T-cell activities Flashcards
Naive T-cell enters lymph node via?
2 routes
- Blood vessel–> HEV
- Afferent lymph vessel from upstream lymph node
Naive t-cell gets directed into lymph node…..
- **Rolling interaction: **L-selectin (t-cell) :: GlyCAM-1 and CD34 (endothelial cell)
- Chemokine interaction: CCR7 (naive t-cell)::SLC/ ELC on endothelial cell
- **Tight binding: **LFA-1 :: ICAM 1
- **Diapedesis **
**Interactions bewteen CD4 and MHC ___ **
(x5)
What’s the end result?
Interactions bewteen CD4 T cell:: MHC II
- **Adhesion: **LFA-1 :: ICAM1/2
- **Adhesion: **CD2: LFA-3
- **Activation Part 1: **CD4 (Lck):: MHC II
- Activation Part 2: CD3 (TCR):: MHC II antigen
- **Coactivation: **CD34:: B71/2
Activation T-cell CD45 Tyrosine kinase–> activation of transcription factors.
**Interaction between CD8+ and MHC ___. **
**End result is? **
Interactions bewteen CD8 T cell:: MHC I
- Adhesion: LFA-1 :: ICAM1/2
- **Adhesion: **CD2: LFA-3
- **Activation Part 1: **CD8 (Lck):: MHC I
- **Activation Part 2: **CD3 (TCR):: MHC I antigen
- **Coactivation: **CD34:: B7-1/2
**Activation of T-cell CD45 tyrosine kinase–> PIP II/ DAG/IP3 cascade **
**notice this is identical to CD4 except for CD4 and MHC parts and final cascade**
What receptor changes depending on whether or not the T-cell is activated? What does that receptor bind and do in active/inactive T-cells?
Inactive/Naive T-cells: CD28 bind B7 on APC==> ++ activation of T-cell
Active T-cell: CTLA-4 binds B7==> LIMITS activation and proliferation.
- What happens if the APC doesn’t have B7? What’s the purpose of this response?
- Why doesn’t it have it?
*
- B7 only expressed by ACTIVATED professional APC
- T-cell + antigen w/o B7==> Anergy
- If an APC has an antigen but no B7, it’s likely presenting a self-antigen.
What induces APC maturation/activation?
Inflammatory cytokines, TLR ligands
What are the professional APC’s
- Dendritic cells, b-cells, macrophages
- Their distribution varies
THESE ARE THE ONLY CELLS THAT WILL EXPRESS B7!!
These cells are especially important for T-cell activation in the lymph nodes!
Dendritic cells.
**B-cells **
- Antigen uptake
- MHC expression
- B7
- Antigen presentation
- location
- Antigen uptake==> Ag specific receptor holds ag
- **MHC expression: * ***++ to ++++ (increases with activation, but always active)
- Stimulation/actvity- Inducible – to +++
- **Antigen presentation: **Soluble Ag, toxins, viruses
- **location: **blood, lymph
**Macrophages **
- Antigen uptake
- MHC expression
- B7
- Antigen presentation
- location
- Antigen uptake==> phagocytosis
- MHC expression: **inducible by bactera and cytokines
- Stimulation/actvity- Inducible – to +++
- **Antigen presentation: **particulate ag, extracellular and intracellular pathogens
- **location: **lymph, CT, body cavity
Dendritic cells
- Antigen uptake
- MHC expression
- B7
- Antigen presentation
- location
- Antigen uptake==> macropinocytosis/phagocytosis
- MHC expression: low in tissues, high in lymph nodes
- Stimulation/actvity- always active
- **Antigen presentation: **peptides, viral antigens, allergens
- **location: **Lymph, CT, epithelia
These cells are pretty good at activating T-cells at the site of infection and inflammation
Macrophages- they present EC bacteria
These present soluble antigens
B-cells
- Immature dendritic cells lack
- Mature dendritic cells lakc
- Immature= No co-stimulatory Ag activity
- Mature= no phagocytic abilities
- What induces differentiation of dendritic cells?
- What do the mature dendritic cells gain (receptors/markers?)
- LPS, cell wall products, TNF alpha (and other inflammatory cytokines?)
- Gain B7 and CCR7 markers.
Things IL-2 Does
- T-cell prolifarion, increased cytokine produciton (IL-4, IFN gamma)
- B-cell proliferation and Ab production
- NK proliferation and cytolytic activity
T-cell expresses different things when naive vs activated. What TWO things change?
- L-selectin in NAIVE cell, VLA-4 in MATURE cell
- CD45RA in NAIVE, CD45R0 in Mature
VLA= very late antigen
Type 1 cytokines promote ____. They are ___ and are released by? ?
Type 1= cell mediated =IFN-gamma, IL-2
Released by TH1 cells
Type 2 cytokines promote, are released by, are/
Type II= Humoral immunity= IL2,3,4,5,9,13
Released by TH2 cells
TH17 cells release?
IL-17 and 22 = promotion of inflammation
- To promote TH1 (over TH2)
- To inhibit TH1?
- Pro TH1: IL-12, IFN-gamma
- Anti TH1: IL-4, IL-10
- Pro TH2
- Anti TH2
- Pro TH2= IL4
- Anti TH2= IFN-gamma
- Pro TH17
- Anti TH17
- IL-1, IL-6 IL-23
- IL-4, IFN gamma
Humoral response can be stimulated by?
BOTH Th1 and Th2 cells.
Th2= acivation of b-cells to make Ab (general)
Th1= Activation of opsonizing Ab like IgG1
TH2
- Induction
- cytokines produced
- effect
TH2
- Induction: IL-4 (basophils) ==> GATA3 ON= committed
- **cytokines produced: **IL-4, IL-5, IL13 (IL-10?)
- effect: increased pdt of neutralizing Ab (IgG4), IgE, Basophil, eosinophil and mast cell activation.
BIG FOR PARASITES
TH1
- Induction
- cytokines produced
- effect
TH1
- Induction: IL-2 (macrophages, DC), IFN-gamma (NK cells)==> T-BET turns on= committed TH1 cell
- **cytokines produced: **IL-2, TNF-apha, IFN-gamma, IL3, CXCL2. GM-CSF
- effect:
- IL2=self proliferation, t-cell proliferation
- TNF-alpha- Endothelial activation (adhesion and diapedesis enhanced)
- **IFN-gamma- **macrophage activation
- **CXCL-8- **draws macrophages to site of infection
- GM-CSF/ IL3= macrophage differentiation in bone marrow and spleen
Functions of the Cell-mediated response?
- Control of intracellular pathogens and tumors
- transplant rejection
- type 4 hypersensitivity
- contribute to granuloma formation
- contribute to chronic inflammation
TFH Cells
Release IL21, IL4 and IFN gamma to activate B-cells, switch asotybe and increase antibody affinity.
TH17
- Precursor cell
- Induction
- **Inhibition **
- **Cytokines released? **
- Precursornaive CD4+ or CD8+ t-cells
- Induced by IL1, IL-6, IL-23
- Inhibited by : Il2, IL4, IFN-gamma
- **Releases: **
- IL-17= induces G-CSF expression, chemokines to attract neutrophil
- IL-22= Antibacterial proteins
- IL 21, 26
T-regulator Cells
**AKA Tregs, FoxP3+ cells **
- TFG-beta, IL-10, IL-35
- Suppresses activity of the other T-effector cells.
- Expersses: CD25, CTLA4
TC cells- cytokines and main objective
Release TNF beta, porforin, granzymes and Fas-induced apoptosis= serial killer cell.
Activation of CD8+ cells
- CD8+ cell needs CD28 from APC to become active/effector CD8+ cell
- Effector cell proliferates and differentiates with IL-2 that it makes or TH cell makes
- Effector CD8+ T-cell can kill cells expressing antigen in MHC I WITHOUT CD28 signal.
But, at first, needs the CD28 signal.
How do we detect cell killing activity of CD8 T cells?
51Cr in cells, when they get killed the release it
Granulomas
- defense mechanism to prevent spread of infection
- aggregation of infected cells (lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts, collagen)
- can be from poor TH1 activation
How does the CNS regulate the immune system?
SNS, PNS, pituitary, neuroendocrine output.
Stress= immunosupressant
Immune system regulation on CNS?
IL1,6, TNF alpha = fever, sleepiness, fatigue, loss of appetite, decreased libido.
Immune system and liver?
Induces synthesis of acute phase proteins= sickness behavior
