POM - MBC - INFLAMMATION OF THE CELL

Question 1

What is the 5 main signs of inflammation?

Answer 1

• dolor (Pain)
• rubor (Redness)
• calor (Heat)
• tumour (swelling)
• function lassa (loss of function)

Question 2

What is the definition of inflammation? What’s its purpose?

Answer 2

Inflammation is the non-specific response to cell injury. t is designed to remove the cause and consequence of injury. It is a tightly regulated process removing damaged cells and recruit cells of the immune system

Question 3

When is inflammation triggered? What triggers it?

Answer 3

Inflammation is initiated when there is non-apoptotic cell death leading to DAMPs or PAMPs being released - damaged tissues release signals and chemokines to recruit immune cells at the site of injury

Question 4

What is acute inflammation?

Answer 4

• Acute inflammation is a rapid, non-specific response to cellular injury
• It is localised
• Process applies to any viable, vascularized tissue

1. There is change in the local blood flow
2. There are structural changes in the microvasculature
3. There is recruitment/accumulation of immune cells and proteins

ACUTE INFLAMMATION MEANS THERE IS A RAPID ONSET AND RESOLUTION

Question 5

Causes of inflammation

Answer 5

 Pathogens
 Allergens
 Physical damage
 Auto-antigens
 Extreme temperature
 Non-apoptotic cell death

Question 6

diseases associated with inflammation (6)

Answer 6

 Infection
 Autoimmunity
 Cancer
 Hypersensitivity
 Trauma
 Fibrotic disease
 cancer

Question 7

cell types involved with inflammation

Answer 7

 Epithelial cells
 Endothelial cells
 Neutrophils
 Macrophages
 Lymphocytes
 Eosinophils
 Mast cells

Question 8

What is exudate? What are the benefits of the exudate?

Answer 8

fluids and proteins of the cells that have seeped out of the blood vessel. the exudate is a PROTECTIVE BARRIER, preventing pathogens entering the blood vessel and the rest of the body.
*This helps prevent a systemic infection**

Question 9

What is the process of acute inflammation?

Answer 9

1. Steady state = mast cells and macrophages are tissue resident. There are leukocytes and neutrophils in the vascular endothelium
2. Damage = thorn, insect bite. Due to non-apoptotic cell death and detection of foreign material, DAMPs and PAMPs are released (inflammatory signals). Vasodilators (histamine, nitric oxide) are released. There are also vascular changes (increased permeability of the vessels, vasodilation, reduced flow of blood and plasma leakage.
3. Neutrophil extravasation
4. resolution of acute inflammation

Question 10

What are benefits of increased plasma permeability?

Answer 10

Benefits of increased vascular permeability means that there is a barrier being formed around cell damage, there is increased antibodies, proteins, leukocyte migration from the vessels to the site of damage.

Question 11

What is the process of neutrophil extravasation?

Answer 11

• Leukocytes have lots of different receptors (ligands)
• Cytokines produced by macrophages are released and regulate the endothelial layer, specifically acting on selectins. Selectins are involved in the tethering of neutrophils to the endothelial layer
• The neutrophil makes low-affinity connections to selectins as the force of blood flow forces the neutrophil to roll along the cell.
• Cytokines also induce chemokine production (either macrophages or endothelial cells). The chemokines are translocated to proteoglycans which present the chemokines.
• When a receptor of the leukocytes binds to the chemokines, the tethering becomes high-affinity, and the leukocytes enter the tissue. The neutrophils release other signals to encourage other neutrophils to come to the site of damage.

Question 12

How is acute inflammation resolved?

Answer 12

1. Pathogen recognition = immune cells (neutrophils) and antimicrobials (eg. Antibodies) will recognise infections or particulates
2. Short half life = neutrophils have a rapid half-life and inflammatory mediators are turned over rapidly
3. Macrophages = clear apoptotic cells and produce inflammatory mediators
4. Repair wounding and healing

Question 13

What are diseases caused by chronic inflammation?

Answer 13

rheumatoid arthritis, asthma, inflammatory bowel disease, hepatitis, psoriasis, multiple sclerosis, glomerulonephritis

Question 14

what are diseases conserved by granulomatous inflammation?

Answer 14

TB, leprosy, foreign body granuloma, tumour reactions, sarcoidosis, Crohn’s disease - granulomas are produced when the body struggles to clear the infection

Question 15

what is granulomatous inflammation?

Answer 15

Chronic inflammation with a distinct pattern of granuloma formation. There is an aggregation of activated macrophages, a barrier designed for clearance. It is triggered by strong T-responses and resistant agent (eg. Mycobacterium, tumours)

Question 16

how does chronic inflammation arise?

Answer 16

Similar but very different from acute inflammation.
 It is caused due to the persistent presence of the inflammatory stimuli (due to prolonged infection, persistent toxic stimuli like allergens, pollutants, unclear able particulates or autoimmunity (self-antigens)
 There is a distinct immune cell infiltrate (presence of inflammatory macrophages, T cells and plasma cells)
 A vicious cycle = no clearance of the inflammatory agents, bystander tissue destruction, and concurrent repair processes (fibrosis and angiogenesis)

Question 17

what role do macrophages play in inflammation?

Answer 17

 Macrophages can be recruited as monocytes to the site of inflammation but is also tissue resident
 They can be phagocytic, cytotoxic, anti-inflammatory (TGF-B, IL-10) and used for wound repair
 They also can be cytotoxic, inflammatory or pro-fibrotic

Question 18

what role does lymphocytes play in inflammation?

Answer 18

 Innate and adaptive immune cells work together
 T cells in inflammation can be pro-inflammatory, (releasing TNF, IL-17, IFN-Y), cytotoxic (releasing granzymes, perforin) or regulatory (releasing TGF-B)
 B cells = generate plasma cells which secretes antibodies, protective clearing inflammation, inflammatory (due to reactions against self antigens). Can be local to inflammatory site operate remotely

Question 19

What are the pros and cons of inflammation?

Answer 19

 Pros = clears inflammatory agent, removes damaged cells and restores normal tissue function
 Cons = excess tissue damage, scarring, loss of organ function leading to organ failure.

Question 20

Give examples of other soluble mediators?

Answer 20

• histamine
• prostaglandins
• cytokines
• chemokines
• complement (C5a, C3a, C4a)

Question 21

DIFFERENCES BETWEEN ACUTE AND CHRONIC INFLAMMATION

Answer 21

acute = immediate onset, lasting a few years. there is vasodilation and increased vascular permeability. neutrophils predominate and histamines are released. there is prominent necrosis. There is either complete resolution OR progression to chronic inflammation

chronic inflammation = delayed onset, may last weeks months or years. there is persistent inflammation and ongoing tissue injury. Macrophages/monocytes predominate. There is ongoing cytokine release/prominent scarring leading to loss of function.