Inflammation

Question 1

Define inflammation.

Answer 1

Response of vascularized tissue to infection and damaged tissues that brings cell and molecules of host defense from the circulation to sited where they are needed in order to eliminate offending agents

Question 2

What are the signs of inflammation?

Answer 2

• Heat (calor)
• Redness (rubor)
• Edema (tumor)
• Pain (dolor)
• Loss of function (functio laesa)

Question 3

What are the goals of inflammation?

Answer 3

Destroys invading microorganisms
Contains and isolate injury
Inactivate toxins
Prepare tissues for healing and repair

Question 4

What are the harmful effects of inflammation?

Answer 4

May cause life threatening hypersensitivity reaction.
Underlies some common chronic diseases (rheumatoid arthritis, atherosclerosis, lung fibrosis)
Repair by fibrosis may lead to scars or fibrous tissues or permanent organ damage

Question 5

Compare the two types of inflammation?

Answer 5

Acute: Rapid onset, short duration, exudation of fluid and plasma proteins, emigration of predominantly neutrophils

Chronic: longer duration, associated with lymphocytes, plasma cells and monocytes/macrophages, proliferation of blood vessels, fibrosis and tissue injury

Question 6

What are the steps of the inflammatory response?

Answer 6

1. Recognition of the injurious agent
2. Recruitment of leukocytes
3. Removal of the agent
4. Regulation (control) of the response
5. Resolution (repair)

Question 7

What is the stimuli for acute inflammation?

Answer 7

Infections: bacteria, viruses, fungi, parasites
Physical and chemical agents: heat, trauma, cold, ionizing, radiation, acids, bacterial toxins
Tissue necrosis: from ischemia & physical and chemical injury
Foreign bodies: sutures, dirt, contact lenses
Immune reactions: hypersensitivity, autoimmune reactions

Question 8

What mechanisms do we have for recognition of harmful agents?

Answer 8

PRR: on phagocytes, dendritic, epithelial cells sense infectious pathogens and substances from dead cells (activated by PAMPs and DAMPs)
Circulating proteins recognize microbes that have entered blood (mannose-binding proteins collections)
Sensors of cell damage (Uric acid- DNA damage, decreased K- plasma mem damage, DNA in cytoplasm)

Question 9

What are the 2 major components of acute inflammation?

Answer 9

Vascular changes: vasodilation (increase blood flow), increase in vascular permeability (structural changes allow plasma proteins and leukocytes to leave circulation to produce inflammatory exudates)

Cellular events: cellular recruitment and activation (emigration of leukocytes from bv to focus of injury, activation to eliminate offending agent)

Question 10

Define vasodilation during acute inflammation.

Answer 10

– earliest manifestation
– involves the arterioles then results in opening of new capillary beds
– increased greater blood flow to the area of inflammation, resulting in redness (rubor) and heat (calor)
– induced by mediators such as histamine and nitric oxide

Question 11

Define vascular permeability in acute inflammation.

Answer 11

Endothelial cells become leaky from direct endothelial injury or chemical mediators
Leads to escape of proteins rich fluid into the extra vascular tissue (exudation to edema)

Question 12

Define vascular stasis in acute inflammation.

Answer 12

Loss of fluid results in concentration of RBC in small vessels and increased viscosity of blood and slowing of the blood in the blood stream
Changes cause by numerous dilated small vessels packed with erythrocytes

Question 13

Define exudation in acute.

Answer 13

Escape of fluid, proteins and blood cells from the vascular system into the interstitial tissue or body cavities

Question 14

Describe serous (transudate) exudate.

Answer 14

Relatively mild inflammation
Low protein content, relatively clear fluid
Blisters, sunburn, shingles, cold sores

Question 15

Describe fibrinous exudate.

Answer 15

Severe injuries or inflammation
Difficult to resolve
Ex: in anterior chamber

Question 16

Describe purulent exudate (pus).

Answer 16

Thick, yellowish-white
Contains protein rich fluid, necrotic debris, leukocytes (mostly neutrophils)
Often due to bacterial infection
May form inside abscess

Ex: Chlamydial infection, Haemophilis influenza infection, abscess

Question 17

Compare hard and soft exudates of the posterior pole.

Answer 17

Hard- lipid residues of serous leakage from damages capillaries, diabetic ret

Soft- cotton wool spots, accumulation of axoplasmic material, ischemia

Question 18

Describe extravasation.

Answer 18

Delivery of leukocytes to site of injury
Leukocytes ingest offending agents, kill bacteria. Get rid of foreigners and necrotic tissue

Question 19

What are the three steps of extravasation.

Answer 19

1) Margination, rolling, & adhesion of leukocytes in the lumen
2) Transmigration across the endothelium (also called diapedesis)
3) Migration through interstitial tissue toward a
chemotactic stimulus

Question 20

Describe margination in extravasation.

Answer 20

Accumulation of leukocytes at the periphery of vessels
Smaller RBC move faster than larger WBC
Better opportunity to interact with lining endothelial cells

Question 21

Describe rolling in extravasation. What mediates it?

Answer 21

Binding, detaching, and tumbling of leukocytes along the endothelial surface
Mediated by selectin (adhesion molecule)

Question 22

Describe adhesion in extravasation. What mediates it?

Answer 22

Firm attachment of leukocytes to endothelial cells
Mediated by integrins
TNF and IL-1 activate Endo cells to increase expression of ligands for integrins
Shape change to leukocytes mediate attachment to substrate

Question 23

Describe transmigration. What mediates it?

Answer 23

Leukocytes squeeze between cells at intercellular junctions (diapedesis)
Mediated by chemokines produced in extravascular tissue
Mediated by PECAM-1

Question 24

What are adhesion molecules? Examples?

Answer 24

Involved in leukocyte recruitment

Ex: selections, integrins, PECAM-1

Question 25

Describe Selectins.

Answer 25

Weak adhesions involved in rolling
Extracellular domain that binds to sugar (sialyl Lewis-X moiety) allows for attachment and rolling
P-selectin (platelets, endothelial cells)
E-selectin (endothelial cells)
L-selectin (leukocytes)
Histamine, thrombin, or other inflammatory cytokines can result in increased movement of P-selectins to the cell surface
IL-1 and TNF stimulate expression of selectins

Question 26

Describe integrins.

Answer 26

Involved in adhesion
On leukocyte surface adhere after chemokine activation, shape change and cluster for high affinity form
TNF and IL-1 activate Endo cells to increase expression of ligands (ICAM-1 and VCAM-1) for integrins
ICAM-1 ligand binds to LFA-1 integrin and Mac-1 integrin
VCAM-1 ligand bind to VLA-4 antigen

Question 27

Describe the mechanism for lifitegrast which is in Xiidra
(dry eye).

Answer 27

Inhibits T cell adhesion to ICAM-1 cells and inhibits secretion of pro-inflammatory cytokines (interferon y, TNF-a, IL)
Xiidra is a lymphocyte function-associated antigen 1 (LFA-1)

Integrin to ligand adheres cells to curface, this binding can be inhibited to prevent inflammation

Question 28

What are the potential roles of the LFA-1/ICAM-1 interaction in the eye?

Answer 28

Homing of dendritic cells to the lymph nodes
T-cell activation and differentiation
T-cell migration to the ocular
Trigger inflammation

Question 29

Describe PECAM-1.

Answer 29

Transmigration
Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31)
Expressed on leukocytes and endothelial cells
Mediates the binding events needed for leukocytes to traverse the endothelium

Question 30

Describe chemotaxis involved in migration.

Answer 30

Leukocyte emigrate in tissue toward injury by chemotaxis
Exo and endogenous substances can act as chemoattractants
Exo- bacterial products (possess N-formyl-methionine terminal amino acid or lipids)
Endo- C5a, leukotriene B4, IL-8

Question 31

Describe the steps involved in chemotaxis.

Answer 31

Binding of chemoattractants
G-protein medicated signal transduction (some cause increased cytosolic calcium which trigger contraction for movement)
Leukocytes move by extending pseudopods that anchor to ECM and pull

Question 32

How long does it take for neutrophils to infiltrate during acute inflammation? Are there any variations?

Answer 32

Type of emigrating leukocyte varies with the age of the
inflammatory response and with the type of stimulus.

In most forms of acute inflammation, neutrophils
predominate in the inflammatory infiltrate during the first 6 to 24 hours and are replaced by monocytes in 24 to 48 hours

Question 33

What is the stimuli for and function of leukocyte activation?

Answer 33

Stimuli: microbes, products of necrotic cells &
mediators

Functions:
– Intracellular destruction of phagocytosed microbes
and dead cells
– Liberation of substances that destroy extracellular
microbes and dead tissues
– Production of mediators

Question 34

Describe the function of lymphatic vessels in inflammation.

Answer 34

Increased lymph flow in inflammation
Drains edema, leukocytes and cell debris
Transports microbes

Question 35

Define lymphangitis.

Answer 35

Inflamed lymphatics

Question 36

Define lymphadenitis.

Answer 36

Inflamed lymph nodes
Enlarged due to hyperplasia of lymphoid follicles, increased number of lymphocytes and phagocytic cells lining the sinuses of lymph nodes

Question 37

Describe the termination of the inflammatory response.

Answer 37

Neutralization, decay, or enzymatic degradation of chemical mediators
Normalization of vascular permeability
Cessation of leukocyte emigration
Death (by apoptosis) of extravasated neutrophils Leukocytes begin to produce mediators that inhibit inflammation
The necrotic debris, edema fluid, and inflammatory cells are cleared by phagocytes and lymphatic drainage

Question 38

What are the outcomes of inflammation?

Answer 38

Complete resolution: regeneration of native cells, restoration of site of acute inflammation to normal

Progression to chronic inflammation

Healing by fibrosis and scarring