Flashcards in Innate Immunity and Bacterial Infection Deck (86):
What is the modulat design of the innate immune system?
collection of mechanisms cobbled over time in response to a new mechanism of microbial virulence
What are teh 2 functions of hte innate immune response?
immediate, non-sepcific host defense; initiation of adaptive respose
What are the 3 main features of PAMPs?
invariant among microbes of a given class; products of pathways unique to microbes; essential roles in microbial physiology
What is the structure of the gram positive cell wall?
plasma membrane with thick layer of peptidoglycan with teichoic acid and lipoteichoic acid
what is the structure of the gram negative cell wall?
plasma membrane; thin layer of peptidoglycan; outer membrane with LPS
What is the function of NOD1?
responds to peptidoglycan with modified aa mesoDAP
What type of bacteria does NOD1 generally recognise?
What type of bacteria does NOD2 generally recognise?
both gram neg and gram positive
What species of extracellular bacteria are protected by a polysaccharide capsule that resists engulfment?
What are the protections against extracellular bacteria at epithelial surfaces
antimicrobial peptides; antibodies esp. IgA
How can intracellular pathogens be categoriesd?
those that replicate freely in the cell and those that replicate within intracellular vesicles
What are exotoxins?
secreted toxin released by extracellular bacterial pathogens that act at the surface of host cells
What are endotoxins?
nonsecreted constituents of bacterial structure taht triggers phagocytes to release cytokines
give an example of an important endotoxin?
What are the chemical barriers of epithleium in the skin?
beta-defensins; lamellar bodies; cathelicidin; fatty acids
What are the chemical barriers of epithelium in the gut?
low pH; enzymes eg pepsin; alpha-defensins (cryptdins); regIII(lecticidins); cathelicidin
What are the chemical barriers of lung epithelium?
pulmonary surfactant; alpha-defensins; cathelicidin
What are the chemical barriers of the eyes/nose/oral cavity epithelium?
enzymes in tears and saliva (lysoszyme); histatins; beta-defensins
Which cells in the skin produce beta-defensins and cathelicidin?
keratinocytes of hte stratum spinosum
What are beta-defensins and cathelicidins in the skin incorporated into?
What happens to the lamellar bodies in the skin?
secreted into the intercellular space to form a waterproof lipid layer
Which cells in the lung produce and secerete antimicrobial defensins?
type II pneumocytes
What cells in the intestine produce alpha defensins and RegIII?
paneth cells in the epithelial crypts
How do commensal microbes help strengthn the barrier functions of hte epithelia?
sitmulate the epithelial cells to produce antimicrobial peptides
What is mucin production in the gut related to?
microbial load e.g lots more microbes in colon than in stomach so colon has lots more mucin
How do antimicrobial peptides attack bacteria?
often positively charged and attracted to the plasma membrane of bacteria causing pore formation
Describe the peptidoglycan polymer?
alternating residues of beta (1,4) N-acetylglucosamine (GlcNAc); N-acetylmuramic acid (MurNAc) that are cross-linked by peptide bridges into a dense 3-D network
What is the function of teichoic acid and lipoteichoic acid?
links the pepptidoglycan layer to bacterial cell membrane
What is the structure of LPS?
lipid A which is attached to a polysaccharide cire
What is the function of lysozyme?
cleaves the beta (1,4) linkages creating a defect in the peptidoglycan layer and exposing the underlying cell membrane
What type of bacteria is lysozyme more effective against?
gam positive (greater accessibility to peptidoglycan)
What is the function of secretory phospholipase A2?
basic enzyme that enters the bacterial cell wall to hydrolyse phospholipids in the cell membraen
Give examples of antimicrobial enzymes?
lysozyme and secretory phosspholipase A2
What are the main classes of antimicrobial peptide?
defensins; cathelicidins; histatins
What is an amphipathic structure?
positively charged region separated from a hydrophobic region
What is the structure of defensins?
short cationic peptides that have 3 disulfide bonds stabilising a common amphipathic structre
What is the mechanism of action of defensins?
elecrostatic attraction of positive defensin to bilyaer then insertion of hydrophobic region into the membrnae bilayer and formation of a pore
Which chromosome encodes most defesins?
What are the 3 subfamilies of defensin?
a; b and theta
How are the subfamilies of defensin differentiated?
basis of amino acid sequence
What are the a-defensins produced by paneth cells?
What cells constitutively produce cathelicidins?
neutrophils and macrophages
How are all the antimicrobial peptides generated?
proteolytic processing from inactive propeptides
What are defensins stored in in neutrophils?
what are cathelicidins in neutrophils stored in?
What cleaves cathelicidins in neutrophils?
neutrophil elastase from primary granules in phagosomes
What is the difference between lectins and C-type lectins?
C-type lectins require calcium
What is the function of RegIII?
produced by paneth cells and bind to peptidoglycan forming a pore (again, gram positive)
what cytokine induces the synthesis of acute phase proteins?
What is the function of CRP released by the liver?
binds phophorylcholine on bacterial surfaces acting as an opsonin and activating complement
what is the function of mannon-binding lectin released by the liver?
binds mannose residues on bacterial surfaces, acting as an opsonin and activating complement
How do pulmonary surfactants A and D bind to pathogen surfaces?
through globular lectin-domains attached to a collagen-like stalk
What is the function of the acute phase response?
early in an infection provies the host proteins with many of hte functional properties of antibodies to bind and target for destruction, but without the specificity
What pathogens do mast cells and basophils play a role in host defense against?
What is the defense strategy against multicellular parasites?
preventing entry and promoting expulsion
What is hte function of histamine and prostaglandins b=produced by mast cell and basophils?
act on smooth muscle- coughing, sneezing and D&V; C-fibres- itch (expulsion of parasite)
What happens upon PRR stimulation of DCs?
upregulates costimulatory moelcules and stimulates cytokines that skew naive T cell differentation
What is tthe function of Th1 cells?
intracellular pathogens; apoptosis of tissue cells; activation-induced cell death
What is the function of Th2 cells?
helminiths; allergic inflammation
What is hte function of th9 cells?
mucous production and tissue inflammation
What is the function of Th17 cells?
What is the function of Th22 cells?
What is the differentation cyyokine of Th1 cells?
What is the differentiation cytokine of Th2 cells?
What is the differentiation cytokine of Th9 cells?
IL-4 and TGF-beta
What is the differentiation cytokine of TH17 cells?
TGFb; IL-6; IL-21 and IL-23
What is the differentiation cytokine of Th22 cells ?
TNFa and IL-6
What are the effector cytokines of Th1 cells?
What are the effector cytokines of Th2 cells?
IL4; IL5; IL13; IL25; IL31 and IL33
What are the effector cytokines of Th9 cells
What are the effector cytokines of Th17 cells?
IL6; IL8; IL17; IL22; IL26
What are the effector cytokines of Th22 cells?
What cells do Th17 cells stimualte?
What cells do Th1 cells stimualte?
What is oten the first step in disease for pathogenic bacteria?
colonization of hte epithelium
What is the transmission of pneumococcal infection?
Where does pneumococcus colonise?
What happens when there is local spread of pneumococcus ?
otitis media/ sinusitis
What happens when there is aspiration of pneumococcus ?
What happens when there is epithelial translocation of pneumococcus ?
What happens when there is endothelial translocation of pneumococcus ?
What chemokines recruit neutrophils?
What effect does activation of DCs at the mucosal surface have on epithelial cells?
downregulation of tight junctions to allow effector cells into lumen
What happens if bacteria breach teh epithelium?
tissue resident cells kill bacteria
What T cells promote a more vigorous response at mucosal surfaces on re-encountering pathogen?