Helper T cells and their response to antigen (12)

*Explain importance of costimulation in T cell activation

Cytokines produced leads to the formation of lots of T cells & get a proper immune response Absence of CO stimulation leads to no response in the top

interleukin-2 (IL-2) made by

T cells

T helper cells (TH) The type of T helper cell is defined by ...

the cytokines secreted and not by any surface molecule (APC when they encounter a micro they engulf & process & secret certain kinds of cytokines Theses cytokines tell naïve T helper cells which way to go)

Naïve TH cells differentiate into TH1, TH2, TH17, Treg depending on ...

the signals naïve TH cells receive from APCs and the local environment

Development of TH1, TH2, and TH17 effector cells Generation of these subsets is regulated by ...

the stimuli that naïve CD4+ T cells receive when they encounter microbial antigens

Each effector T cell subset produces cytokines that amplify itself and inhibit the other subsets Differentiation of each subset is associated with the activation of ...

transcription factors that stimulate production of various cytokines

Whenever seen think about extracellular pathogens & inflammation = Th____ - Number of key cytokines IL-23 is the most important out of these

17

Role of co-stimulation in T cell activation W & W/O it

Absence of CO stimulation leads to no response Need proper host simulation to lead to a response - Activated by certain cytokines - Cytokines produced leads to the formation of lots of T cells & get a proper immune response

Role of CD4 and CD8 What T cells are they called ?

CD4 (Helper T cell) or CD8 (Cytotoxic T cell)

*Explain differences in TCR complex of a T helper cell and a cytotoxic T cell

CD4 (Helper T cell) or CD8 (Cytotoxic T cell) Ag is presented on MHC1 for CD8 CD4 Ag is present on MHC 2

Conventional antigen vs. Superantigen

Conventional Ag binds TCR to Ag on MHC Super antigen is any bacteria protein that bind to nonspecific manner outside the MHC molecule & TCR - ACTIVATE lots of T cells with lots of specificity, leads to strong response - Leading to formation of cytokines - This can lead to toxic shock syndrome because lot of cytokine production

Ag is presented on MHC ___ for CD8 CD4 Ag is present on MHC ___

I II

Innate and adaptive functions of γδ T cells

INNATE: found in skin & uterus Limited TCR diversity resonizing Produce IFN-y & IL-17 AP to alpha/beta cells ADAPTIVE: found in GI tract & secondary lymphoid organ Polyclonal TCRs reconizing multiple Ag Th1 subset IFN-y Th2 subset IL-4

*Explain how T cell - APC interaction results in activation or invactivation of T cell response

Interaction is a hug ( between T cell & APC) There are multiple molecules that are required to make it meaningful Starts with a handshake then ends as a hug 1) T cell found it Ag it ( hand shake) 2) T cell found it Ag is the first step then once this starts gets the signal to produce CD154 molecule on T cell which act with CD40 on the APC - Once bound these leads to more expression of more CD molecules 3) Once CD28 binds to CD80/86 which will leads to activation of T cells which is mediated by IL-2 - IL-2 increases the metabolism of the cell and leads to cell proliferation 4) After 24 / 72 hours of this then leads to inactivation by CD80/86 on APC will bind to CD152 152 bind then they will stop proliferation ( Leads to inactivation) - Indolamine deoxygenase (IDO) ---> destroys tryphtophan ----> T cell response is terminated Acivatded by CD80/86 on APC will bind to CD152 or CD28 - If both present will prefer to bind to CD152 which leads to inactivation All these are called co stimulating molecules which are interaction with receptors only once T cell finds it Ag

Cytokines produced by TH1 cells and their major functions

Interlukin-2 : Activates T, B & NK cells & macropahges Promotes Th1 activateion Controls Tregs Interferon-gamma : Inhibits Th2, stimulates Th1, Activates NK cells Activates macrophages Antiviral

Cytokines produced by TH2 cells and their major functions

Interlukin-4 ( stimulates B cell growth & differetni, activates mast cells, activates macrophages, supress th17 & th1 activation ) Interlukin 5 ( stim. B cells growth , activates eosphinophiles Interlukin-9 ( T cell growth factor) Interllukin -10( inhibits Th1, supresses macrophage function Interlukin-13 ( stim. B cel & supress macrophage function)

T helper cells (TH) recognize antigens displayed on ...

MHC II

____ is what leads to differentiation to Th17 - Talking about inflammation, things that lead to an income of cells - IL-17 Leads to neutrophils accumulation & activation

ROR- gamma

CD4+ αβ T cells are called ...

T helper cells

* Describe the structure of TCR complex

TCR has CD3 no matter what & either CD8 or CD4 attached to it

Can you tell whether it's a T helper cell by looking at this structure - no Now we can tell that it's a T-helper cell by seeing

TCR has CD3 no matter what & either CD8 or CD4 attached to it can tell it is a T helper cell because CD4 is present

* Explain differences in TCR complex of a T helper cell and a cytotoxic T cell

TCR has CD3 no matter what & either CD8 or CD4 attached to it can tell it is a T helper cell because CD4 is present Can tell cytotoxic because of CD8 present Ag is presented on MHC1 for CD8 CD4 Ag is present on MHC 2

Major differences between TH1 and TH2 populations

TH1 IL-2 IFN- y TNF- beta T cell ctyotox Macrophage activation Some IgG production TH2 IL-4,IL-5,IL-10,1L-13 Some IgG production IgA & gE production

IFNγ can be made by ...

Th1 cells , NK cells , & CD8 T cells

*Name different cytokines involved in development of various T cell subsets

Th1- Need IL-12 & IFNy Th2- IL-4 Th17- IL-1, IL-6, IL-23, TGF-beta

Who can make interleukin-4

Th2 cells & mast cells

Immunological synapse - interactions between APC and TH cells SMAC = supramolecular activation clusters is what?

You have a central area of interaction between TCR & APC SMACs arrange in concentric rings to form a characteristic 'bulls eye' Have TCR finding the Ag is the most important than other come in to stabilize the reaction

Most important signal for differentiation of naïve CD4+ T cells into distinct subsets are ...

cytokines produced by APCs, which in turn is determined by the nature of infection

Differentiation of Naïve TH cells happens where ?

lymph nodes APC present Ag to T cells in the lymph node Depends on what they microbe is they have differentiation that happens in the lymph node - Can lead to getting out of the lymhp node & goes to the site they are needed

Successful stimulation of a T cell requires ...

multiple signals Need multiple interaction to make a strong signal Ideal situation is 1 Ag with multiple costimulatory molecules