Acute and chronic inflammation

Question 1

Name an example of a cell-derived and plasma derived immune activation?

Answer 1

Histamine is a cell derived
- Cell-derived can be either be preformed, such as with histamine, or be newly created molecules, such as with prostaglandins and leukotrienes.

Plasma derived is the complement system.

Mast cells produce histamine, prostaglandins and leukotrienes

Question 2

What is the function of histamine and what cells produce it?

Answer 2

Histamine is produced by mast cells, basophils and platelets and it causes vasodilation, increased vascular permeability and endothelial activation.

Question 3

What are the functions of prostaglandins and what cells produce it?

Answer 3

Mast cells, endothelial cells and leucocytes produce prostaglandins. They cause vasodilation, pain and fever

Question 4

What are the functions of leukotrienes and what cells produce them?

Answer 4

Mast cells and leukocytes produce leukotrienes. Their function is increased vascular permeability, chemotaxis, leukocyte adhesion and activation

Question 5

What is the function of TNF?

Answer 5

Leukocyte recruitment, endothelial activation, leukocyte activation, systemic acute phase response (IL-1 also does these)

TNF regulates energy balance by promoting lipid/protein catabolism and suppressing appetite. This causes cachexia

TNF antagonists are used for the treatment for chronic inflammatory conditions, such as rheumatoid arthritis

Question 6

Describe how the metabolites of arachidonic acid are created, what their functions are and what medications can interfere with this process?

Answer 6

p71,72

Question 7

What is the process of leukocytes entering tissues?

Answer 7

1) Margination - slowing of the blood flow because of vasodilation causes the cells to settle towards the vessel wall
2) Rolling - the interaction between the selectins on the endothelial cells and the integrins on the leukocytes causes the rolling of the leukocyte
- Integrin in the low affinity state causes rolling
3) Firm adhesion causes the leukocytes to stop
- Chemokines cause the integrin to shift to the high-affinity state.
4) Transmigration (diapedesis)

Question 8

What actually destroys microbes intracellularly?

Answer 8

1) ROS
2) NO
3) Lysosomal enzymes

In neutrophils, NADPH is oxidised by phagocyte oxidase and in the process reduces oxygen to superoxide. This is then converted to H2O2.

In neutrophils, myeloperoxidase converts H2O2 and Cl- into hypochlorite (OCl2-), which is like bleech.

NO is produced by nitric oxide sytnthase. In macrophages, NO reacts with superoxide to produce the free radicle ONOO-

Question 9

What is the process of complement?

Answer 9

p76

Question 10

What are the possible outcomes of acute inflammation?

Answer 10

1) Complete resolution/regeneration
2) Healing by connective tissue replacement (scarring or fibrosis) - may have loss of function
3) Chronic inflammation

Question 11

What are the morphologic patterns of acute inflammation?

Answer 11

1) Serous inflammation - “effusion’
2) Fibrinous inflammation
3) Purulent (suppurative) inflammation - can be an abscess
4) Ulcers

Question 12

What morphologic features are associated with chronic inflammation?

Answer 12

Infiltration with mononuclear cells, including lymphocytes, macrophages and plasma cells

Tissue destruction, either by the offending agent of by the inflammatory cells

Attempts at healing by fibrosis and angiogenesis.

Question 13

What cytokine generates alternatively activated macrophages and what is their main function?

Answer 13

IL-4 and IL-13 generate lymphocytes (INF-gamma stimulates classically activated macrophages)

Their main function is in tissue repair. They secrete growth factors that promote angiogenesis, activate fibroblasts and stimulate collagen synthesis

Question 14

What are the three main types of CD4 T cells, the cytokines they produce and their functions?

Answer 14

Th1 - IFN-gamma, which activates macrophages by classical activation

Th2 - IL-4, IL-5 and IL-13. They activate macrophages via the alternative pathway- Recruit and activate eosinophils
- Defense against helminth parasites and allergic inflammation

Th17 - IL-17 and other cytokines, which induce the secretion of chemokines responsible for recruiting neutrophils into the reaction

Question 15

What causes a mast cell to release histamine?

Answer 15

The Fc region of an IgE antibody binds to the receptor of a mast cells. When this antibody binds a specific antigen, degranulation occurs

Question 16

How is a fever generated?

Answer 16

Substances that induce fevers are called pyogens.

Prostaglandins produced in the vascular and perivascular cells of the hypothalamus cause fevers.

Bacterial proteins, such as LPS, stimulate leukocytes to release cytokines such as IL-1 and TNF. These increase the function of the cyclopxygenase enzymes that convert aracodonic acid into prostaglandins. In th hypothalamus, the prostaglandins, especially PGE2, stimulate the production of neurotransmitters that reset the temperature set point at a higher level.

NSAIDs reduce fever by inhibiting COX

Question 17

What are the main acute phase proteins and what do they do?

Answer 17

CRP and serum amyloid A protein act as opsonins.

Fibrinogin binds to RBCs and reduces their charge allowing RBCs to bind together and increasing their erythrocyte sedimentation rate

Hepcidin reduces the availability of iron and is responsible for the anemia associated with chronic inflammation

Question 18

What is SIRS?

Answer 18

Systemic inflammatory response syndrome. It is similar to septic shockbut of a non-infectious response, such as severe burns, or pancreatitis.

Question 19

What are some features of sepsis?

Answer 19

Disseminated intravascular coagulation, hypotensive shock, and metabolic disturbances, such as insulin resistance and hyperglycaemia