Lecture 4 Part 1 - inflammatory Mediators

Autocrine

cells that made mediator effected

Paracrine

mediator effects neighbor cells

Endocrine

mediators effect distant cells

Pleiotropic

more than one function

redundant

similar effects

synergistic

act in concert to create different effects

antagonistic

inhibits the action of other mediators

cascade effect

production stimulated by other mediators

stereotypic response

not antigen specfic

What characterizes inflammatory mediators?

distributed widely in early stages of inflammation to act locally, rapidly inactivated locally and vary in chemical structure and species

What is the effect of inflammatory mediators on leukocytes?

Chemotaxis and modulation of function

What are local and systemic effects of inflammatory mediators?

pain, fever, tissue damage

What are the vascular effectws of inflammatory mediators

vasodilation, vasoconstriction, vascular permeability, endothelial effects on leukocyte migration

What are the two types of inflammatory mediators?

cellular or plasma (liver)

What types of inflammatory mediators are in plasma?

acute phase proteins, kinines, coagulation factors, complement proteins

Two acute phase proteins that are negatively decreased during inflammation covered in class

albumin and transferrin

We see major changes in compliment reactive protein during inflammation in which species?

Canine

Cats and horses show a major increase in which acute phase protein during inflammation?

Serum amyloid a (SAA)

What does the kinin-kallikrein system tell the body to do?

Slow down to heal, by producing sustained rubor, calor and dolor

Classical pathway for complement cascade

Activated via antigen-antibody complexes

Lectin pathway for compliment cascade

activated via MBL-MASP complexes, which detect PAMPs

Alternate pathway for complement cascade

Activated via spontaneous C3 hydrolysis, a self amplication loop

What happens during a complement cascade?

C3 is cleaved into C3a and C3b. C3a recruits neutrophils and monocytes while C3b tags bacteria for opsonization and phagocytosis as well as cleaving C5

What happens after C3 cleaves C5 in a compliment cascade?

C5 splits into C5a, where it recruits neutrophils and monocytes. Cb triggers the membrane attack complex

What are the main functions of complement?

Opsonize bacteria, enhance inflammatory response, lysis cells

What is opsonization?

Complement coats bacteria for ingestion by neutrophils

How does complement enhance the inflammatory response?

chemotactic for neutrophils and other WBC and increases vascular permeability

What complements form the MAC?

C5b, C6, C7, C8, C9

What two cellular mediators serve as vasoactive amines?

Histamine and serotonin

What is derived from arachidonic acid?

Eicosanoids

What do vasoactive amines do?

Dilate arterioles and increase vascular permeability

What may not work in ruminants as well as other animals? Why?

Antihistamines, because ruminants primarily used serotonin as a vasoactive amine

Which eicosanoid is responsible for house keeping and protects the GI?

COX-1

Which eicosanoid is responsible for inflammation and neoplasia?

COX-2

What produces platelet activationg factor?

inflammatory and endothelial cells

Reactive oxygen species are released by what? What can they do?

Damaged cells, damage cells around them

What is a cytokine?

small protein produced by nucleated cells, important for cell to cell communication

Type 1 interferons (IFN-A andFN-B )are cytokines that do what?

Inhibit RNA effects and protein trafficking for viruses and stimulated antiviral immune responses

Type 1 (IFN-a and IFN-B) are produced by what cell types? are they pro and anti-inflammatory

all cell types, proinflammatory, triggered by PAMPs

Type II interferons (IFN-Y) are made by what cells? What do they do?

Made by NK and cytotoxic T lymphocytes, they induce Fc and C3b receptors and activate macrophages and induces NO to help with phagocytosis

Interleukins do what? Are they pro or anti inflammatory?

Made by one leukocyte to talk to another leukocyte, can be anti or proinflammatory