response to foreign invasion, tissue damage, or both • Destroys invaders, removes debris, and prepares area for healing • Characterized by redness, swelling, warmth, and pain Inflammation • • • • Mast cells release histamine Capillaries dilate and leak Complement proteins attack bacteria White cells attack invaders and clean up Inflammation • • • • Redness- vessel dilation Warmth- increased blood flow Swelling- edema, leaking Pain- pressure on free nerve endings Three Lines of Defense Barriers at Body Surfaces Nonspecific Responses (Innate Immunity) Specific Immune Responses (Cellular Immunity) • B and T cells • Communication • Antibodies and perforins Immune Responses • Directed against specific invaders • Carried out by T cells, B cells, and macrophages • Communication signals such as interleukins play a vital role Definitions: B cells, T Cells, and Macrophage • B cell – Covered with antibody (one type) – Don’t recognize MHC presented antibody, only free antigens • T Cell (Thymus) – Ignore free antigen – recognize only antigen presented by MHC • Macrophage – Clears particles – Presents MHC antigens Definitions Antibody Structure • Antibody consists of four polypeptide chains • Certain parts of each chain are variable; impart antigen specificity variable region of heavy chain antigen-binding site variable region of light chain constant region of light chain antigen-binding site hinge region (flexible) Definitions Antigen: Any substance that stimulates the production of antibodies Usually a protein or large molecule Little 3-D shapes that antibodies can recognize. Recognition Self and Non-self Recognition MHC antigen framents MHC molecule antigen-MHC complex Displaying non-self Features of Immune System • Immunological specificity – B and T cells zero in on certain kinds of pathogens; response is pathogen specific • Immunological memory – Immune system recognizes and reacts swiftly to a pathogen it has “seen” Memory and Effector Cells • When a B or T cell is stimulated to divide, it produces more than one cell type • Memory cells are set aside for future use; they are the basis for immune memory • Effector cells engage and destroy the current threat Key Component of Immune Response Key Component of Immune Response • MHC markers • Antigen-presenting cells • Helper T cells • Effector cytoxic T cells • Natural killer cells • B cells Overview of an Immune Response Key Components of Immune Response • MHC markers • Antigen-presenting cells • Helper T cells • Effector cytoxic T cells • Natural killer cells • B cells Antibody mediated response Cell - mediated response Antigenpresenting cell Naive B cell Naive helper T cell Naive cytotoxic T cell Effector B cell Activated helper T cell Effector cytotoxic T cell Lymphocyte Battlegrounds • Lymph nodes filter antigens from body fluids • Macrophages, dendritic cells, B cell and T cells in nodes and spleen mount a defense Antibody-Mediated Response • Carried out by B cells • Targets are intracellular pathogens and toxins • Antibodies bind to target and mark it for destruction by phagocytes and complement Antibody- Mediated Response • Virgin B cell becomes antigen-presenting B cell • Helper T cell binds to antigen-MHC complex on the B cell • Interleukins stimulate B cell division and differentiation • Effector cells secrete antibodies Naive B cell Antigenpresenting B cell Helper T cell Interleukins Effector B cell secretes antibodies Memory B cell 5 Classes of Immunoglobulins • IgM are secreted first; trigger complement reactions, agglutination • IgD function is not understood • IgG activates complement; can cross placenta • IgA associates with mucus-coated surfaces • IgE triggers inflammation Cell-Mediated Response One macrophage Another macrophage • Carried out by T cells • Stimulated by antigenpresenting macrophages • Main target is antigenpresenting body cells (cells with intracellular pathogens) or tumor cells interleukins Cytotoxic T cell interleukins Helper T cell Infected body cell Organ Rejection • Cytotoxic T cells can contribute to rejection of transplanted tissue • They recognize a portion of the donor cell’s MHC complex as self, view a portion as foreign • Treat the combination as an antigenMHC complex and attack donor cells Allergies • Immune reaction to a harmless substance • Genetic predisposition • IgE responds to antigen by binding to mast cells and basophils • These cells secrete the substances that cause symptoms Anaphylactic Shock • A life-threatening allergic reaction • Caused by the release of histamine by many mast cells and basophils • Airways constrict and blood pressure drops as capillary permeability soars Autoimmune Disorders • Immune system makes antibodies against self antigens • Grave’s disease • Myasthenia gravis • Rheumatoid arthritis Bacterial Pathogen Category A Threats: • Defined by the CDC as high-priority agents include organisms that pose a risk to national security because they: – Can be easily disseminated or transmitted from person to person – Result in high mortality rates and have the potential for major public health impact – Might cause public panic and social disruption – Require special action for public health preparedness. Bacillus anthracis Infection type Cutaneous Intestinal Inhalation Mortality (untreated) 20% 80-90% 90*-99% *with treatment Major Symptoms • Skin– characteristic sores • Intestinal– fever, intestinal discomfort, intestinal ulceration. • Inhalation– fever, cough, malaise (flu-like) – Sever respiratory distress, chills, edema Pathophysiology Immunization • Process that promotes immunity • Active immunization – Antigen-containing material is injected – Confers long lasting immunity • Passive – Purified antibody is injected – Protection is short lived Immunization first exposure to antigen subsequent exposure to the same antigen HIV Picture All you need to know • • • • • Chapter 35 Table 35.1 Table 35.1 figure 35.5 Figure 35.6 Figure 35.7