Two molecules used in the polymer industry are azodicarbonamide and methyl cyanoacrylate. Their structures are O O O O N N N NH2 N H2C CH3 C C C C C H H a b e f h d g c Azodicarbonamide Methyl cyanoacrylate Azodicarbonamide is used in forming polystyrene. When added to the molten plastic, it decomposes to nitrogen, carbon monoxide, and ammonia gases, which are captured as bubbles in the molten polymer. Methyl cyanoacrylate is the main ingredient in super glue. As the glue sets, methyl cyanoacrylate polymerizes across the carboncarbon double bond. (See Chapter 22.) a. Complete the Lewis structures showing all lone pairs of electrons. b. Which hybrid orbitals are used by the carbon atoms in each molecule and the nitrogen atom in azodicarbonamide? c. How many bonds are present in each molecule? d. Give approximate values for the bond angles marked a through h in the above structures.
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