Immunity                                                                                                    Pathogens
Louis Pasteur (1822-1895)                                             Evolution of immune response
Inflammation                                                                       Inflammation (continued)
   1. Mast cel...
3rd Line of Defense                                                                      Adaptive Immunity Cast
                                                                                                  presenting cell ...
Antibody-Mediated Response                                                  Antibody Structure

Cell-Mediated                                 One
Life Cycle of HIV
    HIV (Virus Particle)

Subsequently, the viral nucleoid enters into the cell, most likely by
  means of other cellular events. Once this stage is...
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Immunity Pathogens


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Immunity Pathogens

  1. 1. Immunity Pathogens A biological agent that causes disease or illness to its host. Pathogen Bacteria Escherichia coli Examples Typical effects honeymoon cystitis or urinary tract infection (UTI), peritonitis, food poisoning Antigens Mycobacterium tuberculosis tuberculosis Salmonella Staphylococcus aureus food poisoning toxic shock syndrome • Every kind of cell, virus, and substance has a Streptococcus pneumoniae Streptococcus pyogenes pneumonia strep throat unique molecular configuration that gives it an Helicobacter pylori Francisella tularensis Stomach ulcers tularemia identity. Viruses Hepatitis liver disease Influenza virus flu • An individual’s own cells can be recognized as Herpes simplex virus herpes Molluscum contagiosum rash “self” and ignored. The body can recognize HIV AIDS Protozoa Cryptosporidium cryptosporidiosis pathogens which are “not self”. Giardia lamblia giardiasis Plasmodium Trypanosoma cruse malaria chagas disease • An example of “not self” is an antigen. An Fungi Pneumocystis jiroveci Tinea opportunistic pneumonia ringworm antigen is any molecular configuration that Parasites Candida Roundworm candidiasis triggers the formation of lymphocyte armies. Scabies Tapeworm • The most important antigens are proteins on the Proteins Flatworm Prions BSE, vCJD surface of pathogens and tumor cells. Robert Koch (1843-1910) Edward Jenner (1749-1823) 1. First to link a specific pathogen to a 1. Smallpox was common during the mid 18th specific disease. century and it was known that milkmaids did 2. Injected blood from anthrax-infected not get smallpox, but did get “cowpox”. animals into healthy animals. 2. Injected material from a cowpox sore into arm 3. Subject animals developed anthrax and of healthy boy (his son). had bacteria in blood. 3. Six weeks later, injected material from 4. When these bacteria were grown in lab, smallpox sores. then injected, they caused anthrax. 4. Boy remained healthy. 5. Showed that endospores could exist in 5. French called Jenner’s procedure vaccination, soil for extended periods and were responsible for “spontaneous” out which means “encowment”. breaks.
  2. 2. Louis Pasteur (1822-1895) Evolution of immune response • Early simple organisms had phagocytes to help ingest food 1. Developed immunization particles. procedures for other • Soon these phagocytes began engulfing other foreign bodies. pathogens. • Lysozymes developed and assisted in breaking down cell membranes of invaders. 2. Called them vaccinations in • Eventually cells and molecules began signaling one another about Jenner’s honor. invaders, which would lead to attacks on them. • Cytokines evolved in invertebrates and coordinated signaled attacks. • About 450 million years ago the jawed fished developed white blood cells called B and T lymphocytes, which could recognize specific pathogens. How does the body protect itself 1st Line of Defense from all these potential invaders? 1. Barriers at Body Surfaces • Intact skin – tough, impermeable, constantly sloughing off. The 3 level security system: • Mucus membranes in respiratory tract, gut, reproductive organs. 1. Barriers at body surfaces • Infection fighting chemicals in tears, saliva, gastric fluid. Lysozymes in all three produce 2. Nonspecific responses enzymes that digest bacterial cells walls. Urine and gastric fluid have low pH. 3. Immune responses • Harmless bacterial inhabitants that can outcompete pathogenic visitors. • Flushing effect of tears, saliva, urine. 2nd Line of Defense 2nd Line of Defense 2. Nonspecific Responses What happens when a pathogen gets past our first line of defense and enters our bodies? A. Inflammation Imagine a skin cut. 1. Fast acting WBCs We get an inflammatory response: 2. Macrophages (phagocytic WBC) • Redness 3. Complement proteins • Swelling B. Organs with pathogen-killing functions • Fever C. Cytotoxic cells with a range of targets • Itchy What causes these symptoms?
  3. 3. Inflammation Inflammation (continued) 1. Mast cells in connective tissue 3. Monocytes from stem cells become macrophages. A. Synthesize and release histamine. A. Macrophages engulf, digest, and clean-up. B. Trigger vasodilation (redness, warmth). B. Macrophages make chemotoxins, interleukins, C. Increases permeability of capillaries and swelling. lactoferin, endogenous pyrogens. 2. Neutrophils, eosinophils, basophils arrive. C. Fever is good. Kills pathogens, helps to rest. A. Neutrophils phagocytize bacteria. 4. Complement proteins (specific and nonspecific). B. Eosinophils release enzymes that create holes A. Trigger cascading reactions. in parasitic worm outer layer. B. Attack complexes punch holes in pathogens. C. Basophils secrete histamine for inflammation. 5. Clotting proteins A. Blood clots form, prevent spread of invaders. Immune Response Figure 34.3 from page 576 of your text Inflammation Response (nonspecific target) e Includes histamines c d a b Fluid and plasma Neutrophils, macrophages Bacteria in tissue proteins leak out and other phagocytes damages cells of capillaries engulf invaders and debris. (swelling and pain) Macrophage secretions also kill targets, attract more Mast cells release Complement phagocytes, induce fever histamine, which proteins attack and call for T and B triggers vasodilation bacterial lymphocyte proliferation. and increased membranes and capillary permeability clotting factors (redness and warmth) wall off area. The Roles of Phagocytes The Roles of Phagocytes 1. Neutrophils • Phagocytize 1. Basophils (=digest) bacteria 2. Eosinophils • Maintain • Secrete enzymes inflammation that make holes in parasitic worms due to histamine 2. Macrophages • Engulf and digest all foreign objects
  4. 4. 3rd Line of Defense Adaptive Immunity Cast B Lymphocytes What happens when a pathogen gets past our first line of defense and •Naïve B cells Sentries second line of defense (inflammation) and infection becomes established? Adaptive Immunity: Two attack strategies: Release specific antibodies •Effector B cells 1. B lymphocytes 1. Antibody-Mediated Response 2. T lymphocytes 2. Cell-Mediated Response Ready for future attacks 4 features of adaptive immunity: •Memory B cells 1. B & T cells distinguish self from nonself entities. 2. Attack specific targets – not activated by tissue damage. 3. B & T cells have a remarkable number of different receptor to antigens. 4. Adaptive immunity has memory. •Antibodies Tag infected cells for destruction. Adaptive Immunity Cast Adaptive Immunity Cast T Lymphocytes Others •Helper T cells Sentries & communicators •Antigen presenting cells Stimulate activation of B & T cells •Cytotoxic T cells Attack infected cells •MHC Major Histocompatability Complex proteins present antigens. •Memory T cells •Interleukins Signaling molecules Ready for future attacks •NK T cells Natural Killer cells •Lymphatic system Rendezvous center for disposal. Classes of Leukocytes (White Blood Cells) Lymphocytes Antigen Presenting Cells Eosinophils Neutrophils form clonal NK cells Monocytes Basophils phagocytes; Macrophages, Naïve B cells and Dendritic cells attack parasitic populations kills virus secrete inflammation worms of effector infected and histamines and memory tumor cells 1. When a pathogen enters the body various cells engulf and digest the cells invaders. 2. The broken up invader bits are processed and combined with MHC on the surface of the presenting cell. 3. MHC – Major Histocompatibility Complex is a self recognition protein Mast cells B lymphocytes T lymphocytes on the surface of cells. MHC binds to pieces of processed antigens and Dendritic cells Macrophages (B-cell) (T-cell) secrete presents them to T & B cells. presents antigen presents histamines secrete five types secrete to helper T-cells antigen to T of antibodies interleukins; kills cells; repairs infected cells tissue damage
  5. 5. Antigen presenting cell Two types of Adaptive Immunity responses antigen framents 1. Antibody-Mediated Response – extracellular pathogens • B Lymphocytes • Antibodies 2. Cell-Mediated Response – pathogens inside cells MHC molecule • T Lymphocytes antigen-MHC complex Fig. 34.5, p. 578 B and T Cell Armies Clonal Selection of a B Cell • B and T lymphocytes have receptors for millions antigen of specific antigens. When they recognize an 1. Only the B cell with antigen, they trigger immune responses. antigen-receptor that • B and T cells undergo repeated cell division to matches antigen is make an army to fight the pathogen. stimulated to divide • The army is divided into subpopulations of 2. Mitosis yields many effector and memory cells. Effector cells kill the pathogen. Memory cells are reserved for future cells with that battles if the pathogen attacks again. receptor • Memory cells are key to immunization. antigen (e.g., at surface ANTIBODY-MEDIATED IMMUNE RESPONSE of body cell infected by intracellular bacteria, protozoans, or viruses; or unbound at a tumor cell’s surface) antigen Antibody-Mediated Response MHC molecule antigen receptor CELL-MEDIATED IMMUNE RESPONSE (in this case, a membrane-bound Naïve B cell antibody molecule binds, processes, of a naïve B cell) and displays this Antigen-presenting particular antigen. cell processes, displays antigen. antigen-MHC complex endocytosed displayed at cell surface antigen being Naïve helper T cell interacts processed with antigen-presenting cell TCR helper T cell antigen-presenting B cell Naïve cytotoxic T cell interacts with unprocessed antigen antigen-presenting interleukins cell Activated helper T cell secretes signals. Signals simulate cell divisions cell division and differentiations produce and differentiation. Huge armies of effector and memory B cells populations of effector cells and memory cells form. Effector cytotoxic Effector B cell T cell touch-kills secretes antibody infected body cell molecules that bind or tumor cell. antigen, promote Fig. 34.6, p. 579 Fig. 34.12, p. 583 its elimination effector B cell memory B cell circulating antibodies
  6. 6. Antibody-Mediated Response Antibody Structure 1. Antibody consists of variable region of heavy chain four polypeptide antigen-binding site antigen-binding site chains hinge 2. Certain parts of each variable region (flexible) region of chain are variable; light chain constant impart antigen region of light chain specificity Antibody-Mediated Response: B Cells Immunoglobulins 1. Antibodies: 5 main types = 1. Ig M 1. Ig A • Secreted first • On mucous surfaces 2. Immunoglobulins “Igs”: protein products of gene shufflings • Activate complement 2. Ig E that take place as B cells mature and an immune response is proteins underway • Triggers inflammation • Ig M 2. Ig G • Parasitic worms • Ig G • Activate complement 3. Ig D • Ig A proteins • Function not understood • Ig E • Neutralize toxins • Cross placenta • Ig D • Secreted in milk Immune Responses to Same Antigen Generating Receptor Diversity first exposure to antigen subsequent exposure to the same antigen 1. Antibody-coding gene recombines as B cell matures transcription 2. Produces variable transcripts that are translation translated to produce receptor portion of the 1. Similar process produces antibody molecule variable T cell antigen receptors Figure 34.9 from page 581 of your text
  7. 7. Cell-Mediated One Another macrophage Response macrophage Cell-Mediated Response 1. Carried out by T cells. 2. Stimulated by antigen- interleukins presenting macrophages. 3. Main target is antigen- Cytotoxic T Helper T cell cell interleukins presenting body cells (cells with intracellular pathogens) Infected body cell or tumor cells. Fig. 34.13, p. 584 HIV and AIDS Lymphocyte Battlegrounds 1. HIV: Human Immunodeficiency Virus • A retrovirus that attacks the body’s immune system 1. Lymph nodes filter antigens from body • Targets antigen-presenting macrophages and helper T-cells fluids. and impairs their function 2. Macrophages, dendritic cells, B cell and T 2. AIDS: Acquired Immune Deficiency Syndrome cells in nodes and spleen mount a • Is the result of a weakened immune system caused by the defense. Then take antigens HIV infection • Is the result of being HIV positive and having one or more to the lymphatic system where of the AIDS defining illnesses they meet B & T cells. • Characterized additionally by having a T cell count of 200 or less Fig. 34.10, p. 581 AIDS: The Immune System Compromised AIDS: The Immune System Compromised Symptoms 1. Transmission: Bodily Fluids • 5-10 year lag after infection • Blood • Flu-like • Semen • Vaginal Secretions • Weight loss, fever, fatigue, night sweats • Breast Milk • Enlarged lymph nodes 2. Treatment • No known cure • Opportunistic infections • Difficult because of high mutation rates • Pneumocystis carinii (pneumonia) 3. Prevention: • Kaposi’s sarcoma (cancer of the • “Safe” sex • No IV drug use connective tissue)
  8. 8. Life Cycle of HIV HIV (Virus Particle) HIV retrovirus and Helper T lymphocyte Illustrations and content based on "Infection by Human Immunodeficiency Virus - CD4 Is Not Enough" by Levy, J.A. - The New England Journal of Medicine, Vol 335, no 20, pages 1525-1527, Nov., 1996. Illustrations (c) Massachusetts Medical Society. HIV-1 interacts with the cell-surface receptor CD4 of Helper T cells, and through conformational changes becomes more closely associated with the cell through interactions with other cell-surface molecules, The CD4-binding site on HIV-1 gp120 interacts with the CD4 such as the chemokine receptors CXCR4 and CCR5. The likely steps in molecule on the cell surface. HIV infection are as follows: Conformational changes in both the viral envelope and the CD4 This second attachment brings the viral envelope closer to the receptor permit the binding of gp120 to another cell-surface cell surface, allowing interaction between gp41 on the viral receptor, such as CCR5. envelope and a fusion domain on the cell surface. HIV then fuses with the cell.
  9. 9. Subsequently, the viral nucleoid enters into the cell, most likely by means of other cellular events. Once this stage is achieved, the cycle of viral replication begins.