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PRRs
Pattern-recognition receptors; recognizes common structural compounds of many different pathogen
PAMPs
Pathogen-associated molecular pattern; any structure on a microbe recognized by PRRs
DAMPs
Damage associated molecular pattern; receptors that detect changes to cells/tissues
Scavenger receptors function
subset of PRRs that identify and bind microbial parts and eliminates them + removes cells that died via apoptosis. triggers phagocytosis, cell adhesion and intracellular signaling
TLRs function + use
signal receptors that recognizes variety of microbial ligands; most important is TLR4 that recognizes lipid A of LPS
TLR structure
pattern recognition domain with repeated motif 20-29 amino acids with leucine-rich repeat regions; variations in LRRs + amino sequence = different ligand specificity
TLR 4 complex
ngl memorize slides 11-12
Extracellular TLR recognition
carbs, lipids, and protein structures on surface of pathogens
intracellular TLR recognition
disdinguish nucleic acids of pathogens vs human cells
Type I interferon function
induce resistance to viral replication, increase of ligands for receptors on NK cells, activate NK cells to kill infected cells
type I interferon pathway
infected cell secretes IFN-B → IFN-B bound to type I interferon receptors which stimulate IFN-a production → IFN-B binds to uninfected cell which produces even more IFN-B
macrophages + neutrophils lifespan and amount
macrophages are long-lived and tissue residing; neutrophils are life span 2 days, circulate in blood waiting for signals. N are most abundant wbc in peripheral circulation (50 bil)
CXCL8 function
cytokine that recruits peripheral neutrophils to infection site
four steps of neutrophils traveling to infected tissue
rolling adhesion, tight binding, diapedesis, migration
Macrophage and neutrophil pathogen range
neutrophils > macrophages
4 types of granules in neutrophils
myeloperoxidase, defensin, lactoferrin, gelatinase
Neutrophil phagocytosis progress
once bacteria engulfed endosome fuses with azurophilic, specific and gelatinase (tertiary?) → pH rises due to NADPH oxidase + superoxide dismutase → lysosomes reduce pH and completely degrade bacteria → neutrophil commits apoptosis
Autocrine secretion
cell releases a chemical messenger that binds to its own surface
paracrine
chemical massagers that act on nearby cells
Immune response time
immediate innate = 0-4 hours, induced innate = 4 hours - 4 days, adaptive = 4+ days
cell that makes 1000x more interferons than other cells
plasmacytoid dendritic cells, <1% of total leukocytes, in peripheral circulation
TNF-a and CXCL8 function
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NK cells and viral infections
innate response to viruses/cancer while T cells are developing; levels of IFN-a+b and IL-12 peak
NK cell subpopulations
CD56 (glycoprotein) bright more abundant in tissues, dim in blood; >100 million in circulation. majority of NK cells in uterine are bright, fluxes during menstrual cycle
NK cell activation
infected cells release type I interferon → causes proliferation of NK cells → differentiation of NK cells to cytotoxic effector cells → kills virus-infected cell via inducing apoptosis
NK + macrophage interactions
Macrophages activated by viral infection secrete cytokines which recruit NK → they conjugate, IL-15 + 12 activates NK → NK proliferate + differentiate and secrete IFN-y → binds to macro receptor which increases phagocytosis + cytokine secretion
plasma proteins function
Pathogen recognition + elimination, inflammatory response, and coagulation
most abundant plasma proteins during acute-phase
c-reactive and serum amyloid A (so predictable it’s diagnostic marker for infection + inflammation, tissue damage)
C-reactive protein
opsonin (binds to foreign things making them easier to phag) which triggers classical complement pathway
MBL
calcium dependent lectin (c-ype) ac phase protein; binds to mannose-containing carbs of bacteria, fungi, protozoans and viruses.
Lectin, classical and alt pathway
sldies 46-49 broski
produces plasma proteins
liver stimulated by cytokines released by macrophages