First 5 steps in the inflammatory process
1. mast cell degranulation
2. activation of coagulation cascade
3. activation of kinin cascade
4. release of
... [Show More] chemotactic factors
5.Activation of the complement cascade
Role/function in the inflammatory process: Complement
Form the membrane attack complex
bacterial lysis
vasodilation
Increased vascular permeability
triggers mast cell degranulation
chemotaxis
opsonization - opsonins tag foreign pathogens for elimination by phagocytes
Role/function in the inflammatory process: kinin
turned into bradykinin which is responsible for pain, chemotaxis and Increased vascular permeability and vasodilation
Role/function in the inflammatory process: Coagulation cascade
plays role in activating the kinin system
Factor XII (Hagemon factor) activates kinin and forms a fibrin mesh to stop bleeding and trap microorganisms
Role/function in the inflammatory process: chemotactic factors
once released attract neutrophils, eosinophils and monocytes for phagocytosis
Role/function in the inflammatory process: Neutrophils
show up at the site of injury in 6-8 hours
Neutrophils express and release cytokines, which in turn amplify inflammatory reactions by several other cell types. In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens.
Role/function in the inflammatory process: monocytes
Show up in 1-7 days
become macrophages
present antigens to the CD4 cell which leads to Tcell immunity which leads to B cell immunity
Releases IL1, IL6, TNF and growth factors
Role/function in the inflammatory process: Mast cell degranulation
triggers the activation of the acute phase reactants
This leads to the release of histamine, cytokines, leukotrienes, platelet activation factor and prostaglandins
Role/function in the inflammatory process: Histamine 1 (H1)
promotes inflammation
smooth muscles, i.e. bronchi - asthma causes bronchoconstriction
Role/function in the inflammatory process: Histamine 2 (H2)
anti-inflammatory properties
gastric mucosa
Role/function in the inflammatory process: cytokines
IL4 early in the inflammation
IL 13 later in inflammation
TNF
Role/function in the inflammatory process: leukotrienes
released when mast cell degranulates cause vasodilation
attract neutrophils, monocytes eosinophils
Singular impacts leukotrienes
Role/function in the inflammatory process: prostaglandins
released when the mast cell degranulates
produced by the arachidonic pathway
cause vasodilation, platelet aggregation, pain and fever
Role/function in the inflammatory process: platelet-activating factor
derived from fatty acids in the plasma membrane
produced by neutrophils, monocytes, endothelial and platelets
cause endothelial cell retraction, increases vascular permeability, activates platelets, enhances leukocyte adhesion to endothelial cell
Steps in the arachidonic acid pathway
Linoleic acid plus phospholipase A2 make arachidonic acid (AA)
AA plus COX1 or COX 2 make Prostaglandins
Prostaglandins from COX1 maintain homeostasis
gastric mucosa
platelet aggregation
fluid/electrolyte imbalance
Prostaglandins from COX2 assist in the inflammatory process via pain, fever
help with homeostasis via renal function
tissue repair
reproduction development
Function of arachidonic acid pathway
The arachidonic pathway is the biochemical process responsible for the synthesis of prostaglandins (See concept map).
It is made from linoleic acid which is part of the phospholipid cell membrane.
COX2 note of caution
While COX2 inhibitors block the inflammatory function of prostaglandins, they can also impair renal function.
NSAIDS
inhibit both COX1 and COX2 prostaglandin synthesis
Risk: gastric ulcerations, GI bleeds, bleeding, edema, renal impairment
Aspirin
blocks both COX1 and COX2
also inhibits Thromboxane A2 and prostaglandins
Corticosteroids
inhibit the action of phospholipase A2 thus preventing the formation of prostaglandins, thromboxane A2 prostacyclin and leukotrienes
Phagocytic Cells
neutrophils, macrophages, dendritic cells
Macrophages
derived from monocytes, which leave the blood stream and differentiate in tissues
dendritic cells
specialized white blood cells that engulf antigens in the epithelia of the skin, GI and respiratory tracts
Organs of the immune system
bone marrow, thymus gland, spleen, lymph nodes, tonsils, peyer patches
Antigen Presenting cells
Include dendritic cells, macrophages and B cells.
Ingest and process antigens
natural killer cells (NK cells)
pursue diseased cells (such as those infected by viruses or cancer)
T lymphocytes (T cells)
cell-mediated immunity
CD4 cells (aka T-helper) T4 cells
[f] activate macrophages, B-cells, cytotoxic T-cells, other CD$ cells
Release lymphokines
mediate delayed hypersensitivity reactions (i.e. TB skin test) [Show Less]