Consider a small surface of area A1 104 m2 , which emits diffusely with a total, hemispherical emissive power of E1 5 104 W/m2 . (a) At what rate is this emission intercepted by a small surface of area A2 5 104 m2 , which is oriented as shown? (b) What is the irradiation G2 on A2? (c) For zenith angles of 2 0, 30, and 60 , plot G2 as a function of the separation distance for 0.25 r2 1.0 m. 12.
Lectures 24 & 25 Animal Immune Systems Overview Innate vs. acquired immunity Acquired immunity and immunological memory o Complex interactions among various cell types, including B and T cells Antigen receptors/ antibodies MHC proteins o Genetic shuffling as a source of variation o Clonal selection enhances immune response o Humoral and cell-mediated immune response Immune Systems Are Necessary for Multicellular Animals (and Plants) Internal environment of organism good for cells & cellular processes: lots of nutrients, etc. Pathogens: foreign invaders that try to co-opt organismal resources; cause disease o Prokaryotes o Eukaryotes: protists & fungi (+ animals) o Viruses Immune system necessary to avoid/ limit infection o Keep foreign invaders out o Recognize self vs. non-self once invaders inside o Detection of non-self accomplished by molecular recognition Among Vertebrates, There Are Two Levels of Immunity: Innate & Acquired Immunity Innate immunity: active all the time (i.e., not dependent on previous infection), non-specific o Found in all animals (even sponges) and plants o Inhibit/ detect broad range of pathogens o First defense o Only line of defense in invertebrates Acquired immunity: adaptive immunity: response enhanced by previous infection, highly specific o Only vertebrates o Responds mostly strongly to pathogens it recognizes o Slower but more specific Innate Immunity provides General Protection From Pathogens In invertebrates: e.g., insects o Barrier: waxy chitin exoskeleton Cant cover all surfaces o Low pH and lysozyme: digest microbes in gut o Hemocytes in hemolymph: phagocytosis and various chemical protections Recognition of pathogens by taxon-specific molecules E.g., fungi have unique cell wall polysaccharides binds Toll receptor; signal transduction leads to antimicrobial peptides Antimicrobial peptides: disrupt pathogen plasma membranes Different pathogens elicit specific responses (i.e., fungi different from bacteria) In vertebrates: e.g., mammals o Barrier: skin epithelium; mucus coverings over exchange surfaces Lysozyme in saliva, mucus, tears, etc. Sweat lowers skin pH; low stomach pH o Toll-like receptor (TLR): receptors that recognize pathogen bits Ds-RNA, lipopolysaccharids, flagellin: molecules not found in animals Activation triggers innate immune response o Macrophages: phagocytosis engulf & digest microbes Some migrate around body, others concentrated in lymphatic system o Antimicrobial peptides and other proteins Interferons: produced by cells infected by viruses; signal other cells to produce anti-viral compounds Complement system: activated by microbial substances; leads of bursting of cells Also part of inflammatory response o Lymphatic system: organs to trap foreign particles E.g., tonsils, spleen, appendix Inflammatory Responses and the Actions of Natural Killer Cells Are Also Innate Inflammatory response: release of signaling molecules following infection/ injury o Mast cells release histamine Causes vessels to dilate, become more permeable o Activated macrophages also release signaling molecules o Blood to site= warmth, swelling: antimicrobial proteins, formation of pus (concentration of macrophages) Systemic (vs. local) inflammatory responses o Increase production of white blood cells (= macrophages + lymphocytes) o Fever: accelerate repair Kill invading cells Caused by pyrogens released by macrophages: increase temperature set point Natural killer cells: can recognize & destroy diseased cells o Normal body cells produce class I MHC surface proteins o Infected or cancerous do not o NK cells look for such cells and kill them Vertebrates – Acquired Immunity Involves Immunological Memory Some white blood cells (lymphocytes) have an enhanced response to infections the body has previously encountered o Immunological memory: can persist for decades Two different types of lymphocytes o B cells: mature in bone marrow o T cells: move from bone to the thymus Here is the gist: o Each lymphocyte has receptors for only a single foreign molecule There are millions of different lymphocytes o Lymphocytes activated by binding to specific foreign molecule displayed on cell surfaces Causes lymphocytes to divide: one daughter used now, one saved for later o B cells secrete soluble receptors (antibodies): bind to foreign molecule o Some T cells detect and kill infected cells o Other T cells “help” activate other lymphocytes Foreign Molecules Recognized by Lymphocytes Are Called Antigens Antigens: small molecules, parts of large molecules o May be on surface of pathogens T & B lymphocytes have antigen receptors in plasma membrane o 100,000 per cell o Differ in morphology Some B lymphocytes (plasma cells) produce soluble antigen receptors = antibodies (immunoglobulin, Ig) Epitope: small part of antigen that is recognized by antigen receptor o Single antigen might have multiple epitopes All of the antigen receptors made by a single lymphocyte are the same – a lymphocyte is specific to a particular antigen Antigen Receptors Are Composed of Variable & Constant Regions B cell receptor: Y-shaped; 4 polypeptides o 2 identical heavy chains + 2 identical light chains Chains linked by sulfide bonds Heavy chains “trans-membrane” o Each chain has constant (C) & variable (V) regions C trans-membrane, with sulfide bonds V at tips: forms 2 asymmetrical antigen binding sites o Antibodies similar: no trans-membrane region Soluble T cell receptor: a & b chains, linked by sulfide bonds o C & V regions, but with 1 antigen binding site Two types of receptors differ in function o B cell receptors bind free antigens o T cells only bind “presented” antigens Lymphocyte Diversity Arises from Genomic Shuffling, Followed by Filtering 1,000,000 different B cells & 10,000,000 T cells but only 20,5000 protein-coding genes Light chain: composed of three regions (variable, joining & constant) o Each with multiple options: 40 V x 5 J x 1 C = 200 o Recombinase: enzyme randomly links a V to a J All subsequent daughter cells identical: genome changed Heavy chain: similar, but with even more options After assemble: 1.65 x 10^6 possible epitopes Lymphocytes tested for self-reactivity: inactivated or destroyed, for self-tolerance Infection Leads to Selection for Activation of Antigen Receptors With so many random antigen receptors, unlikely that any will be specific for particular epitopes o Activated lymphocytes amplified by clonal selection Activated B or T cells divided many times: 2 types of daughter cells o Effector cells: short-lived, attack antigen/ pathogen o Memory cells: long-lived, with same antigen receptor o Leads to 1000s or cells specific for that antigen The next time the antigen is presented, the population of lymphocytes will be enriched for that antigen receptor B Cells Initiate the Humoral Immune Response Against Extra-Cellular Pathogens Humoral immune response: activation & clonal selection of effector B cells o “Antibody mediated response” o Secrete antibodies that circulate in blood & lymph o Defend against extracellular pathogens Primary immune response: first exposure o Production of effectors (plasma cells) peaks 10-17 days o Production of memory cells leads to immunological memory Secondary immune response: second exposure o Peaks faster (2-7 days) and higher st o Relies on increased numbers after 1 exposure The Cell-Mediated Immune Response of T Cells Targets Infected Cells Two kinds of T cells: cytotoxic T cells and helper T cells Helper T cells: enhance humoral and cell-mediated responses o Binds to antigen presenting macrophage: class II MHC, TCR (T cell receptor) & CD4 (holds complex together) o Cells exchange signaling molecules (cytokines): stimulates B cells and cytotoxic T cells Cytotoxic T cells: effector T cells o Activate by binding class I MHC< TCR & CD8 on antigen presenting cell and cytokines from helper T o Secretes proteins that rupture cell membrane MHC Proteins on Surface of Cells Present Antigens to T Cells Genes of the major histocompatibility complex (MHC) make proteins that present antigens on cell surface o Class I MHC: in (almost) all cells Bind foreign peptides synthesized in cell Recognized by cytotoxic T cells o Class II MHC: in macrophages, B cells, etc. (antigen-presenting cells) Bind foreign fragments acquired thru phagocytosis Recognized by helper T cells: influence activities of B and cytotoxic T cells Humoral/ B Cell Response is Mediated by Helper T Cells Activation of B cells (generally) requires interaction with helper T cells o Helper T cell activated by binding with antigens on presenting macrophage Macrophages can present whatever antigens o Activated helper T cell activated B cell presenting matching antigen B cell can only present antigens matching receptor o Activated B cell produced memory cells & plasma cells that release antibodies Antibodies interfere with pathogen function: o Neutralization: bind to virus, bacterium or toxin o Opsonization: binding sites for macrophages o Form “membrane attack complex” with complement proteins There are Other Ways to Get Antibodies Besides Active Immunity from Infections Other ways to get antibodies besides active immunity from natural infections o Vaccination = immunization: introduction of antigens to build immunity E.g., cowpox to immunize against smallpox o Passive immunization: antibodies passed from mother to fetus (no memory) Also thru breast feeding o Artificial passive immunization: inject antibodies directly E.g., snake anti-venom Immune Responses Can Lead to a Number of Practical Concerns Blood groups: A, B, AB, & O o There are blood bacteria with similar antigens o Type A person makes B antigens against bacteria but not A because of self-tolerance o If type A person gets B blood, B antigen lymphocytes will attack them Tissue rejection: differences in MHC alleles o Transplanted tissues make foreign MHC proteins; targeted by immune response Allergies: hypersensitive response to antigens (allergens) o Antigens become associated with mast cells: release histamine, results in inflammation Autoimmune diseases: diseases caused by immune system turning against the body o E.g., lupus: antibodies against histones and DNA o E.g., rheumatoid arthritis: antibodies against cartilage & bone o E.g., type I diabetes: cytotoxic T cells target pancreas o E.g., multiple sclerosis: T cells damage nervous system Immunodeficiency: lowered effectiveness of immune system o Inborn: genetic E.g., severe combined immunodeficiency (SCID): no functional lymphocytes o Acquired: result of biological or chemical exposure E.g., AIDS, acquired immunodeficiency syndrome