3. Inflammation

Question 1

What is the definition of inflammation?

Answer 1

Tissue response to injury/infection characterised by increased blood flow and entry of leukocytes into the tissues

Question 2

What is complement?

Answer 2

Key component of inflammation, 20-40 molecules in a system (many enzymes) which act in an amplification cascade in order to amplify a small stimulus

Question 3

What are the three complement activating pathways? Describe each pathway

Answer 3

1. Classical pathway: complement activated when antibody binds to antigen
2. Lectin pathway: C/A pathway intermediate, mannose binding lectin may bind to bacterial cell walls (mannose) on surface of microbes - activates
3. Alternative pathway: complement activated directly by other stuff on microbial surfaces

Question 4

How many complement activating pathways will be used when infection occurs?

Answer 4

All of them, get activated at different points

Question 5

Which complement activating pathway takes the longest to activate?

Answer 5

Classical

Question 6

Which enzyme is common in all three complement activating pathways? What does it do?

Answer 6

C3 convertase - converts C3 complement component into fragments C3A and C3B - central thing that occurs when complement activated

Question 7

What happens in complement when C(number) split?

Answer 7

They develop a function, e.g. C3 splitting creates C3A and B which both have functions

Question 8

Which is produced first, C3 convertase or C5 convertase?

Answer 8

C3, you fuckwit

Question 9

What does complement do?

Answer 9

1. C5B to C9 produce MAC (membrane attack complex)
2. C3A, C4A, C5A stimulate mast cells to release granules (
3. C3B and C4B coat microorganisms and opsonise them, link organism to phagocytic cell (like glue)
4. C3D activates B lymphocytes

Question 10

Which complement protein is recognised by RBCs?

Answer 10

C3B (infection->antibody produced->complement activated->microorganism coated with C3B->recognised by RBC)

Question 11

After the RBC has recognised C3B what does it do with the pathogen?

Answer 11

Takes pathogen to spleen and liver where lots of macrophages are present in order to destroy the pathogen

Question 12

Why is opsonisation of microorganisms undertaken when Toll-like receptors recognise them relatively well anyway?

Answer 12

Coating microorganism with antibody and complement (phagocyte has receptors for both) provides a very strong binding

Question 13

How exactly is the membrane attack complex formed?

Answer 13

1. C5 convertase deposited on cell surface causes C5 to be split into C5A and B
2. C6 and C7 recruited
3. C8 recruited, punches small hole in membrane
4. Several C9 molecules come and polymerise to form pore

Question 14

What cells cause inflammation and how?

Answer 14

Mast cells

1. C5A, C4A, damager triggers degranulation of mast cells, activation of phospholipase A2 and release of vasoactive amines (histamines), cytokines and chemotactic factors
2. phospholipase A2 produces arachidonic acid which activates lipoxygenase/cyclooxygenase pathways producing leukotrienes and prostaglandins
3. histamine enhances vascular permeability allowing neutrophils out of blood

Acute inflammatory response is reliant on getting neutrophils into tissues

Question 15

Which complement molecules also act as a chemotactic factor?

Answer 15

C5A and C3A - attract neutrophils to site of infection

Question 16

How do macrophages play a role in inflammation?

Answer 16

More dominant in chronic inflammation but release cytokines

Question 17

How are neutrophils alerted?

Answer 17

1. Endothelium expresses E-selectin in response to activating substances
2. E-selectin grabs hold of neutrophil via CD15 (glycoprotein)
3. This slows down neutrophils and cause them to roll along blood vessel wall
4. E-selectin then sends signal into neutrophil to cause it to express integrin (adhesion molecule)
5. Lipopolysaccharides/interleukin 1/tumour necrosis factor causes neutrophils to express ICAM-1 (integrin receptor)
6. C3A, C5A, histamine etc widen gaps in endothelial cells allowing neutrophils to squeeze through (diapedesis)

Question 18

What is diapedesis?

Answer 18

Movement of blood cells (e.g. neutrophils) through intact capillary walls into surrounding bodily tissue