Innate immunity Flashcards
(28 cards)
what are the sites of microbe entry?
→Conjunctiva →Arthropod →Capillary →Scratch → injury →Skin →Anus →Urinogenital tract →Alimentary tract →Respiratory Tract
describe the inflammatory response
→ generic defence mechanism
→to localize and eliminate injurious agents
→remove damaged tissue components
→enhanced permeability and extravasation
→ Neutrophil recruitment
→ Enhanced cell adhesion
→Enhance clotting
→Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
what do cytokines do?
→Act to modify the behaviour of cells in the immune response
→Most of these are called interleukins (eg. IL-1
what do chemokines do?
→Act as chemotactic factors
→ i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
what is IL-1?
→Main producer = Macrophages + keratinocytes
→Acts upon = lymphocytes + liver
→Effect = Enhances response
→ Induces acute-phase protein secretion
what is IL-6?
→ Main producer = Macrophages + dendritic cells
→ Acts upon = lymphocytes + liver
→ Effect = Enhances response
→ Induces acute-phase protein secretion
what is CXCL8 (IL-8)?
→Main producer: Macrophages + dendritic cells
→Acts upon: Phagocytes
→Effect: Chemoattractant for neutrophils
what is IL-12?
→Main producer: Macrophages + dendritic cells
→ Acts upon: Naive T cells
→Effect: Diverts immune response to type 1, →proinflammatory, cytokine secretion
what is TNF - alpha?
→Main producer: Macrophages + dendritic cells
→Acts upon: Vascular endothelium
→Effect: Induces changes in vascular endothelium (expression of cell-adhesion molecules (E- + P- selectin), changes in cell-cell junctions w/increased fluid loss
how do macrophages “see” microbes?
→Passive sampling
→ Scavenger receptors
→Engulfing apoptotic cells
what are examples of Pathogen-associated Molecular Patterns (PAMPs)?
→Gram-negative bacteria; lipopolysaccharides (LPSs) found in outer membrane
→Gram-positive bacteria; teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
what are other PAMPs?
→Bacterial flagellin
→Abnormal protein glycosylation
→Abnormal nucleic acids - viruses
what are Pattern recognition receptors (PRRs)?
→Host factors that specifically recognise a particular type of PAMP
→They are germ-line encoded
what are the three classes of PRRs?
Extracellular
→ they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
Intracellular (cytoplasmic)
→ they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
Secreted
→ they act to tag circulating pathogens for elimination
Lectin receptors
→Ligand: terminal mannose and fucose
→Outcome: phagocytosis
Scavenger receptors
→Ligand: bacterial cell walls modified low-density lipoproteins
→Outcome: phagocytosis
Toll-like receptors (TLRs) (surface and endosomal)
→Ligand: LPS (together with CD14) lipoproteins unmethylated CpG flagellin ds RNA; ss RNA (in endosomes)
→Outcome: inflammation: cytokine release (TNF, IL-1, IL-12) enhanced killing: reactive oxygen species, NO)
NOD-like receptors (NLRs) (cytoplasm)
→Ligand: peptidoglycan from Gram positive and negative bacteria some viral DNA and RNA (indirect?)
→Outcome: inflammation: cytokine release (IL-1, IL-8)
RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)
→Ligand: dsRNA and 5’-triphospho RNA
→Outcome: type I interferon production
how do macrophages “see” microbes?
→Passive sampling
→ Scavenger receptors
→Engulfing apoptotic cells
what is the complement and what does it do?
→system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and “decorate” or “tag” them.
→The microbes are then cleared by phagocytosis, “opsonised” or they have holes punched in them
what are the three ways of activating complement?
→Recognition of LPS and other PAMPs by the C1q component of “classical” pathway (
→Non-host glycosylation is recognised by MBP and other lectins to activate the “lectin” pathway
→ Membranes that are recognised as “non-self” activate the “alternative” pathway
→Complement activation involves a proteolytic cascade
Natural Killer (NK) cells (Large granular lymphocytes)
→4% white blood cells
→Lymphocyte-like but larger with granular cytoplasm
→Kill certain tumour & virally infected cells
→ Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
how are NK cells activated?
→NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
→Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands
