Innate immunity

• What are the components of innate immunity?


  Physical barriers, phagocytes, NK cells- kill viral infected cells, circulating pattern recognition cells, cytokines
• What are the types of physical barriers in innate immunity?

  • Mechanical barriers
  • Chemical barriers
  • Biological barriers
• What is the role of NK cells in innate immunity?

  They kill viral infected cells
• What are circulating pattern recognition molecules?


  They help identify microbial components
• What are cytokines?

  Signaling molecules in immune response
• What are the types of chemical barriers in innate immunity?


  • pH
  • Lipids
  • Complement
  • Acute phase proteins (APP)
  • Type 1 interferons (IFNs)
• What is commensal flora?


  Friendly bacteria in the body
• What is the function of the mucociliary escalator?


  Respiratory mucus traps microbes and pathogens =

  cilia hairs found in resp tract propel microbes outward from airways via their coordinated directional motion
• How does the respiratory mucus contribute to innate immunity?

  It traps microbes and pathogens
• What are Toll-like receptors (TLRs)?


  Pattern recognition receptors in innate immunity
• What do pattern recognition receptors (PRRs) detect?


  Microbial components that are foreign
• What are pathogen-associated molecular patterns (PAMPs)?


  Microbial components recognized by PRRs
• What are biological barriers in innate immunity?


  Living organisms that protect against pathogens
• What are PMNs in the context of innate immunity?


  Polymorphonuclear leukocytes involved in defense
• What is the role of inflammation in innate immunity?


  • Increases blood flow to the affected area
  • Attracts immune cells to the site of infection
  • Helps to isolate and eliminate pathogens
• Physical barriers

  Skin ,mucous membranes
• what is commensal flora

  friendly bacteria

  
• mucous lining of GIT and RT

  water + electrolytes

  glycoproteins and lipids

  antimicrobial compounds - transferrin, lactoferrin

  lysozyme - in phagocytic cells that destroy microbes

  antibodies IgA

  antioxidants- superoxide dismutase, catalase, glutathione peroxidase
• pattern recognition receptors in innate immunity

  PRRs used to detect microbial components which are intrinsically foreign - recognise

  • pathogen associated molecular patterns (PAMPs)
  • mannose - bacterial carbohydrates
  • lipopolysaccharide- lipids
  • petidoglycans
• what is phagocytosis

  the ingestion and destruction of microorganism by individual cells- macrophages, PMN - neutrophils, dendritic cells

  • microorganisms release substances and cause inflammation that attract phagocytic cells and allow them to be digested - opsonization
• Phagocytosis process

  • microbe adheres to phagocyte
  • Phagocyte forms pseudopod that eventually engulfs the particle
  • Phagocytic vesicles containing antigen is fused with a lysosome = phagolysosome
  • Microbe is fused, vesicles is killed and digested by lysosomal enzymes within the phagolysosome leaving a residual body
  • Indigestible and residual material is removed by exocytosis

  
• activation of TLR

  • triggers the production of pro-inflammatory cytokines/ chemokines which can also lead to the initiation of the adaptive immune response.
• keratinocytes

  -express toll like receptors

  Produce cytokines (immunological hormones)

  Produce chemokines ( cell migration factors)
• macrophaages produce

  cytokines

  • IL1b - important
  • Il-12
  • IL-6- important
  • TNF-a-important
  • CXCL8
• inflammatory response of IL-1b, IL-6 and TNF-a 


  cause

  • vasodilation - inc blood flow to tissues - inc redness and heat.
  • increased capillary permeability - inc fluid leakage into tissues- oedema - inc tissue swelling
  • influx of white blood cells- migration of neutrophils- phagocytic cells into tissues at a local level
  • at a systematic level- inc body temp
• systematic effects of cytokines - IL-1b, IL-6 TNF-a

  • hypothalamus = fever
  • liver - acute phase response
  • bone marrow- neutrophil and monocyte mobilization
• acute phase response


  • an innate body defense seen during acute illnesses and involved the inc production of certain blood proteins- acute phase proteins by cytokines released from activated macrophages and other leukocytes
• acute phase proteins 


  a group f proteins such as C -reactive protein and mannose binding protein- produced by cells in liver and promote inflammation, activate the complement cascade and stimulate chemotaxis of phagocytosis
• signs of inflammation 


  • cytokines produced by macrophages cause vasodilation of local small blood vessels. and attracts PMN -neutrophils to the site of infected tissue- extra vasation
  • endothelial cells become sticky due to soluble factors - allow WBCs to stick to endothelial cells and migrate/
  • blood vessels become more permeable allowing plasma protiens and fluid to leak into the tissue - WBCs enter site of infection
  • blood clotting occurs in the microvessels
  • signs of this occuring- redness, heat, swelling, pain and sometimes loss of function
• complement cascade 


  various pathways

  • classical pathway - involves antigen and antibody formation
  • lectin pathway -activation by bacterial infection
  • alternative pathway -activation of complement
  • all result in the initiation of the terminal compliment pathway leading to the formation of membrane attack complexes
  • aim of complement pathways is to destroy microbes by activating C3
• factors used in complement activation


  all factors used are made in the liver as a proenzyme - become enzymes when either the antigen binds and when complement becomes activated or if bacteria is preset another set of factors are present - all trigger MAC
• membrane attack complex

  complement byproducts adhere to the bacteria, MAC then punches holes in the bacterial cell wall and destroy it - removing it from host

  • bacterium swells through uptake of fluid
  • organism burst and is therefore killed
  • this can be done by 3 routes
• innate immunity to viruses

  viruses can infect any nucleated cell

  • all nucleated cells can respond to viral infection by producing type 1 interferons - which tells immune system its infected and needs to be removed
  • viruses are detected by the presence of double stranded RNA - not found in mammalian cells - recognised by TLR3
  • virally infected cells can be recognised and destroyed by natural killer cells
• complement C3


  • vital component in the complement cascade
  • C3 is a proenzyme
  • converted to C3a and C3b
  • C3b is deposited onto the bacterial surface- acts as a marker for recognition by complement receptors on phagocytic cells.
  • C3b acts as an enzyme to facilitate the production of the MAC
  • C3a is released and stimulates an inflammatory response
• innate immunity to viruses once cell infected

  once a cell becomes infected it changes in apperance and NK cells will see this and kill it

  • interferons also inhibit viral replication
  • altered or absent MHC class I cannot stimulate a negative signal - leading to activated NK due to no negative signal produced - activating signal