mechanisms of inflammation Flashcards
Acute inflammation
from tissue damage and/or infection
immediate response beginning within minutes of tissue insult
predominant infiltrating cell type - neutrophil
Inflammation
complex rxn following infection, trauma or noxious agents involving vascular alterations and migration of leukocytes
eliminates microbes and repairs damaged tissues
Excessive tissue damage can occur
Chronic inflammation
often follows unresolved acute inflammation
days after acute inflammation
infiltrating cell type: mononuclear - monocyte derived macs, T cells, rarely B cells
Allergic inflammation
allergens
follows allergen mediated degranulation of mast cells
infiltrating cells - Eosinophils and mononuclear cells - T cells and Macs
Examples of autoimmune diseases
Rheumatoid arthirits
Lupus
Type 1 diabetes
Inflammatory diseases that are not autoimmune or infectious
Asthma
Alzheimer’s
Psoriasis
Atherosclerosis
where are Mast cells found?
Mucosal sub epithelia
Skin
General process of Inflammation
Stimulus Release of inflammatory mediators Increased vascular permeability upregulation of adhesion molecules on endothelial cells and leukocytes attraction and activation of leukocytes Phagocytosis or other effector functions
Cardinal signs of inflammation
Cellulitis Rubor - redness Tumor - swelling Calor - Heat Dolor - Pain Functio - loss of function
Causes of cardinal signs of inflammation
Vascular dilation - slows and increases blood flow
Extravasion of plasma - Edema, swelling
Leukocyte accumulation at site of injury
Kinin stimulation of nerve fibers - pain
molecular basis of inflam stimuli
Microbial PAMP are detected by PRR (TLR) on resident tissue cells.
these cells release pro-inflammatory cytokines
Damaged cells release “warning” chemicals (damage associated molecular patterns) detected by DRR on tissue Macs, DCs and other tissue cells
Where are PRRs?
On the surface of cells and inside cells as well
Vasodilation and increased vascular permeability happen
together
Upon vasodilation, proteins leak out, name some
cytokines
antibodies
complement
clotting factors
Increased vascular permeability
Endothelial cell constriction allows gaps to open up so plasma, proteins and cells can enter tissues
Briefly describe the process of Leukocyte migration through blood vessels
Activation and attraction by inflammatory cytokines of lymphocytes Rolling of lymphocytes Adhesion of lymphocytes Arrest Transmigration
P-selection
Rolling of neutrophils, monocytes, lymphocytes
E-selectin
Rolling, adhesion to activated endothelium - neutrophils, monocytes, T cells
ICAM-1
Adhesion, arrest, transmigration - all leukocytes
VCAM-1
adhesion of eosinophils, monocytes and lymphocytes
CD31(PECAM)
Leukocyte migration through endothelium
What mediators does the Liver contribute to the inflammatory response?
Factor XII - Kinin and coagulation system
Complements
Activation of Hageman Factor (FActor XII) leads to
activation of the Kinin, complement and clotting cascade
IL-1 and TNF-a
Activate endothelial cells to constrict and up regulate adhesion moleucles
Eicosanoids for vasoconstriction
Thromboxane A2
Leukotrienes C4, D4, E4
IL-6
induces release of acute phase proteins from liver
CC chemokines
recruitment of mononuclear cells and eosinophils
MIP, MCP, RANTES eotactin
CXC chemokines
involved in neutrophil recruitment
IL8
IL-17
leads to neutrophil production from bone marrow and neutrophil activation
IL-2
activation of T cells, T cell proliferation
IFN-gamma
from Th1 cells
activates Macs
Mononuclear cells
Monocyte/Macs and lymphocytes
Type of Chronic inflammation
Granuloma formation
seen in TB
Histologically, see Multinucleated Giant cells
round in appearance
What are some sources for inflammatory mediators?
Tissue macrophages, dendritic cells
Mast cells
Leukocytes
Endothelial cells
What stimulates the alternative pathway to inflammation?
C5a, C3a
What stimulates the classic pathway to phagocytosis?
C3b
What stimulates the lectin pathway to lysis of the cell?
MAC formation
What are the three interaction cascades of plasma protein systems?
Clotting
Kinin
Complement
What do all three plasma protein cascades lead to?
Inflammation
What eicosanoids cause vasoconstriction?
Thromboxane A2, leukotrienes C4, D4, E4
What eicosanoids cause vasodilation?
PGI2, PGE1 and 2, PGD2
What eicosanoids cause inc vascular permeability?
Leukotriene B4, HETE, lipoxin
What eicosanoids cause chemotaxis, leukocyte adhesion?
Leukotriene B4, HETE, lipoxin
What are the events for inflammatory mediators?
Fever Pain Vasodilation Inc vascular permeability Attraction of leukocytes Activation of endothelium
What are the chemokines involved in recruitment of monouclear cells into sites of inflammation?
CCL2 (MCP-1)
CCL3 (MIP-1a)
CCL4 (MIP-1b)
CCL5 (RANTES)
Eosinophils and mononuclear cells characterize the;
Infiltrate in allergic inflammation
What are the steps of the inflammatory process in allergic reactions?
Stimulus
Secretion from inflammatory mediators (mast cells)
Vasodilation (histamine)
Inc vascular permeability (TNF and arachidonic acid)
Up-regulation of adhesion molecules to VLA-4
Diapedesis, chemotoxis and activation of leukocytes
What are acute inflammatory disease?
ARDS Acute transplant rejection Acute asthma attack Glomerulonephritis Septic shock Vasculitis
What are chronic inflammation diseases?
Arthritis
Atherosclerosis
Chronic lung disease
Chronic transplant rejection
What are allergic inflammation diseases?
Asthma
Atopic dermatitis
