Lecture 10- Activation and Differentiation of CD4+ T cells part 2

Question 1

What are the different immune responses (for different pathogens) driven by?

Answer 1

Different cytokines. Prodominantly released by CD4+ T helper cells

Question 2

What are cytokines?

Answer 2

Small proteins released by cells that have specific effects on interactions between cells, on communications between cells or on the behaviour of cells, usually act over short distances

Question 3

What do different cytokine messages promote? (different combinations in time and space)

Answer 3

Promote the differentiation and function of CD4+ T cells

Question 4

What are the functions of Th1 and Th2 cells?

Answer 4

Th1= essential in responses to intracellular pathogens, e.g. viruses and some bacteria

Th2= essential in responses to extracellular pathogens e.g. some bacteria and parasites

Question 5

How were Th1 and Th2 cells categorised?

Answer 5

By the different cytokines they produced

Question 6

What do Th1 and Th2 cells produce?

Answer 6

Th1 produces-
IL2,
Interferon-gamma= classic Lymphotoxin (LT)

Th2 produces-
IL4, IL5, IL9, IL13

Question 7

What do the th1 and th2 helper cells differentiate to have functions of?

Answer 7

Th1: Activate macrophages, stimulate CD8+ T cells, Stimulate B cells to produce opsinizing antibodies
All of these are activated to help deal with an intracellular pathogen

Th2: Stimulate B cells to produce neutralising antibodies, attract and activate eosinophils and basophils. This is to deal with large extracellular pathogens

Question 8

Recap of how you get specific T cells, last lecture?

Answer 8

Signal 1- antigen recognition by TCR
Signal 2- co-stimulatory molecule cd28-cd80/86
interaction strengthened by adhesion receptors
clonal expansion

Question 9

What do you need for differentiation into different Th cells?

Answer 9

Need signal 3= cytokine signal to the T cell

Question 10

What are the classic signal 3 cytokines for th1 cells?

Answer 10

Il-12 (produced by dendritic cells)

IFNgamma (produced by th1 cell, chicken and egg sitch)

Question 11

What are the classic signal 3 cytokines for th2 cells?

Answer 11

A number of cytokines from epithelial cells e.g. TSLP

IL4 (from th2 cells, chicken egg again, maybe basophils are initial il4 source?)

Question 12

How do Th1 and Th2 subsets cross regulate each other?

Answer 12

Th1 cells down regulate the production of th2 cells by the secretion of IFN-gamma
Th2 cells down regulate the production of th1 cells by secretion of IL4
-> get polarised immune response to th1 or th2 dominated responses,

Question 13

How can th1 cells be harmful?

Answer 13

autoimmunity and transplantation rejection

Question 14

How can th2 cells be harmful?

Answer 14

allergy and some situations of autoimmunity

Question 15

Where is all this happening?

Answer 15

1. initial t cell activation, prolif. and differentiation= in lymphoid organs
2. Once differentiates, move from lymph nodes to carry out job

Question 16

Whilst differentiation what do th cells acquire?

Answer 16

Homing molecules on their sufrace, enabling them to migrate within the lymph node and to other tissues of the body

Question 17

What cd4+t cell lineages have been discovered within the ppast 10-15 years?

Answer 17

Novel effector subsets- t helper 17 cells(Th17), t follicular helper cells (Tfh)

Special regulatory subset: regulatory t cells (Tregs)

Question 18

Th17 cells main features?

Answer 18

regulate immune response at epithelial surfaces e.g. lung and intestine
Primarily characterised by secretion of IL17- why its called 17

Question 19

What are the signal 3s that drive Th17 cells?

Answer 19

TGF-beta, IL6, IL1

once differentiated it produces IL17, IL21. IL22.

Question 20

What is the main function of Th17 cells?

Answer 20

Important in fighting some fungal and bacterial infections

but implicated in some autoimmune diseases

Question 21

T follicular helper T cells

Answer 21

Helper T cells that go to B cell follicles (germinal centres) of lumph nodes to help B cells make antibody.
They acquire a special receptor on their surface to be able to move there.

Question 22

How come we have some self-harmful t cells?

Answer 22

Potentially self-harmful cd4+ t cells can arise in the periphery, try get rid of them but still have a few potentially harmful t cells floating around

Question 23

Tregs function?

Answer 23

Suppress self-harmful immune responses. stop the t cells that are self-harmful

Question 24

how are Tregs formed?

Answer 24

2 ways:
1. made in thymus in normal t cell development. Signals that Upregulate transcription factor foxp3.= normal or thymus Tregs

2. during t cell activation certain signal 3s and antigen strengths can cause differentiation to Treg rather than t helper lineage. Il2+TGF-beta. = induced or peripheral Tregs

Question 25

What do Tregs produce?

Answer 25

(tgf-beta regulates tregs)
Tregs also make TGF-beta and IL10 cytokines
These are important in their suppressing function

Question 26

Treg function, how does it work?

Answer 26

Produce anti-inflammatory cytokines.
Outcompete effector t cells for resources (e.g. mops up IL2)
kill self-reactive t cells

Question 27

What does lack of Tregs cause?

Answer 27

autoimmune diseases

Question 28

What is T cell plasticity?

Answer 28

Not so simple as just t cell goes to one lineage. CD4+ t cells subsets can become other subsets when needed. Perhaps to allow more rapid response to different types of infection (complicated dw too much)