Transcript Document
Chap 14 - 18 Selected Topics in Immunology 11/11/11 MDufilho 1 The Nature of Infectious Disease • Infection is the invasion of the host by a pathogen • Disease results if the invading pathogen alters normal body functions • Disease is also referred to as morbidity 11/11/11 MDufilho 2 The Nature of Infectious Disease • Manifestations of Disease: Symptoms, Signs, and Syndromes – Symptoms – Subjective characteristics of disease felt only by the patient – Signs – Objective manifestations of disease observed or measured by others – Syndrome – Symptoms and signs that characterize a disease or abnormal condition – Asymptomatic, or subclinical, infections lack symptoms but may still have signs of infection 11/11/11 MDufilho 3 The Nature of Infectious Disease • Causation of Disease: Etiology – Study of the cause of disease – Germ theory of disease – Disease caused by infections of pathogenic microorganisms – Robert Koch developed a set of postulates to prove a particular pathogen causes a particular disease 11/11/11 MDufilho 4 Figure 14.7 Koch’s postulates Agent not typically found in healthy subjects The suspected agent must be present in every case of the disease. Diseased subjects Healthy subjects Petri plate Bacterial colonies The agent must be isolated and grown in pure culture. Streaked plates Injection The cultured agent must cause the disease when it is inoculated into a healthy, susceptible experimental host (animal or plant). The same agent must be reisolated from the diseased experimental host. 11/11/11 MDufilho 5 The Nature of Infectious Disease • Causation of Disease: Etiology – Exceptions to Koch’s postulates – Some pathogens can’t be cultured in the laboratory – Diseases caused by a combination of pathogens and other cofactors – Pathogens that require a human host – Difficulties in satisfying Koch’s postulates – Diseases can be caused by more than one pathogen – Pathogens that are ignored as potential causes of disease 11/11/11 . MDufilho 6 The Nature of Infectious Disease • Virulence Factors of Infectious Agents – Pathogenicity – Ability of a microorganism to cause disease – Virulence – Degree of pathogenicity – Virulence factors contribute to virulence – Adhesion factors – Biofilms – Extracellular enzymes – Toxins – Antiphagocytic factors 11/11/11 MDufilho 7 Figure 14.9a Some virulence factors: Extracellular enzymes Hyaluronidase and collagenase Bacterium Coagulase and kinase Bacterium Hyaluronidase Coagulase Clot Clotting protein Epithelial cells Kinase Collagenase Collagen layer Invasive bacteria reach epithelial surface. Bacteria produce hyaluronidase and collagenase. Bacteria invade deeper tissues. Bacteria produce coagulase. Clot forms. Bacteria later produce kinase, dissolving clot and releasing bacteria. Extracellular enzymes 11/11/11 MDufilho 8 The Nature of Infectious Disease • Virulence Factors of Infectious Agents – Toxins – Chemicals that harm tissues or trigger host immune responses that cause damage – Toxemia refers to toxins in the bloodstream that are carried beyond the site of infection – Two types – Exotoxins – Endotoxins 11/11/11 . MDufilho 9 Figure 14.9b Some virulence factors: Toxins Exotoxin Bacterium Endotoxin Exotoxin Phagocyte Phagocytized Gram bacteria Exocytosis Endotoxin Dead Gram bacteria Blood vessel Bacteria secrete exotoxins, in this Cytotoxin kills host’s cells. case a cytotoxin. Dead Gram-negative bacteria release endotoxin (lipid A), which induces effects such as fever, inflammation, diaarrhea, shock, and blood coagulation. Toxins 11/11/11 MDufilho 10 The Nature of Infectious Disease • Virulence Factors of Infectious Agents – Antiphagocytic factors – Factors prevent phagocytosis by the host’s phagocytic cells – Bacterial capsule – Composed of chemicals not recognized as foreign – Slippery – Antiphagocytic chemicals – Prevent fusion of lysosome and phagocytic vesicles – Leukocidins directly destroy phagocytic white blood cells 11/11/11 MDufilho 11 Figure 14.9c Some virulence factors: Antiphagocytic factors Phagocytosis blocked by capsule Incomplete phagocytosis Capsule around bacterium Capsule around bacterium Bacteria reproduce Phagocytic vesicle Phagocyte Lysosome Antiphagocytic factors 11/11/11 MDufilho 12 The Nature of Infectious Disease • The Stages of Infectious Disease – The disease process occurs following infection – Many infectious diseases have five stages following infection – Incubation period – Prodromal period – Illness – Decline – Convalescence 11/11/11 MDufilho 13 Modes of Infectious Disease Transmission • Transmission is from a reservoir or a portal of exit to another host’s portal of entry • Three groups of transmission – Contact transmission – Direct, indirect, or droplet – Vehicle transmission – Airborne, waterborne, or foodborne – Vector transmission – Biological or mechanical 11/11/11 MDufilho 14 Figure 14.12 Droplet transmission 11/11/11 MDufilho 15 Figure 14.13 Poorly refrigerated foods can harbor pathogens and transmit diseases 11/11/11 MDufilho 16 The Body’s Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens – Interferons – Released by host cells to nonspecifically inhibit the spread of viral infections – Cause many symptoms associated with viral infections – Two types – Types I (alpha and beta) – Type II (gamma) 11/11/11 MDufilho 17 Figure 15.7 The actions of alpha and beta interferons Virus infects cell. Virus Doublestranded RNA Viral replication in cell triggers transcription and translation of IFN- or IFN-, depending on type of host cell. IFN gene Time passes Meanwhile, the infected cell dies, releasing viruses. Nucleus mRNA IFN Infected cell Infected cell at a later time Interferon is released, diffuses to neighboring uninfected cells, and binds to receptors. Interferon receptor When the second cell becomes infected with viruses, doublestranded RNA of the virus activates AVP. Inactive AVP Binding triggers transcription and translation of inactive antiviral proteins (AVPs). AVP gene Doublestranded viral RNA Active AVPs Time passes Ribosome mRNA mRNA Inactive AVPs 11/11/11 Uninfected neighboring cell MDufilho Same neighboring cell now protected at the later time Active AVPs degrade mRNA and bind to ribosomes, which stops protein synthesis and viral replication. 18 The Body’s Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens – Complement – Set of serum proteins designated numerically according to their order of discovery – Complement activation results in lysis of the foreign cell – Complement can be activated in three ways – Classical pathway – Alternative pathway – Lectin pathway 11/11/11 MDufilho 19 Figure 15.8 Pathways by which complement is activated Classical pathway Alternative pathway Antigen Mannose C3b Endotoxin and glycoproteins Antibody Lectin pathway Lectins C3b Factors B, D, and P Complement proteins 1, 2, 4 Complement cascade Opsonization Activation (C3 C3a C3b) Inflammation C5 convertases C5 C5a C5b 11/11/11 Inflammation Membrane MDufilho attack complex and cell lysis 20 Figure 15.9 The classical pathway and complement cascade C3b opsonin Cytoplasmic membrane Membrane attack complexes Pathogen Causes chemotaxis of phagocytes and inflammation Antigen Antibody C1 becomes an active enzyme when it binds to antibody-antigen complexes. This enzyme cleaves C5 into C5a and C5b. Acts as opsonin Enzymatic C1 Enzyme C1 splits molecules of C2 and of C4. C5b combines with C6, C7, C8, and several molecules of C9 to form a membrane attack complex (MAC). A MAC drills a circular hole in the pathogen’s cytoplasmic membrane, leading to lysis of the cell. Enzyme C3b combines with the remaining fragments of C2 and C4 to form a third enzyme. Fragments of C2 and C4 combine to form a third enzyme that splits C3 into C3a and C3b. 11/11/11 Enzyme Causes chemotaxis MDufilho of phagocytes and inflammation Acts as opsonin 21 Figure 15.10 Membrane attack complexes 11/11/11 Membrane attack complex MDufilho 22 The Body’s Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens – Complement – Inactivation of complement – Body’s own cells withstand complement cascade – Proteins on many cells bind and break down activated complement proteins 11/11/11 MDufilho 23 Immunization • Two Artificial Methods of Immunity – Active immunization – Administration of antigens so patient actively mounts a protective immune response – Passive immunization – Individual acquires immunity through the transfer of antibodies formed by immune individual or animal 11/11/11 MDufilho 24 Immunization • Brief History of Immunization – Chinese noticed children who recovered from smallpox did not contract the disease again – They infected children with material from a smallpox scab to induce immunity – This process known as variolation – Variolation spread to England and America but was stopped because of risk of death 11/11/11 . MDufilho 25 Immunization • Brief History of Immunization – 1796 – Edward Jenner discovered process of vaccination – 1879 – Louis Pasteur developed a vaccine against Pasteurella multocida – Antibody transfer developed when it was discovered vaccines protected through the action of antibodies 11/11/11 MDufilho 26 Figure 17.1 Effect of immunization-overview 11/11/11 MDufilho 27 Immunization • Brief History of Immunization – Many developing nations do not receive vaccines – Effective vaccines not developed for some pathogens – Vaccine-associated risks discourage investment in developing new vaccines 11/11/11 MDufilho 28 Immunization • Active Immunization – Vaccine types – Attenuated (live) vaccines – Use pathogens with reduced virulence – Can result in mild infections – Active microbes stimulate a strong immune response – Can provide contact immunity – Modified microbes may retain enough residual virulence to cause disease 11/11/11 MDufilho 29 Immunization • Active Immunization – Vaccine types – Inactivated (killed) vaccines – Whole-agent vaccines – Subunit vaccines – Both safer than live vaccines – Microbes don’t provide many antigenic molecules to stimulate the immune response – Often contain adjuvants – Chemicals added to increase effective antigenicity 11/11/11 MDufilho 30 Immunization • Active Immunization – Vaccine types – Toxoid vaccines – Chemically or thermally modified toxins used to stimulate immunity – Useful for some bacterial diseases – Stimulate antibody-mediated immunity – Require multiple doses because they possess few antigenic determinants 11/11/11 MDufilho 31 Immunization • Active Immunization – Vaccine types – Combination vaccines – Administration of antigens from several pathogens – Vaccines using recombinant gene technology – Attempts to make vaccines more effective, cheaper, safer – Variety of techniques used to improve vaccines 11/11/11 MDufilho 32 Figure 17.2 Some uses of recombinant DNA technology for making improved vaccines-overview 11/11/11 MDufilho 33 Immunization • Active Immunization – Vaccine safety – Problems associated with immunization – Mild toxicity most common – Risk of anaphylactic shock – Residual virulence from attenuated viruses – Allegations that certain vaccines cause autism, diabetes, and asthma – Research has not substantiated these allegations 11/11/11 MDufilho 34 Figure 17.3 The CDC's recommended immunization schedule for the general population 11/11/11 MDufilho 35 Immunization • Passive Immunotherapy – Administration of antiserum containing preformed antibodies – Immediate protection against recent infection or ongoing disease – Antisera have several limitations – Contain antibodies against many antigens – Can trigger allergic reactions called serum sickness – Viral pathogens may contaminate antisera – Antibodies of antisera are degraded relatively quickly – Limitations are overcome through development of hybridomas 11/11/11 MDufilho 36 Figure 17.4 The production of hybridomas Mouse is injected with antigen. Long-lived myeloma cell lines are grown in culture. Plasma cells, which secrete antibodies, are removed. Antibodies Hybridomas are formed by mixing and fusing plasma cells and myeloma cells; they are long lived and produce antibodies. Hybridoma Hybridomas are placed individually in small wells, and their antibodies are tested for reactivity against the antigen. A hybridoma that makes antibodies that react with the antigen is cloned. Monoclonal antibodies Hybridoma clone 11/11/11 MDufilho 37 Antibody (IgG, IgM) concentration (titer) Figure 17.5 The characteristics of immunity produced by active immunization and passive immunotherapy Passive immunotherapy Injection Boosters Active immunization Initial inoculation 11/11/11 MDufilho Time 38