Inflammation Flashcards
What are the 4 classical descriptions of inflammation?
Rubor, tumor, calor and dolor (redness, swelling, heat and pain respectively).
What is cellulitis?
List 2 common causes.
- Acute skin infection.
- Commonly caused by:
1 - Streptococcus pyogenes.
2 - Staphylococcus aureus.
What is the function of inflammation?
To destroy, dilute or wall off an injurious agent and induce repair.
List 6 components of barrier immunity.
Physical barriers:
1 - Skin.
2 - Lungs.
3 - Gut.
Active barriers:
4 - Cilia.
5 - Secretions.
6 - Antibacterial peptides.
Give an overview of the acute phase response of the innate immune system.
1 - Recognition of the danger signal by innate immune cells.
2 - Response mediated by:
- Cellular activation.
- Cellular recruitment.
- Cytokine activation.
- Complement activation.
3 - Destruction of the pathogen and resolution of inflammation or recruitment of adaptive immune response.
How are threats recognised by the innate immune system?
Via pattern recognition receptors (especially on mast cells, however pattern recognition receptors are present on every innate immune cell).
List 3 functions of mast cells.
1 - To detect injuries via pattern recognition receptors.
2 - To release histamine and other mediators.
3 - To initiate the inflammatory response.
List 3 functions of histamine.
1 - To cause vasodilation.
2 - To widen the endothelial junction, increasing permeability.
3 - To cause irritation of nerve endings, causing itching and pain.
List 2 mediators of inflammation.
1 - Histamine.
2 - Arachidonic acid metabolites (eicosanoids).
List 3 eicosanoids that mediate inflammation.
Through which pathways are they produced?
Through the COX pathway:
1 - Prostaglandins.
2 - Thromboxane.
Through the lipoxygenase pathway:
3 - Leukotrienes.
List 2 effects of COX pathway products.
1 - Vasodilation.
2 - Prolongation of oedema.
List 4 effects of leukotrienes.
1 - Vasoconstriction.
2 - Chemotaxis.
3 - Increase vascular permeability.
4 - Bronchospasm.
What is montelukast?
A leukotriene receptor antagonist used in asthma.
List 2 drugs that block the COX pathway.
1 - Aspirin.
2 - NSAIDs.
Give an example of a use of prostaglandins.
Prostaglandins are used to treat pulmonary hypertension.
How do nonsteroidal anti-inflammatory drugs (NSAIDs) prevent inflammation?
By blocking the COX pathway.
What is the cause of erythema?
Vasodilation.
What is the cause of oedema?
Increased vascular permeability.
Which type of proteins are the cause of localised heat during inflammation?
Cytokines.
List 2 advantages of vasodilation during inflammation.
1 - Increases blood flow and pooling, increasing migration of activated cells to the tissues.
2 - Increases local temperature.
What is the advantage of increased endothelial permeability during inflammation?
The fluid loss into tissue leads to concentration and stasis of red blood cells in local vessels.
Why is blood stasis advantageous during inflammation?
Because blood stasis contributes towards the migration of immune cells towards the offending agent.
List 3 acute phase cytokines.
1 - IL-1.
2 - TNF-alpha.
3 - IL-6.
List 6 responses of the body to acute phase cytokines.
1 - The endothelium vasodilates and increases permeability.
2 - The hypothalamus increases the ‘set’ temperature.
3 - Fat and muscle increase mobilisation of energy stores.
4 - The liver increases production of acute phase proteins such as C-reactive protein (CRP).
5 - The bone marrow increases mobilisation of neutrophils.
6 - Dendritic cells release tumour necrosis factor, which stimulates maturation and migration to lymph nodes (initiates the adaptive immune response).
List 3 drugs that are blockers of the acute phase response.
Which diseases are these drugs used to treat?
Used to treat inflammatory bowel disease and rheumatoid arthritis:
1 - Anti TNF-alpha.
Used to treat rheumatoid arthritis:
2 - Anti IL-1.
3 - Anti IL-6.
What is a risk of overproduction of TNF-alpha and IL-1?
Septic shock.
List the stages of development of septic shock.
1 - Endotoxins (lipopolysaccharides) are released from gram-negative bacteria such as E. coli.
2 - The endotoxins enter the circulation and cause massive activation of macrophages in the liver and spleen.
3 - This results in the overproduction of TNF-alpha and IL-1.
4 - This leads to dilation of blood vessels, leakage of fluid into tissues throughout the body and widespread clotting.
5 - These factors collectively cause multiple organ failure.
What are granulomas?
What is their function?
- Large organisations of macrophages.
- They function to wall off infections.
List 4 outcomes of acute inflammation.
1 - Healing with scar formation.
2 - Abscess formation (encapsulation and pus).
3 - Granuloma formation.
4 - Chronic inflammation (when acute phase can’t be resolved).
List 2 factors that might contribute to an unresolved acute phase.
1 - Persistent injury or infection.
2 - Autoimmune disease states such as rheumatoid arthritis and systemic lupus erythematosus.
List 3 mechanisms of chronic inflammation.
1 - Cellular infiltration (granuloma formation).
2 - Tissue destruction by inflammatory cells (such as with COPD).
3 - Attempts at repair with fibrosis and angiogenesis.
What is the average lifespan of a neutrophil?
Why is this important?
- Between a few hours and a day.
- This is important for terminating acute inflammation when necessary.
List 2 anti-inflammatory cytokines.
1 - TGF-beta.
2 - IL-10.
How do anti-inflammatory cytokines prevent inflammation?
By inhibiting the production of pro-inflammatory cytokines.
List 5 acute phase proteins (APPs).
1 - C-reactive protein (CRP).
2 - C3.
3 - C4.
4 - Fibrinogen.
5 - Ferritin.
List 3 negative control proteins for the acute phase response.
1 - Alpha-1 antitrypsin.
2 - Albumin.
3 - Transferrin.
List 2 functions of C-reactive protein (CRP).
1 - To opsonise bacteria and fungi.
2 - To activate the classical complement cascade by binding to C1q.
What is erythrocyte sedimentation rate (ESR)?
The rate at which erythrocytes settle out of unclotted blood in one hour.
Why does erythrocyte sedimentation rate (ESR) change with inflammation?
- Normally, erythrocytes are very buoyant and settle slowly.
- Erythrocytes are negatively charged and repel, preventing aggregation.
- In the presence of acute phase reactants, erythrocytes aggregate due to the loss of their negative charge, resulting in increased sedimentation.
What is the effect of IL-1 and IL-6 on bone marrow?
Release of neutrophils from bone marrow neutrophil stores.
What is a leukaemoid reaction?
What might cause a leukaemoid reaction?
- Leukocytosis in response to stress or infection.
- Can be caused by exaggeration of leukocyte release in response to IL-1 and IL-6 at the bone marrow.
