T cells Flashcards
Which type of T cells kill virus infected cells?
CD8 Cytotoxic T cells
Which type of T cells target microbes that persist in macrophage vesicles by activating the macrophages and help B cells produce antibodies?
CD4 Th1 cells
Which type of T cells target helminths and provide help to B cells for antibody production, especially switching to IgE?
Cd4 Th2 cells
Which Type of T cells targets klebsiella pneumonias and fungi by enhancing neutrophil response and promoting barrier integrity?
CD4 Th17 cells
Which type of T cells targets all types of T cells by helping B cells isotype switch and product antibodies?
Tfh Cells
Which type of T cells suppress T cell responses?
CD4 regulatory T cells
What interacts with MHC presented antigens, is an incidence detector, is similar structurally to immunoglobulins but only bind amino acid sequences and defines T cells?
T Cell Receptors
Which class of T cell receptor is the “Classic”, is involved in adaptive immunity, is common in the circulation (not tissues), develops and matures in the thymus and undergoes positive and negative selection?
α:β T cell receptors
*T cells only express 1 class. δ chain genes are embedded within the α chain genes
Which class of T cell receptor is not involved in classic adaptive immunity, monitors tissue health, is found in tissues (not circulation) develops but does not mature in the thymus, and has limited positive and negative selection?
γ:δ T cells
*T cells only express 1 class. δ chain genes are embedded within the α chain genes
Which chain has the V,J,C segments and has junctional diversity?
α Chain
*3 hypervariable/complementarity-determining regions per chain. RAG 1/2 complexes
Which chain has the V,J,D,C segments and has junctional diversity?
β Chain
*3 hypervariable/complementarity-determining regions per chain. RAG 1/2 complexes
What complex do TCRs require for signal transduction?
CD3 complexes
*TCR plasma membrane expression does not occur without the CD3 complex
What do Major histocompatibility complexes (MHCs) present?
They present antigens to TCRs
Which class of MHC presents intracellular antigen, is expressed on all cells, ER antigen loading, binds the CD8 co-receptor and has an α chain and β2 micro globulin
MHC class 1
*All MHC are associated with Human Leukocyte Antigen (HLA) complex
Which class of MHC presents internalized antigen, is expressed on antigen presenting cells, binds CD4 co-receptor, is a vesicular ER loader and has α and β chains?
MHC class II
*All MHC are associated with Human Leukocyte Antigen (HLA) complex
In the ER, which protein stabilizes the Class I heavy chain until β2M binds?
Calnexin
In the ER what 4 proteins make up the peptide-loading complex with the class I heavy chain and β2m?
1-clareticulin
2-tapasin
3-TAP (delivers the peptide to form the mature MHC I)
4-ERp57
When the peptide loaded on to MHC I is too long, which enzyme removes N-terminal AAs to give a 8-10 residue peptide?
ERAP
The invariant chain blocks the binding or peptides to MHC II in the ER and is then cleaved in vesicles leaving what?
CLIP fragment which blocks binding of peptides in vesicles
What protein facilitates release of CLIP from MHC II?
HLA-DM
CD8 binds what domain of the MHC I?
α3 domain
CD4 binds what domain of the MHC II?
β2 domain
Developing T cells within the thymus are called what?
Thymocytes
Which T cells maintain tissue integrity, do not express CD4 or CD4 co-receptors and interact with non-classical receptors?
γδ T cells
Which T cells are helper T cells, have several types, regulate adaptive and innate immune function and interact with MHC Class II?
CD4 T cells
*MHC class II typically on Dendritic cells, B cells and macrophages (antigen presenters)
Which T cells are cytotoxic T cells, have direct effector function and interact with MHC class I?
CD8 T cells
The thymus is the site of all T cell development. Selection of thymocytes occurs as they move in what direction?
From Cortex to medulla
*TCR development within the cortex
What happens to the thymus with age?
It involutes (gets smaller)
*CD4 half life=4.2 yr CD8= 6.5 yr
Stem cell surface marker CD34 and Adhesion CD44 are present in what stage of T cell development?
Uncommitted progenitor cell (prior to reaching thymus)
CD2 and CD5 adhesion/signaling proteins along with IL-7 cytokine receptor and CD1A (MHC class I-like molecule) are found in what stage of T cell development?
Double-negative thymocyte committed to the T-cell lineage
*TCR has begun to rearrange
What molecule is a T Cell transcription factor involved in T cell arrival to thymus?
Notch1
Which molecule is a B cell transcription factor?
Pax-5
What are the 3 major stages of T cell development?
1-Double-negative
2-Double-positive
3-Single-positive
What are the four stages of the double-negative stage?
1-Committed T cell progenitor
2-Rearrange β,γ,δ (mainly β)
3-First checkpoint (Pre-TCR)
4-Proliferating pre-T cells (has pTα as surrogate α chain)
What are the two stages of the double-positive stage?
1-Rearrange α (if γ,δ has not formed)
2-Second checkpoint (has both CD8 and CD4, positive and negative selection take place)
What happens then the γ or δ gene rearrangement takes place?
Suppressed the β and α
- β, γ, δ, rearrangement are first. γ:δ cells leave the thymus with little selection.
β-chain production drives what?
CD4 and CD8 expression (double positive)
How many attempts are made to achieve the productive rearrangement of the β-chain locus?
Four attempts (two attempts per locus, two genes)
B-chain rearrangement forms a Pre-T cell receptor, and is the first checkpoint. It must then bind what and assemble what to then drive the signal forward?
- Must bind pTα (surrogate α-chain analogue)
- Assembles the CD3 complex
*forms a super dimer
What three things does the formation of the CD3 complex and passing the 1st checkpoint drive?
1-Halts Rag funtion
2-Proliferation
3-Expression of CD4 and CD8
What is eliminated when the α-chain is rearranged?
The γ:δ locus thus excluding γ:δ cells.
*Prior to rearrangment, cell can still develop into γ:δ
What are the 5 major genes that are expressed during T cell development?
1-Notch 2-Kit/stem cell factor (SCF) 3-RAG 4-CD3 5-IL-7
What are the 4 stages of development as the T cells move from the sub-capsular region toward the medulla?
1-Proliferation and differentiation to double-positive CD3+ thymocytes (sub-capsular cortex)
2-Positive selection (cortex)
3-Negative selection (corticomedulary junction)
4-Entry to the circulation (medulla)
Ensuring that the MHC is bound by cortical epithelial cells presenting self-peptides on MHC I/II in the thymusis the second checkpoint and is called what?
Positive selection
*TCR must bind mHC within 3-4 days. a-chain may rearrange but once bound it turns off RAG 1/2
What process determines CD4 or CD8 expression and requires co-signaling?
Positive selection
*CD4 binds MHC II and CD8 binds MHC I
What process prevents self-antigen binding through the use of centric cells and macrophages presenting self-peptides to create central tolerance?
Negative selection
*peripheral tolerance may also occur. Naive mature T cells can still undergo differentiation
Once a Mature, naive T cell is formed, where does it go?
Blood stream or lymph system
