T cell Mediated Immunity Flashcards
What is present on a Mature Naive T cell
CD4+ or CD8+ CD28+ MHC/HLA class 1 TCR complex including CD3 molecules and Zeta LFA-1 and VLA -4 adhesion molecules Chemokine receptor CCR7
Where does T cell activation occur
Lymph organs
by Dendritic cells
What activates Memory T cells
B cells and Macrophages and Dendritic cells
Who activates B cells and Macrophages
CD4+ T cells
What happens in the process of activation of DCs
once a peripheral DC is activated itloses its adhesive markers and up regulates CCR7
Increses expression in MHC/HLA and CD80 (B7)
Travel to the secondary lymphpoid tissue and they mature as they migrate
Finally they present Ag to T cell
How do the Naive T cell migrate into the Peripheral Lymphoid organ
go across the High endothelium venules (HEV) in the cortex
L selectin
L selectin ligand
Naive T cells
Initial weak adhesion to naive T cells to the high endothelial Venule in lymph node
LFA-1
B2 Integrin
binds ICAM-1
Stable arrest on HEV
CCR7
on Naive T cell
binds CCL19 or CCL21
Activation of integrins and chemotaxis
E and P selectin ligand
Found on Effector T cells
binds E and P selectin on Endothelial
Initial weak adhesion of effecto and memory T cell to cytokine activated endothelium at peripheral site of infection
LFA-1
VLA-4
B2 and B1 integrin respectively
binds ICAM or VCAM on endothelial cell
Stable arrest on cytokine activated endothelium at peripheral site of infection
CXCR3
on Effector and activated T cell
binds CXCL10
activation of Integrins and chemotaxis usual in the direction of the follicle wear the B cell is located
Surface molecules of T Lymphocytes: CD3
signal transduction by TCR complex
Surface molecules of T Lymphocytes: Zeta
Signal transduction by TCR complex
Surface molecules of T Lymphocytes: CD4
SIgnal transduction
binds to Class II MHC on antigen presenting cells
Surface molecules of T Lymphocytes: CD8
signal Transduction
Binds to Class I MHC presented on all nucleated cells
Surface molecules of T Lymphocytes: CD28
Signal transduction (costimulation)
Binds B7-1/B7-2 on antigen presenting cell (CD80)
Surface molecules of T Lymphocytes: CTLA-4
Inhibition signal
Binds B7-1 and B7-2 ligands on Antigen presenting cells
Surface molecules of T Lymphocytes: PD-1
Inhibition signal
Binds to PD-L1/PD-L2
on antigen presenting cells, tissue cells, and tumor cells
Surface molecules of T Lymphocytes: LFA-1
Adhesion signal transduction
Binds ICAM-1
on Antigen binding cells and endothelium
what happens to integrins when there is TCR/HLA antigen recognition
Changes its affinity from low to high
causes clustering and makes a strong T cell and APC adhesion leading to a strong T-cell response
What is the First Signal of the T cell activation
Binding of the MHC/peptide complex to the TCR
What is the second signal to get a T cell activation
Co stimulatory molecules:
CD40L on T cell binds to the CD40 on the APC
B7 binds to CD28 on the T Cell and then cytokines are released and taken in by the T cell (IL-12)
What Cytokine is released from the APC and taken up by the naive T cell
IL-12 to enhance T cell proliferation and differentiation
T cell activation signal cascade
LcK activates the ITAM and tyrosine kinase ZAP-70
THis activates PLCy, Ras, Rac, and PI3
PLCy increaseds cytocolic Ca2+ and DAG which produces calcineurin and PKC
RAS and RAC in its GTP form activate ERK and JNK
PI3 kinase activates PIP3 and akt and mTOR
All of these produce NFAT and NFkB and AP-1 which increases protein synthesis
Protein production after T cells triggered
Fos-minutes myc-hours CD40 ligand-hours Fas ligand-hours IL-2 IFN-Y IL-4
IL-2Ra or CDC25
Why do we increase the amount of CD40L
increase the Tcell and APC adhesion and prolongs the T cell APC contact
What happens if there is no co stimulatory ligands or cytokines supporting the APC T cell interaction
T cell will become anergic and tolerand
No response
IL-2
T cell proliferation and T cell survival
Activated T cells
IFN-y
Activation of Macrophages
released by: CD4/CD8 T cells and NK cells
IL-4
B cell switching to IgE
released by: CD4 T cells and mast cells
IL-5
Activation of Eosinophils
released by: CD4 T cells, mast cells, and innate lymphoid cells
IL-17
Stimulation of acute inflammation
released by:CD4 T cells
IL-22
Maintenance of Epithelial barrier function
released by: CD4 T cells, NK cells, and innate lymphoid cells
TGF-B and IL-10
Inhibition of T cell activation, differentiation of regulatory T cells
released by: CD4 T cells and may other cell types
How do T cells self stimulate IL-2
IL-2 is autocrine signal
Binds IL-2RByc which is at a low affinity
Expression of IL-2RA chain adds to the receptor to increase its affinity and help induce T cell proliferation and differentiation
How are Naive T cells trapped and activated
Signal from IFN A/B increases Expression of CD69
CD69 binds to S1PR and internalizes signal to allow for the cell to proliferate and activate t
Takes about 5 days
what Cytokines cause Differentiation into what T helper cell: Th1
IFN-y and IL-12
what Cytokines cause Differentiation into what T helper cell: Th2
IL-4
what Cytokines cause Differentiation into what T helper cell: Th17
IL-1 and IL-6
what Cytokines cause Differentiation into what T helper cell: Tfh
IL-21,
(IFN -y/IL-4)
What are important components of CTL deveolpment
CD4 T helper cells
production of IFN-y and IL-2
Cross presentation of B7 via APC or IL-2 via CD4 cells
Components of T regulatory Cells
CD4 T cells
Influenced by IL-2 and TGF-B
Express CTLA-4 and CD25
Novel Transcription factor FOXp3
Secrete IL-10 and TGF-B
Gamma Delta T cells
Found in Epithelial boundaries especially the gut Mucosa
Can recognize non protein AG
limited diversity of peptides recognized
Not restricted to MHC/HLA presentation
What is major difference between effector T cell and resting Naive T cell?
Effector T cell is able to respond to a specific antigen without need for Co stimulation via B7 or CD28 interaction
Th1 cell components
Proliferate in response to Il-12 and IFN-y
work on macrophages and NK
secrete IL-2 and IFN-y
novel transcription is T-bet
What does IFN-y do
activates Macrophages classical activates B cells to do class switching to IgG antibodies and complement binding Stimulates class II HLA and B7 expression
Th2 cells components
Proliferate in response to IL-4
Targets allergens and helmnths
Novel transcription is GSTA-3
secretes IL-4, IL-5, IL-13
Th2 cell mediation
cause B cells to switch to IgE
- Antibody production
- Mast cell degranulation
Eosinphil activation
intestinal mucus secretion and peristalsis
Alternative macrophage activation: tissue repair
What happens if the Th1/Th2 ratio is off
Th1 is necessary to fight off microbe
therefore a predominate Th2 response can lead to a bad outcome and lots of microbes
-Leprosy`
Th17 cells components
Proliferate via IL-1 and IL-7
REsponse to bacteria and fungus
Induce inflammation
and leukocyte recruitment
Novel transcription RORyt
secrete IL-17 and IL-22
Not every effector T cell that enters the area will be specific for that antigen
Do to the various specificity of the effectors and that tissue may not contain the antigen it is specific for
what are the 2 methods of killing for the CTL
Granular proteins
- granzymes
- Perforin
FasL and Fas (CD95)
-induction of the apoptic pathway
What do CTL-A cells release
IFNa/B
inhibits replication of viruses
increases expression of MHC class I on other infected cells
Treg cells components
CD4 T cells
express CTLA, and CD25
FOXp3 transcription factor
CTLA-4 binds B7 and shuts co-stimulatory ligand signaling
stronger binding that CD28
What do Memory T cells require for survivial
IL-7 and IL-15
What happens to T cells over chronic illnesses
Exhaustion
inabillity to respond to virus and high expression of CTLA-1 and PD-1
No cytokine secretion
reduced proliferation,
no target cell killing
Evasive mechanisms: Mycobacteria
Inhibit Phagolysosome fusion
survive in phagoosome
Evasive mechanisms: Herpes (HSV)
Inhibition of antigen presentation by attacking TAP transporter
Evasive mechanisms: Cytomegalovirus (CMV)
inhibition of antigen presentation by affecting the proteasomal activity and removeing MHC molecules from ER
Evasive mechanisms: Epstein Barr (EBV)
inhibition of antigen presenting by inactivating proteasomes
Evasive mechanisms:Epstein Barr (EBV)
Production of IL 10 to inhibit macrophages and DC activation
Evasive mechanisms:Pox virus
Block cytokine activation of effector cells