Chemical Mediators of Inflammation I

Question 1

What are some categories of non-neoplastic causes of abnormal signs and symptoms in a patient?

Answer 1

Developmental, traumatic, degenerative, infectious, inflammatory, vascular, toxic-metabolic, others

Question 2

What is the sequence of events from irreversible cell damage to repaired tissue?

Answer 2

Irreversible injury -> Necrosis -> Vasodilation (heat, redness, swelling) -> Acute Inflammatory Phase -> Chronic Inflammatory Phase -> Repair Phase (Firbroblasts, endothelial cells) -> Repaired Tissue

Question 3

How do cells communicate without synapses?

Answer 3

Local, short range communications: Autocrine and paracrine signaling; Systemic, long range communications: Endocrine-like. Receptor mediated.

Question 4

How are mediators synthesized?

Answer 4

Chemical mediators can be synthesized in advance - preformed and stored in secretory vesicles (histamine, serotonin, substance P, enzymes (in cytoplasmic granules)) Mediators may also be synthesized as needed in response to stimuli. Most are synthesized as needed.

Question 5

What sources of mediators are there?

Answer 5

Mediators may be derived from local cells - inflammatory, endothelial, epithelial, fibroblasts. They may be derived from the liver through the plasma - coagulation factors, kinins, complement, acute phase proteins. They may also come from exogenous sources - bacterial lipopolysaccharides, endotoxins, or simple tissue debris.

Question 6

What stimulates the release of chemical mediators?

Answer 6

Chemical mediators are released in response to alterations in homeostasis/innate immunity. They may be caused by microbes and their breakdown products, cellular breakdown products (necrotic cells), or by complement, coagulation, and kinin system components.

Question 7

What physiologic effects do chemical mediators have?

Answer 7

1 - Vessel effects (dilation, constriction, permeability) 2 - Inflammatory cell effects (chemotaxis, activation) 3 - Bronchial smooth muscle effects (constriction) 4 - Tissue/microbe damage 5 - Physiologic/systemic effects (pain, fever, acute phase reaction)

Question 8

Which chemical mediators are preformed by inflammatory cells and held in their granules?

Answer 8

Histamine (Mast cells, basophils, platelets); Serotonin (Platelets); (Both histamine and serotonin are vasoactive amines.) Lysosomal Enzymes (Neutrophils, macrophages)

Question 9

What chemical mediators are synthesized when needed by inflammatory cells?

Answer 9

Prostaglandins, leukotrienes, platelet activating factors, activated oxygen species, nitric oxide (macrophages), cytokines

Question 10

Where are vasoactive amines found and what is the immediate reaction they cause?

Answer 10

Vasoactive amines include histamines and serotonin (acts much like histamine). They are found in the granules of Basophils circulating in the blood, and in platelets. They cause vasodilation, vascular leakage, and smooth muscle spasms (think anaphylaxis).

Question 11

What is the process by which histamine is released by the cells in asthma?

Answer 11

A trigger (pollen) activates a T-cell, which activates an IgE producing B-cell, causing the release of IgE. IgE binds to receptors on mast cells, stimulating release of histamine and causing systemic smooth muscle spasms, epithelial damage, and mucous production. Histamine is inactivated by histaminase to end the reaction.

Question 12

What molecules are eicosanoids, and what roles do they play?

Answer 12

Lipid based signaling molecules derived from archidonic acid (20 C acid, eicosa = 20). They are the prostaglandins PG, leukotrienes LT, thromboxanes TX, and lipoxins LX. They are mediators and signaling molecules.

Question 13

What is Platelet Activating Factor, what sources does it have, and what are its actions?

Answer 13

PAF is a phospholipid which comes from platelets, neutrophils, basophils, mast cells, macrophages and endothelial cells. It works to stop bleeding through activation of platelets, vasoconstriction (at low concentrations it causes dilation and permeability), chemotaxis, bronchospasm, and neutrophil oxidative burst.

Question 14

What are reactive/activated O2 species, what are their sources, and what are their effects?

Answer 14

ROS are all constituents of the NADPH oxidase system. They are the superoxide anion, hydrogen peroxide, hydroxyl radical, or reactive nitrogen species (when ROS react with NO). They are produced by leukocytes or endothelial cells. They cause microbe damage, collateral tissue damage, and inactivation of antiproteases. They are inactivated by proteins produced by the liver.

Question 15

What types of NO species are there and where are they sourced from?

Answer 15

All NOs are formed from L-arginine by NO Synthase. nNOS from Neural Parenchymal cells - vasodilation, neurotransmitter release. iNOS from endothelium, smooth muscle, macrophages - vasodilation, chemotaxis, toxic to microbes. eNOS from endothelial cells - vasodilation, reduces platelet/leukocyte adhesion

Question 16

What are the types of cytokines?

Answer 16

TNF, IL-1, IFN. Peptides and polypeptides produced by macrophages, lymphocytes, endothelial cells, and maybe others.

Question 17

What is TNF, where is it from, and what effects does it have?

Answer 17

Tumor Necrotic Factor. Principally produced by activated macrophages, and also by lymphocytes and mast cells. Made in response to bacteria, immune complex, tissue damage, tumors. Functions locally in endothelial activation, fibroblast stimulation, activation of PMNs, acute phase reactions. Systemic functions include fever, anorexia, sleeplessness, up regulates liver production of many factors (C-reactive protein, etc.)

Question 18

What are interleukins, where are they sourced, and what effects do they have?

Answer 18

Interleukins (IL1, IL2…IL8, etc.) are cytokines, principally from macrophages, They function similarly to TNF. Individual ILs stimulate or activate different leukocytes.

Question 19

What are interferons, where are they sourced, and what effects do they have?

Answer 19

Interferons are glycoproteins produced by T-cells (helper and cytotoxic). They activate inflammatory cells and interfere with viral replication.

Question 20

What are chemokines, where are they sourced, and what effects do they have?

Answer 20

Chemokines are small proteins, expressed transiently or constitutively by many inflammatory cells. They mainly function in chemotaxis and in controlling the migration of cells in and out of tissue.

Question 21

What cytokines are involved in acute inflammation? In chronic inflammation?

Answer 21

Acute inflammation involves: TNF, IL-1, IL-6, Chemokines. Chronic inflammation involves: IL-12, IL-17, IFN-g.

Question 22

What is stored mediator content, where is it sourced, and what effect does it have?

Answer 22

Stored mediator content is a collection of a huge variety of enzymes released by macrophages and neutrophils. They are used in the digestion of microbes or foreign material, but also can cause collateral damage. Can be controlled by anti-proteases.