T Cell Activation and Humoral Immunity
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- What is the co-receptor for helper T cells?
- CD4
- What is the co-receptor for cytotoxic T cells?
- CD8
- Antigen presenting cells present to CD4 T cells using which MHC class?
- MHC II
- Antigen presenting cells present antigens to cytotoxic T cells using which MHC class?
- MHC class 1
- MHC II peptides come from what type of antigens?
- exogenous antigens
- Stem cells that become T cells are directed to thymus by way of what molecules? Which interleukin?
-
Thymic hormones
IL-7 - Where in the thymus are cells located that have MHC I and MHC II molecules? What cells are these?
-
Stroma
Dendritic cells and Epithelial Cells - What is the first step of thymocyte maturation?
- thymocytes interact with MHC molecules on epithelial cells.
- What is positive selection in T cell maturation?
- Thymocytes that bind slightly to MHC have become MHC restricted to self. This is Positive selection.
- What happens in the cortex when thymocyte cells bind too tightly to MHC molecules?
- apoptosis
- What are the two types of T cell receptors?
-
αβ T-cell receptor
AND
γδ T-cell receptor
- When do Naïve T cells differentiate into effector cells?
- once they encounter and bind to foreign peptide:MHC complexes on target/APC cell.
- What type of cells to Cytotoxic T cells target?
- target cells, virally infected cells, tumor cells and allograft rejection
- What percentage of TCR are αβ TCR or γδ TCR?
-
95% T- cells = αβ TCR.
3-5% T- cells= γδ T-cells
- What is the function of effector cell CD4+ TH1:
- activate macrophages, provide help to B cells.
- What is the function of effector cell CD4+ TH2?
- Help B cells make antibodies, plays role in class switching, switches to IgE in allergic reaction.
- What is the function of effector cell CD4+ TH17?
- produce interleukin 17, been shown to play role in up regulating and enhancing neutrophil regulation in immune responses.
- What is the function of effector cell CD4 T reg?
- regulates the immune response
- What are effector cells?
- T cells that have been activated and differentiated to perform a specific function; traffic to tertiary tissue sites; Effector cells can go into gut and out into skin-they go further out to combat.
- Decribe the TCR.
-
1. Membrane Bound
2. 4 extracellular domains
3. heterodimer (alpha-beta or gamma-delta)
4. associated with CD3 - Why is the TCR associated with the CD3 molecule?
- CD3 molecule complements T cell receptor. This receptor fails to signal messages into the cell because short tail can’t interact with much of the biochemical components within the cell. SO it is complemented by CD3
- What are the 3 forms of the CD3 cytoplasmic tail? How do they compliment the TCR?
- CD3-have epsilon delta, gamma delta and zeta zeta chains. Their cytoplasmic tails are longer; where biochemical signals enter the cell and biochemical molecules initiate response.
- To what structure/molecule does TCR co-receptors bind?
- Bind to conserved, nonpolymorphic regions of MHC class II or class I molecules on APCs or target cells
- What is one role of TCR co-receptors?
- Stabilize the MHC-TCR iteraction
- What molecule associates with CD4 and CD3 to stabilize the TCR-MHC interaction?
- p56
- List the 4 adhesion molecules and their ligands.
-
CD2 (ligand LFA-3)
2. LFA-1 (ligand ICAM-1)
3. CD28 (ligand B-7): the second signal
4. CD45R (ligand CD22) - What are the functions of adhesion molecules?
-
All of these bind T cell to antigen presenting cell to lock the complex in place.
Some adhesion molecules also play a role in trafficking; associated with the vasculature; help release products from circulation.
- What type of molecule are MHC?
- glycoproteins
- What are the extracellular domains of MHC Class I?
-
Alpha 1, 2 and 3.
Associated Beta2-microglobulin - What are the extracellular domains of the MHC II molecule?
- Alpha 1 and alpha 2 and Beta 1 and beta 2
- Which domains form the peptide binding cleft of the MHC I molecule?
- Alpha 1 and alpha 2
- Which domains form the peptide-binding cleft of the MHC II molecules?
- Alpha 1 and beta 1
- What is required for antigen processing?
- T-cell recognition of antigen and activation
- Which cells are antigen-presenting cells?
- macrophages, dendritic cells, B cells
- What is the "prime" antigen presenting cell?
- dendritic cells
- Which cells express MHC I?
- ALL NUCLEATED CELLS
- Which antigen presenting cell can present to all classes of T cells?
- Dendritic Cells
- When macrophages are activated, what changes occur in the membrane?
- Once stimulated, MHC II and B7 expression is induced
- What is B7?
- B7 is a type of peripheral membrane protein found on activated antigen presenting cells (APC) that, when paired with either a CD28 or CD152 (CTLA-4) surface protein on a T cell, can produce a costimulatory signal to enhance or decrease the activity of a MHC-TCR signal between the APC and the T cell
- Activated macrophages can present to which cells?
-
Effector T cells
Memory T cells - Activated B cells can present to which cells?
-
Naive T cells
Effector T cells
Memory T cells - Which Antigen Presenting cells have inducible B7?
- Macrophages and B lymphocytes
- Two pathways for antigen presentation. . .
-
1. Endogenous antigens presented through CYTOSOLIC PATHWAY
2. Exogenous antigens presented through ENDOCYTIC PATHWAY - What is the function of the TAP protein?
- Endogenous Antigen Processing Pathway, TAP carries peptides from the proteasome to the RER
- Which antigen processing pathway uses the invariant chain to block the MHC binding site?
- exogenous antigens. Have MHC II in ER. The binding groove is protected by invariant chain.
- Where is the invariant chain digested during exogenous antigen processing? What is left behind?
- In the ER. Clip
- What are the cellular products of T cell activation?
- effector and memory cells
- What are the immediate genes (30mins) of T cell activation?
-
encode transcription factors
c-fos,
c-Jun,
c-Myc,
NF-AT and NF-κB - What are the early genes (1-2 hrs) of T cell activation?
- IL-2, IL-2R (receptor), IL-3, IL-6, IFNγ
- What are the late genes (> 2 days) of T cell activation?
- adhesion molecules
- What are the two signals that naive T cells need for activation?
-
Signal 1 – generated by interaction of MHC:peptide with TCR:CD3 complex
Signal 2 – results from the interaction between CD28 on the T cell and B7 on the APC - What are the ligands of B7?
- CD28 and CTLA-4
- How do the B7 ligands act antagonistically?
- signaling through CD28 yields a positive signal while signaling through CTLA-4 yields a negative signal
- What is the function of CD28?
-
- stabilizes cytokine mRNA particularly interleukin 2
- it induces the cell that is activated to proliferate.
- Turns on the IL-2 gene and the interleukin receptor gene. - Cytokine is produced, bind to receptor, and allows proliferation. - How can CTLA4 act to block the function of CD28?
- CTLA4 structurally like CD28 and can bind to B7. This blocks CD28 and this stops cell from being activated -method to regulate itself.
- What are the steps of T cell differentiation?
-
1. naive T cells enlarge to blast cell
2. enters the cells cycle and induces IL-2 and CD25
3. IL-2 mRNA half-life increases and stabilizes
4. secretion of IL-2 leads to proliferation and differentiation - CD4 helper T cells form 2 subpopulations based on their
-
- cytokine profile
- CD4TH1 and CD4TH2 - What are the cytokines of CD4TH2?
- IL-4, IL-5, IL-6, IL-10
- What are the cytokines of CD4TH1
- IL-2, IFNγ, TNFβ
- What is the role of CD4 TH17 association with IL-17?
- amplifies neutrophils
- Both T helper cells populations produce which cytokines?
- interleukin 3 and GM-CSF
- GM-CSF
- granulocyte macrophage colony stimulating factor
- How are memory T cells different/similar to naive T cells?
-
- Memory cells, like naïve cells, are resting cells, but they have less stringent requirements than naïve cells
- naïve cells are activated exclusively by dendritic cells, memory cells can be activated by all 3 APCs - What are the two types of regulatory T cells?
- CD4 AND CD25
- What is the function of regulatory T cells?
- Inhibit proliferation of other T cells AND play a crucial role in preventing the immune system from attacking the body's cells and tissues.
- What role does apoptosis play in lymphocyte homeostasis ?
- Apoptosis plays a major role in deletion of potentially autoreactive thymocytes during T cell maturation in the thymus
- In the apoptosis cascade, which caspases are usually the first cleaved to an active form?
- caspases 8, 9
- n the apoptosis cascade, which caspase is the final caspase?
- caspase 3
- What percentage of B cells develop into mature cells? Why?
-
- Only 10% of the many B cells that are produced will enter the recirculating pool of B cells
- apoptosis because they express auto-antibodies against self antigens - activated B cells will proliferate and differentiate into
- Plasma cells and Memory cells
- Activation and Proliferation of B cells can occur in what two methods?
- thymus-dependent and thymus-independent antigens
- B cell response to thymus dependent antigens requires
- direct contact with the TH cell
- thymus-independent antigens
-
- can activate B cells in the absence of T cell help
- repetitious molecules - Similarly to T Cell Activation, B Cell activation requires
- two signals
- What are the two signals of B cell activation?
-
- Signal 1: antigen binding to the BCR
- Signal 2: T cell activation leads to up-regulation of CD40L which bind to CD40 providing “Signal 2†to B cell.
- During signal transduction in B cells, the cytoplamic tails of the Ig molecules are two short to interact with tyrosine kinase so what molecule acts as the signaling complex?
- Ig-α/Ig-β heterodimer acts as the signaling complex, while the mIg acts as the ligand binding molecule