lecture 18 -- barrier defenses

adaptive vs innate immunity

• innate — rapid, non-spec.

• adaptive — slower, very specific (^ effective)

barrier defenses

site | specific defense | protective mechanism

• skin — epidermal surface — keratinization

• skin (sweat/secretions) — sweat glands, sebaceous glands — low pH, washing action

• oral cavity — salivary glands — enzyme → lysozyme (digest cell walls)

• stomach — GI tract — low pH

• mucosal surfaces — mucosal epithelium — nonkeratinized → goblet, cilia

• normal flora (nonpathogenic bacteria) — mucosal tissues — prevent overgrowth of pathogens

cells of innate immune response — phagocytes

• fast acting

• first line of defense after barriers

• engulf particles/cells

• main types involved in innate immunity

  • macrophages/monocytes, neutrophils

• some pathogens are easily cleared by phagocytes, others have become resistant

cells of innate immune response — NK cells

• natural killer cells

  • type of lymphocyte

  • can induce apoptosis 2 ways:

    • extrinsic apoptosis via fas ligand

    • intracellular apoptosis via perforins and granzymes

  • cell recognition mechanism unclear

extrinsic apoptosis via fas ligand for NK

• external fas R connected to fas-associated DEATH DOMAIN (FADD)

intracellular apoptosis via perforins and granzymes

• perforins = form pores on infected cell membranes

• granzymes = trigger apoptosis

macrophages

• type of while blood cell

• irregularly shaped

• agranulocyte

• versatile - can be fixed or mobile; participate in various physiological processes

• present in many tissues; primary location = body cavities/organs

• monocytes are the precursors for macrophages

neutrophils

• type of white blood cell

• granulocytes

  • granules = vasoactive mediators

• circulate in the blood, attracted to infected tissues via chemotaxis (directed migration in response to chemical signaling)

• primary location = blood

pattern recognition receptors (PRRs) — what are they, what patterns do they recognize? present where?

• immune cells recognize patterns of pathogen-specific molecules using PRRs

• PRRs = membrane-bound receptors that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)

  • PAMPs'/DAMPs can be on pathogens or body cells

  • PAMPs'/DAMPs may be soluble molecules or structural characteristics

• PRRs can be present

  • intracellularly → endosomal or cytosolic

  • extracellularly → cell surface or soluble

soluble mediators of innate immune responses (cyto and chemo)

• cytokines

  • signaling molecules for short distance communication

  • secreted into the receiving cells’ intracellular space; induces change

• chemokines

  • similar function to cytokines, but long distance

  • facilitate chemotaxis

soluble mediators of innate immune responses? (early induced proteins)

• not constitutively present; made as needed

• ex: interferons

  • cells infected with viruses secrete interferons

  • the interferons induce adjacent cells to make antiviral proteins

• phagocytes also have receptors for EIPs

  • enhances phagocytosis via opsonization

    • “tag” a pathogen for phagocytosis

soluble mediators of innate immune responses — the complement system

• series of constitutive proteins in blood plasma

• made in the liver

• function in the adaptive immune responses too

• once the first protein (C1) is activated, it triggers a cascade of events that will result in 3 things:

  • opsonization of the pathogen

  • chemotaxis of phagocytes

  • physical destruction of the pathogen

  • ** not part of early immune response

the inflammatory response

• hallmark of the innate immune system response

  • 4 characteristics: heat, redness, pain, swelling

  • does not have to be initiated by infection

  • recruits phagocytic cells to clear cellular debris and prep for wound repair

  • recruits other innate immune cells to clear potential infection

  • isolates the site — prevent/decrease spread of any pathogens

  • may be acute or chronic

4 phases of inflammatory response

1. tissue injury

   1. injured cell → release contents → stimulate release mast cell granules + inflammatory mediators (IMs)

2. vasodilation

   1. inflammatory mediation cause vasodilation

      1. relaxing vascular smooth muscle

   2. ^ heat, ^ redness, ^ access

3. ^ vascular permeability

   1. stimulated by IMs

   2. causes fluid to leak into interstitium → edema

4. phagocyte recruitment

   1. LOTs of chemotaxis, neutrophils, macrophages

   2. pus → accumulated cellular remains of phagocytes (purulent)