Inflammation 1

Question 1

Why does inflammation occur?

Answer 1

In response to :
Infection
Trauma
Foreign bodies
Immune reaction
Necrosis of any cause

Question 2

Why is inflammation both helpful and unhelpful?

Answer 2

Aid recovery from tissue damage but may also contribute to tissue damage

Question 3

What is the inflammatory response?

Answer 3

Acute inflammation

Chronic inflammation

Question 4

Acute inflammation and what happens?

Answer 4

Initial response to tissue injury (delivery of cells and mediators to injury):

Vascular phase of increased flow
Exudate formation
Neutorphil polymorph infiltration of tissue
bacterial phagocytosis and killing
Resolution, suppuration, organisation or chronicity

Question 5

Phases of acute inflammation, in order?

Answer 5

Vascular phase

Cellular phase

Question 6

Morphological features (signs) of inflammation due to phases?

Answer 6

Calor (heat)
Dolor (pain)
Rubor (redness)
Tumour (swelling)
Loss of function

Question 7

Basic steps of the vascular phase in acute inflammation and what vessels does this affect?

Answer 7

Marked changes in blood flow:
Initially, vasoconstriction followed by prolonged VASODILATION, accompanied by increased vascular PERMEABILITY (slow blood flow)

First occurs in arterioles and then capillary beds.

Leads to formation of protein-rich exudate and tissue oedema

Question 8

Why does the tissue appear red and warm?

Answer 8

Due to the increased blood flow to the site (vasodilation)

Question 9

What is vascular permeability?

Answer 9

Results in “leaky” vessels; loss of proteins

Question 10

Why does the tissue swell?

Answer 10

Vascular permeability leads to changes in osmotic pressure; water follow protein causing swelling (tumour)

Question 11

Why does vascular permeability occur?

Answer 11

Endothelial contraction - response to inflammatory mediators, like histamine, bradykinin, leukotrienes, nitric oxide

Direct injury - burns or bacterial infection

White cell injury - from leukocytes (release of cytotoxic agents causes endothelial injury)

Question 12

What does the cellular phase involve? Steps?

Answer 12

Movement of wbcs (particularly neutrophils) from circulation to injured site:

White cell margination
Rolling
Adhesions
Migration

Question 13

What is white cell margination and why does it occur?

Answer 13

During slowing of blood flow (vascular phase), larger wbcs move towards blood vessel peripheries (near endothelium)

Question 14

What is rolling of wbcs?

Answer 14

Wbcs roll along endothelial surface of blood vessels due to slow blood flow

Question 15

What does adhesion of wbcs involve?

Answer 15

During rolling, wbcs adhere to endothelial surface.

Question 16

Why does adhesion occur?

Answer 16

Endothelial cells express selectins of their surfaces - recognise specific carb groups (ligands) found on macrophage/neutrophil cell surfaces

Intergrins bind to blood vessel walls, specifically to ligands (like VCAM and ICAM)

VCAMs - Vascular Cell Adhesion Molcule (immunoglobins on endothelial cell surface)

ICAMs - Intercellular Cell Adhesion Molecule (immunoglobins on endothelial cell surface)

Question 17

How is adhesion enhanced and why?

Answer 17

Integrin/selectin interaction with ligands is of low affinity (binding on and off is fast)

HISTAMINE (release by mast cells, basophils and platelets) and thrombin increase selectin expression

Pro-inflammatory cytokines TNF (Tumour Necrosis Factor) and Interleukin 1 (IL-1) increase endothelial cell expression of VCAM AND ICAM

Question 18

What are cytokines?

Answer 18

Small protein that are involved with cell signalling

Question 19

What are chemokines?

Answer 19

Cell signalling molecules involves with inducing chemotaxis (movement of a molecule along a chemical gradient)

Question 20

How is the avidity between adhesive molecules increased?

Answer 20

Chemokines from injury site bind to proteoglycans on endothelial cell surface

Proteoglycans increase affinity of VCAMs and ICAMs for integrins

Question 21

What occurs after adhesion?

Answer 21

The wbcs pass between adjacent endothelial cells (permeability) out of circulation

Migrate to injured site via chemotaxis (respond to conc. gradient of chemotaxins)

Question 22

What are the 3 phases of phagocytosis?

Answer 22

Recognition and attachment
Engulfment
Killing and Degradation

Question 23

Recognition and attachment of neutrophils to injurious agent?

Answer 23

Via opsonins, which coat the e.g: bacteria. Opsonins can be immunoglobins, complements and carb molecules

Via mannose sugars, recognised by car-binding proteins/lectins in plasma which attach. In turn, mannose receptors are recognised by neutrophils

Scavenger receptors on neutrophils recognise LDL (similar mechanism)

Question 24

What does engulfing of the injurious agent involve?

Answer 24

Pseudopods (cytoplasmic extensions) flow around bacterium and cell membranes fuse, enclosing bacterium in phagosome

Lysosome binds, forming phagolysosome leading to bacterial killing

Question 25

What types of killing mechanisms exist for neutrophils/macrophages?

Answer 25

Oxygen dependent (more important)
Oxygen independent

Question 26

Mechanism for oxygen-dependent killing?

Answer 26

Reactive oxygen metabolites generated during phagocytosis due to rapid action of NADPH oxidase on NADPH (oxygen gains electron from NADPH and becomes a superoxide)

Conversion into hydrogen peroxide which is converted into killing agents

Also, reactive nitrogen metabolites are formed (nitric oxide synthase combines NO with superoxide and produces ONOO)

Question 27

Why does pain (dolor) occur due to inflammation?

Answer 27

Mediated by prostaglandins and bradykinin

Question 28

What are neutrophils and how do they appear?

Answer 28

Short-lived inflammatory wbc that characterises inflammation

Polymorph - many lobes to one nucleus

Granulocyte - has granules (secretory vesicles) in cytoplasm

Has phagocytic and cytotoxic abilities