Cell subsets

How does the 3:d signal of T cell activation happen?

The T cell 3:d signal need signal like cytokine that being produced by the innate immune cells from differente intruders like viruses, intracellular bacteria, extracellular bacteria or helminths for it to differentiate into different T cells.

How does an activated T cell recognize and respond to polarizing cytokines from innate immune sensing?

1. The polarizing cytokine comes and bind into the cytokine receptor which is a transmembrane receptor that is connected to tyrosine kinase activity that is called JAK/Janus -kinases

2. The complex get activated after the signal binding into the receptor

3. Which leads to activation (phosphorylation) of STATS protein in the cytosol

4. And then form a STAT dimer

5. They then translocate from the cytosol to the nucleus and activate transcription factor and gene expression for T CD4 T cell types

Which cytokines and transcription factors generate each CD4 T-cell subset?

Tell me about Th1 cell differentiation:

• Interleukin 12- is an antibacterial cytokine

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• It is not just the IL12 that can differentiate Th1 cell there is also TNF-alpha, IL18 or IL Beta (it’s like a cocktail) but the main it IL-12 = pro-inflammatory cytokine

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• NK cells can also produce cytokines in an early bacterial infection and one of it is Interferon Gamma that help with differentiation of the Th 1 cell.

Tell me about Th2 cell differentiation:

• The Th 2 is activated in response of the epithelial damage that is done by large parasites

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• Basophils and mast cells get activated and then they produce the anti-inflammatory cytokine like IL-4

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• Which leads to activation of STAT6 and then GATA3

Tell me about Th17 cell differentiation:

• Th17 are not only activated by these inflammatory cytokines, but also these local, cytokines that is TGF-beta.

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• It can differentiates by a combination of anti and pro-inflammatory

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• TGF-beta has another pathway than the IL-6

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Tell me about Tfh (T follicular) cell differentiation:

IL-6 + IL-21
↓
STAT3 activation
↓
BCL6 expression
↓
T cell differentiates toward a T follicular helper (Tfh) cell
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↑ CXCR5 expression
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CXCR5 guides the Tfh cell toward the B-cell follicle by following CXCL13
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Tfh cell interacts with B cells and helps them.

Tell me about Treg (Regulatory T) cell differentiation:

	Thymic Treg	Peripheral Treg
Where?	Thymus	Periphery
Starting cell	Developing CD4⁺ T cell	Mature CD4⁺ T cell
Important signals	Self-antigen + IL-2	TGF-β + IL-2 + tolerogenic environment
Key transcription factor	FOXP3	FOXP3
Function	Immune tolerance	Immune tolerance

• These cells are important for maintaining self-tolerance and preventing excessive immune responses.

What are the roles of polarizing and effector cytokines?

• Polarizing cytokines act on the activated CD4 T cell and

determine its differentiation.

• Effector cytokines are produced by the differentiated T cell and

act on other cells.

What does effector cytokines do?

• Effector cytokines activate the cells needed to eliminate each type of pathogen

(Subset → effector molecules → target cell → main function)

What does effector cytokines that is secreted by Th 1 do?

ROS= reactive oxygen species - that is used to kill microbes in macrophage

In this process there i co-stimulation (2 of them) one is by IFN-gamma and the other by CD40L-CD40

What does effector cytokines that is secreted by Th 2 do?

• It boosts the function of the granulocytes

What is Reciprocally inhibit?

What does effector cytokines that is secreted by Th 17 do?

• They induce antimicrobial peptides

What does effector cytokines that is secreted by Tfh do?

What does effector cytokines that is secreted by Treg do?

How is the CD8 develop?

NAd how is the CD8 activated?

HOw can DC activate CD8 when it is not infected?

By using cross-presentation process

How do CD8 recognize and kill infected cells?

Give me summery about differentiation of the CD4 cells:

Give me summery about activation of the CD8 cells: