Immunology for microorganisms

• IMMUNITY TO MICROORGANISM
• PHC 460
• PHARMACEUTICAL IMMUNOLOGY
• Overview


  • Immunity to Bacteria & Fungi
  • Immunity to Viruses
  • Immunity to Parasites (protozoa/helminths
  • SUMMARY

  
• Major classes of pathogens

  • Characteristics of the microorganism
  • Number of organisms
  • Mode of transmission (how and where they contact the host)
  • Stability of the organism (in and outside of the host)

  
• The establishment of an infection depends on several factors:


  • Immediate immune response
  • Early immune response
  • Late immune response
• How Do Microorganisms Cause Disease?


  • Contact or enter host cells and directly cause cell death
  • Release toxins that kill cells at a distance
  • Release enzymes that degrade tissue components
  • Damage blood vessels and cause cell injury or death due to lack of blood supply
  • Induce host cellular responses that, although directed against the invader, cause additional tissue damage, usually by immune-mediated mechanisms

  
• Commensals


  Good neighbors
• Soluble factors


  • Complements & others
• Innate immunity against bacterial infection

  • Pattern-recognition receptors recognize bacterial components and then trigger innate immune responses
  • Macrophage-mediated antibacterial defenses
• Host barriers to infection


  • low PH-gastric secretions
  • Physical barriers to infection, Skin & mucus membranes
  • Cells - phagocytic cells, NK cells
  • plasma proteins (complement proteins, cytokines, acute phase reactants)
• Evasion of host barriers


  • Cut/break in mucosa
  • penetrate through breaks in the skin e.g. cuts, burns, foot sores, animal/human bites
  • penetrate unbroken skin (some specific parasites)
  • Non-functional mucosa and ciliary function e.g. in smokers, individuals with Cystic Fibrosis
  • Toxins that paralyze mucosal cilia (e.g. causing the flu, pertussis)
  • Entry through urethra leading to kidney infections
• Immune evasion by microbes


  • Carbohydrate capsule prevents phagocytosis
  • Replication within phagocytes
  • Resistance to antimicrobial peptides
  • Change/shed antigens
  • remain inaccessible to the host immune system
  • Activate/interfere with signaling pathways
  • Inhibit antigen presentation
• Extracellular bacteria are those that multiply and reside outside the host cell
• How extracellular bacteria affect cells


  • They either attack by causing inflammation and tissue damage
  • They either attack by producing toxins
• Innate immunity to extracellular bacteria

  • Stimulation of phagocytes
  • inflammatory response
  • Activation of complement system
• Adaptive immunity to extracellular bacteria

  • Humoral or antibody mediated immunity plays major role
  • Antibodies defend the body by neutralization, opsonization, phagocytosis and stimulation of complement system
  • CD4+ helper T cells induce inflammation and phagocytic activity
• Immune evasion by extracellular bacteria

  • Polysaccharide antigens or encapsulated bacteria resist phagocytosis
  • Capsulated bacteria inhibit alternate pathway of complement system
  • Genetic edition of surface antigens
• Some intracellular bacteria like pathogenic or facultative are able to multiply within the phagocytes
• Innate immunity to intracellular bacteria


  • Phagocytes and natural killer cells provide innate immunity
  • Bacteria secretions recognized by TLRs and NOD-like receptor (NLR) family stimulate phagocytes
  • Activated natural killer cells produce IFN-γ, which stimulates macrophages and cytokines
• Adaptive immunity to intracellular bacteria


  • CD4+ T-cells and CD8+ cytotoxic T lymphocytes participate in phagocytosis or killing of infected cells
  • Granulomatous inflammation acts as a marker for most of the infections due to intracellular bacteria
• Immunity to extracellular bacteria


  • Innate immunity: Phagocytosis, activation of complement pathway, cytokines
  • Adaptive immunity: Antibodies block infection, neutralize toxins, promote microbial elimination, T helper cells
  • Evasion: Resistance to complement activation, antigenic variation
• Immunity to intracellular bacteria

  • Innate immunity: Injury to host due to immune responses, secondary infections
  • Adaptive immunity: Cell mediated immunity by Cytotoxic T cells, persistent bacteria leads to granuloma
  • Evasion: Phagocytosis/intracellular killing resistant, adapted to survive within host cells
• Mycoses is another term for fungal infections
• Immunity to fungal infection

  • Neutrophils and macrophages serve as the outstanding mediators of innate immunity
  • Cell-mediated immunity is effective mechanism of adaptive immunity
• Viruses are obligate intracellular microorganisms
• Innate immunity to viruses

  • Interferon type 1 –inhibit/prevent viral replication
  • Nk cells –kill & identify infected cells
• Adaptive immunity to viruses


  • High affinity antibodies prevent virus binding to host cells
  • CTLs identify viral peptides and kill infected cells
  • Some viruses persist in latent infection
  • CTLs may lead to tissue injury
• How viruses deceive the immune system

  • Change surface antigens to avoid immune response
  • Inhibit antigen presentation and inactivate immunocompetent cells
  • Suppress immunosuppressive molecules
• Parasitic infections are mostly the infections caused by protozoa, ectoparasites and helminths
• Features of parasitic infection

  • Infect large number of people
  • Variety and large quantity of Ag
  • Ability to change their surface Ag
  • Complicate life cycle
  • Different mode of entry
  • Most are host specific
  • Host resistance may be genetic
  • Many are chronic
• Innate immunity to parasites


  • Phagocytosis is the main innate immune response
  • Some parasites evade immune system with thick teguments
• Adaptive immunity to parasites

  • Cell mediated immunity is the principal defense mechanism
  • Stimulation of macrophages by Th1 cell derived cytokines
  • Helminths removed by IgE antibody and eosinophil-mediated killing
• Immune evasion by parasites


  • Preventing host immune response and discounting immunogenicity
  • Antigenic variation including changes in surface antigens
  • Developing resistance to immune effector mechanisms
• Humans consist of multiple levels of immune protective mechanisms to eliminate or restrict pathogen spread in the body
• Immune protective mechanisms


  • Physical barrier
  • Innate immunity
  • Adaptive immunity
• To kill a pathogen, often immune operations involving both innate and adaptive components are used
• Pathogens develop diverse strategies to promote their survival in the host => Immune Escape
• IMMUNITY TO MICROORGANISM
• PHC 460