Innate Immune System

components of innate immunity

Phagocytosis, Complement system, Interferons, Natural killer cells

Infection

some stopped by innate, to many microbs overwhlem innate system causing disease, adaptive might kick in, active adpative cause recovery, adaptive holds memory preventing reinfections

Soluble factors and cells of innate immune system

lysozyme, complements, acute phase proteins, Natural killer cells, Phagocytes

antigenic drift

mutation and changes to virus as transferred

antigenic change

strains change to be able to change host

Defences agaisnt entry into body

lysozyme, Sebaceous gland secretions, commensal organsims in gut/vagina, spermine in semen, mucus, cilia, stomach acid, skiin

Innate or Nonspecific immune system

always present (not induced), doesn’t improve, no memory or specificity, 2 mechanisms - limit entry and growth

Skin and limit entry

normally impermeable, hostile environment to bacteria - lower pH (lactic acid and fatty acid from sweat and sebaceous secretions)

Limit entry and membranes

line inner membranes, secrete mucus, inhibit bacterial adherence, ciliary action, fluching action

Cilia

appendage, Ciliary action, helps remove pathogens from respiratory track, harmed by nicotine/smoking

Flushing action

tears/saliva/urine, protect epithelial surfaces, presence of antimicrobial compounds

antimicrobial compunds in flushing action

acid in gastric juice, spermine and zinc in semen, lactoperoxidase in milk, lysozyme in nasalsecretion/tears/saliva

Gastric acid

tries to reduce number of bacteria before passing to intestine, HCl

Normal flora

permanent bacteria/fungi on body surfaces, suppress growth of pathogenic microbes

how normal flora suppress growth of pathogens

protective layer, compete for nutrients, produce inhibitory compounds (acids and colicins)

mechanism of limits growth

phagocytosis, soluble chemical factors (bactericidal enzymes)

Phagocytes types

Macrophages, Polymorphonuclear granulocytes (Neutrophils)

Polymorphonuclear granulocytes other names

Neutrophils, polymorphs

Phagocytes

cells that eat other cells, from stem cells in bone marrow, release damaging enzymes

Never let monkey eat banana (WBC)

Neutrophils, Lymphocytes, Monocytes (become macrophages), eosinophils, basophils

Macrophages

promonocytes in bone marrow into monocytes in blood until mature in tissue, Filter for tissue, concentrated in lung/liver/lymph node lining

Polymorphs (PMNs)

Dominat WBC in blood, common hematopoietic precursor(bone marrow), granular cytoplasm(substances that kill pathogen), non dividing short lived segmented nucleus, 3 Groups (BEN) - Basophils/Eosinophils/Neutrophils

PAMPs (pathogen associated molecular patterns)

on microbe, recognized by phagocyte, bind PRRs

PRRs (pathogen recognition receptors)

on phagocyte, recognize pathogen, bind PAMPs

Process of Phagocytosis

PRR bind PAMPs, pseudopodia forms phagosome (engulfing pathogen), granule fusion kills pathogen (oxygen (in)dependent), release microbial products

Formyl methionyl peptide

signal to attract leukocytes (chemotaxis), weak need complement to amplify

Pathways that trigger complement system

Classical, Alternative, Lectin

Complement system

cascade, product of 1 reaction is enzymatic cataylst of next

Serum vs plasma

serum lacks clotting factors

A complement proteins

C3a/C5a, trigger analphylatic reaction, causing faster travel to site of infection

B complement proteins

C3b/C5b, Binding proteins, flags pathogens for WBC/Macrophages

Properdin

protein, regulates C3/C5, only in alternative pathway

C3 activation

breakdown into C3b and C3a, by C3 convertase (C3bBb)

C3 convertase (C3bBb)

Begins alternative complement pathway, can activate C3 (split into C3a/C3b), unstable and degrades, in presence of bacterial surface molecule (ex: CHO) no longer suspceptible to breakdown

C3b

binds microbial surface, acts as opsonin, works with C3bBb (convertase) to activate C5, chemotactic attration of polymorphs, WBC/Macrophage bind to

C5 activation

C3b and C3bBb (convertase) splits into C5b and C5a

C5b

binds microbial membrane, recruits C6/C7/C8/C9, first protein of Membrane attack complex (MAC), involved in cell lysis, structural protein

Membrane attack complex (MAC)

cell lysis, C5b first to bind microbial surface, insertes in cell membrane (ports to leak cell), more effective in gram neg (no peptidoglycan)

C5a and C3a

may cause mast cell degranulation (release chemicals), increase vascular/capillary permeability (inflammatory response

Acute phase proteins

increase plasm concentration in response to injury/inflammation,

example of acute phase proteins??

C reactive proteins, Mannose binding protein (MBL), bind to PAMP, fix complement and opsonize bacteria

Antimicrobial factors

acts with phagocytic cells but also in body fluids, tears and saliva - lysozymes, blood - transferrin, lactoferrin (snatch iron)

Intherferons (IFNs)

viral interferences, infected cell resiant to superinfection (2nd infection), secreted by infected cells, bind uninfected cell to induce antiviral state (limit spread), produce 2 enzymes that interfere with virus replication

Natural killer cells (NK)

bind receptors on virus infected cells, binding cause release of granules, allow entry of secondary molecules (granzyme b) that leads to apoptosis, from bone marrow stem cells, Fas binds leading to cas cascade (apoptosis)

Eosinophils

combats large parasites (cannot be engulfed), binds to C3b which activation, release several toxic compunds, create hole in parasite membrane