Humoral immunity acts through _______ while cellular immunity directly ___________
molecules secreted by fluids
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kills pathogens by immune cells
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Mechanisms of innate immune response
- recognizes pathogen
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- activates cells + complement system
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Main fxns of innate immunity
- slows spread
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- attracts immune cells to site
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- activates complement system
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- breaks down immune complexes + affected cells
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- activates adaptive immunity w/ antigens
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biological barriers use _________ to prevent pathogen colonization
commensal bacteria
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______ sense the presence of infectious agents and substances released from dead cells
receptors (of phagocytes, dendritic cells, etc)
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Pathogen-associated molecular patterns (PAMPs)
Molecules associated with groups of pathogens that are recognized by cells of the innate immune system.
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Damage-associated molecular patterns (DAMPs)
products of cellular damage that can be recognized by PRRs.
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PRPs in plasma membrane detect ____________, endosomal ones detect _______________, cytosolic one detect _____________
extracell pathogens
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ingested microbes
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microbes in cytoplasm
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Toll-like receptors (TLRs)
PRP that activates transcription factors that stimulate production of immune proteins
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plasma membrane TLRs detect _________ and endosomal TLRs detect __________
bacterial products (LPS)
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viral and bacterial RNA and DNA
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NOD-like receptors (NLRs)
cytosolic receptors, plays role in inflammation (fever) and chronic disorders
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Inflammasome
cytosolic multiprotein complex that is signaled by NLRs to activate caspase-1 that forms IL-1
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Interleukin-1
mediator of inflammation that recruits leukocytes and induces fever
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C-type lectin receptors (CLRs)
on plasma membrane of macrophages and DCs that detect fungal glycans, inflammatory rxn to fungi
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G protein-coupled receptors
on leukocytes that detect short bacterial peptides w/ N-formylmethionyl, stimulates chemotaxis
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Mannose receptors
detect microbial sugars and induce microbe phagocytosis
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Innate immune system provides host defense by 2 rxns
- inflammation (cytokines + complement)
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- anti-viral defense (type I interferons)
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Steps of inflammatory rxn
- offending agent recognized
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- leukocytes + plasma proteins recruited from circ to site
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- leukocytes + proteins activated to destroy offending agent
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____________ is a response of vascularized tissues to infections and tissue damage that brings cells and molecules of host defense from the circulation to the sites where they are needed, to eliminate the offending agents.
Inflammation
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Inflammation results in exudation of fluid and plasma proteins and emigration of leukocytes, predominantly ____________
neutrophils
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Inflammatory mediators are also produced from ____________ that react to the microbes or to products of necrotic cells.
plasma proteins
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Inflammatory mediators do what?
- promote plasma efflux
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- recruit + activate leukocytes
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urate crystals in gout and cholesterol crystals in atherosclerosis can cause what
inflammation
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In inflammation, as stasis develops, how does endothelium change?
leukocytes accumulate along + adhere to endothelium (migrates to interstitial tissue)
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increased levels adhesion molecules
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______ are rapidly recruited while ______ are slower in response to inflammation
neutrophils
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macrophages
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how do neutrophils phagocytose
use cytoskeletal rearrangements and enzymes assemble to create rapid responses
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how do macrophages phagocytose
make slow and prolonged responses w/ growth factors
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When leukocytes are strongly activated, what may occur?
collateral tissue damage that prolongs inflammation
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Selectin
receptors expressed on leukocytes + endothelial cells
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(mediate initial weak interactions bw them)
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- bind sugars
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E, P, L selectins
E - endothelial cells
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P - platelets and endothelium
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L - on leukocyte surface
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________ are expressed at low levels or not at all on unactivated endothelium
E-selectins
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Integrins
surface transmembrane glycoproteins that mediate leukocyte adhesion to endothelium (+ cells to extracell matrix)
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Integrins don't adhere to a specific ligand until:
leukocytes are activated by chemokines
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Chemokines
chemoattractant cytokines, secreted by cells at inflammation site
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Role of chemokines
Induce leukocyte migration and accumulation in tissue sites of inflammation (endothelial surface)
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cytokines TNF and IL-1
activate endothelial cells to increase ligand expression for integrins
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firm integrin-mediated binding of luekocytes to endothelium (@ inflammation site) is due to what combo?
cytokine-induced expression of integrin ligands on endothelium + increased integrin affinity on leukocytes