COD Inflammation

Question 1

What is inflammation?

Answer 1

The body’s attempt at self-protection
To remove harmful stimuli and begin the healing process
Generally non-specific
No long lasting immunity to the host in the acute stage
Evolutionary older defense strategy

Question 2

What is chronic inflammation?

Answer 2

Persist longer than necessary
Cause more harm than good
Severe and progressive

Question 3

What are the symptoms of inflammation? How is it classically defined?

Answer 3

Redness
Warmth
Pain
Swelling
Loss of function

Question 4

How are cytokines involved in inflammation?

Answer 4

They orchestrate the immune and inflammatory responses
Include chemokines, interleukins, tumour necrosis factors
Produced by a range of cells including macrophages, B and T lymphocytes, mast cells, fibroblasts
They act by binding to the cell surface receptors that then trigger intracellular signal transduction cascades
Decoy receptors negate cytokine actions. Can also inhibit by use of neutralising monoclonal antibodies

Question 5

What are the 2 major systems in the complement system?

Answer 5

Classical: starts when antibody binds to pathogen/bacteria
Alternative: Starts spontaneously

Question 6

Describe the complement system

Answer 6

Consists of several small proteins generally synthesised in the liver and normally circulate as inactive precursors (pro-protein)
Series of proteolytic reactions with the end result of:

Stimulation of phagocytosis to clear foreign and damaged material

Proxy inflammation to attract additional phagocytes

Activation of cell-killing membrane attack complex

Question 7

Describe the adaptive immune system

Answer 7

2nd line of defense
Highly specialised
Highly specific
Long lasting
Immunological memory
Recognition of “non-self” antigens from “self”
Humoral immunity and cell-mediated immunity
B lymphocytes: produce antibodies (immunoglobulins)
T lymphocytes: cell-mediated immune response (Th1, Th2, Th17, Tregs) in response to antigen presenting cell (e.g. dendritic cells). Antigen presentation is in conjunction with major histocompatibility complex

Question 8

Describe acute phase proteins

Answer 8

Class of secreted plasma proteins
Concentration increases or decreases in response to inflammation
Response is called acute phase reaction
Changes in mainly transcription of genes in liver due to increase plasma concentrations of cytokines such as IL-1, IL-6 and TNF-α due to inflammation

Protective function:
C-reactive protein, complement factors, serum amyloid A, haptoglobin: inhibit growth of microbes
Fibrinogen, prothrombin, Factor VIII: Coagulation factors that trap invading microbes in blood clots
Haptoglobin: binds haemoglobin, inhibits microbe iron uptake

Question 9

What are the basis of the 5 cardinal signs?

Answer 9

Increased blood flow due to vascular dilatation gives redness and heat

Increased vascular permeability gives oedema causing tissue swelling

Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching from oedema

Pain and swelling result in loss of function

Question 10

What are inducers?

Answer 10

Pathogen-associated molecular patterns (PAMPs): Defined set of conserved molecular patterns/structures carried by pathogens that are essential for their survival. Host has evolved a corresponding set of receptors (Pattern-recognition receptors) that detect their presence

Virulence Factors: Restricted to pathogens. They are generally not sensed directly by dedicated receptors but the effects of their activity, particularly adverse, are responsible for triggering inflammatory response

Damage-associated molecular patterns (DAMPs) are endogenous molecules/molecular patterns that signal damage (endogenous stress signals)