Inflammation

Question 1

Define Inflammation

Answer 1

Defensive process that a living body initiates against infection and damaged tissue.
Inflammation recruits cells and molecules from circulation to where they are needed to eliminate offending agents.
An “itis” suffix is put for inflammatory diseases

Question 2

List the factors that cause inflammation.

Answer 2

Physical agents-temperature
Chemical agents- drugs
Biological agents-Bacteria
Immune reactions- abnormal inflammatory response is chronic inflammation

Question 3

What are the 5 pillars of inflammation?

Answer 3

Question 4

Name 4 common side effects of inflammation

Answer 4

Suppurative or purulent inflammation, abscess. Pus consists of neutrophils, dead cells, tissue fluid
Ulcers
Serous inflammation (blisters)
Fibrinous inflammation: fibrin leaks into the tissue from blood vessels causing scaring

Question 5

What is the difference between chronic and acute inflammation?

Answer 5

Acute inflammation: a rapid response to deliver leucocytes and plasma proteins to infection sites or tissue injury, short duration. E.g. acute appendicitis/ bronchitis, abscess.

Chronic inflammation: prolonged inflammation (weeks/months) where inflammation, tissue injury and attempts at repair coexist. Eg tb, autoimmune disease. Macrophphage, Lymphocytes, Plasma cells involved.

Question 6

What are characteristics of acute inflammation?

Answer 6

Innate immune response- occurs in mins/hours, lasts for hours/days
Main cell: neutrophil
Mostly local, can be systemic (e.g. fever, neutrophilia)
Exudation of fluid and plasma proteins (edema) + emigration of leukocytes
Obvious clinical signs= 5 pillars

Question 7

What is the purpose of acute inflammation?

Answer 7

Recognition of injury
Recruitment of leukocytes
Removal of causative agent
Regulation (closure of inflammatory response)
Repair of affected tissue

Question 8

Describe termination of acute inflammation

Answer 8

V important, controls response and prevents it excessively damaging host tissues
Occurs when causative agent is removed
Mediators broken down and dissipated
Leukocytes have short life span in tissues so die
Anti-inflammatory mechanisms activated.

Question 9

What are the 4 outcomes of acute inflammation?

Answer 9

Complete resolution: causative agent removed early, limited tissue damage, cells at site able to regenerate

Abscess: purulent inflammation caused by certain bacteria. Can become chronic if not reabsorbed/ drained

Repair by scarring/fibrosis: Greater tissue destruction, native tissue cannot regenerate (eg m.infarction). Depends on tissue regeneration ability (labile> stable >permanent tissues)

Progression to chronic inflammation: Causative agent could not be removed

Question 10

What are the main events of acute inflammation?

Answer 10

Histamine produced by mast cells attract more mast cells
Vasodilation & stasis widen internal diameter of blood
vessels. Dilated blood vessels but same HR means blood volume ⇡ and slows down. This ensures neutrophil/monocytes migrate to infection site in time.

Endothelial cells contract, ⇡ vascular permeability. Fluid and cells leak out blood vessel walls

Endothelial cells have adhesion molecules for leukocytes to bind by margination. Leukocytes roll along blood vessel walls. Activated integrins on leukocytes binds them tighter to adhesion molecules.

Leukocytes transmigrate into surrounding tissues by chemotaxis, meaning they move to the area w the highest conc of distress molecules. They’re activated. Phagocytosis starts.

Question 11

The cells that are involved in acute inflammation are the leukocytes of the innate immune response. How do neutrophils behave?

Answer 11

Neutrophils phagocytose pathogens

• Release granules to counteract histamine
• Release chemokines to attract mote leukocytes
• Generate reactive oxygen/nitrogen species to kill
• Form Extracellular Traps (NETs) that trap pathogens
• Short lived, becomes pus

Question 12

The cells that are involved in acute inflammation are the leukocytes of the innate immune response. How do macrophages and others behave?

Answer 12

Macrophage

• Differentiate from monocyte
• Do phagocytosis
• Release factors that promote tissue repair (TGF-B)

Eosinophils- combat parasites and allergies
Lymphocytes- for viral infections (target cell mediated)

Question 13

Give mediators and their functions

Answer 13

C5a: -releases oxygen species (for chemical warfare)

• Attracts neutrophils and monocytes
• Increases vascular permeability
• Mast cells release histamine and TNF- alpha

Histamine: vasodilation, contracts endothelial cells

TNF- alpha

• Released by mast calls and macrophages
• causes endothelial adhesion for leukocytes

Others: contribute to the 5 signs of inflammation

Question 14

What is the main causes of inflammation?

Answer 14

o Persistent infections
o Persistent exposure to agent
o Immune mediated (auto immune disease/ allergies)

Question 15

What are the mediators of chronic inflammation?

Answer 15

• All the acute mediators
• Chemokines IL17 and IL12
• INF-γ: Produced by T cells and NK cells. It activates macrophages and increases microbicidal activity

Question 16

Give the different types of chronic inflammation

Answer 16

• Non-specific chronic inflammation
• Autoimmune chronic inflammation
• Chronic suppurative inflammation
• Chronic granulomatous inflammation

Question 17

Describe Non specific chronic inflammation

Answer 17

Develops when acute inflammation can’t eliminate causative agent

Involves gastritis and gastric ulcers caused by H.pylori or non-steroidal anti-inflammatory drugs (NSAIDs). Ulceration is loss of surface cells or tissue necrosis to form a cavity

Inflammatory cells involved: lymphocytes, plasma cells

Question 18

Describe H.pylori

Answer 18

When H.pylori infects the body, it evades the innate and adaptive immune system:

Neutrophils during the innate response release reactive oxygen and nitrogen species and proteases. Helicobacter hides in thick gastric mucus and is unaffected. Instead, these molecules harm normal gastric epithelial cells.

The adaptive i.system still can’t get rid of the bacteria so it becomes chronic gastritis.

Question 19

Describe autoimmune chronic inflammation

Answer 19

Immune response to self-antigens e.g. Rheumatoid arthritis, Crohn’s disease

Inflammatory cells involved are macrophages, lymphocytes

Insidious start- no specific acute inflammatory events that triggers it.

Question 20

What is Rheumatoid arthritis?

Answer 20

Chronic inflammation in synovium (lining of joints). Cell infiltrates from the blood stream go into the synovium during inflammation, causing swelling

This causes pannus formation, an abnormal tissue layer created by fibrin deposition. Pannus growth causes loss of cartilage and bone erosion

~70% of patients have anti-rheumatoid factor (later found to be autoantibodies against Fc portion of IgG)

Question 21

What causes chronic suppurative inflammation? What cells are involved?

Answer 21

Persistent suppurative inflammation (puss)
Neutrophils involved (+ eosinophils only if a parasite)
In chronic suppurative inflammation, pus inflammation cant be cleared spontaneously, creating abscess
Surgical incision and drainage needed

Question 22

Describe chronic granulomatous inflammation

Answer 22

Causative agent cannot be eradicated, so granulomas form to isolate and prevent spread.

Inflammatory cells involved: epitheloid cells, giant cells, lymphocytes

Hay T cell activation after macrophage fails to eradicate infection (switch innate to adaptive)

T cells activate macrophage to change into Epitheloid cells. Macrophages can fuse to form multinucleated giant cells which forms granulomas.

Persistent inflammation=significant tissue damage

Question 23

What are the different causes of granulomas?

Answer 23

Immune granulomas: from persistent T cell activation fighting tough infectious agents (TB, leprosy, syphilis, parasitic Schistosomiasis), as well as AI disease.

Foreign body granulomas to fight Talc, sutures, fibres, silica. No T cell activation as these are not made of proteins.

Sometimes hay lung granulomas from Sarcoidosis.

In the adaptive response, granulomas form when hay eqm entre the number of T cells/macrophages, and the number of dividing bacteria. If the host is immunocompromised and the eqm breaks then reinfection occurs

Question 24

Describe the appearance of a granuloma and what is inside it

Answer 24

Question 25

What is the difference between caseating and non caseating granulomas?

Answer 25

Caseating granulomas have necrotic tissue in the middle. Non-caseating granulomas do not.

Caseating necrosis are found in the middle of caseating granulomas in TB. As the cells disintegrate, they aren’t completely digested- the debris of the cells clump together to form a soft granular mass

Question 26

Using TB, describe the outcomes of granulomatous inflammation

Answer 26

Causative agent eradicated: Hay tissue healing, scarring/fibrosis, calcium deposits in scarred tissue which is x-ray visible

Causative agent persists but is blocked by fibrous tissue. Infection is kept in check by T cells and macrophages (bacteria slowdividing). Granulomas normally calcified (seen on x-ray, diagnoses tb)

TB reactivates when immunity is compromised (steroids, HIV)

Question 27

What is the primary intention of inflammation?

Answer 27

Cell regeneration: only possible if the injury is limited to the epithelial layer as they are labile tissues.

Stable tissues don’t differentiate from stem cells as labile tissues do. Therefore it can regenerate if hay growth factors and cytokines such as TNF-α and IL-6

Question 28

what is the secondary intention of inflammation?

Answer 28

Secondary intention: Cell regeneration (epithelium) and fibrous repair(patching and scaring)

Occurs w more extensive tissue loss or permanent (non-dividing) tissue types–e.g. large wounds, abscesses, ulcerations, ischemic necrosis