What is inflammation?
complex reaction to tissue injury -involves alteration to epithelial cells - recruits WBC -always lead to at least some tissue damage
What is inflammation usually linked to ?
elimination of microbial cause and repair of damaged tissue
What are three different categories of inflammation?
What is acute inflammation?
- initial response to tissue damage regardless of cause - recruit neutrophils (infiltrate)
What is chronic inflammation?
if acute cannot clear infection - more mononuclear (lymphocyte or monocyte)cells will infiltrate
What is allergic inflammation?
kind of response associated with allergies (hay fever, allergic rhinitis) -mucosal tissue - eosinophils (and mononuclear cells)
What are some autoimmune diseases?
What are the components of inflammatory response?
Connective tissue cells: - mast cells - macrophages - everywhere connective tissue matrix - elastic fibers, collagen fiber proteoglycan
Where are mast cells commonly found?
mucosal subepithelial skin
What are the common processes in inflammation?
-release of inflammatory mediators
-increased vascular permeability
- up-regulation of adhesion molecules on endothelial cells and leukocytes
-diapedesis, chemotaxis, and acivation of leukocytes
What are the cardinal signs of inflammation?
Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Functio (loss of function)
What are the causes of the cardinal signs of inflammation?
redness , warmth >>> erythema due to vascular dilation, increased blood flow
swelling >>> extravasation of plasma
-leukocyte accumulation at site of injury
pain >>> kinin stimulation of nerve fibers
What are inflammatory stimuli?
physical and chemical agents
immune hypersensitivities (fight against own body)
What about the stimulus leads to the response?
microorganisms have PAMPs that are detected by PRR(pathogen recognition receptors on every cell) - once recognized, damaged cells release DAMPS (damage-associated molecular pathogens) which are recognized by DRR (damage recognition receptors)
What interaction releases inflammatory mediators??
DAMPS also interact with PRR or DRRs to release inflammatory mediators
interaction of PAMPS with PRRS leads to the production of mediators by variety of cells.
What happens in a capillary when inflammation is occurring?
stimulus causes the endothelial cells to constrict to cause a gap (vasodilation) to release antibodies, complement components, platelets
What are some vasoactive mediators?
eicosanoids (PG, TX)
The upregulation of adhesion molecules will result in ?
*P-selectin - rolling (neutrophils, monocytes, lymphocytes)
*E-selectin - rolling & adhesion (neutrophils,monocytes, Tcell)
*ICAM-1 - (intercellular adhesion molecule for leukocytes) - attaches to LFA-1 *VCAM - adhesion of eosinophils, monocytes, lymphocytes -attaches to VLA4
*PCAM - expressed on both leukocyte and endothelium
Where does Sialyl-Lewis x-modified glycoprotein attach?
What are chemo attractant substances?
What is diapedesis?
outward passage of blood cells through intact vessel walls
What are the cellular sources of inflammatory mediators?
tissue macrophages and dendritic cells
What inflammatory mediators are produced by the liver?
Factor XII activation
-C3a - anaphylatoxins
-C5a - anaphylatoxins
-C5b-9 - MAC
Review 3 complement activation pathways.
Alternate - microbe
Classical - antibody
Lectin - mannose binding lectin
Plasma protein system interacts between?
What pathways does the Hagemna factor activate?
Actions of eicosanoids
Vasoconstriction - Thromboxine A2
leukotrienes C4, D4, E4
Vasodilation - PGI1, PGE1, PGE2, PGD2
Increased vascular permeability - leukotrienes C4, D4, E4
Chemotaxis, leukocyte adhesion - leukotriene B4, HETE, lipoxins
What are the roles of cytokines in inflammation?
IL1 - numerous
TNF-a - numerous
IL-6 induces release of acute phase proteins from liver
IL-17 - leads to neutrophil production from bone marrow and neutrophil act.
IL2 - activation of Tcells
IFN-gamma - activation of macrophages
Recruitment of mononuclear cells and eosinophils -CC Chemokines
neutrophil recruitment - CXC chemokines
Which cytokines are pro-inflammatory?
IL-1 - numerous; activates endothelial, upregulates expression of adhesion molecules
TNF-alpha - numerous; activates endothelial, upregulates expression of adhesion molecules
IL-6 - induces release of acute phase proteins from liver
IL-17 - (TH17) ultimately leads to neutrophil production from bone marrow and neutrophil activation
IL-2 - activation of Tcells
IFN-gamma - (TH1) activation of macrophages
What is IFN- gamma responsible for?
activation of macrophages
What does IL-17 lead to?
ultimately leads to neutrophil production from bone marrow and neutrophil activation
What does IL-2 activate?
T cells (not needed in acute response)
What does IL-6 induce?
induces release of acute phase proteins from liver
What do CC chemokines recruit?
mononuclear cells and eosinophils
What are the acute phase effects of IL-1 and TNF?
***Hemodynamic effect (shock)
What are the endothelial effects of IL-1 and TNF?
increased leukocyte adherence
increased PGI synthesis
increased procoagulate acivity
decreased anticoagulative activity
Increased IL1, IL8, IL6 PDGF
Compare Acute, Chronic, and allergic inflammation
Duration short longer
Time frame fast response slower
Type of infiltrating cell neutrophil monocyte/lymphocyt
use of ICAM vs. VCAM
What are the stages of inflammation pathologically?
Look at slide for granuloma formation
slide -round in appearance
What happens in chronic inflammation?
1. Acute inflammation with upregulation of chemokine, adhesion molecules
2. TH1 cells release IFN, TNF, IL-2, RANTESq
What attracts mononuclear cells?
CC Chemokines -CCL2 - CCl3 - CCL4 -CCL5
What is an allergic inflammation?
reaction to harmless proteins (grass, cockroach crap)
Which cell is harmless protein presented to?
Which IL causes change in B cell?
What happens when the mast cell degranulates?
cytokine breaks down arachanodonic acid
Table 2–1 Features of Acute and Chronic Inflammation
First curve - edema
Second curve - neutrophils (acute)
Third curve - macrophages (chronic)