Acute Inflammation 2 Flashcards
Describe what the vascular response results in.
- Exudation of fluid & plasma protein
- Emigration of leukocytes
Describe what the acute cell response results in.
-accumulation of inflam cells at site of injury
-phagocytosis
Describe the different cells involved in acute inflammation.
- Mast cells = found around blood vessels & early responder to injury
- Endothelial cells = inflam & coagulation
- Granulocytes = short lived, host defense
>neutrophils, basophils, eosinophils - Monocytes/macrophages
Describe neutrophils.
-made in BM -> blood
-inflam -> tissue via selectin (rolling), integrins (adhere), & chemotaxis
-die in 1-3d (short lived) = ‘kamikaze’
-phagocytose & destroy bacteria via granules
-primary/azurophilic = myeloperoxidase, hydrolase, defensins, lysozyme
-2ndary/specific = lactoferrin (chelates Fe), collagenase
-heterophils = granules stain eosinophilic (rabbits, birds, etc) * [no myeloperoxidase = caseous not liquid]
-surface receptors:
>Fc: antibody receptor & CR1/CR3: complement receptors = opsonins
>adhesion molecules: integrins/selectins
Describe reactive oxygen species.
-released from neutrophils & macrophages into phagolysosome
-damage to cell membrane, protein, DNA
-gen thru respiration & stress like UV
-anti oxidant pathways protective
Describe eosinophils.
-similar origin & fate of neutrophils
-BM production stim by IL5/GM-CSF *
-survive in tissue for weeks
-function: allergy & parasites
-attracted by eosinophilic chemotatic factor (mast cells), IgE, histamine *
-activated by IL5, IL3, Th2
Describe monocytes.
-monocytes in circ
-change into macrophage in tissue *
-resting macrophage: kuppfer, alveolar, type A synoviocytes, microglial cells
-APC: skin, LN
-live longer than neutrophils
-phagocytic
-arrive after neutrophils
-role in chronic inflammation
Describe monocyte functions.
-complement/ab receptors, TLR, integrins
-phagocytosis, gen NO *
-make IL1/6, TNFa -> liver
>sick: fever, loss of appetite, depress
>acute phase protein, clotting/complement factor *
-MHCII receptors: adaptive IR *
-central cell of chronic inflam *
-recovery from inflam *
Describe mast cells.
-around blood vessels of CT of skin & mucous membrane
>initiate acute inflam *
>allergic/Type 1 HS reaction (IgE) *
>defense against parasites *
-long lived
-granules release: histamine, TNF, GF, substance P (pain) degranulation
Describe basophils.
-BM prod by IL3
-tissue emigration by IL1, TNF
-survive for 2wk
-activated by IL1, IgE -> degranulation
>promote hypersensitive reactions
>attract eosinophils
-low # in blood
-similar func to mast cells*
Describe the chemical response summary.
Describe cell derived preformed vasoactive amines.
- Histamine
-mast cells, basophils, platelets
>mast cell = initiate acute inflam resp
-inc mucus prod & bronchial constriction
-vasodilation & inc vascular permeability - Serotonin
-platelets
-imp neurotransmitter
-vasodilation & inc vascular permeability
*red, heat, swell
Describe cell derived newly synthesized arachidonic acid metabolites.
-damage to cell membrane -> activation of phospholipase A2 that acts on cell membrane -> releasing arachidonic acid
-2 enzymes that act on the arachidonic acid to make metabolites:
1. Cyclooxygenase (Cox 1 & 2)
-prostaglandins & prostacyclins
-COX1 in gut & kidney
2. Lipoxygenase
-leukotrienes (LTs) & lipoxins
Describe cytokines & chemokines.
- Cytokines
-proteins made by many cell types
-inflam + other func - Chemokines
-small protein cytokines that act as chemoattractants
-bind to 7 trans membrane GPCR
-secreted by activated macrophages, endothelial cells, and other cells
-stim leukocyte recruitment in inflam & control migration of cells in tissues
-production induced by microbes & other cytokines (IL1 & TNF)
Describe inflammatory cytokines: IL1 & TNFa.
-secretion stim by physical injury, endotoxin, immune complex, toxins
-Autocrine, paracrine, endocrine
-actions on endothelium, leukocytes, fibroblasts, acute phase proteins
-‘acute phase resp’
Describe the acute phase response.
-systemic early defense system activated by trauma, inf, stress, neoplasia, inflam
-tissue injury -> local inflam cells secrete cytokines into blood like IL1, IL6, TNFa
-liver -> makes lg # of acute phase reactants: C reactive protein, complement factors, mannose binding protein, ferritin
-goal: prevent inf, clear pathogen, initiate inflam process, contribute to healing
Describe the acute phase response CS.
-fever
-inc sleep
-pain
-neutrophilia
-dec appetite (TNF inc lipid & protein mobilization)
>prolonged TNF -> cachexia (weight loss - cancer & inf)
-corticotropin & corticosteroid released
-severe = hypotension, dec vascular resistance, inc HR, dec blood pH -> SHOCK
Describe the complement system.
-innate IS
-inflam activates circ complement proteins
-activation stim by Ab, microbes, endotoxins, venom *
-Ab & phagocytic cells to remove pathogens
-made by liver (20+ proteins & products in plasma)
>proteins #’d C1-C9
-activation = inc vascular permeability, chemotaxis, oponisation
>activation by Ag+Ab complex or contact w microbial surface molecules
Describe the clotting system.
-clotting + inflam
-2 pathways:
1. Activation of thrombin
2. Formation of fibrin
Describe the clotting cascade.
- Plasma derived (intrinsic)
-hageman factor (F12) activated secondary to exposure of collagen & BM when endothelium is damaged - Tissue derived (extrinsic)
-tissue factor released when sub endothelial damage
-fibrin = pink
-framework for repair
Describe the summary of acute inflammation.
Describe leukocyte induced tissue damage.
-neutrophils & macrophages release:
>lysosomal enzymes
>ROS
>arachidonic acid metabolism
—prostaglandins, leukotrienes into extravascular space
-endothelial & tissue damage = amplifying effects of initial injury
-leukocyte becomes bad guy if unchecked
Describe the resolution of inflammation.
Describe the outcomes of acute inflammation.
