Lecture 16: Immune activation, Helper cells and regulation

Question 1

T Cell antigen recognition?

Answer 1

T cell receptors (red) read what antigen is being presented by the HLA molecule whilst the CD4 and CD8 molecules recognise a conserved region present on the HLA.

Question 2

Rare genetic defects in TAP genes? What does it show us?

Answer 2

T antigen presenting gene defects are rare but lead to:

• Poor endogenous antigen processing
• Low HLA-A, B and C expression
• Few CD8 T Cells, normal CD4 T cell numbers
• Recurrent respiratory viral infections

1. HLA class 1 is required for CD8 T cell development
2. CD8 T cells are important in viral infection

Question 3

Adhesion molecules?

Answer 3

Are upregulated on the surface of BV by local infection (eg. bacteria) and diffusion of chemotactic factors, slowing down WBC eventually causing them to stop.

Selectins = Weak interactions, direct cell traffic around body

Integrins = Strong cell-cell adesions, hold cells in tissues together and hold lymphocytes together for activation.

IgSF = immunoglobulin superfamily (ligands for integrins, contain Ig-like domains)

Question 4

Selectin sub-categories?

Answer 4

L-selectin

• Circulating non-memory lymphocytes (high endothelial venules)

P-selectin

• Platelets
• Endothelial cells <—> neutrophils

E-selectin

• Vascular endothelium
• induced by pro-inflammatory cytokines (IL-1, TNF-alpha)
• <–> leukocytes

Question 5

Lymphocyte activation steps?

Answer 5

1. Integrin binds with IgSF molecule
2. CD4 and TCR bind to the MHC class II molecule
3. Co-stmulator/chechpoint regulators then decide

Question 6

Costimulators/Checkpoint Regulators?

Answer 6

Pairs of surface molecules expressed in cell-cell interaction

• B7 on APC with CD28 on T cells
• CD40 on B cells eith CD40L on T cells

Expressed transiently and modulate immun activation processes

Co-inhibitors

• Interactions switch off response
• CTLA-4 (present on TR cells and competes with CD28) with B7
• PD-1 with PD-L1 (programmed cell death protein 1)

Question 7

How do checkpoint regulators work?

Answer 7

• Upon uptake of foreign antigens/bacteria along with danger signals from surrounding cells the co-stimulator is expressed on the surface of the APC.
• As these travel to the secondary lymphoid organs and present to the T cells there is the 1st signal
• The 2nd signal is sent if it finds the costimulator (eg. B7) with its receptor (eg. CD28) and the T Cell is Activated.
• Without this second signal there is no activation of the T cell but rather is becomes anergic. This occurs when there is no danger signals and is one of the ways we develop tolerance to self antigens.

Question 8

B cell antigen presentation?

Answer 8

B Cells like APC can take up antigens bound to their surface and present them on their surface in MHC class II molecules.

These can then be recognised by TH Cells and through a process can decide if the B cell needs help with the problem.

Question 9

CD4 T cell clonal activation?

Answer 9

Question 10

What are cytokines?

Answer 10

• Small glycoprotein messenger molecules
• Usually synthesized de novo.
• Act on the surface of other cells via specific membrane receptors
• Paracrine, autocrine and sometimes endocrine

Question 11

Cytokine properties?

Answer 11

Pleiotropic - Can have different outcomes depending on what they are acting on

Redundant - More than one cytokine to the same end

Synergistic - Often intensify the action of another cytokine

Antagonistic - Often can act against eachother