Cell mediated Immunity

Role of CD8 T cells

Direct killing of target cells

Role of CD4 cells

Release cytokines to activate B cells and macrophages

Locations of intracellular pathogens

Vesicular or cytoplasmic

When are effector T cells activated

When encounter antigens

What is the T cells growth Factor and which T cell produces it

IL 2 produced primarily by CD4

Three pathways of effector T cells

Remain in lymph node, lymphoid organs, or Memory T cells

What molecules are involved in T cell activation

TCR-MHC

CD28-B7

Accessory Moleucles: LFA-1 - ICAM-1

What is the role of accessory molecules in T cell activation

Increase binding strength

What molecules can lead to T cell inhibition

CTLA-4 or PD-1 interactions with CD28

What is the major differentiation point in superantigen activation

Binding cite inside vs. outside the MHC 2 complex groove; superantigen = outside groove

What type of T cell binding causes a higher percentage of T cells to respond

Super antigen

What is the effect of superantigen binding

Cytokines storms

What would happen if CD28 binds B7 on APC

Activation

What would happen if CTLA-4 is bound to B7 on APC

Inhibition

What happens if PD-1 binds PD-L1/PDL-2 on APC

Inhibition

Which receptor on the APC has a stronger affinity for B7

CTLA - 4; overrides CD28

What is the significance of CD40(APC) -CD40 ligand(T cell)

Makes better APCS; increase proliferation and recognition of antigen

Is CD40 initially presented on the T cell

No, once activated it “upgrades”

How do CD40 interactions help macrophages

Activation and killing of phagocytosed microbes

How do CD40 interactions help B cells

Secretion of antibodies and enchances abilities to neutralize or eliminate antigens; Isotype switching

What is cross presentation

CD8 T cells and CD4 T cells recognize antigen on APC that has ingested infected cell

What are the genetic switches

NFAT, NFkB, AP-1

ITAMs

Immunoreceptaros related to transcription activation

What cyclosporin

Imunosuppressant by inhibiting T cell growth by inhibiting IL-2 production

How is IL-2 produced

Kinases and phosphatases ( phosphorylation and dephosphorylation)

How is cyclosporin involved in IL-2 suppresion

Prevents NFAT from accessing the DNA in the nucleus by disabling calcineruin by adding a phosphate group

When is IL-2R BY complex converted to Il-2RABY and how does it affect affinity

Alpha arrives only after activation of the cells; increasing affinity

What is the other name for IL-2RABY

CD25

What type of T cell does IL-2 maintain

T Reg Cells

Homing of effector T cells to a site of infection is independent of antigen recognition but antigen specific lymphocytes are preferentially retained at the site. HOW?

Because they bind to an antigen present in the peripheral tissues, those who don’t will return to circulation

Following infections which T cells have a higher response overall

CD8 T cells

Negative regulation of T cell activation: who shuts off T cell activation

CTLA-4 and PD-1

EXC: how do you attenuate T cell activation using CTLA-4 IG fusion protein

Binds B7 and prevents binding too CD28

Outline T cell activation

Explain the role of CD4 T helper cells in intracellular infection

Explain the role of CD4 T helper cells in extracellular infections

What are the types of Effector T cells

Th1, Th2, Th17, Tfh

What cytokines and do Th1 release and what is the target cells

IFN-y targets Macrophages

What cytokines do Th2 release and what cells do they target

IL-4, IL5, IL-13 and targets eosinophils

What cytokines are released by Th17 and what cells do they target

IL-17 and IL-22 which target neutrophils

What cytokines are released by Tfh and what cells do they target

IL-21 and IFN-y targeting B cells

What Th subset provides beneficial autoimmunity

Th2

What Th subset causes detrimental autoimmunity

Th1 and Th17

What are the key factors in Th1 development

IL-12 incuding cytokines - IFN-y signature Th1 cytokines/ amplification

What are the functions of Th1 cells

Produce INF-y to activate M1 macrophages, up-regulate MHC2

What aids in Development of Th2 cells

IL-4 inducing cytokines - IL4/5/13 signature Th2 cytokines. IL 4 amplifies response

What is the function of Th2 cells

immunity again the helminths via ADCC. Production of antibodies by B cells.

How does ADCC act via Th2 cells

Th2 cells produce IL5 which recruits eosinophils which then become cytotoxic and self destruct via ADCC

What T cell cytokines activates M1 vs M2 macrophages

Th1 cytokine = M1

Th2 cytokine = M2

How are Th1 and Th2 cells cross regulated

The cytokines they produce inhibit the functions of the other Th cell

What cytokines help in development of Th17 cells

IL-1,IL-6, TGF beta inducing cytokines

IL-23 stabilizes Th17 response

IL17 and IL22 signature Th17 cytokines

Il21 amplifies response

What is the primary function of Th17 cells

produce IL17 and IL22 to help recruit neutrophils and monocytes

What is the role of helper T cells in activation of CD8 T cells

Bind DC and produce cytokines (IL-2,IL-12, IFN-y) to a naive T CD8 Tcell to activate it

What are the steps in CTL mediated lysis of target cells ( Assassins)

Antigen recognition — granule exocytosis — detachment of CTL — Targeted cell death

What is the major mechanism for cell killing

Granzymes → cytochrome C → apoptosome → Caspase 3 → CAD

What is the minor mechanism for cell killing

FAS or TNFR →caspase 8 → Caspase 3 → CAD

What is a Virokine

Cytokine produced by a virus to inhibit macrophages