Chapter 43: The Body’s Defenses How does your body protect you from invaders? Immune System Review Microorganism/Microbe Pathogen Antibiotic Antibody Antigen Key Concepts 3 Lines of Defense Innate vs. Acquired immunity Phagocytes, Lymphocytes, Antibodies, etc… Humoral vs. Cell-Mediated immunity Distinguishing self from non-self Tissue transplantation Immune Diseases/Disorders Using HIV to treat Cancer?? http://abcnews.go.com/WNT/video/doctors-hivtreat-cancer-17929437 What do you think? How does your body INITIALLY defend itself from invasion? (1st line – specific or non?) What happens if the invader gets past the 1st line? (2nd line – specific or nonspecific?) What about more serious infections? (3rd line) 1st line Defense!! Skin, mucus, cilia, saliva, acids, tears, oils, bacteria, coughing, sneezing, vomiting Antimicrobial proteins & Lysozymes Innate vs. Acquired Immunity Innate Immunity: – Present before exposure; since birth – Includes natural bodily defenses, mother’s milk, or casual exposure – Broad-range capabilities, non-specific – External defenses: • skin, mucus membranes, tears – Internal Phagocytic cells • A.K.A.: “macrophages”; engulf invaders Innate vs. Acquired Immunity Acquired Immunity: – Develops only after exposure – Highly microbe-specific… how? – Employ lymphocytes & antibodies • Involves both Humoral & Cell-Mediated responses Innate Immunity: Your first line of defense Phagocytic White Blood Cells Recognize & bind to carbohydrate markers on foreign cell membranes – Triggers receptor-mediated endocytosis – Engulf & digest pathogens via Phagocytosis Types of White Blood Cells Neutrophils: 60-70% of WBCs; engulf and destroy microbes at infected tissue; short lived Monocytes: 5% of WBCs; develop into…. Macrophages: “big eaters” enzymatically destroy microbes; can be found in spleen, lymph nodes, and other organs Eosinophils: 1.5% of WBCs; destroy large parasites extracellularly Natural killer (NK) cells: trigger apoptosis in virusinfected cells & cancer cells Leukocyte vs. Lymphocyte Leukocyte = – White blood cells (WBC’s) Lymphocyte = – Specific type of WBC that mature and migrate through the lymphatic system and target specific antigens via antibodies, receptors and toxin release The Inflammatory Response “Inflammation” = pain, swelling, fever, redness, itching, and pus Causes of Inflammation Injuries Exposure to microbes/pathogens Exposure to foreign objects or chemicals (insect bites, stings, medications, etc) Exposure to allergens (pollen, pet dander, foods, etc) Rare: sunlight, temperature, self! The Inflammatory Response 3 Steps: 1. Tissue damage = release of chemical signals~ – Mast cells release chemicals known as Histamine & Prostaglandins that trigger inflammation 2. Dilation increases permeability of capillaries~ – Increased blood flow; leukocytes leak out to infected area – Delivery of clotting factors & antimicrobial proteins 3. Phagocytosis of pathogens~ – WBC’s engulf microbes or damaged tissue – Fever: leukocyte-released chemicals increase body temperature Acquired Immunity: Lymphocytes are the Key Defenders Specific Immunity Antigen: – a foreign molecule that elicits a response from a lymphocyte Lymphocyctes: – WBC’s that originate from stem cells in bone marrow – B Cells (mature in bone marrow) – T Cells (mature in thymus) Antibodies: – antigen-binding immunoglobulin, produced by B cells Antigen receptors: – membrane receptors on B and T cells Ch. 43 Research: Humoral vs. Cell-mediated Responses B cells vs. T cells Memory cells Clonal selection Autoimmune disease T cells vs. B cells B cells: – Mature in Bone Marrow – Target in-tact Antigens – Part of Humoral Response T cells: – Mature in Thymus – Target antigen fragments bound to MHC molecules on Infected Cells – Part of Cell Mediated Response Humoral vs. Cell-Mediated Humoral immunity B cell activation Production of antibodies Defend against intact antigens free in the lymph and blood plasma – (bacteria, toxins, and viruses) Humoral response: B cells Stimulated by an antigen-presenting macrophage (WBC w/ a germ on it) Activates Helper T cells T cells secrete cytokine chemicals that activate B cells B cells differentiate into memory B cells and antibody-producing plasma cells Cytokines Cytokine: – Proteins secreted by phagocytic cells (macrophages, etc.) and T-helper cells – Activate Lymphocytes (B & T cells) Humoral Response: 1. 2. 3. 4. B cells activate. Plasma cells secrete antibodies. Antibodies attach to antigens. Antigens agglutinate (stick together) & get disposed. 5. Macrophages phagocytose or lyse the cell. Cell-Mediated Cell-mediated immunity T cells are activated. T cells bind to and/or lyse infected cells. Defend against cells infected with bacteria, viruses, fungi, protozoa, parasites, even cancer! Cell-mediated Response 1) Cell surface molecules expose antigens (foreign proteins). 2) Cytotoxic T cell releases perforin, a protein that forms pores in the target cell membrane. – causes cell lysis and exposes pathogens to circulating antibodies for disposal Humoral Response In Tact Antigens B Cell Activation Secrete antibodies that defend against pathogens & toxins in extracellular fluid Cell Mediated Response Antigens on Infected Cells T Cell Activation Defend against infected cells, cancer and transplanted tissues Clonal Selection Clonal selection: – antigen-driven cloning of lymphocytes Effector cells: – short-lived cells that combat the antigen initially Memory cells: – long-lived cells that bear receptors for the antigen and activate upon subsequent exposure. Active vs. Passive Immunity Active: natural exposure to antigens causes one’s own lymphocytes to activate and produce antibodies – May also be acquired by Immunizations Passive: direct transfer of antibodies through placenta or mother’s milk HIV Human Immunodeficiency Virus Causes AIDS (Acquired Immune Deficiency Virus) HIV (a retrovirus) attacks helper T cells by binding with their cell receptor (CD4) This impacts both the Humoral and Cell Mediated responses Clonal Selection Hypothesis Each lymphocyte bears one specific type of receptor. Receptor/antigen binding is required for cell activation. Activated lymphocytes divide and give rise to cells with identical receptors to the parent. – This is how your immune system “remembers” a pathogen later! Clonal Selection Hypothesis First, those lymphocytes bearing receptors compatible to “self” tissues are destroyed (3) Second, those bearing receptors that match foreign antigens are activated then cloned (5/6) Self/Nonself Recognition Self-tolerance: – Capacity to distinguish self from non-self molecules Autoimmune diseases: – Failure of self-tolerance mechanisms – Multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, Crohn’s disease Abnormal immune function Allergies: – hypersensitive responses to environmental antigens (allergens) – causes dilation and blood vessel permeability – Histamines are released from Mast cells Autoimmune disease: – – – – multiple sclerosis Lupus rheumatoid arthritis insulin-dependent diabetes mellitus Immunodeficiency disease: – SCIDS (bubble-boy) – A.I.D.S. (HIV) Cancer & the Immune System Tumor cells are targeted by both Cytotoxic T cells and Natural Killer (NK) cells – How might some tumors escape detection?? Treg research: Article Review What are “Regulatory T Cells” (Tregs)? What is their role in immunity? How might they be linked with cancer? – Article: “Regulatory T cells and tumour immunity – observations in mice and men” by Gallimore and Godkin, 2007 Major Histocompatibility Complex Aka: “MHC” Cell surface proteins that display fragments of antigens or processed proteins on the cell surface Epitope: – region of antigen surface recognized by antibodies Induction of Immune Responses Primary immune response: – lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen Plasma cells: – antibody-producing B-cells Secondary immune response: – immune response if the individual is exposed to the same antigen at a later time~ Immunological memory Types of Immunoglobins IgM: – 1st to circulate; indicates infection; too large to cross placenta IgG: – most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement IgA: – produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration IgE: – very large; small quantity; releases histamines-allergic reaction Antibody-Mediated Antigen Disposal Neutralization (opsonization): – antibody binds to and blocks antigen activity Agglutination: – antigen clumping Precipitation: – cross-linking of soluble antigens Complement fixation: – lyses viruses and pathogenic cells & activates cell surface proteins to break down the cell Immunity in Health & Disease Active immunity: – natural: conferred immunity by recovering from disease – artificial: immunization and vaccination; produces a primary response Passive immunity: – transfer of immunity from one individual to another – natural: mother to fetus; breast milk – artificial: rabies antibodies ABO & Rh blood groups (antigen presence)