Acute phase reaction

Question 1

Acute phase reaction is considered to be a local or systemic response?

Answer 1

Systemic

Question 2

What are acute phase proteins?

Answer 2

Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response).

In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages) secrete a number of cytokines into the bloodstream, most notable of which are the interleukins IL1, IL6 and IL8, and TNFα. The liver responds by producing a large number of acute-phase reactants. At the same time, the production of a number of other proteins is reduced; these are, therefore, referred to as “negative” acute-phase reactants. Increased acute phase proteins from the liver may also contribute to the promotion of sepsis

Question 3

What are negative acute phase reactants? can you name some?

Answer 3

“Negative” acute-phase proteins decrease in inflammation.

Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin.

The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing “positive” acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptors, but the latter does not appear to change with inflammation.

Question 4

What are positive acute phase reactants? can you name some?

Answer 4

Positive acute-phase proteins serve (part of the innate immune system) different physiological functions for the immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding protein, complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin. Others give negative feedback on the inflammatory response, e.g. serpins. Alpha 2-macroglobulin and coagulation factors affect coagulation, mainly stimulating it. This pro-coagulant effect may limit infection by trapping pathogens in local blood clots. Also, some products of the coagulation system can contribute to the innate immune system by their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells.

Question 5

Name an acute phase protein that are commonly used in diagnostics of inflammation? what is its function and what increase its secretion?

Answer 5

C-reative protein. Opsonin on microbes

Increases following interleukin-6 secretion by macrophages and T cells

Question 6

3 major cytokines are released in acute inflammation, which?

Answer 6

IL1, IL 6 and TNFa

Question 7

what are the systemic effects of IL1 IL6 and TNFalpha

Answer 7

liver- Acute phase proteins- CRP, SAP, Mannose binding protein, fibrinogen.

To be more precise- positive are C3, Bf, coeruloplasmine –1.5-2X

a1antitrypsin,
haptoglobulin, 2-4 X
fibrinogen

C1inhibitor- 6-8X

CRP, SAA -100- 1000X !!!!!

decrease-
transferrin,
albumin, fibronectin
0.4- 0.6 X

from bone marrow- neutrophil mobilization-> phagocytosis.

From hypothalamus- increase in body temp
from Fat and muscle- protein and energy mobilization to generate increased body temperature.

Question 8

functions of various apps

Answer 8

The transcription and secretion of APP’s are upregulated when
the liver are exposed to inflammatory mediators
o Fibrinogen synthesis increases, which will result in more
effective blood clotting
o The C-Reactive Protein (CRP) are secreted in huge
amounts and are very important due to their function as
opsonins, enabling them to increase the phagocytosis of
bacteria’s and autoantigens
 Keep in mind that is has been discovered that high
levels of CRP is a greater risk factor for the
development cardiovascular diseases than high
cholesterol levels
o Another group of proteins whose expression is upregulated are the protease
inhibitors like α2-macroglobulin (A2M), α2-acid-glygoprotein (AGP) and α1-
antitrypsin (AAT), whose expression inhibits the function of various protease
enzymes
 As we mentioned earlier, activated lymphocytes will express various
proteases which helps with their extravasation by degrading tight
junctions between endothelial cells, however, these proteases can also
act in the ECM which leads to tissue desctruction
 This kind of tissue destruction is inhibited by the release of the AP
protease inhibitors
o Other APP’s include antioxidants like ceruloplasmin, heptoglobin (inhibits
macrophage activation) as well as some complement components like C3 and
C1- inhibitors, all of which functions to inhibit the inflammatory reaction
o Some APP’s are carrier proteins, like haptoglobin (binds haemoglobin) and
Serum Amyloid a protein (SAA, binds cholesterol)
 Collectively, the various mechanisms of these APP’s functions to silence the
inflammatory response, which limits tissue damage brought upon by the inflammation