L3. Adhesion, Chemotactic and Cytokine molecules

Question 1

What are the steps in neutrophil migration from blood to tissues

Answer 1

1. AMPs from bacterial infection in tissues can activate complement components
2. Result in
   - diffusion of chemotactic factors and
   - increased selectins and integrins expression on nearby endothelium
   - spaces between cells expand to allow neutrophils to pass through
3. Neutrophil in blood lumen gets weak binding to selectins to slow down
4. This triggers integrin expression on neutrophil and endothelium
5. Strong binding stops it and triggers migration
6. Neutrophil moves between the tight junctions along the chemotactic gradient to the target

Question 2

Compare the binding strength and purpose of Selectins vs Integrins

Different names depending on site of expression

Answer 2

Selectins have low affinity and rapid association and dissociation.
Their purpose is to direct cell traffic around body

Integrins have strong cell-cell adhesion.
Role is in tissue integrity and hold lymphocytes to target cells for activation

Question 3

What are IgSF molecules and Cadherins

Answer 3

IgSF are ligands for integrins and contain Ig-like domains

Cadherins are involved in binding tissues together to make organs in embryogenesis

Question 4

What are the steps of CD4 (helper) T cell clonal activation

Answer 4

1. In 2’ lymphoid organs an antigen is presented by APC/B cell with Class 2 HLA to CD4 T cell
2. A small # of mature T cell with good affinity binds to it = recognise
3. Co stimulation from APC activates it, as well as other helper signals + IL1 which is required.
4. It responds by dividing and proliferating into two populations

a) Activated T cells that go around looking for that
They produce cytokines which modulate B cells and other immune cell groups to respond

b) Memory cells - replace the original and help subsequent responses to the same antigen be quicker, more vigorous and without needing helper signals

Question 5

What tissues make cytokines (are they paracrine, autocrine or endocrine? ),

when are they made and what receptors do they effect

Answer 5

Cytokines are all 3 crines - but mostly paracrine (self limited locally acting) - they are made when they are needed by cells. A diverse range of tissues can produce the same cytokine

They affect target cells via very high affinity interaction with specific membrane receptors.

Question 6

Define the Pleiotropic, Redundant, Synergistic and Antagonistic shared cytokine properties

Answer 6

1. Pleiotropic: One cytokine can act on different cell types/targets
2. Redundant: Many cytokines do the same thing - overlapping actions
3. Synergistic: Two or more cytokines often work together to get a bigger overall effect (e.g. IL4+5
4. Antagonistic: They can block the effect of other cytokines eg. IFN-y blocks IL4 induced class switch

Question 7

What are the 3 different names for cytokines

Answer 7

Interleukins, (IL-#)
Interferons (INF)
Colony stimulating factor (CSF)