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Immune responsetoinfectiousdiseasesfinal[2]

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  • Host defenses against viral infection aim to first slow viral replication and then eradicate infection.
  • INFs function to inhibit viral replication. . IFNα and IFNβ produced by virally infected cells defuse to adjoining cells and activate genes that interfere with viral replication. INF-alpha and INF-beta also stimulate production of MHC class I molecules NK cells may be one of the principal mechanisms of immunity against viruses early in the course of infection, be fore more specific immune responses have developed. NK cells also effectively recognize and lyse infected cells in which the virus may have inhibited antigen presentation and class I MHC expression IFN α and IFN β can enhance the ability of NK cells to lyse infected target cells, limiting viral infection
  • Most viruses express surface receptor molecules that enable them to initiate infection by binding to host cell molecules. If antibody is produced to the viral receptor, it can block infection altogether by preventing binding of viral particles to host cell. IgA in mucus secretions plays an important role in host defense against viruses by blocking viral attachment to mucosal epithelial cells Neutralizing antibodies bind to envelope or capsid proteins and prevent viral attachment and entry into host cells. IgG appears to be the most active isotype against viruses. Opsonizing antibodies may enhance phagocytic clearance of viral particles. Secondary immunoglobulins of the IgA isotype may be important for neutralizing viruses that enter via respiratory or intestinal tract. If the induced antibody is of a compliment-activating isotype, lysis of envelope virion can happen. Antibody or compliment can also agglutinate viral particles and functions an oposonizing agent to facilitate Fc or C3b receptor-mediated phagocytosis of the viral particles.
  • CD8 + T c cells require cytokines produced by CD4 + T h 1 cells. Activated T h 1 cells produce a number of cytokines, including IL-2 , INF-γ, and TNF. These cytokines either directly or indirectly, defend against viruses. INF-γ acts directly by inducing an antiviral state in cells. IL-2 acts indirectly by assisting in the activation of CD8 + T c cell precursors into an effector population. Both IL-2 and INF-γ activate NK cells, which play an important role in host defense during the first days of many viral infections. CD4 + T cells also produce important cytokines to stimulate inflammatory responses at sites of viral infection and activate macrophage function.
  • CD8 + T c cells recognize endogenous synthesized cytosolic viral antigens in association with class I MHC molecules on any nucleated cell (antigen presenting cell APC), thus represents an important component of the specific immune response against infections.
  • A persistent infection with some viruses can cause the formation of circulating immune complexes composed of viral antigens and specific antibodies. These complexes deposit in the blood vessels and lead to systemic vasculitis. Some viruses are known to contain amino acid sequences that are also present in host self cells, leading to an immune response to self
  • Despite their restricted genome size, a number of viruses have been found to encode proteins that interfere at various levels with specific or innate host defenses. By blocking or inhibiting the antiviral proteins induced in uninfected cells, viruses have been shown to over come the antiviral effect of interferons. By secreting a protein that binds the c4b complement component, inhibiting the classical complement pathway or by binding to the c3b complement component, inhibiting both the classical and alternative pathway.
  • Continual antigenic variation, by either antigenic drift or antigenic shift, results in the frequent emergence of new infectious strains of the virus. by: direct viral infection of the lymphocytes or macrophages, suppressing cytokine production, and by suppressing class I MHC.
  • , e.g., in the circulation, in extracellular connective tissues, and in various tissue spaces such as the airways genitourinary tract, and intestinal lumens. ., resulting in tissue destruction at the site of infection which are components of bacterial cell walls ., which are actively secreted by the bacteria.
  • , an immunogenic component of the cell walls and capsules of these pathogens. Polysaccharides are prototypical thymus-independent antigens that directly stimulate B cells (Abbas, 1991).
  • caused by cytokines produced mainly by activated macrophages. . Septic shock is the most severe cytokine-induced pathologic effect of infection by gram-negative and some gram-positive bacteria.
  • Despite their restricted genome size, a number of viruses have been found to encode proteins that interfere at various levels with specific or innate host defenses. By blocking or inhibiting the antiviral proteins induced in uninfected cells, viruses have been shown to over come the antiviral effect of interferons. By secreting a protein that binds the c4b complement component, inhibiting the classical complement pathway or by binding to the c3b complement component, inhibiting both the classical and alternative pathway.
  • , e.g., in the circulation, in extracellular connective tissues, and in various tissue spaces such as the airways genitourinary tract, and intestinal lumens. ., resulting in tissue destruction at the site of infection which are components of bacterial cell walls ., which are actively secreted by the bacteria.
  • Innate immunity is ineffective in controlling colonization by and spread of these microorganisms NK cells produce IFN-γ, which in turn activates macrophages and promotes killing of phagocytosed bacteria. NK cell provide an early defense against intracellular bacteria, prior to the development of specific immunity
  • Protein antigens of intracellular bacteria stimulate CD4+ and CD8+ T cells. CD4+ T cells respond to intracellular antigens presented by class II MHC expressed on APCs. Intracellular bacteria are potent inducers of the differentiation of CD4+ helper T cells to the TH1 phenotype. The cytokines produced in the innate immune response to intracellular bacteria, IL-2 by macrophages and IFN-γ by NK cells; also promote the development of TH1 cells that secretes IFN-γ. IFN-γ activates macrophages to produce reactive oxygen species and enzymes that kill phagocytosed bacteria. If the bacteria survive within cells and release their antigen into the cytoplasm, they stimulate CD8+ CTLs activation and they function by producing more IFN-γ and by killing any macrophages that may be harboring bacteria in the cytoplasm (Abbas, 1991).
  • The localized concentration of lysosomal enzymes in the granulomas can cause extensive tissue necrosis
  • Macrophages are also capable of combating fungal infections.
  • Fungi often cause specific antibody responses, which are useful for serological diagnosis. However, the protective efficacy of humoral immunity is not established
  • Humans are usually infected by bites from infected intermediate hosts or by sharing a particular habitat with an intermediate host.
  • This may be due to the loss of surface molecules that bind complement or acquisition of host regulatory proteins such as decay accelerating factor (DAF).
  • CD4+ T cell –derived cytokines activate macrophages. A special type of antibody-dependent cellular cytotoxicity (ADCC), in which IgE antibodies bind to the surface of the helminth, eosinphils then attach to Fc receptors. The eosinophils are activated to secrete granule enzymes that destroy the parasites. These responses are attributed to the propensity of helminthes to stimulate the TH2 subset of CD4+ helper T cells, which secrete IL-4 and IL-5. IL-4 stimulates the production of IgE, and IL-5 stimulates the development of eosinophils.
  • The granulomas serve to contain the parasite, but severe fibrosis associated with this chronic cell-mediated immune response leads to disruption of venous blood flow in the liver, portal hypertension, and cirrhosis
  • Helminthic parasites can reside in intestinal lumens and are sheltered from cell-mediated immune responses As the parasite travels through the host, it encloses itself in a glycolipid and glycoprotein coat derived from the host, masking the presence of its own antigens This resistance is due to a biochemical change in the surface coat.
  • Helminthic parasites can reside in intestinal lumens and are sheltered from cell-mediated immune responses As the parasite travels through the host, it encloses itself in a glycolipid and glycoprotein coat derived from the host, masking the presence of its own antigens This resistance is due to a biochemical change in the surface coat. In stage specific variation the mature tissue stages of parasites produce different antigens from the infectious stage. In continuous variation of major surface antigens each replication of the parasite produces a new variation of the parasites surface antigens.
  • If pathogens are able to breach the innate immune system, the specific immune system is capable of defending the host against infection by means of humoral and/or cell-mediated immune response. If you take into account the number of pathogens present, there are few pathogens that the immune system is incapable of handling, unless the pathogen has ability to suppress the immune system. Although scientist have learned much about the immune system, they continue to study how the body launches attacks that destroy invading microbes, infected cells, and tumors while ignoring the healthy tissue. New technologies for identifying individual immune cells allow scientists to determine which targets are triggering an immune response. The combination of new technology and expanded genetic information will teach us more about how the body protects itself from disease.
  • Transcript

    • 1. The Immune Response to Infectious Disease By: Prof M.I.N. Matee Head, Department of Microbiology and Immunology, MUCHS
    • 2. The Immune System
      • The principal function of the immune system is to protect the host against pathogenic microbes.
      • Immunity may be innate or specific.
    • 3. Pathogens & Disease
      • Pathogens are defined as microbes capable of causing host damage.
      • When host damage reaches a certain threshold, it can manifest itself as a disease.
        • The evolution of an infectious disease in an individual involves complex interactions between the pathogen and the host.
    • 4. Important General Features of Immunity to Pathogens.
        • Defense against pathogens is mediated by both innate and specific immunity.
        • The innate immune response to pathogens plays an important role in determining the nature of the specific immune response.
        • The immune response is capable of responding in distinct and specialized ways to different pathogens in order to combat these infectious agents most effectively.
    • 5.
        • The survival and pathogenicity of pathogens in a host are critically influenced by their ability to evade or resist protective immunity.
        • Tissue injury and disease consequent to infections may be caused by the host response to the pathogen and its products rather than the pathogen itself.
    • 6. Agents That Cause Disease. Pathogens Viruses Bacteria Parasites Fungi
    • 7. Viruses
      • Obligatory intercellular pathogens that replicate within cells.
      • Use the nucleic acid and protein synthetic machineries of the host cell.
      • Infect a variety of cell populations by utilizing normal cell surface molecules as receptors to enter cell.
    • 8. Innate Immune Response to Viruses
      • Viral infection directly stimulates the production of interferons (INF).
        • Interferons are antiviral proteins, or glycoproteins produced by several types of cells in response to viral infection.
          • INF α by leucocytes
          • INF β by fibroblast
          • INF γ by natural killers (NK) cells
      • Natural killer (NK) cells lyse a wide variety of virally infected cells.
    • 9. Specific Immune Response to Viruses
      • Mediated by a combination of humoral and cell mediated immune mechanisms.
        • Humoral mediated immune response.
          • Antibodies specific for viral surface antigens are often crucial in containing the spread of a virus during acute infection and in protecting against re-infection.
          • Specific antibodies are important in defense against viruses early in the course of infection and in defense against cytopathic viruses that are liberated from lysed infected cells.
    • 10. Opsonization
      • Opsonizing antibodies may enhance phagocytic clearance of viral particles.
    • 11. Specific Immune Response to Viruses
      • Cell-mediated immune responses.
          • Most important in host defense, once a viral infection is established.
          • CD8 + T c cells (Cytotoxic T lymphocytes; CTLs) and CD4 + t h 1 cells (helper T lymphocytes) are the main components of cell mediated antiviral defense.
    • 12. CD8 + T and CD4 + T
    • 13. CTL activating macrophage function
    • 14. Tissue Injury
      • In some cases, infections with non-cytopathic viruses, CTLs may be responsible for tissue damage to the host.
    • 15. Evasion of Immune Mechanisms by Viruses
      • Viruses have evolved numerous mechanisms for evading host immunity.
      • A number of viruses have strategies to evade complement-mediated destruction.
    • 16. Evasion of Immune Mechanisms by Viruses
      • Viruses can also escape immune attack by changing their antigens.
      • A large number of viruses evade the immune response by causing generalized immunosuppression.
    • 17. Bacteria
      • Immunity to bacterial infection is achieved by means of antibody unless the bacteria are capable of intracellular growth.
      • Two types of bacteria infection.
            • Extracellular.
            • Intracellular.
    • 18. Extracellular Bacteria
      • Extracellular bacteria are capable of replicating outside of the host cells.
      • They cause disease by two principle mechanisms.
        • They induce inflammation.
        • Many of these bacteria produce toxins.
            • Endotoxins.
            • Exotoxins.
      • The immune responses against extracellular bacteria are aimed at eliminating the bacteria and at neutralizing the effects of their toxins .
    • 19.
      • Phagocytosis by neutrophils, monocytes, and the tissue macrophages.
      • Activation of the compliment system, in the absence of antibody.
      Innate Immunity Extracellular Bacteria
    • 20.
      • Humoral immunity is the principle specific immune response against extracellular bacteria.
        • Strong IgM responses are caused by polysaccharides.
        • Antibodies IgM and IgG against bacteria surface antigens and toxins stimulate three types of effector mechanisms:
      Specific Immunity Extracellular Bacteria
    • 21. Three Types of Effector Mechanisms:
      • 1.       IgG antibodies opsonize bacteria and enhance phagocytosis.
      • 2.       Antibodies neutralize bacterial toxins.
      • 3.       IgM and IgG antibodies activate the complement system.
    • 22. Tissue Injury
      • Principal injuries of host responses to extracellular bacteria are:
          • Inflammation
          • Septic shock
    • 23. Evasion of Immune Mechanisms by Extracellular Bacteria
      • Genetic variation of the surface antigen is one of the mechanisms used by bacteria to evade specific immunity.
        • The capsule of many gram-negative and gram positive bacteria contain one or more sialic acid residues that inhibit complement activation by the alternative pathway
    • 24. Intracellular Bacteria
      • Intercellular bacteria have the ability to survive and even replicate within phagocytes where they are inaccessible to circulating antibodies.
        • Elimination of intracellular bacteria requires immune responses that are very different from the responses against extracellular bacteria.
    • 25.
      • During the innate immune response to intracellular bacteria phagocytes ingest and attempt to destroy.
        • Intracellular bacteria are resistant to degradation within phagocytes.
        • Intracellular bacteria also activate NK cells, either directly or by stimulating macrophages production of IL-12, a powerful NK cell – activating cytokine.
      Innate Immunity Intracellular Bacteria
    • 26. Specific Immunity to Intracellular Bacteria
      • Cell-mediated immune response is the major specific immune response against intracellular bacteria.
        • . There are two types of cell-mediated reactions:
          • Killing of phagocytosed intracellular bacteria as a result of macrophage activation by T cell – derived cytokines, particularly IFN-y.
          • Lysis of infected cells by CTLs.
    • 27. Tissue Injury
      • Tissue damage can be caused by macrophage activation that occurs in response to intracellular bacteria.
        • The macrophages accumulate and result in the formation of a granuloma.
    • 28. Evasion of Immune Mechanisms by Intracellular Bacteria
      • Intracellular bacteria’s ability to resist elimination by phagocytes is an important mechanism for survival in evasion of the immune response.
        • Some intracellular bacteria do this by:
          • inhibiting phagolysosome fusion.
          • while others produce hemolysin that blocks bacterial killing in macrophages.
    • 29. Fungi
      • Fungal infections are eukaryotes that tend to cause serious infections primarily in individuals with impaired immunity
    • 30.
      • The principal mediator of innate immunity against fungi is the neutrophils.
        • Neutrophils liberate fungicidal substances, such as reactive oxygen species and lysosome enzymes.
        • They also phagocytose fungi for intracellular killing.
      Innate Immunity Fungi
    • 31. Specific Immunity to Fungi
      • Cell-mediated specific immunity is the major defense against fungal infections.
        • Fungi that are present intercellularly in macrophages are eliminated by the same cellular mechanisms that are effective against intracellular bacteria.
    • 32. Evasion of Immune Mechanisms by Fungi
      • Since individuals with healthy immune systems are not susceptible to opportunistic fungal infections, very little is know about the ability of fungi to evade host immunity
    • 33. Parasites
      • In infectious disease terminology, “ parasitic infection” refers to infection with animal parasites, such as protozoa, helminthes, and ectoparasites.
        • Humans are only part of the complex life cycle of parasites.
    • 34.
      • Protozoa and helminthic parasites that enter the blood stream or tissue are often able to survive and replicate because they are resistant to host innate immune responses.
        • Parasites in humane host are usually resistant to complement.
        • Macrophages can phagocytose protozoa, but the tegument of helminthic parasites makes them resistant to the cytocidal effects of both neutrophils and macrophages.
      Innate Immunity Parasites
    • 35. Specific Immunity to Parasites
      • Different parasites elicit quite distinct specific immune responses.
        • Cell-mediated immunity is the principal defense against protozoa that survive within macrophages.
        • Protozoa that replicate inside cells and lyse host cells stimulate specific CTL responses, similar to cytopathic viruses.
        • IgE antibodies and eosinophils mediate defense against many helminthic infections.
    • 36. Tissue Injury
      • Tissue injury can be caused when parasites deposited in the liver stimulate CD4+ T cell.
        • Cause macrophages to activate and induce DTH reactions.
        • Resulting in the formation of granulomas.
    • 37. Evasion of Immune Mechanisms by Parasites
      • Evolutionary adaptations give parasites their ability to evade and resist immune responses.
        • Some parasites survive and replicate inside cells.
        • Others develop cysts that are resistant to immune responses.
        • Antigen masking is an effective form of immune response evasion by some parasites.
        • Parasites can develop a tegument that is resistant to damage by antibodies and complement or CTLs.
    • 38. Evasion of Immune Mechanisms by Parasites
        • Some parasites have mechanisms for surface antigen variation.
          • There are two forms of antigenic variation:
            • Stage specific
            • Continuous variation of major surface antigens.
    • 39. Conclusion
      • The immune responses to infectious disease are an efficient and effective mechanism against the bombardment of pathogens we face everyday.
    • 40. Quote of the day “ Why leave the tail……. … .if you ate the rest of the cow.”