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1
Q

What do nitric oxide, prostaglandins and histamines do?

A

Vasodilation
Increase vascular permeability
Smooth muscle contraction
Pain

2
Q

What do pro-inflammatory cytokines do?

A

Increase vascular permeability

Activate the endothelial cells

3
Q

What do chemokines do?

A

Chemotaxis and recruit neutrophils to the site of infection

4
Q

What occurs during vascular permeability?

A

The tight junctions between endothelial cells are lost creating gaps between the cells

5
Q

What occurs during vasodilation and increased blood flow?

A

The vessels swell and and the increase in blood volume creates a slower flow which allows neutrophils to marginate to the side of the venule

6
Q

What occurs during endothelial cell activation?

A

The endothelial cells become activated leading to the expression of adhesion molecules - selectins and ICAM/VCAM

7
Q

What occurs during the transendotheial migration of leukocytes?

A

Neutorphils will bind weakly to selectins and so will roll alond the endothelial surface as bonds are made and broken. They will bind strongly to ICAM/VCAM ligands present on the cell surface. The receptors on leukocytes is called intergrins - Integrins will bind to ICAM/VCAM.

8
Q

What is diapedesis?

A

When leukocytes squeeze through the endothelial cells

9
Q

What occurs during chemotaxis of neutrophils?

A

The leukocyte will follow a chemokine gradient to the site of inflammation through a process of chemotaxis. Compounds that neutrohphils will follow are bacerial products, complement components and chemokines

10
Q

Where are chemokines produced?

A

Activated macrophages and mast cells

11
Q

What is a neutrophil?

A

A polymorphonuclear cell that performs phagocytosis. It is recruited to inflammatory sites by cytokines and other pro-inflammatory signales. It will aslo produce TNFα

12
Q

What are the 3 ways a neutrophil can kill?

A

Phagocytosis
Degranulation
NETs

13
Q

How so neutrophils kill via phagocytosis?

A

Infected tissues will release chemokine like signals that attract neutrophils
These neutrophils use PRRs to bind to and phagocytose the pathogen.

14
Q

What are the 2 mechanisms of phagocytosis a neutrophil can use?

A

Antimicrobial proteins and enzymes

Reactive oxygen species

15
Q

How do antimicrobial proteins and enzymes phagocytose?

A

Antimicrobial proteins and lysosomes will fuse with the phagosome:
Lysozyme = degrades cell wall of gram +ve bacteria
Acidification = bactericidal/ bacteriostatic
Lactoferrin = Starves bacteria of iron
Defensins
Acid hydrolyases = digest bacteria

16
Q

How do reactive oxygen species phagocytose?

A

The NADHP oxidase complex is made after neutrophil activation
The toxic reactive oxygen species (ROS) is released into the phagolysosome

17
Q

How does degranulation phagocytose?

A

It will release anti-bacterial proteins from the neutrohpil granules into the extracellular space. This induces the direct killing of extracellular pathogens.
BUT will cause tissue damage and inflammation as it will kill healthy cells as well as infected cells

18
Q

How does NETs phagocytose?

A

Activated neutrohpils will release NETs into the extracellular environment to immobilize pathogens. It prevents them from spreading and facilitates phagocytosis

19
Q

How long do neutrophils live?

A

Short lived

20
Q

What is the complement system?

A

Family of proteins produced in the liver that circulate the blood and enter infected or inflamed tissues.
They are activated directly or indirectly by pathogens. When triggered, the complement proteins will activate each other in a cascade

21
Q

What are the functions of the complement system?

A

Pathogen killing
Pathogen opsonisation
Leukocyte recruitment and inflammation
Removal of immune-complexes

22
Q

What is the mannose-binding lectin pathway?

A

The mannose-binding protein, is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding to pathogen surfaces.
C3 - C3b + C3a

23
Q

What can C3b activate?

A

C5b and C5a which will attack the membrane of cells called MAC (Membrane Attack Complex)
This is particularly important in the defence against encapsulated bacteria

24
Q

What is opsonisation?

A

The coating of pathogens by opsonins to facilitate phagocytosis

25
Q

What are examples of opsonins?

A

C3b
CRP - (C-reactive Protein)
IgG/ IgM (antibodies)

26
Q

What are C3a and C5a known as?

A

Anaphylatoxins as they promote inflammation and activate mast cells

27
Q

What are some characteristics of the complement system?

A

Very small inital signal but has a very large effect
Very rapid activation
Potent amplification loop

28
Q

How is the complement system regulated?

A

Only cleaved complement proteins are active
They have a very short half life
Some only produced in the acute phase response
Some do not bind to human cells
Inhibitors and regulators limit the activation of the system

29
Q

What are dendritic cells?

A

Professional antigen presenting cells. They are present in the peripheral tissues in an immature state and then will phagocytose antigens, cell debris and particles
They then mature and migrate into secondary lymphoid tissues where they present the antigens