innate

• Innate immunity


  • Also called non-specific immunity, natural immunity, native immunity
  • The first and second line of defense
  • Most of the components exist before meet with foreign substance
  • It's response is fast response (takes few hours)
  • Prevent entry of pathogens or foreign substances
• Components of innate immunity

  • Physical barriers
  • Normal flora
  • Cellular barriers
  • Chemical barriers
  • Acute inflammatory reaction & fever
• Physical barriers


  • A cover or coat which wrap and protect the body from external environment
• Skin


  • Layers of epithelial cells with outer layers of dead cells and waterproof keratin - stop foreign substance from entering body
  • Keratin not affected by weak acids and bases; resistant to bacterial enzymes and toxins
  • Sweat from sweat glands contains high salt concentration – can inhibit growth of many microorganisms except the normal flora of the skin
  • Microorganisms that live all over the skin cannot get through the skin unless it is broken
• Mucous membrane


  • Moist cover lining the digestive tract, respiratory tract, urogenital tract and eyes
  • Epithelial cell secrete (produce) mucus (a viscous / thick fluid)
  • Mucus trap foreign substance that attempt to entre the body
  • Sites of secretion of other substances that contribute to body defenses
• Substances secreted by mucous membrane

  • Lysozyme – breaks down the cell wall of many bacteria
  • Acids - secreted in stomach (pH2), kills most microorganisms that enter body via food
  • Digestive enzymes and bile salts – kills microorganisms
  • Lactoferrin – found in saliva, milk and seminal fluid - protect against infections from bacteria, viruses, and fungi
  • Spermine – antibacterial substance found in semen
• Fluid flow


  • Saliva, tear or mucous secretion wash away foreign substance
  • Some mucous membrane have cilia (hairlike protrusion on epithelial cell)
  • Cilia sweep mucus-trapped foreign substance out
  • Reaction and reflex which expel mucus-trap foreign substance
• Normal flora

  • Microbes which live on our body but do not cause any complication or disease
  • Compete with pathogenic microbes and prevent invasion by these microbes
  • Can inhibit growth of bacteria and fungi which are potential pathogen
• Cellular barriers


  • Differential WBC can be used to detect the increase and decrease of leukocytes
  • During many kinds of bacterial infections, WBC counts are high (leukocytosis)
  • During other bacterial infections, WBC counts can be lower (leucopemia)
• Phagocytic leukocytes


  Cells which ingest (swallow) foreign substance and destroy them
• Phagocytic and non-phagocytic leukocytes

  • Phagocytic leukocytes: Monocytes, Macrophages, Neutrophils, Eosinophils
  • Non-phagocytic leukocytes: Basophils, NK cells
• Monocytes


  • Primary function is to be recruited to site of infection
  • Not actively phagocytic until they leave the blood, enter tissue and organs, matured → macrophages
  • Cytoplasm contains pseudopodia, phagosome, lysosome, phagolysosome
• Monocytes maturation to macrophages

  1. Monocytes enlarged, 5-10x

  2. Number of intracellular organells increased

  3. Acquired phagocytic ability
• Macrophages


  • A phagocytic tissue cell with a single nucleus
  • Stay in the tissue where microbe may enter the host
  • Derived from a monocyte
  • Identify, ingest and kill microbes
  • Processing antigens, so that can stimulate immune response
  • Serve as an antigen-presenting cell
  • Secrete cytokines (protein) to enhance immune response
  • Controlling inflammation and healing
  • Cytoplasm contains pseudopodia, phagosome, lysosome, phagolysosome
• Neutrophils

  • Polymorphonuclear leucocytes (PMNs) because nucleus has multiple lobes (2-5)
  • Most abundant leucocytes
  • Possess both, antibody & complement receptors
  • Identify, ingest and destroy microbes
  • Highly phagocytic and actively mobile
  • Phagocytose foreign cells in bloodstream; also migrate from blood into infected tissue during early stages of infection and inflammation
  • Granulated cytoplasms (2 types of granules; primary and secondary granules)
• Eosinophils


  • Like neutrophil, it can be recruited to tissue and function as a phagocytes
  • Primary function is secreting the contents of eosinophilic granules which destroy and kill parasites
  • Possesses both, antibody and complement receptors
  • Phagocytic role is less important than neutrophils
  • Numbers increase during certain parasitic and worm infections and allergy reactions
  • Polymorphonuclear granulocytes
  • Granules contain acid phosphatase & peroxidase and major basic protein which is highly toxic for invading parasitic worms
• Phagocytosis


  Process of ingesting and digesting by engulfment and degradation of microbes and other foreign particulate matter by cell
• Phases of Phagocytosis


  • Identification / recognition the microbes
  • Chemotaxis of phagocyte
  • Adherence
  • Ingestion of microbe
  • Digestion of microbe
• Identification / recognition the microbes

  • Phagocytes have receptors which bind structures on microbes' membrane
  • These structures do not exist on mammalian cells' membrane
  • This enable phagocytes to recognize foreign substances from self
• Chemotaxis of phagocyte


  • Chemical attraction of phagocytes to microorganism
  • Chemostatic chemicals that attract phagocytes are: Microbial product, Damaged tissue cells, Peptide derive from complement system
• Adherence

  • Attachment of phagocyte's plasma membrane to the surface of the microorgansim or other foreign material
  • Microorganism coated with certain plasma protein to promote attachment via opsonization
• Ingestion of microbe


  • Following adherence, ingestion occurs
  • Microorganism is engulfed by extensions of the cytoplasm and cell membrane called pseudopodia
  • Pseudopods is drawn into cell by internalization or endocytosis
  • Once internalized, bacteria are trapped within phagocytic vacuoles (phagosomes) → Activated phagocytes
• Digestion


  • Phagosomes pinches off from the plasma membrane and enters the cytoplasm
  • In cytoplasm, it contracts the lysosomes that contain digestive enzymes
  • Phagosome and lysosome fuse to form single layer structure called a phagolysosome
  • Lysosomal enzyme digest the content of phagolysosomes the end product is called residual body
  • This residual body moves towards the cell boundary and discharges its waste outside the cell
• Antigen-presentation


  • Macrophages also play a role as antigen-presenting cells
  • After destroy the microbe in phagolysosome, peptides are generated from microbe's protein
  • The peptides generated are presented to T lymphocytes
• Non-phagocytic leukocytes


  • Basophils - Inflammatory leukocytes, granules can release histamine
  • Natural killer cells - Lymphocytes that recognize infected and stressed cells and respond by killing these cells and by secreting the macrophage-activating cytokine IFN-ɣ
• Chemical barriers


  • Acute phase proteins
  • Interferons
  • Complement
• Acute phase proteins


  • A number of different proteins found in the bloodstream that increases during an infection
  • Act as opsonins by enhancing the rate of phagocytosis
  • Facilitating complement activation
  • An indicator of progression or reemission of infection (acute phase reaction)
• Interferons


  • A family of proteins secreted by viral-infected cells
  • Host specific but not viral specific
  • Interferons produced by a viral-infected cells will protect other uninfected neighbouring cells from being infected
  • Interferons also enhanced the activity of natural killer cells
• Complement system


  • The complement system consists of serum and cell surface proteins
  • Helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens
  • Heat-labile and can be destroyed
• Acute phase reaction


  Indicator of progression or reemission of infection
• Interferons


  A family of proteins secreted by viral-infected cells
• Interferons


  • Host specific but not viral specific
  • Interferons produced in rabbits is not effective in humans but interferons produced against one viral species is effective against any other virus provided the host is the same
• Roles of interferons


  1. Interferons produced by a viral-infected cells will protect other uninfected neighbouring cells from being infected (interferons induced uninfected neighbouring cells to produce enzymes that will inhibit replication of virus)

  2. Interferons also enhanced the activity of natural killer cells
• Complement system


  • The complement system consists of serum and cell surface proteins
  • Helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens
• Characteristics of complement system

  • Heat-labile and can be destroyed at 56°C or more
  • Few of them are protease
  • Most of them are inactive until cleaved by a protease
  • After cleaved by a protease, they become a protease, which cleave the next complement protein
  • This continues activity is called a cascade
• Function of complement system

  • Opsonization - enhancing phagocytosis of antigens
  • Chemotaxis - attracting macrophages and neutrophils
  • Lysis - rupturing membranes of foreign cells
  • Clumping of antigen - bearing agents
• Components of the complement system

  • C1, C2, C3, C4, C5, C6, C7, C8, C9, Factor B, Factor D, Factor H, Factor I, Properdin, C1 inhibitor, C4-binding protein and S protein
  • Plasma proteins (is also known as complement components)
  • Complement receptors
  • Co-factor protein
• Activation of complement


  • Classical pathway
  • Alternative pathway
  • Lectin pathway
• Classical pathway


  1. Activation is initiated when C1 binds to antibody (either IgM or IgG) that is bound to a bacterial cell surface

  2. Activation of C1

  3. Activation of C4

  4. Activation of C2

  5. Activation of C3

  6. Activation of C5, C6 and C7

  7. Activation of C8 and C9
• Alternative pathway


  1. Activation

  2. C3 Convertase Alternative Pathway

  3. C5 Convertase Alternative Pathway

  4. Membrane Attack Complex (MAC)