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Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
Bio 151 lecture 15 continued
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Bio 151 lecture 15 continued

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  • 1. IMMUNITY & INFECTIOUS DISEASES (Continued.....) Parungao-Balolong 2011Saturday, March 12, 2011
  • 2. CONTINUATION... Overview: Innate and Adaptive Immune Response Immunity to Viruses TODAY: Immunity to Bacteria Immunity to Fungi Immunity to Helminths Emerging and re-emerging Infections SPECIAL CASES Parungao-Balolong 2011Saturday, March 12, 2011
  • 3. IMMUNITY AND BACTERIAL INFECTIONS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 4. Achieved by means of antibody : unless the bacterium is capable of intracellular IMMUNITY TO growth (delayed-type hypersensitivity) BACTERIA ROUTES OF ENTRY: respiratory tract, the gastrointestinal tract, and the genitourinary tract OR inaccessible routes opened up by breaks in mucous membranes or skin ROLE OF number of organisms entering and their virulence to host defense LOW inoculum size + LOW virulence = localized tissue phagocytes may be able to eliminate the bacteria with an innate, nonspecific defense HIGH inoculum size + HIGH virulence = induce an adaptive, specific immune response Parungao-Balolong 2011Saturday, March 12, 2011
  • 5. Primary steps in bacterial infection: Invasion of host tissue Attachment to host cells Toxin-induced damage to host cells Proliferation Parungao-Balolong 2011Saturday, March 12, 2011
  • 6. RESPONSE TO EXTRACELLULAR & INTRACELLULAR BACTERIA Infection by extracellular bacteria induces production of humoral antibodies, which are ordinarily secreted by plasma cells in regional lymph nodes and the submucosa of the respiratory and gastrointestinal tracts The humoral immune response is the main protective response against extracellular bacteria The antibodies act in several ways to protect the host from the invading organisms, including removal of the bacteria and inactivation of bacterial toxins Parungao-Balolong 2011Saturday, March 12, 2011
  • 7. RESPONSE TO EXTRACELLULAR & INTRACELLULAR BACTERIA While innate immunity is not very effective against intracellular bacterial pathogens, intracellular bacteria can activate NK cells, which, in turn, provide an early defense against these bacteria Intracellular bacterial infections tend to induce a cell-mediated immune response, specifically, delayed- type hypersensitivity In this response, cytokines secreted by CD4+ T cells are important—notably IFN-gamma, which activates macrophages to kill ingested pathogens more effectively Parungao-Balolong 2011Saturday, March 12, 2011
  • 8. IMMUNITY AND PROTOZOA, PARASITIC HELMINTHS INFECTIONS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 9. IMMUNITY TO PROTOZOAN DISEASES EXAMPLE: Amoebiasis, Chagas’ disease, African sleeping sickness, Malaria, Leishmaniasis, and Toxoplasmosis IMMUNE RESPONSE: depend in part on the location of the parasite within the host (NOTE: Life cycle is unique for each) HUMORAL ANTIBODY: effective when life-cycle stages are free within the bloodstream CELL-MEDIATED: effective during intracellular growth IMPORTANT: In the development of vaccines for protozoan diseases, the branch of the immune system that is most likely to confer protection must be carefully considered Parungao-Balolong 2011Saturday, March 12, 2011
  • 10. IMMUNITY TO PROTOZOAN DISEASES Both humoral and cell-mediated immune responses have been implicated in immunity to protozoan infections In general, humoral antibody is effective against blood-borne stages of the protozoan life-cycle, but once protozoans have infected host cells, cell-mediated immunity is necessary Protozoans escape the immune response through several mechanisms EXAMPLE: Trypanosoma brucei—are covered by a glycoprotein coat that is constantly changed by a genetic-switch mechanism (see photos on next slide) EXAMPLE: Plasmodium, the causative agent of malaria slough off their glycoprotein coat after antibody has bound to it Parungao-Balolong 2011Saturday, March 12, 2011
  • 11. EVASION OF IMMUNE RESPONSE: PROTOZOA Parungao-Balolong 2011Saturday, March 12, 2011
  • 12. EVASION OF IMMUNE RESPONSE: PROTOZOA Parungao-Balolong 2011Saturday, March 12, 2011
  • 13. IMMUNITY TO HELMINTHS Helminths are more accessible to the immune system than protozoans Immune system is not strongly engaged and the level of immunity generated to helminths is often very poor (since only FEW can have this) EXAMPLE: Ascaris, Schistosoma, Taenia (tapeworm), Trichinella (roundworm) Parungao-Balolong 2011Saturday, March 12, 2011
  • 14. IMMUNITY TO HELMINTHS Helminths are large parasites that normally do not multi- ply within cells Because few of these organisms are carried by an affected individual, immune-system exposure to helminths is limited; consequently, only a low level of immunity is induced Although helminths generally are attacked by antibody-mediated defenses, these may be ineffective A cell-mediated response by CD4+ T cells plays a critical role in the response to Schistosoma Parungao-Balolong 2011Saturday, March 12, 2011
  • 15. IMMUNITY AND FUNGAL INFECTIONS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 16. IMMUNITY TO FUNGI Anti-fungal vaccines: promising A better understanding of the role of the host/ pathogen interaction will probably lead to further development of these and other potential novel antifungal therapies Parungao-Balolong 2011Saturday, March 12, 2011
  • 17. SPECIAL CASES 1. Influenza 2. HIV/AIDS 3. Tuberculosis 4. Malaria 5. Schistosomiasis 6. Aspergillosis PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 18. INFLUENZA PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 19. WHAT DETERMINES VIRULENCE? Host factors: Viral factors: Presence of target receptors on host cells Ability to bind to host cells and Ability of virus shedding Availability of enzymes in host cells which are essential for viral entry and replication Restriction of cytopathogenic effects to allow for an appropriate balance between viral State of immunocompetence of the replication and control by the host individual host Escape from immunosurveillance by evolution Specific immunity against certain viral of antigenic variation driven by selective epitopes in the individual host and target pressure of the immune response population Escape from immunosurveillance by Ability of the immune system to control the recombination with different virus strains from viral replication effectively without causing zoonotic disease serious collateral damage for the host by its inflammatory response Modulation of the immune response to attenuate effective host defense mechanisms Parungao-Balolong 2011Saturday, March 12, 2011
  • 20. THE VIRUS AND ITS IMMUNOLOGICAL DETERMINANTS neuraminidase : enables the virus to be released from the host cell; cleave SIALIC ACID groups from glycoproteins; required for influenza virus replication hemagglutinin: an antigenic glycoprotein for binding the virus to infected cell Parungao-Balolong 2011Saturday, March 12, 2011
  • 21. ANTIGENIC SHIFT VS ANTIGENIC DRIFT Parungao-Balolong 2011Saturday, March 12, 2011
  • 22. INFLUENZA SUBTYPES: CHALLENGE FOR VACCINES Parungao-Balolong 2011Saturday, March 12, 2011
  • 23. Parungao-Balolong 2011Saturday, March 12, 2011
  • 24. HIV/AIDS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 25. HIV/AIDS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 26. PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 27. HIV/AIDS: T CELLS CD4 cell count: This measures how many infection-fighting cells are in a sample of blood way to track how well your immune system is working HIV treatment should increase your CD4 (T-cell) count or at least keep it from going down CD4 (T-cell) cell counts above 500 cells/mm3 are said to be normal CD4 (T-cell) count below 200 cells/mm3 means that the immune system is very weak; it is also one of the ways to tell that someone with HIV has AIDS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 28. HIV/AIDS INHIBITORS: POTENTIAL DRUGS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 29. TUBERCULOSIS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 30. TUBERCULOSIS Upon infection with M. tuberculosis, the most common clinical pattern, termed pulmonary tuberculosis, appears in about 90% of those infected. In this pattern, CD4+ T cells are activated within 2–6 weeks after infection, inducing the infiltration of large numbers of activated macrophages RIGHT PHOTO: These cells wall off the organism inside a granulomatous lesion called a tubercle The massive activation of macrophages that occurs within tubercles often results in the concentrated release of lytic enzymes These enzymes destroy nearby healthy cells, resulting in circular regions of necrotic tissue, which eventually form a lesion with a caseous TUBERCULE: consists of a few small lymphocytes and a compact collection of activated (cheese-like) consistency macrophages, which sometimes differentiate into epithelioid cells or multinucleated giant cells As these caseous lesions heal, they become calcified and are readily visible on x-rays, where they are called Ghon complexes. Parungao-Balolong 2011Saturday, March 12, 2011
  • 31. TUBERCULOSIS The intracellular growth of M. tuberculosis makes it difficult for drugs to reach the bacilli (THUS : drug therapy must be continued for at least 9 months to eradicate the bacteria) Presently, the only vaccine for M. tuberculosis is an attenuated strain of M. bovis called BCG (Bacillus Calmette-Guerin) The vaccine appears to provide fairly effective protection against extrapulmonary tuberculosis but has been inconsistent against pulmonary tuberculosis BCG: provided protection in anywhere from 0% to 80% of vaccinated individuals; in some cases, BCG vaccination has even increased the risk of infection BCG vaccination, the tuberculin skin test cannot be used as an effective monitor of exposure to M. tuberculosis because of the variable effectiveness of the BCG vaccine and the inability to monitor for exposure with the skin test after vaccination The alarming increase in multidrug-resistant strains has stimulated renewed efforts to develop a more effective tuberculosis vaccine Parungao-Balolong 2011Saturday, March 12, 2011
  • 32. MALARIA PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 33. IMMUNOLOGICAL PROCESSES: MALARIA Parungao-Balolong 2011Saturday, March 12, 2011
  • 34. SPECIAL CASE: MALARIA A number of factors may contribute to the low levels of immune responsiveness to Plasmodium The maturational changes from sporozoite to merozoite to gametocyte allow the organism to keep changing its surface molecules, resulting in continual changes in the antigens seen by the immune system The intracellular phases of the life cycle in liver cells and erythrocytes also reduce the degree of immune activation generated by the pathogen and allow the organism to multiply while it is shielded from attack Furthermore, the most accessible stage, the sporozoite, circulates in the blood for only about 30 min before it infects liver hepatocytes; it is unlikely that much immune activation can occur in such a short period of time And even when an antibody response does develop to sporozoites, Plasmodium has evolved a way of overcoming that response by sloughing off the surface CS- antigen coat, thus rendering the antibodies ineffective Parungao-Balolong 2011Saturday, March 12, 2011
  • 35. TREATMENT? An effective vaccine for malaria should maximize the most effective immune defense mechanisms Unfortunately, little is known of the roles that humoral and cell-mediated responses play in the development of protective immunity to this disease Current approaches to design of malaria vaccines focus largely on the sporozoite stage One experimental vaccine, for example, consists of Plasmodium sporozoites attenuated by x- irradiation Results are encouraging, but translating these findings into mass immunization remains problematic Sporozoites do not grow well in cultured cells, so an enormous insectory would be required to breed mosquitoes in which to prepare enough irradiated sporozoites to vaccinate just one small village. Current vaccine strategies are aimed at producing synthetic subunit vaccines consisting of epitopes that can be recognized by T cells and B cells While no effective vaccine has been developed, this is an active area of investigation Parungao-Balolong 2011Saturday, March 12, 2011
  • 36. REGULATION OF IMMUNE RESPONSE TO MALARIA Parungao-Balolong 2011Saturday, March 12, 2011
  • 37. SCHISTOSOMIASIS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 38. SPECIAL CASE: SCHISTOSOMIASIS Most of the symptoms of schistosomiasis are initiated by the eggs A chronic state can then develop in which the adult worms persist and the unexcreted eggs induce cell-mediated delayed-type hypersensitive reactions, resulting in large granulomas that are gradually walled off by fibrous tissue Although the eggs are contained by the formation of the granuloma, often the granuloma itself obstructs the venous blood flow to the liver or bladder Antigens present on the membrane of cercariae and young schistosomules are promising vaccine components because these stages appear to be most susceptible to immune attack Parungao-Balolong 2011Saturday, March 12, 2011
  • 39. SPECIAL CASE: SCHISTOSOMIASIS The humoral response to infection with S. mansoni is characterized by high titers of antischistosome IgE antibodies, localized increases in mast cells and their sub-sequent degranulation, and increased numbers of eosinophils These manifestations suggest that cytokines produced by a TH2-like subset are important for the immune response: IL-4, which induces B cells to class- switch to IgE production; IL-5, which induces bone-marrow precursors to differentiate into eosinophils; and IL-3, which (along with IL-4) stimulates growth of mast cells Degranulation of mast cells releases mediators that increase the infiltration of such inflammatory cells as macrophages and eosinophils The eosinophils express Fc receptors for IgE and IgG and bind to the antibody-coated parasite Once bound to the parasite, an eosinophil can participate in antibody- dependent cell-mediated cytotoxicity (ADCC), releasing mediators from its granules that damage the parasite Parungao-Balolong 2011Saturday, March 12, 2011
  • 40. IMMUNE CELLS AT VARIOUS LIFE STAGES: SCHISTOSOMIASIS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 41. SCHISTOSOMIASIS: GRANULOMA PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 42. SCHISTOSOMIASIS: PATHOLOGY PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 43. EVASION: SCHISTOSOMIASIS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 44. ASPERGILLOSIS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 45. IMMUNE RESPONSE TO ASPERGILLOSIS An essential aspect of the immune response to Aspergillus is recognition and killing of conidia and activation of appropriate host defenses to confront fungi that have escaped killing and transitioned to the hyphal form In highly compromised patients, early detection of IA, institution of antifungal therapy and improvement in host immune status are crucial determinants in the outcome of infection Humoral factors participate in the host response to Aspergillus Resting conidia, germinating conidia and hyphae are potent activators of the complement cascade and induce deposition of complement components upon the fungal surface Resting conidia activate the alternative pathway and induce neutrophil chemotaxis Parungao-Balolong 2011Saturday, March 12, 2011
  • 46. IMMUNE RESPONSE TO ASPERGILLOSIS As the fungus matures into swollen conidia and then hyphae there is progressive dependence on the classical pathway (Kozel et al, 1989) Macrophages and dendritic cells activate host defenses in response to Aspergillus At the surface of these cells are TLRs that identify microbial products (Akira et al, 2001) Signalling pathways associated with each TLR vary and activation of different receptors may result in dissimilar biological responses Parungao-Balolong 2011Saturday, March 12, 2011
  • 47. IMMUNE RESPONSE TO ASPERGILLOSIS Dendritic cells modulate the antifungal host response Aspergillus antigens induce activation and maturation of these cells Ingestion of Aspergillus conidia and hyphae proceeds through distinct phagocytic mechanisms and elicited responses differ depending upon the morphotype encountered. Following exposure to Aspergillus, dendritic cells migrate to the spleen and draining lymph nodes and induce local and peripheral Th cell reactivity to the fungus Parungao-Balolong 2011Saturday, March 12, 2011
  • 48. EMERGING & RE- EMERGING INFECTIONS PARUNGAO-BALOLONG 2011Saturday, March 12, 2011
  • 49. EMERGING & RE-EMERGING INFECTIONS: TIMELINE Parungao-Balolong 2011Saturday, March 12, 2011
  • 50. EMERGING & RE-EMERGING INFECTIONS Emerging and re-emerging pathogens include some that are newly described and others that had been thought to be controlled by public-health practices Factors leading to the emergence of such pathogens include increased travel and intense crowding of some populations Parungao-Balolong 2011Saturday, March 12, 2011
  • 51. THREAT TO BIOTERRORISM Parungao-Balolong 2011Saturday, March 12, 2011
  • 52. Parungao-Balolong 2011Saturday, March 12, 2011
  • 53. Parungao-Balolong 2011Saturday, March 12, 2011
  • 54. EMERGING & RE-EMERGING INFECTIONS Parungao-Balolong 2011Saturday, March 12, 2011
  • 55. EMERGING & RE-EMERGING INFECTIONS Parungao-Balolong 2011Saturday, March 12, 2011
  • 56. NEXT: VACCINES...Saturday, March 12, 2011

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