Module 2, pt. 1: Inflammation and immunity alterations (Ch. 7, 8 and 9)

Video lecture

1st line of defence

• physical and mechanical barriers
• biochemical barriers
• normal microbiome

2nd line of defence

• inflammation

inflammation

• quick, nonspecific, localized most of the time
• goals; in order
  • neutralize, limit cause of injury
  • clean (phagocytosis)
  • heal

response

• injury = vasodialation = release of cytokines (controls other immune cells) = endothelial cell contraction and leukocyte diapedesis (passage of blood cells through capillaries) = allow passage of leukocytes (including macrophages) in to site where injury happened = phagocytosis, removal, neutrolizing = activation of adaptive immunity

inflammatory and immune cells

• neutrophils
  • neutralize destroy
  • capture and destory invading bacteria or microorganisms by ingesting
  • travel through blood stream and will know how to exit through the injury site
  • body will react with inflammation
• monocytes
  • later become macrophages (eats microorganisms) or dentritic cells (antigen presenting, informs to fight pathogens)when invading a germ or bacteria entered in body
  • either kill it or alert other blood cells to help kill it
  • experts on phagocytosis
• eosinophils
  • allergies
• lymphocytes
  • lymphocyte

inflammatory cells in action: neutrophils and macrophages

• cell injury activates tissue macrophages
• produces cytokines
  • small proteins that sends a message to endothelial cells to sticky to white blood cells
• neutrophil will bind and migrate towards activated macrophages through chemotaxis
• macrophages to attract neutrophils and they'll know where to go
• between the neutrophils an macrophages, phagocytosis happens
  • eat bacteria, in to phagosome
• recognition and attachment
  • opsonization
    • when phagocytosis is coded by antibodies of compliment proteins that will help macrophages phagocytosis better
    • it tags pathogens so neutrophil and macrophages can find them easier
    • without opsonization (immunocompromised), phagocytosis will still happen but just inefficently
    • without complement proteins (liver disease), less efficient inflammation

the compliment system: helping the inflammatory cells

• compliment produces opsonization
• a bunch of proteins that are all produced by liver
• latent in plasma normally as long as we have healthy liver
• gets activated by bacteria, antibodies, pathogens
• when activated, cascade of activations
  • induces chemotaxis, attract neutrophils in injury site
  • polymerize, membrane attack complex: polimer of proteins binding to bacteria and opens a hole in the bacteria (destroys it)

chemical mediators of inflammation

• vasodilation
  • prostaglandin
    • produced during inflammation
    • vasodilators
    • inhibit with asprin
  • histamine
    • increases vascular permeability
    • anti histamine for allergies induces vasoconstriction
  • nitric oxide
• pain
  • prostaglandin
    • activates nociceptors
    • aspirin is an analgesic blocks pain similar to inflammation
• fever
  • systemic effect
  • IL-1, IL-6, TNF and prostaglandis are produced
  • can escape inflammatory site and in to bloodstream, up to brain stem
  • brain stem is where thermoregulation is
  • fever is good, other enzymes for metabolism thats not essential will slow down, give time for body to regroup
• wound healing
  • relate to production of collagen and new blood vessels
• phagocytosis
  • ways to increase

acute inflammatory response

• tissue injury = activation of macrophages = produces cytokines, inflammatory mediators = redness, swelling, pain
• can also activate blood vessels to make sure the cells needed arrive = vasodialators

chronic inflammatory response

• acute inflammation = resolution = termination of inflammation = homeostasis
• ineffective resolution/persistent injury = contiuation of inflammatory process = chronic inflammatory disease
  • ex. arthritis, TB, tendinitis

chronic inflammatory response

• neutrophils will keep going = they ask for help from lymphocytes and fibroblasts = lymphocytes will try to isolate the acute inflammation happened = if not resolved, fibroblasts deposits collagen to the inflammatory site, seals it off = can sometimes lead to deformation of scars

phases wound healing

1. clotting to stop bleeding
2. inflammation to clean up the mess and neutralize (neutrophils, lymphocytes, macrophages)
3. inflammation will decrease and heal through proliferation (rapid reproduction of cells)
   1. angiogenesis: formation of new blood vessels
   2. fibroblasts: produces collagen
   3. granulation tissue: the wound rebuilding itself from the bottom up. it also protects the surface from microbial invasion and more injury
      1. what someone wants to see clinically with wound healing
4. remodelling
   1. epithelium closes again
   2. when not ideal, scar formation or contracts

wound repair by primary intention

• edges are closely re-approximated, most of the time intentional
• most of the time, minimal scarring
• ex. sutures = fibrin clot = neutrophils will clean up and neutrolize = fibrobalst will start rebuilding from the floor up

wound repair by secondary intention

• when the wound had to be left open rather than being stitched together
• usually leaves a scar
• ex. necrosis = angiogenesis (formation of new capillaries) = macrophages cleans up = formation of granulation tissue (red, full of blood vessels, pushes upwards) = fibroblasts deposits collagen but might not know where to stop producing collagen = might leave a scar/keloid

Adaptive immunity

• lymphoid tissues
• thymus shrinks through puberty

overview of immune response

• two types of immuno response
  • cell mediated immunity
    • b and t cells formed in thymus
    • ready to detect a new antigen and differentiate that can help the immune response by remembering the antigen
  • humoral or antibody mediated immunity
    • produces in antibodies 5 different types
    • produced by plasma cells
      • differentiated B cells
      • differentiate to plasma cells
    • when exposed to antigen = B cells will look at the antigen and develop to plasma cells = plasma cells will produce antibodies specific to that antigen

humoral immunity response

• antibodies
• IgG and IgM are most common, look for it in the blood
  • exposure to vaccine = body is not use to it = immune system develops IgG and IgM so body will be prepared for REAL exposure
  • primary response: when we get vaccinated
  • secondary response: being exposed to the real thing. its faster and faster
    • IgG is big, IgM is small = can cross the placenta, passive immunity to fetus in utero
• IgA
  • found in membranes in many epithelium
  • ex. crying, mucus, saliva, human milk
  • this is another way to give passive immunity to baby\
• IgE
  • allergies

functions of antibodies

• why is it good?
  • neutrolizes viruses
  • neutrolizes toxins (even bacterial) ex. tetanus
  • complement mediated killing activated by antibodies (immune complex)
  • phagocytosis

cellular immunity

• cytotoxic T cells
  • can kill cells
  • ex. cancer cells, transplants
  • helped by T helper (Th1)cells. motivates other cells, orchastrating alot of the immune system
    • poroduces cytokines to make cytotoxic T cell be more efficient

Hypersensitivity

• anltered immonologic response to an antigen that results in disease or damage to the individual
• four types

1. IgE-mediated type 1

• allergies, anaphylaxis, athsma
• antigen detected by dendritic cells (antigen presenting cells) = presents itself to T helper cells = it stimulates formation og IgE antibodies, these antibodies bind to IgE receptors that are on top of mast cells (mast cells produce vasoactive mediators like histamine) = mucose secretion, smooth muscle spasm
• histamine blockers = no reaction

2. tissue specific type 2

• when specific cell gets targeted
• blood transfusion reactions, hymolytic disease of new borns
• wrong blood cells received = Igm and IgG will recognize its foreign = binds to it and activates the compliment = polymerizes and membrane attack complex (opens a hole in to the cell, osmoticlysis, destroying it)

3. Immune complexes mediated type 3

• immune complexes
• systemic lupus etithematosus, rheumatic fever, rheumatoid arthritis
• vascular plasma had immune complexes floating around = gets stuck in an organ by the organ trying to remove them = compliment will be activated = C5A will attract neutrophils = compliment activation inflammation

4. cell mediated type 4

• mediatedby the cytotoxic t cells, meant to kill other cells
• t cells get close to target cell = bind to it = produces perforin, opens the cell with a hole
• important with organ transplant
  • not compatible organ = immune system develop cytotoxic t cells = destroys the organ
  • transplant receivers need to me immunosuppressed