17_lecture_ppt_final. .ppt
- 3. Skin and mucous membranes provide anatomical barriers to infection › Also supply foundation for microbial ecosystem › Microbial community offers protection from disease-causing organisms Intimate interaction between microorganisms and human body is an example of symbiosis
- 4. Symbiotic relationships between microorganism and host › Organisms can have variety of relationships › Symbiotic relationships can be one of several forms Relationships may change depending on state of host and attributes of microbes Forms of symbiotic relationships › Mutualism Association in which both partners benefit Bacteria and synthesis of vitamins K and B › Commensalism Association in which one partner benefits and other is unharmed Flora living on skin › Parasitism Association in which the microbe benefits at expense of host Pathogenic infection
- 5. Normal Microbiota defined as populations of microorganisms routinely found growing on the body of healthy individual Resident flora typically inhabit body sites for extended periods Transient flora are temporary › They form associations for a short time and are replaced
- 6. Protection against potentially harmful organisms › Normal flora competitively exclude pathogens through Covering binding sites used for pathogenic attachment Consuming available nutrients Producing toxic compounds such as antibiotics Development of immune system tolerance › Prevents overreaction to harmless microbes/substances
- 7. Dynamic nature of normal Microbiota › Normal flora established during birth process › Once established, composition of flora is dynamic Changes in response to physiological variation within the host Each member of flora ecosystem influenced by presence and condition of other members
- 8. If colonized organisms have parasitic relationship with host, the term infection applies › Infection does not always lead to noticeable adverse effects Termed subclinical or inapparent Symptoms do not appear or are mild enough to go unnoticed › Infection that results in disease is termed infectious disease Disease causes characteristic signs and symptoms Symptoms are effects experienced by patient such as pain and nausea Signs are effects that can be observed through examination Rash, puss formation and swelling
- 9. One infectious disease may leave individual predisposed to developing new disease › Initial disease is termed primary infection › Additional infections resulting from primary infection are termed secondary infection
- 10. Pathogens are organisms that can cause disease in otherwise healthy people › That pathogen termed primary pathogen Microbes that cause disease when the body’s defenses are down termed opportunistic pathogen Virulence is quantitative term referring to pathogen’s disease-causing ability › Highly virulent organisms have high degree of pathogenicity These organisms more likely to cause disease Example: Streptococcus pyogenes Causes disease from strep throat to necrotizing fasciitis
- 11. Disease that spreads from host to host termed communicable or contagious Ease of spread partly determined by infectious dose › Infectious dose is number of organisms required to establish infection › Diseases with small infectious dose more easily spread than those requiring large numbers
- 12. Disease course follows several stages › Incubation Time between introduction of organism to onset of symptoms Incubation period depends on numerous factors › Illness Follows incubation Individual experiences signs and symptoms of disease › Convalescence Period of recuperation and recovery Infectious agents may still be spread
- 13. Acute › Symptoms have rapid onset and last only short time Chronic › Symptoms develop slowly and persist Latent › Infection never completely eliminated › Infection becomes reactive
- 14. Infections often described according to distribution within the body › Localized Infection limited to small area Example = boil › Systemic or generalized Agent has spread or disseminated throughout the body Example = measles › Toxemia Toxins circulating in blood › Viremia Viruses circulating in blood › Septicemia Acute life-threatening illness causes by infectious agent or its products circulating in blood
- 15. Koch’s Postulates › Robert Koch proposed postulates to conclude that a particular organism causes a specific disease › Causative relationship established if these postulates fulfilled: 1. The microbe must be present in every case of disease 2. Must be pure culture from diseased host 3. Same disease must be produced in susceptible experimental host 4. Must be recovered from experimental host
- 16. Molecular Koch’s Postulates 1. Virulence factor—gene or products should be found in pathogenic strain 2. Mutating the virulence gene to disrupt function should reduce virulence of the pathogen 3. Reversion of mutated virulence gene or replacement with wild type version should restore virulence to strain
- 17. Mechanisms of pathogenesis › Human body is a source of nutrient as long as the innate and adaptive immunity can be overcome Ability to overcome obstacles of immunity separates pathogens from non-disease causing organisms › Mechanism used to overcome immune response termed mechanisms of pathogenicity Arsenal of mechanisms referred to as virulence determinants
- 18. Mechanisms of pathogenesis › Immune responses do not need to be overcome indefinitely Only long enough for organisms to multiply and leave host › Pathogens and host evolve over time to state of balanced pathogenicity Pathogen becomes less virulent while host becomes less susceptible
- 19. › Mechanisms of disease follow several patterns Production of toxins that are ingested Foodborne intoxication Clostridium botulinum and Staphylococcus aureus Colonization of mucous membranes followed by toxin production Organism multiplies to high numbers on host surface then produces toxin that interferes with cell function E. coli O157:H7 and Vibrio cholerae Invasion of host tissue Microbes penetrate barriers and multiply in tissues Generally have mechanism to avoid destruction by macrophages Mycobacterium tuberculosis and Yersinia pestis Invasion of host tissues followed by toxin production Penetration of host barriers with addition of toxin production Streptococcus pyogenes
- 20. In order to cause disease, pathogen must follow a series of steps › Adherence › Colonization › Delivery of effector molecules Adherence › Pathogen must adhere to host cells to establish infection › Bacteria use adhesins Often located at the top of pili or fimbriae › Binding of adhesins to host cell receptors is highly specific Often dictates type of cell to which bacteria can attach
- 21. Colonization › Organism must multiply in order to colonize › New organisms must compete with established organisms for nutrients and space New organism must also overcome toxic products produced by existing organisms as well as host immune responses › Microbes have developed counterstrategies, including rapid turnover of pili Some organisms produce iron-binding molecules called siderophores Compete with host proteins for circulating iron
- 22. Delivery of effector molecules to host cells › After colonization some bacteria are able to deliver molecules directly to host Induce changes to recipient cell that include Loss of microvilli Directed uptake of bacterial cells Type III secretion system
- 23. Penetration of skin › Skin is most difficult barrier to penetrate › Bacteria that penetrate via this route rely on trauma that destroys skin integrity Penetration of mucous membranes › Most common route of entry › Two general mechanisms Directed uptake Exploitation of antigen sampling
- 24. Penetration of mucous membranes › Directed uptake of cells Some pathogens induce non- phagocytic cells into endocytosis Causes uptake of bacterial cells Bacteria attaches to cell then triggers uptake Disruption of cytoskeleton due to endocytosis may cause changes in cell membrane Termed ruffling
- 25. Penetration of mucous membranes › Exploitation of antigen sampling Occurs often in intestinal tissues Between M cells and Peyer’s patches M cells conduit between intestinal lumen and lymphoid tissue Microbes move to tissues through transcytosis Most organisms are destroyed by macrophages Some organisms have developed mechanisms to survive phagocytosis Bacteria escape cells by inducing apoptosis
- 26. Hiding within the host › Some organisms evade host defenses by remaining within host Out of reach of phagocytosis › Once inside certain bacteria orchestrate transfer from cell to cell Actin tails Propels bacteria within cell Can propel with such force that it drives microbe through membrane into neighboring cell
- 27. Avoiding being killed by complement proteins › Gram-negative cells susceptible to MAC attack MAC has little effect on gram-positive cells › Certain bacteria can circumvent killing by complement (MAC) Termed serum resistant Bacterial cells hijack protective mechanism used by host cells Inhibits formation of MAC
- 28. Avoiding destruction by phagocytosis › Preventing encounters with phagocytes Some pathogens prevent phagocytosis by avoiding phagocytic cells Some cells destroy complement components that attract phagocytes through C5a peptidase – degrades component C5a Producing membrane- damaging toxins – kills phagocytes by forming pores in membrane
- 29. Avoiding destruction by phagocytosis › Mechanisms include Capsule Interfere with alternative pathway of complement activation Bind host regulatory protein to inactivate C3b M protein Binds complement regulatory protein Inactivates C3b Fc receptors Foil opsonization Bind Fc region of antibodies interferes with binding to bacteria
- 30. Surviving within the phagocyte › Allows bacteria to hide from antibodies and control immune response › Mechanisms include Escape from phagosome Escapes before phagosome-lysosome fusion Allows bacteria to multiply in cytoplasm Preventing phagosome-lysosome fusion Avoids exposure to degradative enzymes of lysosome Surviving within phagolysosome Delay fusion to allow organism time to equip itself for growth within phagosome
- 31. Avoiding antibodies › Mechanisms IgA protease Cleaves IgA antibodies Antigenic variation Alteration of surface antigens Allows bacteria to stay ahead of antibody production Mimicking host molecules Pathogens can cover themselves with molecules that resemble normal host “self” molecules
- 32. In order to cause disease, pathogen must cause damage › Damage facilitates dispersal of organisms Vibrio cholerae causes diarrhea Bordetella pertussis causes coughing › Damage can be direct result of pathogen, such as toxin production, or indirect via immune response
- 33. Exotoxins › Numerous organisms produce exotoxins › Have very specific damaging effects › Among most potent toxins known › Often major cause of damage to infected host › Exotoxins are secreted by bacterium or leak into surrounding fluids following cell lysis › Toxins act locally or systemically › Made of protein Makes them heat labile › So powerful fatal damage can occur before adequate immune response mounted Passive immunity in form of antitoxin can be given as treatment
- 34. Exotoxins › Can be grouped into functional categories Neurotoxins Cause damage to nervous system Major symptom is paralysis Enterotoxins Damage to intestines and tissues of digestive tract Major symptom is vomiting and diarrhea Cytotoxins Damage to variety of cells Damage caused by interference with cell function or cell lysis
- 35. A-B toxins › Toxins consist of two parts A subunit Toxic or active part B subunit Binding part Binds to specific host cell receptors › Structure offers novel approaches to development of vaccine and other therapies Use toxin structure as binding a delivery system
- 36. Membrane-damaging toxins › Disrupt plasma membrane Cause cell lysis › Some membrane-damaging toxins produce pores that allow fluids to enter causing cell destruction › Phospholipases are group of potent membrane- damaging toxins Remove polar heads of phospholipid Destabilizes membrane
- 37. Superantigens › Override specificity of T cell response Causes toxic effects due to massive release of cytokines by large number of helper T cells › Superantigens short-circuit normal control mechanisms of antigen process and presentation Binds MHC class II and T cell receptor Causes activation of 1 in 5 T cells
- 38. Endotoxins › Endotoxins are LPS of gram-negative cell wall Toxin fundamental part of gram-negative organism › Endotoxins are heat stable › Lipid A responsible for toxic properties › Symptoms associated with vigorous immune response › Toxin responsible for septic shock a.k.a endotoxic shock
- 39. Binding to host cells and invasion › All viruses have surface proteins to interact with specific host cell receptors › Once attached, viruses are taken up through receptor mediated endocytosis or membrane fusion Membrane fusion occurs in enveloped viruses › Viruses released from infected cell may infect new cell or disseminate into bloodstream
- 40. Avoiding immune responses › Avoiding antiviral effects of interferon Interferons alter regulatory responses of cell in event of viral infection Helps limit viral replication Some viruses encode specific proteins to interrupt inhibition of viral replication › Regulation of host cell death by viruses Kill host after production of large numbers of viral copies Allows spread to other cells Viruses prevent apoptosis Inhibits protein that regulates apoptosis Block antigen presentation of MHC class I No sign of infection Cause production of “counterfit” MHC class I molecules All appears “well”
- 41. Avoiding immune responses › Antibodies and viruses Antibodies interact with extracellular viruses only To avoid antibody exposure some viruses develop mechanisms to directly transfer from one cell to immediate neighbor Viruses can remain intracellular by forcing neighboring cells to fuse in the formation of syncytium Viruses can modify viral surface antigens Viruses replicate and change faster than the human body can replicate antibody