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Transcript
College Board 2.D.3 – Biological Systems Are Affected By Disruptions to Their Dynamic Homeostasis • Disruptions at the molecular level and cellular levels affect the health of the organism – Dehydration – Immunological responses to pathogens, toxins, and allergens 2.D.4 - Plants and Animals Have a Variety of Chemical Defenses Against Infections That Affect Dynamic Homeostasis • Plants, invertebrates and vertebrates have multiple, nonspecific immune responses – Invertebrates lack pathogen-specific defense responses – Plant defenses include molecular recognition with systemic responses, infection triggers chemical responses that destroy infected and adjacent cells, localizing the effects. • Mammals use specific immune response triggered by natural or artificial agents – Two types of response: humoral and cell-mediated – Cell-mediated – cytotoxic T cells target pathogens when antigens are displayed on the outside of cells – Humoral – B cells produce antibodies against specific antigens – Antigens are recognized by antibodies – Antibodies are proteins produced by B cells and are specific – A second exposure to the antigen produces a faster and enhanced response • • • • • • • • • • Acquired immunity Antibody Antigen APC B cell CD4 CD8 Clonal selection Cytokines Histamine • • • • • • • • • Inflammatory response Innate immunity Interferons Lymphocyte MHC I MHC II Non specific response Specific response T cell Innate vs Acquired Immunity Defend against ‘non-self’ Get rid of abnormal cells Two kinds of defense Innate immunity – nonspecific Acquired immunity - specific Nonspecific – effective at birth Specific Abnormal signals from ‘self’ cells Nonspecific Immunity - External • • • • Skin – low pH, oily Lysozyme – breaks down bacterial cell walls Gastric juice Symbiotic bacteria in gut and on skin NonSpecific - Chemicals • Interferons – secreted by virus-invaded cells to warn other cells • Inflammatory response – Histamine • Vasodilation (swelling, heat and redness) • Attracts phagocytes Damage causes release of histamine Capillaries dilate: clotting factors, WBC’s arrive Interleukins + histamine attract leukocytes WBC’s eat microbes. More histamine (+ feedback) Specific Immunity • Cell receptors for antigens – Distinguish ‘Self’ from ‘nonself’ Macrophages • Antigen-presenting cell (APC) – macrophage that has engulfed a microbe and displays pieces on its surface MHC • Major Histocompatibility Complex – molecules encoded by a family of genes – ‘Self’ recognition – Prevents your body from attacking itself – Glycoproteins • Diversity – – 20 different genes (polygenic) – 50 different alleles – (multi-allelic) – MHC is a unique ‘fingerprint’ of you ‘Regular’ A fragment of (antigen) inside an invaded cell attaches to an MHC molecule and is transported to the cell surface MHC/antigen combo is recognized by a T cell Infected body cells use MHC to display foreign antigens Antigen inside an Antigen-presenting cell attaches to an MHC molecule and is transported to the cell surface. MHC – antigen combo is recognized by a T cell Acquired Immunity: Specificity • Antigen – molecule that elicits an immune response • Viruses, pollen, parasites, venom, transplants – Unique molecular (3-d) shape – Wide variety of lymphocyte’s in your blood in order to recognize all the possible antigens (genetic variation) • Antibody – bind to antigens – Immunoglobulin – protein (specific 3d shape for each antigen) – Inactivate antigens by binding to the epitope – Also bind to surface antigens of ‘non-self’ cells Acquired Immunity • Lymphocytes – produced in bone marrow, hang out in lymph • B and T cells • Respond to specific ‘invaders’ (transplants, cancer) • Have 100,000 antigen-specific receptors in their membranes • Antigen receptors (‘membrane antibodies’, ‘membrane immunoglobulins’) - bind to specific antigens Lymphocytes – Leukocytes Produced in Bone Marrow • B cells: – Mature in bone marrow – Respond to antigens – Clone into Plasma cells or Memory cells • T Cells: – Mature in thymus – Respond to funky self or non-self antigens – Clone into cytotoxic T’s or Helper T’s T Cell Receptors and MHC • T cell antigen receptors recognize specific pieces of antigens bound to MHC molecules • T cells detect the antigen fragment in two ways: – An ‘infected’ body cell – An APC Humoral and Cell-mediated Immunity • Lymphocytes only respond to specific antigens • Clonal selection – when the lymphocyte attaches to an antigen the lymphocyte clones itself: – One clone - effector cells • Short-lived cells that fight that antigen – One clone - memory cells • Long-lived cells with receptors for that antigen Two Branches of Acquired Immunity • Humoral Response: • Activate and clone B cells • B’s differentiate into: – Plasma cells – Memory cells • Antibodies are secreted and attack antigens in body fluids • Cell-mediated Response: • Activate and clone cytotoxic T cells • T’s differentiate into: – Cytotoxic T’s – Memory T’s • Attack targeted specific body cells with an MHC-antigen complex Clonal Selection of Lymphocytes • Primary (specific) immune response • Clonal selection – an antigen binds to a B or T cell receptor and activates it to clone and differentiate • Secondary response – memory cell clones – Faster response (2-7 days) • Provides resistance to infection – Vaccines Helper T’s • Both humoral and cell-mediated • Helper T’s are activated by APCs, or infected cells – MHC Cytotoxic T Cells • Cytotoxic T becomes a killer (effector) cell when it binds to an infected body cell – Secretes perforin • Body cell releases antigens into humor and B cells attack released antigens • Also attack cancer – (cancer cells have ‘non-self’ molecules) Cytotoxic T cell binds to a class I MHC– antigen complex on a target cell (TCR + CD8). TCR/MHC, + cytokines from helper T cells, activates cytotoxic T’s Activated T cell releases perforin, proteolytic enzymes (granzymes); enter the cell by endocytosis Granzymes initiate apoptosis; (‘cell suicide’). Cytotoxic T’s then attack other target cells B Cells: Humoral Response • Helper T’s activate B cells • B cells clone into plasma cells and memory cells – Plasma cells (effectors) secrete antibodies into fluids (humor) – Memory cells enable rapid response to subsequent infections B cell w/same antigens display them to helper T. TCR + CD4 + cytokines stimulates B to clone + cytokines Primary immune response; Plasma cells secrete antibodies (2000/sec); short-lived (4-5 days) Effectors Types of Immunity • Active: – Immunity develops from exposure to a pathogen (memory) – Naturally – Artificially – vaccination • Pathogens change • Passive – Passed via placenta or mother’s milk – Lasts weeks – months – Can be via immunization • Emergency – short term (rabies) Autoimmune Diseases • Immune system loses ‘self-tolerance’ – Systemic lupus erythematosus (lupus) • Rash, fever, kidney problems, arthritis – Multiple sclerosis • T cells attack myelin sheath of CNS • Senses weakened, muscular control, paralysis Auto Immune Disorders • Insulin-dependent diabetes mellitus – T’s attack Beta cells of pancreas (insulin) • Rheumatoid arthritis – Damage and painful inflammation of the cartilage and bone of joints • Acquired immunodeficiency Syndrome (AIDS) – Loss of Helper T’s (HIV) – Patients die from opportunistic infections and cancers – – Kaposi’s sarcoma Pneumonia (Pneumocystis carinii) Non-Specific; Innate Immunity • Response is always the same • Physical barriers – skin, mucous, tears • Inflammatory response – Histamine – mast cells – Dilation, fever activates other players • Chemicals – interferon • Phagocytic cells – macrophages • NK cells – abnormal cells (cancer, transplants)