L12 - Helper T Cells

Explain T Cell and APC Dialogue

1. MHC presents antigen to TCR on T Cell

2. Upregulation of CD154 (receptor) → binds with CD40 on APC

3. Upregulation of CD28 → binds with CD80/86 on APC

4. T Cell is activatred → secretes IL-2 → T cell differentiation

5. CD152 → binds to CD80/86 → inactivates T Cell

6. Formation of indolamine deoxygenase (IDO) → destroys tryptophan → T cell response terminated

cSMAC

Central Supramolecular Activation Cluster → MHC and TCR interaction (activation signal)

pSMAC

Peripheral supramolecular activation clusters

CD2/CD4/8 → adhesion/co-stimulatory molecules

Why is costimulation important in T cell activation?

Costimulation increases the signal that antigen wouldn’t be able to provide by itself → allows small foreign material to produce large signal

What are super antigens?

Don’t bind within groove → induces strong immune responses quickly from non-specific T cells

(ex. Rabies)

How do naive T cells turn into specific T helper subtypes?

T subtypes are based on cytokines (proteins) → which are encoded by DNA → which are translated by transcription factors → some cytokines will activate certain transcription factors during MHC-TCR interaction

Th1 from naive T Cell (polarizing cytokines, transcription factors and effector cytokines, function)

Polarizing Cytokines: IL-12 and IFN-y

Transcription Factors: T bet

Effector Cytokines: IFN-y, TNF-a and IL-2

Function: T cell responses

Th2 from naive T Cell (polarizing cytokines, transcription factors and effector cytokines)

Polarizing Cytokines: IL-4, IL-33, TSLP

Transcription Factors: GATA3

Effector Cytokines: IL-4, IL-5, IL-9, IL-13

Functions: B cell responses → IgE

Th17 from naive T Cell (polarizing cytokines, transcription factors and effector cytokines)

Polarizing Cytokines: IL-6, IL-23, TGFB

Transcription Factors: ROR-yt

Effector Cytokines: IL-17, IL-21, IL-22

Functions: Increased inflammation

What happens when macrophages aren’t activated by T helper cells via IFN-y?

Macrophages will not be able to kill bacteria entirely → they grow back

What does IgE do?

Mast cell degranulation → kills parasites

What is iNOS and what increases its production?

Increases macrophage killing of bacteria

IFNy

What do Th1, Th2 and Th17 respectively defend against?

Th1 → intracellular pathogens

Th2 → parasites

Th17 → extracellular pathogens

In what species does y/delta helper T cells dominate?

Young ruminants and pigs