Inflammation Flashcards
What is inflammation?
defense reaction of living tissue against damage, aimed at removing the cause of injury and repairing the tissue
- plays an integral role in both innate and adaptive immunity
What are the types of inflammation? What do they do?
- Acute - fights early stages of infection and prepares the process that leads to tissue repair
- Chronic - characterized by the dominating presence of macrophages in the injured tissue
What are the exogenous causes of inflammation?
- Physical agents - mechanical (fractures, foreign objects, sand, etc) and Thermal agents (burns, freezing)
- Chemical agents - toxic gases, acids, bases
- Biological agents - bacteria, viruses, parasites
What are endogenous causes of inflammation?
- circulation disorders - thrombosis, infarction, hemorrhage
- metabolic products - uric acid, urea
What are the signs of acute inflammation?
- calor (heat)
- Rubor (redness)
- tumor (swelling)
- dolor (pain)
- functio laesa (loss of function)
What are the mediators of inflammation?
- pro-inflammatory cytokines (IL-1, IL-6, IL-8, TNFalpha)
- complement components
- prostaglandins
- leukotrienes
- Histamine
- platelet-activating factor (PAF)
- plasma proteases
How do prostaglandins contribute to inflammation?
- contribute to vasodilation, capillary permeability, pain and fever during inflammation
How do leukotrienes contribute to inflammation?
induce smooth muscle contraction
How do histamines contribute to inflammation?
- cause dilation and increased permeability of capillaries
How do platelet activating factor (PAF) contribute to inflammation?
induces platelet aggregation
How do plasma proteases contribute to inflammation?
- kinins (particularly bradykinin) increase capillary permeability and pain
What happens during the vascular response of inflammation?
- phase I - vasoconstriction
- phase II - active vasodilation
- phase III - passive dilation
What is included in the sequence of events of the cellular response of inflammation?
- chemotaxis - of leukocytes
- rolling - slow down leukocytes and increase their expression of adhesion molecules
- migration - into tissue spaces
- phagocytosis
What cells are the first to arrive at a site on infection?
cells of the innate immunity (neutrophils, macrophages, NK cells)
What are CAMs?
Cell adhesion molecules
What are the types of CAMs?
- selectins
- mucins
- integrins
- Ig-superfamily CAM
What are the most important selectins and what do they bind?
selecin P, L, and E
- bind carbohydrate moieties on mucin-like molecules
Where are the important selectins found?
- Selectin L is expressed on leukocytes
- Selectin P and E are expressed on the endothelium during inflammation
What are selectins responsible for?
- leukocyte interaction with the endothelium during the initial phase of inflammation
What are mucin CAMs?
group of heavily glycosylated, serine and threonine rich proteins that bind to selectins
- bind to selectins
What are integrin CAMs?
heterodimeric proteins consisting of alpha and beta chains that are covalently joined at the cell surface
- bind to Ig superfamily domains
What type of integrins do leukocytes express?
integrins with beta2 chains
What happens if there is a defficiency in beta2 integrins?
leads to immunodeficiency call leukocyte adhesion deficiency (LAD) - an autosomal recessive disease manifested by recurrent bacterial infections
- neutrophils are unable to extravasate
What do Ig-superfamily CAMs bind to?
integrins
Where are Ig-superfamily CAMs expressed?
on endothelial cells
What happens during the initiation of inflammation?
cytokines and other mediators of inflammation stimulate the endothelial cells, leading to increased expression of CAMs -> endothelial cell activation
What are the four phases of leukocyte extravasation?
- Phase I - rolling (leukocytes loosely bind to selectin E and P on endothelial cells. begins to roll on endothelium
- Phase II - activation (increase in cytokine, especially chemokine secretion. increase in chemokine receptor expression on leukocytes -> activation of leukocytes
- Phase III - Adhesion (integrins on leukocytes can now bind firmly to the endothelium)
- Phase IV - transendothelial migration or diapedesis ( leukocytes squeeze through endothelium and use homotypic binding of platelet-endothelial-cell adhesion molecule 1 on the endothelium (self-to-self binding))
What do effector lymphocytes do?
migrate to tissues where inflammation is taking place
What do helper T lymphocytes do?
migrate to areas where they first encountered antigen
