Adaptive immunity Cell-Mediated (complete) Flashcards
what is the B-cell antigen receptor
a membrane bound immunoglobin (two heavy chains, two light chains)
what kinds of regions do the B and T cell antigen receptors have
proximal constant regions, and variable distal regions
just like antibodies
what is DiGeorge syndrome
when an individual has no T-cells, subject to many overwhelming infections
how are naive T cells activated
coming into contact with mature activated dendritic cells that have their MHC/antigen complex and lots of B7 molecules
what happens once a T-cell is activated
they proliferate and differentiate into effector T-cells that destroy or eliminate the antigen once they come into contact with it again
the first signal a T-cell needs to become activated is
the binding of the MHC/Antigen complex binding to the T-cell antigen receptor from a dendritic cell
the second signal that a T-cell needs to become activated is…
costimulatory signal
what are the most important costimulatory factors that assist in the activation of T-cells
B7-1 and B7-2 on dendritic cells, interacting with CD28 on T-cells
What is the function of T-helper cells
activate antigen producing B-cells
recruit and activate phagocytes
activate eosinophils, basophils and mast cells
What happens to the T-cells once the immune response has ended
they must return to normal levels (controlled by cytokines)
does the T-cell receptor (TCR) have cytoplasmic tails with any function
their cytoplasmic tails have no signaling function
since the cytoplasmic tails of TCR have no signaling function, how does the TCR send signals once it has bound
they have CD3
what is CD3
6 chains that are bound to the TCR with ITAM in the cytoplasm
what is ITAM
a part of the CD3 of TCRs
Immunoreceptor Tyrosine-based Activation Motifs
the part that signals to the cell when the TCR has bound an antigen/costimulator
the BCR (B-cell receptor) is immunoglobin that is membrane bound, what is the structure of the TCR (T-cell receptor)
2 immunoglobin domains that aren’t identical
it is an alpha-beta heterodimer with two proximal constant regions, and two variable distal regions
what are the three hypervariable regions of the variable region of the TCR. and what is their function
CDR1, CDR2, and CDR3
these contact the peptide-MHC complex
what are the four sources of variability to the TCR
- different V and J segments of the alpha chain
- different V, D, and J segments of the beta chain
- different combinations of the alpha and beta chains
- variability of the junctions between alpha and beta
what does positive selection of T-cells get rid of
those T-cells with weak binding to the Self-peptide/self-MHC complex
what does negative selection of T-cells get rid of
those T-cells with too strong of a binding to self-peptide/self-MHC complex
the three parts of the variable region of TCRs each bind to what
CDCR1 binds to the MHC molecule
CDCR2 binds to both the MHC and the peptide/antigen
CDCR3 binds to the peptide/antigen
of the three parts of the variable region of TCRs, which one is the most variable
CDCR3 the one that binds the peptide/antigen
Where do the coreceptors (CD8 and CD4) on T-cells bind to the MHC/antigen complex
they bind to the MHC
what does the binding of CD8 and CD4 do for the binding between the TCR and the Antigen MHC complex
it increases the avidity of the binding
and helps the T-cell bind to the right MHC class
what class of MHC does the CD8 of T-cells bind to
Class 1
what class of MHC does the CD4 od T-cells bind to
Class 2
what does CTLA4 do, and what happens if you don’t have it
it doesn’t cause an increase in CD40L and there fore CD28 on the T-cell. This keeps the T-cell from expressing out of control.
in mice that didn’t have CTLA4, they died of lymphoproliferative diseases
What are the different types of T-cells that can come from CD4 T-cells
Th1
Th2
TREG
TH17
what cytokine is associated with TH1 T-cells
IFN-y
what do TH1 T-cells do
activate: macrophages NK cells CD8 T-cells (attacks viruses, intracellular bacteria)
What cytokine is associated with TH2 cells
IL-4, IL-5, and IL-13
what do TH2 cells do
activate:
eosinophils, basophils, and mast cells
(attacks worms and bloodsucking insects)
What cytokine is associated with TH-17 T-cells
IL-17
what do TH-17 cells do
activate neutrophils
attacks extracellular bacteria and fungi
What cytokine is associated with TREG cells
IL-10, TGF-beta
what do TREG cells do
activate dendritic cells
inhibits other effector T-cell types
what do most CD8 T-cells differentiate into
cytotoxic T-cells
what cytokine do cytotoxic T-cells produce, and what do they do
IFN-y (upregulates MHC class 1 and immunoproteasome)
TNF (can activate apoptosis in some cells)
Chemokines (attrack other immune cells)
What are the cytotoxic mechanisms of Cytotoxic T-cells
- Perforin
- granzymes
- Fas ligand
what causes perforin and granzymes to be secreted from Cytotoxic T-cells
the binding of the T-cell to the MHC/antigen complex causes a release of Ca++. this causes the release of Perforin and granzymes
how does perforin kill cells
creates pores in the cell membrane, which allows the granzymes to enter
how do granzymes kill cells
they enter the cell through perforins and cleave caspase 3 and Bid. these cause DNA fragmentation, and inactivates cellular repair
the binding between cytotoxic T-cells and the target cell is transient, but what can cause it to be stronger
LFA-1 and ICAM interactions (these also help focus the secretory apparatus toward the target cell)
how do cytotoxic T-cells prevent perforination of themselves that would lead to their own destruction
the vesicles that contain the perforin and granzymes have Cathepsin B on their membrane, and when the vesicle makes it to the cell membrane, they remain at the cell membrane and prevent the fusion of perforin to the cell
what leads to the decrease of T-cells after an immune response to maintain homeostasis
they are programmed to die unless they receive survival signals (cytokines, costimulatory signals)
what is lymphopenia
low lymphocyte levels in the blood
what can cause lymphopenia
viral infection or age
