Acute Inflammation 1 Flashcards
Describe inflammation.
-reaction of vascularized living tissues to injury
-goal:
>inactivation, dilute, destroy pathogens, toxins, foreign material
>bring phagocytes & immune cells to site of injury
>begin repair
-acute VS chronic
-prolonged or excessive inflam = detrimental
Describe infection VS inflammation.
- Infection
-invasion & multiplication of pathogen in body - Inflammation
-body protective response against infection
Describe innate VS adaptive response to inflammation.
- Innate (initial response)
-non specific
-no memory
-incl epi barrier, inflam, NK cells - Adaptive
-antigen specific recognition molecules
-T & B lymphocytes
Describe the types of tissue injury.
- Physical trauma = cut, abrasion, friction, crush, pressure
- Chemical = acid/alkali, pancreatitis
- Thermal = burn, frost
- Infection = virus, bacteria, fungi, Protozoa, parasites
- Radiation = UV light
- Immunological = autoimmunity, hypersensitivity
- Ischemia = inflam when blood flow re established
- Necrosis = inflam at margins
Describe history of inflammation.
- Celsus = redness, heat, swelling, pain
- Virchow = loss of function
- John hunter = response, not disease
- Metchnikoff = demonstrate phagocytosis via drawings
- Nuttal = antibacterial properties of blood
Describe the 5 cardinal signs of acute inflammation.
- Redness = rubor
-inc blood flow (hyperaemia) - Swelling = tumor
-accumulation of fluid (edema, hyperemia) & cells - Heat = calor
-inc blood flow from core - Pain = dolor
-release of chemicals that stim nerve endings - Loss of function = functio laesa
-multiple causes
Describe the role of chemical mediators in inflammation.
-initiate & orchestrate vascular & cellular response
-goal: accumulation of fluid, protein, & leukocytes in extravascular space -> elim injurious agent & begin tissue repair
Describe the vascular response.
- vasodilation (hyperaemia, congestion)
-inc blood flow & widen endothelial gaps
>inc vascular permeability -> vascular stasis
-exduation of fluid (plasma), plasma protein, & leukocytes into extravascular space
-plasma dilutes effects of inciting stimulus
-fibrin formation in extravascular area *
>confine stimulus to an isolated area
>provide leukocyte w target
>framework for fibroblast & endothelial cell migration in wound healing
-extravascular fluid = ‘exudate’
>forms in inflam bc inc inter endothelial space
>exudates have high protein & nucleated cell counts (NCC)
Describe the formation of transudates & exudates.
Describe exudates VS transudates.
- Exudate
-inflam
-high protein (TP)
-high NCC
-active process (inc vascular permeability) - Transudates
-non inflam
-low protein
-low NCC
-passive process (imbalance in osmotic or hydrostatic pressure)
Describe the different morphological types of acute inflammation.
- Suppurative/purulent
-fluid w many neutrophils, inc protein - Fibrinous
-fluid w few cells, high protein - Serous
-fluid w few cells, low protein - Catarrhal/mucoid
-thick fluid w mucus (GIT, respiratory tract)
Describe step 1 of acute inflammation.
Vasodilation
-follow transient period of vasospasm (facilitate hemostasis)
-histamine, NO, PGs = from damaged cells, mast cells
-serotonin = from platelets
-leads to hyperemia *
Describe step 2 of acute inflammation.
Inc vascular permeability
-loosening of junctions between endothelial cells
-vasoactive amines, complement, LTs
-leak plasma (dilutes)
>complement
>antibodies
>clotting factors: fibrinogen -> fibrin *
Describe step 3 of acute inflammation.
Emigration of leukocytes cell response
Leukocyte adhesion cascade: KNOW STEPS
1. Margination/pavementing of neutrophils
-move toward periphery of lumen
2. Rolling
-weak binding of selectin
3. Adhesion
-B2 integrins (leukocyte) bind ICAM (endothelial cells)
4. Emigration
-transendothelial migration
5. Chemotaxis
-migration within exudate
Describe adhesion molecules.
-surface receptors on leukocytes & endothelium
>sites of interaction
-facilitate movement of leukocytes
-diff types:
>selectins - tethering, weak (E,P,L) mostly on endothelium
>integrins - firmer (B1 & B2 integrins on leukocytes)
>immunoglobulin fam - ICAM, VCAM, PECAM (on endothelium)
Describe extravasation, chemotaxis, activation.
-chemotaxis & activation -> phagocytosis & degranulation
-function of cell response:
>destruction of microbes & foreign material
>neutralization of toxins
>mediation of immune response
>clearing of necrotic tissue
>regen of tissue
Describe leukocyte extravasation.
‘Diapedesis’
-occurs in post capillary venules
-chemokines act on leukocytes = stim cells to migrate thru inter endothelial spaces
-leukocytes pierce BM = enter extravascular space & follow chemotatic gradient
-leukocytes adhere via adhesion mol (integrins) to glycoproteins in extracellular matrix
Describe chemotaxis.
-migration of leukocytes to site of injury along chem gradient
-exogenous attracting agent = bacterial products
-endogenous chemoattractants = component of complement system (C5a), arachidonic acid metabolites (leukotriene B4) & chemokines
>neutrophils 1st to arrive in acute inflam *
>eosinophils migrate to area if allergy or parasite *
Describe leukocyte activation for phagocytosis.
*once neutrophils & monocytes are at the injury site they express receptors:
1. TLR = recog microbial prod & stim prod of cytokines & microbicides by leukocytes
2. GPCR = recog bacterial peptides, chemokines, complement & induce migration of cells from blood & prod of microbicidal substances
3. Receptors for opsonins = bind to particles covered by protein/opsonins (antibodies, complement) -> cell activation & enhanced phagocytosis & intracellular killing
4. Receptors for cytokines = cytokine, gamma interferon is made by NK cells reacting to antigens -> macrophage activation
Describe the result of activation of surface receptors on leukocytes.
- Prod of arachidonic acid metabolites from phospholipid (membranes) -> due to activation of phospholipase (secondary to inc intracellular Ca)
- Degranulation & secretion of lysosomal enzymes & oxidative burst
- Cytokine secretion amplify & regulate inflam response via activated macrophages
- Modulation of leukocyte adhesion mol -> expression of adhesion mol on endothelial cells & -> leukocyte avidity
Describe step 4 of acute inflammation.
Phagocytosis cell response
-neutrophils first leukocyte to arrive
-engulf & destroy injurious agents
>internalize bacteria, foreign body, dead cell, debris
>fuse w lysosomes & digest content
>oxidative burst produce ROS - free radicals
-secrete substances into exudate like collagenase to degrade dead & damaged tissue components but can also damage vital tissue
Describe the summary of acute cell response (steps 3 & 4).
- Leukocyte adhesion
-express adhesion mol on surface of leukocytes & endothelial cells in blood vessels (selectins & integrins)
-induced by secretion of chemical mediators (cytokines & chemokines) - Leukocyte extravasation
-migration out of blood vessel into extravascular tissue - Leukocyte chemotaxis
-movement to site of inflam via exogenous & endogenous chemoattractants - Leukocyte activation
-TLR, GPCR - Leukocyte phagocytosis
-cell engulf & neutralize injurious agents
