Pathogen: Inflammation.

Question 1

What is inflammation?

Answer 1

-Protective response to injury or infection.
-Eliminates the initial cause of injury and initiates repair.
-Inflammation is a component of the immune system.

Question 2

Acute vs Chronic Inflammation?

Answer 2

-Acute:
1.) Allergic reaction.
2.) Infection.
3.) Trauma.
4.) Burn.
5.) Frostbite.
6.) Cuts, Lacerations.
-Chronic:
1.) Cardiovascular disease.
2.) Rheumatoid Arthritis.
3.) Autoimmune disease.
4.) Cardiovascular disease.
5.) Cancer

Question 3

Phases of Acute inflammation?

Answer 3

-Fluidic Phase:
1.) Increased blood flow.
2.) Accumulation of fluids in tissues- oedema.
-Cellular Phase:
1.) Inflammatory cells clean up damaged tissue.
2.) Fight infection.
-Resolution Phase:
1.) Inflammation recedes.
2.) Tissue healing starts.

Question 4

Fluidic phase of acute inflammation?

Answer 4

-The fluid phase begins immediately after tissue insult.
-Fluid from the circulatory system travels into the affect tissue:
1.) Increased vascular permeability.
2.) Vasculature dilation.

Question 5

Effectors of fluidic phase?

Answer 5

-Protagonist of the fluidic phase is the vasculature with:
1.) Endothelial cells.
2.) Smooth muscle cells.
-Helped by:
1.) Prostaglandins.
2.) Mast cells.
3.) Complement.

Question 6

Endothelial cells?

Answer 6

-Form a single-cell layer lining all blood vessels and the lymphatic system.
-They play a crucial role in regulating blood fluidity, vascular tone, and immune responses.
-They actively participate in all phases of acute inflammation.

Question 7

Vascular smooth muscles?
Vasodilation: increased blood flow.

Answer 7

-Arterioles are surrounded by a cuff of contractile cells.
-Dilation of the arteriole musculature (vasodilation) increases blood flow to the site of inflammation.
-Vasodilation is induced by:
1.) Prostacyclin, NO (endothelial cells).
2.) Histamine (mast cells).

Question 8

Exudate?

Answer 8

Caused by increased capillary permeability due to inflammation- high protein and cell content.

Question 9

Transudate?

Answer 9

Caused by high hydrostatic pressure or low blood protein (oncotic pressure).

Question 10

Mast cells?

Answer 10

-Resident cells are found in the skin, respiratory, and intestinal mucosa.
-Contain granules filled with various chemical mediators, including histamine, heparin, and cytokines, which are released upon activation: Degranulation.
-Histamine: Vasodilation, increased permeability.
-Early activation against pathogens like bacteria and parasites.
-Allergic reactions: itching, swelling, and nasal congestion.

Question 11

Complement system overview?

Answer 11

-The complement system is a network of proteins that interact with each other in a well-defined cascade.
-Part of the innate immune system.
-Causes destruction of harmful substances and enhances inflammation.

Question 12

Complement system?

Answer 12

-Activation:
1.) Specific carbohydrates on pathogen surfaces (lectin pathway).
2.) Spontaneous activation on microbial surfaces (alternative pathway).
3.) The presence of antibodies bound to pathogens (classical pathway).

Question 13

Compolement System functions?

Answer 13

-C3a and C5a:
1.) Increasing vascular permeability.
2.) Triggering degranulation of mast cells (anaphylatoxin activity).
3.) Chemoattractant, drawing immune cells to the site of infection.

Question 14

Effectors of cellular phase?

Answer 14

-Increased blood flow and vascular permeability produced in the fluidic phase help the recruitment of cells during this phase.
-Protagonists of the cellular phase are the innate immune cells:
1.) Neutrophils.
2.) Marcophages.
-Helped by:
1.) Endothelial cells.

Question 15

Immune cell recruitment?

Answer 15

-Interactions with endothelial cells allow the extravasation of the immune cells.
-Chemoattractant molecules guide neutrophils and macrophages to the site of inflammation.

Question 16

Regulating immune cell recruitment?

Answer 16

-Chemoattraction:
1.) Damaged tissues release inflammatory signals like cytokines.
*Interleukin-1 (IL-1).
*Interleukin-8 (IL-8) is a chemokine specific for neutrophils.
*Tumor Necrosis Factor alpha (TNFa).
-Don’t forget Complement factors 3a (C3a) and 5a (C5a).
-Circulating leukocytes migrate towards the inflamed area due to the presence of chemokines.
-Shape change of neutrophil leukocytes.
-Scanning electron microscope before (left) and 5 seconds after (right) stimulation with a chemoattractant.

Question 17

Neutrophils?

Answer 17

-The first immune cells to arrive at the site of an infection or injury are recruited from the blood.
-Neutrophils trap and kill microorganisms, invading pathogens, and cellular debris.
-Short-lived granulocytes.

Question 18

Neutrophils’ granules?

Answer 18

-Neutrophilic granules store a diverse array of molecules and enzymes that damage microbial biomolecules, including DNA, proteins, and lipids, leading to pathogen inactivation and death such as:
1.) Antimicrobial peptides: lysozyme.
2.) Proteases: digest several types of protein.
3.) Reactive oxygen species (ROS).

Question 19

NETosis?

Answer 19

Scanning electron microscopy image of polymorphonuclear neutrophils undergoing NETosis, after in vitro treatment with PMA for 3 hours.

Question 20

Macrophages?

Answer 20

-Derived from blood monocytes.
-Also, in the resident forms in the tissues.
-Slower than neutrophils to arrive (unless they are residents).
-Long-lived monomuclear cells.
-Important role in orchestrating inflammation and immune defence.

Question 21

Collateral tissue damage?

Answer 21

-While beneficial in combating infection:
1.) Uncontrolled or excessive release of NETs and granule proteins can cause significant tissue damage and exacerbate inflammation.
2.) ROS can cause significant damage to tissues when their production overwhelms the cells’ antioxidant defences: Oxidative stress.

Question 22

Macrophages M1 vs M2 activation?

Answer 22

-M1 and M2 macrophages represent distinct activation states.
-They can switch between these states depending on the surrounding environment.
-M1 macrophages are typically associated with pro-inflammatory responses.
-M2 macrophages are associated with anti-inflammatory and tissue repair functions.
-Anti-inflammatory cell (M2):
1.) M2 macrophages play a role in resolving inflammation and promoting tissue repair.
2.) Express anti-inflammatory cytokines.
3.) Promote tissue wound healing.
4.) Promote new blood vessel formation (endothelial cell).

Question 23

M1 Macrophages?

Answer 23

-Like Neutrophils:
1.) Degranulation.
2.) Phagocytosis.
-Similar effect on pathogen and cell destruction and tissue collateral damage.
-Express pro-inflammatory cytokines to sustain inflammation.
-After phagocytosis, cells can present antigens from degraded pathogens to lymphocytes, causing activation of the adaptive immune response.

Question 24

Phases of acute inflammation-Resolution?

Answer 24

-An active, regulated process, not a passive return to homeostasis.
-This process is crucial for preventing chronic inflammation and restoring tissue function.

Question 25

Resolution of Acute inflammation-Molecules?

Answer 25

-Anti-inflammatory cytokines: 1.) IL-10, transforming growth factor-B (TGF-B) -Specialized Pro-resolving Mediators: 1.) Lipoxins, Resolvins.

Question 26

M2 Macrophages?

Answer 26

-Efferocytosis: phagocytosis of apoptotic cells (also neutrophils). - Clean-up and containment of inflammatory stimuli.

Question 27

Resolution of Acute inflammation-Cellular events?

Answer 27

1.) Limiting neutrophil influx. 2.) Neutrophil apoptosis and clearance. 3.) Efferocytosis: macrophages then engulf and clear away the apoptotic cells. 4.) Macrophage reprogramming from a pro-inflammatory state to an anti-inflammatory state. 5.) Immune cell egress, including macrophages, leaves the inflamed area. 6.) Tissue repair: Return to homeostasis, avoiding scar formation- fibroblasts and endothelial cells.

Question 28

Eicosanoids-Arachidonic Acid (AA) Pathway?

Answer 28

-Potent lipid mediators produced from arachidonic acid (AA). -AA is stored in membrane phospholipids and is fed by the enzyme phospholipase A2 (PLA2). -AA is converted into signalling molecules (eicosanoids) through different enzymes: 1.) Cyclooxygenase (COX). 2.) Lipoxygenase (LOX). 3.) Cytochrome P450 (CYP).

Question 29

Eicosanoids-Prostaglandins?

Answer 29

-Prostaglandins (PG) are made by mast cells, macrophages, and endothelial cells using COX enzymes. -Key prostaglandins are PGE2 and PGI2 (prostacyclin): 1.) Increasing vascular permeability. 2.) Promoting vasodilation. 3.) Sensitizing nerve endings to pain. 4.) Attracting immune cells. -Enzymes: 1.) COX-1 is constitutively expressed in most tissues, where it may serve a homeostatic function. 2.) COX-2 is induced by inflammatory stimuli and is involved in inflammatory reactions, but it is low or absent in most normal tissues.

Question 30

Molecules-Cytokines?

Answer 30

-Pro-inflammatory cytokines trigger the recruitment and activation of immune cells. -Most important are: 1.) Tumor Necrosis Factor alpha (TNF-α). 2.) IL-1. 3.) IL-8. -These mediators initiate systemic effects of inflammation.

Question 31

Systemic effects of inflammation?

Answer 31

-TNF and IL-1 stimulate: 1.) Fever (pyrexia) through PG synthesis by the hypothalamus. 2.) Acute-phase proteins are synthesized by the liver. 3.) Leukocytes (increased release of white blood cells) from bone marrow.

Question 32

Anti-inflammatory cytokines?

Answer 32

-Anti-inflammatory cytokines reduce inflammatory response. -Prevent prolonged or excessive inflammation. -Reduce tissue damage. -Most important: 1.) IL-10. 2.) Transforming Growth Factor-B (TGF-B).

Question 33

Types of Acute inflammation?

Answer 33

1.) Serous inflammation. 2.) Fibrinous inflammation. 3.) Suppurative (purulent) inflammation. 4.) Catarrhal (mucous) inflammation. 5.) Haemorrhagic inflammation.

Question 34

Serous Inflammation?

Answer 34

-Serous inflammation is characterized by a thin, watery fluid derived from plasma. 1.) Blisters (e.g., from a burn). 2.) Effusions in body cavities like the pleura or peritoneum.

Question 35

Fibrinous inflammation?

Answer 35

-Abundant fibrinogen molecules pass into the tissue space, where they form fibrin. - Fibrinogen polymerize forming fibrin. -Lining surfaces of the body cavity.

Question 36

Catarrhal (Mucous) inflammation?

Answer 36

-Excess mucus secretion from mucosal surfaces. -Epithelia respond by producing mucus. -The exudate is mainly mucous + fluid, with variable inflammatory cells. -Characteristic of respiratory and gastrointestinal mucosa.

Question 37

Purulent inflammation?

Answer 37

-Accumulation of pus, which consists of (dead cells, neutrophils, and fluid). -Commonly associated with a bacterial infection.

Question 38

Haemorrhagic inflammation?

Answer 38

-Presence of red blood cells due to leakage of blood from the capillaries. -Bacterial infections like Bacillus anthracis (anthrax) or viral haemorrhagic fevers are some of the common examples.

Question 39

Mixed types?

Answer 39

-Inflammation types can be mixed examples: 1.) Fibrinocatarrhal exudate on the haemorrhagic colonic mucosa. 2.) Serofibrinous. 3.) Mucopurulent. 4.) Necrohaemorrhagic.