7. The immune system: Innate immunity

  1. the immune system
    • attemtpts to distinguish self from non-self:
    • defends against pathogens
    • eliminates cancerous cells
    • mediates allergy
    • mediates graft rejection
    • mediates autoimmunie disease
  2. host defense systems
    • nonspecific defenses =
    • physical barriers
    • secretions
    • physical functions
    • normal flora
    • innate immunity

    • specific defenses =
    • adaptive immunity
  3. innate immunity
    • preprogrammed through genetic composition
    • provides defense in early stages of infection
    • responds to microbes and damaged host cells
    • has limited specificity
    • communicates with and elicits adaptive immunity
    • has no memory
  4. components of innate immunity
    • physical and mechanical barriers: epithelial cells, secretions
    • cells: phagocytes, natural killer cells
    • proteins: pattern-recognition receptors, complement system, cytokines and chemokines, other plasma proteins
  5. pattern recognition receptors
    • toll-like receptors: family of membrane receptors on mammalian cellst that recognize conserved structures on microorganisms, prepare cell for inflammatory response
    • nucleotide-binding domain, leucine-rich repeat containing protein receptors: intracellular receptors that recognize bacterial peptidoglycan
    • mannose receptor
    • scavenger receptor
  6. innate immune cells
    • macrophages: phagocytic cells in tissue, engulf foreign objects and dead cells, first line of defense upon pathogen entry
    • nuetrophils: phagocytic cells in blood, engulf invading pathogens
    • natural killer cells: destroy virus infected cells, identify and kill tumor cells
    • mast cells: involved in defense against helminths and arthropods, allergy, upon activation, recruit basophils and eosinophils
  7. complement
    • blood proteins
    • bind to pathogens and prepare them for phagocytosis (opsonization)
    • either directlly bind, or bind in conjunction with antibodies
    • three components = classical pathway, alternative pathway, lectin pathway
  8. differences in the beginnings of the three pathways
    • classical - antibody dependent
    • althernative - antibody independent
    • lectin - initiated by a lectin (a host, sugar binding protein present in the blood) that binds to mannose residues on the surface of bacterial cells
  9. formation of the C3 covertase in all three complement pathways
    • C3 convertase cleaves C3 into C3a and C3b
    • C3b deposits on the surface of bacterial cells in a process called opsonization
    • C3b coated on bacteria interacts with the C3b receptor on phagocytes thereby facilitating phagocytosis - an opsonized pathogen is much more likely to be phagocytosed than a pathogen that is not
    • C3b interacts with other complement proteins and forms the C5 convertase
  10. pathway of C5 convertase
    • C5 convertase cleaves C5 into C5a and C5b
    • C5b recruits other complement proteins (membrane attack complex) to the
    • surface of the bacterial membrane forming a hollow pore -> the
    • osmotic stress induced by pores kills the bacteria
  11. pathway of C3a and C5a
    • called anaphylatoxins
    • mediate chemotaxis (signal immune cells to move toward the site of the infection)
    • make the vascular endothelium permeable so that immune cells in the blood can traverse the endothelium (lining of the blood vessels) for direct access to the tissues and the site of infection
    • induces inflammation, sustained activation of inflammatory cells leads to more efficient resolution of an infection
  12. outcomes of complement cascade
    • recruitment of inflammatory cells
    • opsonization of pathogens
    • killing of pathogens
  13. cytokines
    • produced by activated macrophages (others)
    • affect function and behavior of other cells
  14. chemokines
    • small chemoattractant proteins
    • activate a facilitate migration of phagocytic cells and lymphocytes
    • bind to receptors on phagocytes and lymphocytes
    • functions - chemotaxis, extravasion (movement of white blood cells from capillaries to tissues) hemtopoesis, angiogenesis (tumor formation), adhesion (viral infection)
  15. inflammatory response
    • bacteria trigger macrophages to release cytokines and chemokines
    • vasodilation and increased vascular permeability cause redness, heat and swelling
    • inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
  16. phagocytosis
    • uptake via receptors and co-receptors into phagosome
    • phagosome fuses with lysosome containing antimicrobial peptides and enzymes
    • acidification of the phagolysosome may be necessary to activate the peptides and enzymes

    • cells involved - macrophages, NK cells, mast cells, dendritic cells
    • ligands recognized- complement receptors TLRs and NODs, Fc receptors, mannose receptors, scavenger receptors
  17. dendritic cells
    • major antigen presenting cells (APCs)
    • ingest antigens in a tissue
    • migrate to lymph nodes
    • present processed antigens on their surface to lymphocytes
    • link innate and adaptive immunity
Card Set
7. The immune system: Innate immunity
public health microbiology lecture 7