Lecture 9: Immune activation, helper cells and regulation

Question 1

Write some notes on antigen transport and presentation:

Answer 1

Typically dendritic cells are sampling all the proteins in their environment and present these to immune cells in the lymph nodes. Majority of presentations do not illicit a response.

Question 2

What are the properties of HLA exogenous pathway class 2?

Answer 2

• Found on B cells and specialized APCs
• Co-dominant
• Polymorphic
• Present peptides to CD4 T cells

Question 3

What are the properties of HLA endogenous pathway class 1?

Answer 3

• Found on virtually all nucleated cells
• Co-dominant
• Polymorphic
• Present peptides to CD8 cells

Question 4

Describe the relationship of antigens and class 1 HLA:

Answer 4

Class 1 HLA is present on all nucleated cells and will present samples from the cellular environment i.e self and non-self such as viral proteins.`

Question 5

Whats the MHC 1 structure?

Answer 5

Alpha chain + B2 microglobulin

Question 6

Describe the relationship of antigens and class 2 HLA:

Answer 6

Phagocytic cell ingests and breaks down pathogen, peptides are presented on surface by class 2 MHC (HLA-DP, DQ or DR)

Also some cross representation by MHC class one (present on all nucleated cells) (HLA-A,B or C)

Question 7

Describe MHC stucture:

Answer 7

Alpha chain and beta chain

Question 8

Write some notes on the peptide groove for MHC1&2:

Answer 8

HLA is unique to everyone. It can determine which parts of an antigen are presented and this in turn influences response.

Question 9

Write some notes on the process of CD8 T cell antigen recognition:

Answer 9

Cytotoxic T cells:

CD8 (essential for class one recognition)
TCR(alpha,beta) - Recognises peptide and part of HL
CD3 (When TCR bound, this undergoes conformational change to relay back to internal cell)

Target cell:

Class 1 MHC with peptide being presented

Question 10

Write some notes on the process of CD4 T cell antigen recognition:

Answer 10

CD4+TCR+CD3 <-> Class 2 MHC + Peptide

Question 11

What happens to patients with defects in TAP genes?

Answer 11

• Poor endogenous antigen processing
• Low HLA-A, B, C expression
• Few CD8 T cells, normal CD4 T cell numbers
• Recurrent resp. viral infections

= (tells us that HLA class 1 is required for CD8 t cell development, and CD8 t cells are important in viral infections)

Question 12

What prevents CD8 T cells from reacting to the presentation of self peptide?

Answer 12

Accessory molecules: Adhesion, co-stimulators, checkpoint regulators, cytokines

Question 13

What are the extravasation adhesion molecules?

Answer 13

Selectins (Weak interactions, direct cell traffic around body, like velcro)

Integrins (Strong cell:cell adhesion, hold cells in tissues together, hold lymphocytes together for activation)

Question 14

What are the weak adhesion molecules involved in extravasation?

Answer 14

L-Selectin: Circulating non-memory lymphocytes

P-selectin: Platelets, endothelial cells and neutrophils

E-selectin: Vascular Endothelium, induced by proinflam cytokines (i.e IL1, TNFa), b/w leukocytes

Low affinity, Rapid association and dissociation

Question 15

Write some notes on integrins: how are immunoglobulin superfamily molecules related (IgSF)?

Answer 15

• Strong adhesion, tissue integrity, site-specific addressins, involved in lymphocyte activation

IgSF - Ligands for integrins, contain Ig-like domain

Question 16

Describe extravasation:

Answer 16

Neutrophil

• Weak binding to endothelium via selectins
• Triggers integrin expression
• Strong binding triggers migration and diapedesis

Neutrophils follow chemotactic gradient

Question 17

What are cadherins?

Answer 17

Cadherins

• Embryogenesis
• Tissue development
• Homophilic interactions

Question 18

Whats the first step of lymphocyte activation?

Answer 18

Integrin/IgSF interaction

i.e T cell, LFA-1 interact with APC ICAM-3

Allows MHC class 2 and TCR to test for affinity

Question 19

Whats the second step of lymphocyte activation?

Answer 19

Co-stimulators or checkpoint regulators are upregulated following TCR-MHC2 strong affinity

Question 20

Write some notes on checkpoint regulators / costimulators:

Answer 20

• Pairs of surface molecules expressedin cell-cell interactions

i. e B7 on APC <-> CD28 on T cells
i. e CD40 on B cells <-> CD40L on T cells

• Expressed transiently
• Modulate immune activation processess
• Prevents reacting against self antigen because the APC wont upregulate their checkpoint regulators without DAMP/PAMP being present in the protein

Question 21

How do T cells help B cells?

Answer 21

Ig binds many things, B cells which recognize Ig Fe regions require T helper cell co-stimulation to initiate action

i.e B cells endocytose Ig-AB complex. Breaks down AB and presents it on MHC-2. This interacts with T cell, Co-timulators/checkpoints upregulated and if responses needed Th releases cytokines to activated the B cell, expansion etc.

Question 22

What are some co-stimulators and co-inhibitors?

Answer 22

Costimulators:
- Interaction = activation i.e CD28:B7, CD40:CD40L

Co-inhibitors
- Interaction = switch off respoinse i.e CTLA-4:B7, PD-1:PD-L1

Question 23

Describe CD4 t cell clonal activation:

Answer 23

MHC class 2 : CD4 t cell (Costim+Cytokines)

• > Gets Th cytokine signal
• > Proliferate and differentiat4e into memory cells and cytokine secreting cells

Question 24

What are cyotkines?

Answer 24

• Small glycoprotein messenger molecules
• Paracrine, endocrine and autocrine
• Specific receptors

Question 25

What are cytokine properties?

Answer 25

Pleiotropic : B and Th cell proliferation, mast cell activation

Redundant : B cell proliferation

Synergistic : AB class switch to IgE

Antagonistic : Block IL-4 induced IgE class switch

Question 26

What is cytokines synonymous with?

Answer 26

Interleukins: Between leukocytes
Interferon : Interferes with viral replication
CSF : Colony stimulating factor