Acute & Chronic Inflammation Flashcards
List and describe the five cardinal signs of inflammation.
Redness: rubor
Swelling: tumor
Heat: calor
Pain: dolor
Fifth sign: Loss of function
List and describe the key stimuli for acute inflammation.
INFECTIONS - Receptors recognize microbes and microbial products, triggering signaling pathways
TISSUE NECROSIS - Ischemia, trauma, chemical or thermal injury, irradiation lead to release of molecules from dead cells which elicit the inflammatory response
FOREIGN BODIES - Splinters, dirt, sutures elicit inflammation and carry microbes
IMMUNE RXNS (hypersensitivity)
–Normally protective immune system damages the individual’s own tissues.
–can be directed against self antigens (autoimmune diseases) or can be excessive reactions against environmental substances or microbes
List and describe the three major components of the acute inflammatory response.
- -Alterations in vascular caliber that increase blood flow
- -Structural changes in the microvasculature that allow plasma proteins and leukocytes to leave the circulation
- -Emigration of leukocytes from the microcirculation, accumulation at the site of injury, and removal of the offending agent
What can lead to increased blood flow in the case of inflammatory response?
Vasodilation: results in increased blood flow; induced by several mediators, including histamine, NO (nitric oxide), and prostacylin, which act on vascular smooth muscle
What changes in microvasculature might allow plasma proteins and leukocytes to leave circulation?
- -Histamine, NO, 5H-T, etc. –> constriction of endothelial cells –> increased interendothelial spaces
- Sunburn, etc. –> Endothelial injury, with endothelial necrosis and detachment (direct or neutrophil mediated)
- -Increased transport of fluids and proteins (trancytosis)
List and describe the three key steps involved in extravasation of neutrophils
- Leukocyte adhesion to endothelium (margination, rolling, and adhesion)
- -Margination (leukocytes in a peripheral position) occurs secondary to the effects of stasis
- -Adhesion of leukocytes to the endothelium is mediated by complementary adhesion molecules on the two cell types, enhanced by secreted proteins called cytokines. - Leukocyte migration through the endothelium and into the extracellular space (called transmigration or diapedesis). Mediated by chemokines. Once in the connective tissue, leukocytes adhere to the extracellular matrix where needed.
- Chemotaxis of leukocytes: driven by [bacterial acctractants] & components of the complement system (arachadonic acid metabolites)
Discuss the mechanisms by which leukocytes recognize microbes and dead tissue, and remove offending agents.
Leukocytes have receptors (TLR’s) that recognize external stimuli; once bound to these receptors, activating signals are delivered to the leukocyte. These receptors include:
- G protein coupled receptors
- Receptors (Fc & C3) for opsonins; anitbodies & complement factors to coat microbe for phagocytosis.
- Receptors for cytokines: IFN-gamma is the major macrophage-activating cytokine secreted by NK cells and by anitgen activated T-lymphocytes.
What are the two steps to removing offending pathogens?
Phagocytosis and engulfment: Mannose receptors, scavenger receptors, and receptors for various opsonins (IgG & C5a) function to bind and ingest microbes, leading to engulfment of the particle into a phagosome, which then fuses with a lysosomal granule, resulting in a phagolysome.
-Killing and degradation within the neutrophil or macrophage is the final step; microbial killing is accomplished largely by reactive oxygen species (ROS) and reactive nitrogen species (mainly derived from NO), generated within the phagolysosome. This requires a rapid oxidative reaction, called the respiratory or oxidative burst.
Explain the key cell derived mediators of the inflammatory response.
cell derived mediators are often sequestered in intracellular granules which can be rapidly released by exocytosis.
- Histamine: Release from mast cell degranulation causes dilation of arterioles and increased vessel permeability.
-Serotonin: Primarily found in platelets, with similar actions to histamine; released when platelets aggregate (clotting)
Arachidonic Acid (AA) metabolites: Stimulated cells can convert membrane-bound arach. acid into prostaglandins and leukotrienes.
*Prostaglandins are produced by many cell types, including mast cells, macrophages, and endothelial cells. They are involved in the vascular response of inflammation but also mediate the systemic reaction (pain and fever).
*Leukotrienes are primarily secreted from leukocytes and have chemoattractant and vascular effects. The cysteinyl-containing leukotrienes cause vasoconstriction and bronchospasm.
*Lipoxins are generated from AA and inhibit inflammation.
Explain the key cell derived mediators of the inflammatory response (Ctd).
Platelet aggregating factor (PAF):elicits most of the vascular and cellular reactions of inflammation, vasoconstriction, bronchospasm, and platelet aggregation. Reactive oxygen species (ROS): Nitric Oxide (NO): From endothelial cells --> vasodilation; NO-derived free radicals are microbicidal (and can also damage host cells) Cytokines: Key cytokines involved in inflammation include tumor necrosis factor (TNF) and interleukin-1 (IL-1).
Explain the key cell derived mediators of the inflammatory response (Ctd, ctd).
Chemokines: proteins that act as chemoattractants for specific leukocytesleukocytes (neutrophils, monocytes, eosinophils, basophils, lymphocytes)
Lysosomal constituents of leukocytes:
Neuropeptides: an initiate and propagate the inflammatory response (substance P). Along w/ prostaglandins and cytokines, can also produce pain.
Explain the key protein derived mediators of the inflammatory response
Complement system: Complement proteins on microbial surfaces lead to 1) Inflammation 2) Phagocytosis or 3) Cell lysis
Coagulation and Kinin systems: involved in blood clotting, which is often intertwined w/ inflammation. Products of the clotting system that can be mediators of the inflammatory response include:
- -Bradykinin, C3a, C5a: mediators of increased vascular permeability.
- -C5a: mediator of chemotaxis
- -Thrombin:
List and describe the three outcomes of the acute inflammatory response.
- Complete resolution: removal of cellular debris and microbes by macrophages, and resorption of edema fluid
- Healing by connective tissue replacement (fibrosis): connective tissue grows into the area of damage or exudate, converting it into a mass of fibrous tissue (this process is also called organization)
- Progression of the acute inflammatory response to chronic inflammation
List and describe the types of conditions or situations that give rise to chronic inflammation.
Persistent infections: viral, mycobacterial, fungal; may get a granulomatous reaction
- Immune-mediated inflammatory disease: autoimmune diseases, allergic diseases
- Prolonged exposure to toxic agents, exogenous or endogenous: e.g. silicosis, atherosclerosis
List and describe the cell types and key functions of the cells involved in chronic inflammation.
- Macrophages: the products of activated macrophages eliminate injurious agents and initiate the process of repair, and are responsible for much of the tissue injury in chronic inflammation. in chronic inflammation, macrophages persist.
- Lymphocytes: T’s and B’s migrate into inflammatory sites via intx’n w/ adhesion molecules and chemokines. T’s and mac’s intx bidirectionally, so that once the immune system is involved, the inflammation tends to be chronic and severe.
- Plasma cells: Develop from mature B’s & yield antibodies directed towards pathogen or self antigens
- Eosinophils: Mediated by IgE. Release granules that contain protein toxic to parasites but also causes lysis within mammal epith cells. Contribute to tissue damage in allergies.
- Mast cells: Bind to IgE antibodies w/ their Fc receptors. Degranulization –> release his & prost.
