Chap 14 - 18

1. Chap 14 - 18 Selected Topics in Immunology MDufilho

2. 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 MDufilho

3. 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 MDufilho

4. 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 MDufilho

5. Agent not typically foundin healthy subjects The suspected agent must be presentin every case of the disease. Diseased subjects Healthy subjects Figure 14.7 Koch’s postulates Petri plate Bacterialcolonies The agent must beisolated and grownin pure culture. Streaked plates Injection The cultured agent must causethe disease when it is inoculatedinto a healthy, susceptibleexperimental host (animal or plant). The same agent mustbe reisolated from thediseased experimentalhost. MDufilho

6. 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 MDufilho .

7. 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 MDufilho

8. Figure 14.9a Some virulence factors: Extracellular enzymes Hyaluronidase and collagenase Coagulase and kinase Bacterium Bacterium Hyaluronidase Coagulase Clot Clottingprotein Kinase Epithelialcells Collagenase Collagen layer Bacteria producehyaluronidase andcollagenase. Invasive bacteriareach epithelialsurface. Bacteria producecoagulase. Clot forms. Bacteria later producekinase, dissolving clotand releasing bacteria. Bacteria invade deeper tissues. Extracellular enzymes MDufilho

9. 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 MDufilho .

10. Figure 14.9b Some virulence factors: Toxins Exotoxin Endotoxin Bacterium Exotoxin Phagocyte PhagocytizedGram bacteria Exocytosis Endotoxin Dead Grambacteria Blood vessel Cytotoxin kills host’s cells. Bacteria secrete exotoxins, in thiscase a cytotoxin. Dead Gram-negative bacteria release endotoxin (lipid A), which induceseffects such as fever, inflammation, diaarrhea, shock, and blood coagulation. Toxins MDufilho

11. 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 MDufilho

12. Figure 14.9c Some virulence factors: Antiphagocytic factors Incomplete phagocytosis Phagocytosis blocked by capsule Capsule aroundbacterium Capsule aroundbacterium Bacteria reproduce Phagocyticvesicle Phagocyte Lysosome Antiphagocytic factors MDufilho

13. 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 MDufilho

14. 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 MDufilho

15. Figure 14.12 Droplet transmission MDufilho

16. Figure 14.13 Poorly refrigerated foods can harbor pathogens and transmit diseases MDufilho

17. 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) MDufilho

18. Virus infects cell. Virus Double-strandedRNA Viral replicationin cell triggerstranscription andtranslation of IFN- or IFN-,depending ontype of host cell. IFNgene Timepasses Meanwhile, theinfected cell dies,releasing viruses. Figure 15.7 The actions of alpha and beta interferons Nucleus mRNA IFN Infected cell Infected cellat a later time Interferon is released,diffuses to neighboringuninfected cells, andbinds to receptors. Interferon receptor When the secondcell becomes infectedwith viruses, double-stranded RNA of thevirus activates AVP. Inactive AVP Double-strandedviral RNA Binding triggerstranscriptionand translation ofinactive antiviralproteins (AVPs). AVPgene Active AVPs Timepasses Ribosome mRNA mRNA Active AVPs degrade mRNAand bind to ribosomes,which stops proteinsynthesis and viralreplication. Inactive AVPs Sameneighboringcell now protectedat the later time MDufilho Uninfectedneighboring cell

19. 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 MDufilho

20. Classical pathway Alternative pathway Lectin pathway Mannose C3b Antigen Endotoxin andglycoproteins Lectins Antibody Factors B,D, and P C3b Figure 15.8 Pathways by which complement is activated Complementproteins1, 2, 4 Complement cascade OpsonizationInflammation Activation(C3  C3a  C3b) C5 convertasesC5  C5a  C5b Inflammation Membrane attackcomplex and cell lysis MDufilho

21. C3b opsonin Cytoplasmic membrane Membraneattackcomplexes Pathogen Figure 15.9 The classical pathway and complement cascade C5b combines with C6, C7, C8,and several molecules of C9to form a membrane attackcomplex (MAC). A MAC drills acircular hole in the pathogen’s cytoplasmic membrane,leading to lysis ofthe cell. Causes chemotaxisof phagocytesand inflammation Antigen Antibody C1 becomesan active enzymewhen it binds toantibody-antigencomplexes. This enzyme cleavesC5 into C5a and C5b. Acts as opsonin Enzymatic C1 Enzyme C1splits moleculesof C2 and of C4. Enzyme C3b combineswith the remainingfragments of C2and C4 to form athird enzyme. Fragments of C2and C4 combineto form a thirdenzyme thatsplits C3 intoC3a and C3b. Enzyme MDufilho Causes chemotaxisof phagocytesand inflammation Acts as opsonin

22. Membrane attack complex Figure 15.10 Membrane attack complexes MDufilho

23. 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 MDufilho

24. 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 MDufilho

25. 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 MDufilho .

26. 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 MDufilho

27. Figure 17.1 Effect of immunization-overview MDufilho

28. 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 MDufilho

29. 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 MDufilho

30. 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 MDufilho

31. 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 MDufilho

32. 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 MDufilho

33. Figure 17.2 Some uses of recombinant DNA technology for making improved vaccines-overview MDufilho

34. 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 MDufilho

35. Figure 17.3 The CDC's recommended immunization schedule for the general population MDufilho

36. 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 MDufilho

37. Mouse is injectedwith antigen. Long-lived myeloma celllines are grown in culture. Plasma cells,which secreteantibodies,are removed. Figure 17.4 The production of hybridomas Antibodies Hybridomas are formedby mixing and fusingplasma cells and myelomacells; they are long livedand produce antibodies. Hybridoma Hybridomas areplaced individuallyin small wells, andtheir antibodies aretested for reactivityagainst the antigen. A hybridoma that makesantibodies that reactwith the antigen is cloned. Monoclonalantibodies Hybridoma clone MDufilho

38. Passiveimmunotherapy Injection Figure 17.5 The characteristics of immunity produced by active immunization and passive immunotherapy Activeimmunization Antibody (IgG, IgM) concentration (titer) Boosters Initialinoculation MDufilho Time