Acute Inflammation

Question 1

what are some sources of infection?

Answer 1

Injury
Trauma
Foreign bodies
Immune reaction, e.g. allergic reaction
Necrosis of any cause

Question 2

What are the possible responses to injury?

Answer 2

Vascular changes
Cellular changes
Chemical changes
Chemical Mediators
Morphologic Patterns

Question 3

What is the process of vascular changes in response to infection?

Answer 3

Changes in flow and vessel calibre
Vasodilation
First involves arterioles and then capillary beds.
Mediated by histamine and nitric oxide.
Results in increased heat (calor) and redness/erythema (rubor).

Question 4

What are some differences between in the blood vessels in normal tissue and tissue with acute inflammation?

Answer 4

In normal tissue the blood vessels have a closed precapillary sphincter.
In tissue with acute inflammation, the blood vessels have an open precapillary sphincter.
Normally the vessel walls are slippy and blood cells don’t stick.
In inflammation the vessels express various proteins on the luminal surface that have a matching protein on white cell surface.
Key and lock (ligands)

Question 5

What are some examples of cellular changes?

Answer 5

• Stasis
• White cell margination
• Rolling
• Adhesions
• Migration

Question 6

What happens in Normal flow?

Answer 6

Blood flows centrally within a vessel.
With vascular dilation the rate of flow slows.
Cells are able to move peripherally - especially larger white cells.
White cell margination.

Question 7

What are the roles of histamine, thrombin and Tumour necrosis factor (TNF) which are all inflammatory cell?

Answer 7

Histamine and thrombin from inflammatory cells increase selectin expression.
Tumour necrosis factor (TNF) and interleukin-1 (IL-1) increase endothelial cell expression of VCAM and ICAM.

Question 8

How does increased avidity occur and what does it mean?

Answer 8

Chemokines from the site of injury bind to proteoglycans on endothelial cell surface.
These proteoglycans then increase the affinity of VCAMs and ICAMs for integrins.
Increased affinity makes things more attracted to each other.

Question 9

What is the result of Vascular Permeability?

Answer 9

Leaky Vessels - loss of proteins
Change in osmotic pressure
Water follows protein - swelling (tumour)

Question 10

What are some reasons that blood vessels could be leaky?

Answer 10

Endothelial contraction - histamine, bradykinin, substance P, leukotrienes.
Direct Injury - toxins, burns.
White cells - self harm.
Transcytosis - VEGF mediated.
New vessel formation - VEGF makes new vessels but also increases leakiness.

Question 11

What are chemotaxis?

Answer 11

Cells follow a chemical gradient and move along it.
Bacterial components.
Complement.
Leukotrienes.
Cytokines - interleukins

Question 12

What are the 3 phases of Phagocytosis?

Answer 12

3 phases.
Recognition and attachment.
Engulfment.
Killing and degradation.

Question 13

What is the process of Recognition and Attachment, the first stage of phagocytosis?

Answer 13

Mannose receptors.
Bacterial surface glycoproteins and glycolipids contain terminal mannose residues.
Mammalian glycoproteins and glycolipids do not (sialic acid or N-acetylgalactosamine)
. Scavenger Receptors.
Similar to mechanism that phagocytes recognise low density lipoprotein.
Opsonins.
Bacteria etc. are coated with proteins making them standout from the crowd.
Include components of the complement cascade as well as immunoglobin (IgG).

Question 14

What is the process of Engulfment, the second stage of phagocytosis?

Answer 14

Pseudopods
Vesicle formation - phagosome
Joins with lysosome - phagolysosome

Question 15

What is the process of Killing and Degradation, the third and final stage of phagocytosis?

Answer 15

Reactive oxygen species.
NADPH oxidase - oxygen gains an electron from NADPH and becomes superoxide.
Reactive nitrogen species.
Nitric oxide synthase - combines NO with superoxide ONOO.
Many other cytotoxic granules.

Question 16

What are the clinical features of inflammation?

Answer 16

Rubor = Redness.
- Increased perfusion. Slow flow. Increased permeability of vessels.
Calor = Colour
- Heat
- Again - increased perfusion, slow flow rate, increased vascular permeability.
Tumor
- Literal translation - swelling
- Again due to vascular changes
Dolor = Painful
- Mediated by prostaglandins and bradykinin

Question 17

What is Functiono Laesa?

Answer 17

Loss of function

Question 18

What are the Microscopic Appearances of a neutrophil?

Answer 18

The inflammatory cell that characterises acute inflammation is the neutrophil.
"Polymorph"
Many lobes to nucleus (poly)
Granulocyte
Phagoytic and Cytotoxic abilities

Question 19

In acute inflammation:
What stages are drug target?
What two general types of changes occur?
What is the main cell of acute inflammation?

Answer 19

The chemical signals etc. are al potential drug targets.
Vascular changes
Cellular changes
The main cell of acute inflammation is the neutrophil.

Question 20

What are the selectins, Integrins, Vascular cell adhesion molecules and Intercellular adhesion molecules?

Answer 20

Selectins - expressed on various cells (endothelial cells and white cells).
Integrins - over 30 types. Bind to ICAM.
Vascular cell adhesion molecules (VCAM). They are important in inflammation, immune responses and in intercellular signalling events.
Intercellular adhesion molecule (ICAM). Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial cells and is crucial in promoting adhesion and transmigration of circulating leukocytes across the blood–brain barrier.

Question 21

Leukocytes play an important role in eliminating offending agents. Neutrophils and macrophages are capable of destroying microbes, necrotic tissue, and foreign substances.
The process of leukocytes migrating from the blood vessel to tissue involves multiple steps and are mediated by adhesion molecules and chemokines. Can you describe this process?

Answer 21

Margination - accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in the early stages of inflammation. (leukocytes become redistributed closer to the vessel wall).
Rolling - leukocytes transiently attach to endothelium and then detach
these cells therefore “roll” on the vessel wall. The endothelium possesses E-selectin and P-selectin.
Cytokines from the inflamed tissue regulate selectin expression.
Sialyl-Lewis X protein binds to E-selectin and P-selectin.
Found on leukocytes.
Pavementing-Term used to describe the margination of leucocytes on the endothelium near a site of damage.Dictionary of molecular biology. The sticking of white blood cells to the linings of the finest blood vessels (capillaries) when inflammation occurs.
Firm endothelial adhesion - mediated by integrin proteins.
Vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule-1 (ICAM-1) are found on the endothelium.
Low affinity integrin are found on leukocytes.
Migration through the vessel wall and migration to tissue.
The integrin/selectin interaction with their ligands is of low affinity and binding on is fast and binding off is also fast.