Acute /chronic inflammation and sepsis

Question 1

What are the 5 classical signs of inflammation?

Answer 1

1) Heat
2) Pain
3) Redness
4) Swelling
5) Loss function

Question 2

What are some postives and negatives about inflammation?

Answer 2

Pros 
Helps clears up infection
Prevents the spread if infection
Promotes wound healing 
Help activates memory

Cons
Causes long term pain and loss of function
Scarring
May predispose to autoimmunity 
May lead to cancer
Dysregulated immunity

Question 3

Describe the key cell types that promote acute inflammatory processes

Answer 3

Neutrophils
Macrophages
Eosinophil
Basophils

Question 4

Describe in detail the vascular and cellular stages of acute inflammation

Answer 4

Vascular stage:
1) Vessels vasodilate via histamine
2)Vessels become permeable -endothelial cells contract(Histamine,bradykinin,leukotrienes)
Direct damage can cause endothelial cells to contract

Cellular stage:

1) Tissue injury:release of chemical signal such as histamine
2) Dilation and increased leakiness of local blood vessels:migration of phagocytes to the area
3) Phagocytes(macrophages and neutrophils)consume bacteria and cell debris;tissue heals

Question 5

Define the major soluble mediators of inflammation and describe their major functions (histamine, serotonin, ROS, cytokines, eicosanoids, CRP, SAA, fibrinogen)

Answer 5

The major soluble mediators of inflammation include histamine(vasodilation), serotonin(stimulate monocytes and lymphocytes),cytokines,eicosanoids,ROS and NO.
ROS-(PNMs)Neutrophils produces ROS at the site of inflammation which cause enodothelial dysfunction and tissue injury.
Cytokines-They initate the inflammatory response and to regulate the host defence against pathogens medatiating the innate immune response
Eicocosanoids-(involved in vasodilation,and vasoconstriction also they play a role in up and down regulation of inflammatory cytokines.
CRP(Role of C reactive protein)-it increases in response to inflammation and also involved in host defense.
SAA(serum amyloid A)-it is released in response to inflammation or infection(help activate the complement)
Fibrogen -responsible for blood clotting and when you start bleeding it initiates a process called the coagulation cascade or clotting cascade.

Question 6

Name several anti-inflammatory drugs (NSAIDs and corticosteroids) and describe how they exert their effects

Answer 6

nSAIDS-they exert their effect by the inhibition of the enzyme COX.This stops the production eiacosanoids e.g prostaglandins which reduces inflammation.
Corticostreriods-they reduce inflammation by suppressing the immune system by affecting how the white blood cells work.

Question 7

Provide examples of pyrogens

Answer 7

LPS
Neurotoxins 
TNF alpha
IL-1
IL-6 
Super antigens

Question 8

Understand how membrane phospholipids can be broken down into inflammatory mediators(leukotreines,prostaglandidn)

Answer 8

Prostagladindins is derived from Cox 1 and cox 2

Question 9

Name the three major cytokines that promote fever and their functions

Answer 9

TNF -alpha
IL-6
IL-1

Question 10

Describe the major function of macrophages and how these cell contributes to inflammation and immunity.

Answer 10

In inflammation, macrophages have three major function; antigen presentation, phagocytosis, and immunomodulation through production of various cytokines and growth factors. Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation.

Question 11

Define what is meant by sepsis and SIRs

Answer 11

Sepsis- life threatening organ dysfunction caused by dysregulated host response.
SIRs-systemic inflammatory response syndrome-an exaggerated defense response of the body to a noxious stressor..

Question 12

Describe the pathogenesis of fever

Answer 12

Fever is the result of exogenous pyrogens that induce release of endogenous pyrogens, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6 and other cytokines, which then trigger cytokine receptors, or of exogenous pyrogens that directly trigger Toll-like receptors. EXogenous pyrones are normally microbes/pathogenn e.g LPS.

Question 13

Explain the complexity of its underlying

sepsis pathogenesis

Answer 13

1) LPS and other microbial proteins activating immunity
2) Production of cytokines (IL-1, IL-6, TNF-a, IL-18)
3) Acute phase protein production (CRP and complement) 4)Production of eicosanoids which amplify inflammation
6) Coagulation activation (more next lecture)
7) nitial activation of neutrophils and macrophages
8) Subsequent activation of lymphocytes