Acute Inflammation

Question 1

What are signs of an inflammatory response?

Answer 1

Heat/redness, pain, swelling
Physical or infectious stimuli
Increased blood flow to tissues
Pain receptors (sensitised)
Increase permeability, fluid leakage into tissues (tissue swelling)
Influx of white blood cells, migration of phagocytic cells into tissues

Question 2

Why do we get heat and redness as an inflammatory response?

Answer 2

Redness: due to dilation of blood vessels (arterioles)
Heat: Increased blood flow gives an impression of heat
- vasodilation refers to the widening of blood vessels from the relaxation of smooth muscle cells with vessel walls
- affected by mediators (chemicals) produced by local immune cells or local neuron activity

Question 3

Why do we get swelling as an inflammatory response?

Answer 3

Protein concentration of the exudate is less than that of blood (blood + osmotic pressure)
- Endothelial cells are “immune cells”
Increase in permeability of capillary walls in response to specific mediators (histamine/cytokines)
Exudate may simply dilute a noxious substance, helps immobilise a damaged area
- different process to endothelial cell damage

Question 4

What is nociception (pain)?

Answer 4

Nociceptors are nerve endings that react to damaging stimuli and send signals to the brain and spinal cord
- perception of pain

Question 5

How are nociceptors classified?

Answer 5

Mechano-sensitive: stimulated by excessive mechanical stress/damage to tissues
Thermo-sensitive: stimulated by extremes of heat + cold
Chemo-sensitive: stimulated by chemicals, pH

Question 6

What is fast sharp pain?

Answer 6

Transmitted rapidly in sensory A nerve fibres, accurately localised (small receptive field)
Affected by mediators released by platelets, granulocytes or macrophages
Sensation does not outlast the stimulus, leads to avoidance of behaviour

Question 7

What is slow chronic pain?

Answer 7

Transmitted by sensory type C fibres (relatively slow conduction)
Duration of sensation outlasts stimulus (phantom limb)

Question 8

What is trans-endothelial cell migration?

Answer 8

Cell accumulation caused by mediators causing:

• increased blood flow (vasodilation) - delivers most immune cells to inflammed site
• normally leukocytes are confined to bloodstream, cells need to be directed to the site of injury - localised effect
• • It is where leukocytes move out of blood cells - in absence of endothelial cell injury - occurs in post capillary venules (pressure too high in arteries)

Question 9

What are platelets?

Answer 9

Small anuclear cells derived from megakaryocyte

• 1 megakaryocyte can give rise to between 5000-10000 platelets, produce approx. 1x10^11 per day
• last between 7-10 circulating in the blood

Question 10

What are platelets activated by?

Answer 10

Thrombin: coagulation cascade
Phosphatidyliarine: on cell surface of damaged cells
Collagen exposed following endothelial cell damage

Question 11

What is the function of platelets?

Answer 11

Adhere/aggregate to damaged tissue - initiate clotting and help prevent blood loss
Initiate blood clotting:
- too low: excessive bleeding
- too high: intravascular clotting

Question 12

What cells are present as the 1st line of defence?

Answer 12

Sentinels (tissue resident cells)
- mast cells predominantly found at mucosal surface
- degranulation = histamine
Macrophages
- express “non-specific” or “pattern recognition receptors”
- recognise foreign antigen or tissue damage and initiate inflammation
- can phagocytose and kill bacteria and release specific mediators i.e. attracting polymorphs

Question 13

What cells are present at the 2nd line of defence?

Answer 13

Infiltration of polymorphs
- polymorphonuclear cells = granulocytes/polymorphs
- neutrophils, basophils, eosinophils
- all have granules
Neutrophil infiltration
- migrate into tissue under specific signals - chemotaxis
- highly phagocytic
- granules contain performin - proteases, bacterial peptides, toxic oxygen intermediates
- die in the act
- send signals that attract monocytes

Question 14

What cells are present at the 3rd line of defence?

Answer 14

Monocyte infiltration

• move out of circulation into inflamed tissue in response to chemokines secreted by damaged tissues or neutrophils or in response to bacterial toxins
• respond to different chemokines rather than neutrophils, rate of recruitment slower
• macrophages clear dead host cells (neutrophils), bacteria/parasites
• do not die
• highly phagocytic - release mediators including cytokines, chemokines when activated

Question 15

How do macrophages produce cytokines?

Answer 15

Gene regulation and protein transcription

• ultimately dominant cellular infiltrate
• express MHC molecules and present antigen, start adaptive immune response

Question 16

What cells are involved in the 4th line of defence?

Answer 16

Increased production of monocytes and polymorphs

• mediators released from macrophages can stimulate production of polymorphs/macrophages by the bone marrow , this occurs through the stimulation of progenitor cells in bone marrow by colony stimulating factors (CSF’s)
• in cases of severe inflammation can be blood neutrophils/eosinophils

Question 17

What is systemic inflammation?

Answer 17

Production of acute phase proteins from the liver, may help clear pathogens

• diagnosis - measurement of raised circulating concentrations of acute phase proteins (C reactive protein + serum analysis)
• used as a marker of inflammation

Question 18

What causes fever?

Answer 18

Release of cytokines into circulation causing elevation of the set point of the hypothalamus - affects brain function via the hypothalamus - pituitary - adrenal (HPA) axis

Question 19

What is shock?

Answer 19

Aim of the acute inflammatory response is to prevent spread of the bacteria or parasites from the site of infection
- if bacteria/parasites enter bloodstream then whole body systems are activated

Question 20

What is a cytokine storm?

Answer 20

Hype- production of cytokines leading to shock

Is is the cytokine storm that causes pathology - not the infectious agent