Inflammation Flashcards
Defense reaction of living tissue against damage, aimed at removing the cause of injury and repairing the tissue
Inflammation
Chronic inflammation is characterized by the presence of ______ in the injured tissue
macrophages
Exogenous causes of inflammation
Physical - mechanical or thermal agents
Chemical - gases, acids
Biological - bacteria, viruses, parsites
Endogenous causes of inflammation
Circulation - thrombosis, infarction, hemorrhage
Metabolic - uric acid, urea
What are the hallmark signs of inflammation?
CALOR - heat RUBOR - redness TUMOR - swelling DOLOR - pain FUNCTIO LAESA - loss of function
Stages in the development of inflammation
Vasodilation increases the temperature (calor/heat)
Large volume of blood in the area causes hyperaemia (rubor/redness)
Vascular permeability causes leakage of fluids and leads to edema (tumor/swelling)
Leukocytes extravasate, phagocytose pathogens, and release mediators which may induce pain (dolor)
Injured tissue is usually eliminated from normal function (functio laesa)
Mediators of inflammation (7)
Pro-inflammatory cytokines Complement components Prostaglandins Leukotrienes Vasoactive amines Platelet activating factor Plasma proteases
TNFa, IL-1, IL-6, IL-8 are all ______ ______ released within the first minutes after injury
pro-inflammatory cytokines
Cytokines that induce fever and stress hormone production
TNFa (tumor necrosis factor alpha)
IL-1 (interleukin-1)
IL-1, IL-6, and IL-8 are responsible for
promoting chemotaxis
inducing extravasation of granulocytes
degranulation of neutrophils
Complement components that increase vascular permeability and stimulate chemotaxis of neutrophils, eosinophils, and monocytes
C3a and C5a
_______ contribute to vasodilation, capillary permeability, pain, and fever during inflammation.
Prostaglandins
LTB4, LTC4, LTD4 and LTE4 are all
leukotrienes
Leukotrienes that induce smooth muscle contraction
LTC4, LTD4, LTE4
Leukotriene that functions as a chemoattractant of neutrophils
LTB4
2 vasoactive amines
histamine and serotonin
Functions of vasoactive amines
dilation and increased permeability of capillaries
Functions of platelet activating factor (PAF)
induce platelet aggregation
activate neutrophils
attract eosinophils
efflux of plasma proteins = edema
Plasma proteases that increase capillary permeability and are the main mediators of pain
Kinins (bradykinin)
2 important stages/responses of inflammation
vascular and cellular
Steps in the vascular response of inflammation
I: Vasoconstriction
II: Active vasodilation (rubor and calor)
III: Passive vasodilation (tumor)
Sequence of events in the cellular response of inflammation
Chemotaxis
Rolling
Migration
Phagocytosis
The first cells to arrive at the sight of injury are cells of the _____ immunity, such as granulocytes, monocytes, and natural killer cells.
innate
Immune cells have to use _____ to get from the vasculature into the tissues to respond to injury.
CAM: cell adhesion molecules
4 types of CAM
Selectins
Mucins
Integrins
Ig-superfamily CAM
CAMs that bind carbohydrate moieties and are responsible for leukocyte interaction with the endothelium during the initial phase of inflammation.
Selectins
Important Selectins
Selectin E (CD62E) Selectin L (CD62L) Selectin P (CD62P)
Selectin expressed on leukocytes
Selectin L (CD62L)
Selectins expressed on endothelium during inflammation
Selectin P (CD62P) - contained in granules in endothelial cells
Selectin E (CD62E) - synthesized following stimulation by cytokines
Heavily glycosylated, serine and threonine rich CAM proteins that bond to selectins
Mucins
Mucin on endothelial cells that binds to CD62L on leukocytes
CD34
Mucin on neutrophils that binds to Selectin E and P on endothelial cells
PSGL-1
Heterodimeric CAM proteins that have a and b chains that form a binding site for Ig-superfamily
Integrins
Leukocytes express integrins with ___ chains
B2 (CD18)
Deficiency in B2 integrin leads to what disease?
Leukocyte Adhesion Deficiency (LAD)
*autosomal recessive immunodeficiency
How do symptoms of LAD manifest?
Recurrent bacterial infections. Neutrophils are unable to extravasate.
CAMs of the _______ are expressed on endothelial cells and bind to integrins.
Ig-superfamily
MAdCAM-1 is responsible for
migration of leukocytes to the mucosa
If CAMs such as CD62L (selectin) and CD18 (integrin) are non functional, what will happen to the immune cells?
Won’t be able to extravasate into the tissues
Stimulation of the endothelial cells in the initial phase of inflammation, which leads to increased expression of CAMs is known as…
endothelial cell activation
4 phases of extravasation of leukocytes
Rolling
Activation
Arrest/adhesion
Transendothelial migration
