T cellDRRSCD4 CD8LC Flashcards
How do Tcells migrate to the thymus?
→thymus produce chemokine
→Tcells follow trail of chemokines to thymus
What does the trabeculae divide the thymus into?
→lobules
What does the lobule contain?
→an outer cortex
→an inner medulla
What is the cortex of the lobule formed from?
→dense lymphoid which lacks nodules
Where do immature lymphoid cells enter to proliferate?
→cortex
What is the function of epithelial reticular cells?
→sequester developing lymphocytes
→form a sheath covering capillaries and lymphatic vessels
What does the sheath in thymus do?
→forms what is called the blood-thymus barrier
→prevents antigen contamination of developing and programmed T lymphocytes.
How is the thymus different from lymph nodes?
→no lymph sinuses
→ afferent lymphatic vessels
Where is the Hassall corpuscles found in the thymus?
→deep in the medulla
What is the Hassall’s corpuscle?
→aggregation of mature lymphocytes
When are Tcells mature?
→when they express CD4 or CD8
How can Tcell development be chracterised?
→flow cytometry
If Tcell progenitors are injected into circulation what do they change into?
→Bcells
→NK cells
What do NK Tcells recognise?
→CD1 molecule
What are some cells that can be found in the fully developed thymus?
→NK Tcells
→gamma delta Tcell
→DN Tcells
What can DN cells be subdivided into?
→DN1 and DN4
What molecules are analysed for on CD4 and CD8 molecules?
→CD44 and CD25
What type of Tcells appear in foetal thymus before DP cells?
→DN cells
At what stage do gamma delta cells become phenotyped?
→between DN2 and DN3
What type of Tcells are favoured in early foetal development?
→gamma delta
What type of Tcells are favoured in later stages of foetal development?
→alpha beta
What do skin gamma delta Tcells express?
→Vg5
What do gut gamma delta cells express?
→Vg2
What do uterus gamma delta cells express?
→Vg6
What restriction do gamma delta cells have?
→not MHC restricted
In what way are gamma delta cells similar to antibodies?
→Antigen is recognized directly
What roles do gamma delta cells have?
→circulating gamma cells recognize a phospholipid antigen from Mycobacterium tuberculosis
→role in cancer surveillance
What are the proportions of alpha beta cells and gamma delta cells?
→gamma delta= 10%
→alpha beta = 90%
What are the beta and alpha chains analogous to in Ig rearrangement
→beta chain as analogous to the heavy chain
→Alpha chain analogous to the light chain
Which chain arrangement occurs first?
→beta chain
→begins at DN stage
What gene rearrangement occurs at the DN stage?
→D-Jbeta
→V-DJbeta
What rearrangement occurs at the DP stage?
→V-Jalpha
What does a DP Thymocyte Need to Progress to the SP Stage?
→Functional TCRa chain rearrangement
→CD4 and MHC II (To be a CD4+ cell)
→CD8, MHC I and TAP (To be a CD8+ cell)
→ERK signaling
→Calcineurin signaling
What interaction lead to thymocyte apoptosis?
→FasL and Fas
What molecule inhibits thymocyte apoptosis?
→sFasL and sFas
What happens if DP cells bind strongly to CD4 on thymic tissue?
→it will result in downregulation of CD8 mols
What happens with low signal intensity to CD4 and CD8 cells?
→death by neglect
Where are MHC2 expressed in the thymus?
→expressed on medullary cells
→q-arm of chromosome
Which chromosome are MHC complex genes found?
→6
Where are MHC molecules found in thymus?
→thymic stromal cells
→low level on APC (DC and macrophages)
What is positive selection?
→cell receptor binds to HLA with self antigen
Which HLA molecules express MHC1 and MHC2 molecules?
→MHC1= HLA A,B,C →MHC2= HLA-DR
What does positive selection ensure?
→that only T cells are that are useful and can and can engage in recognition are selected
What is negative selection?
→exclusion of self-reactive T cells
What are the outcomes of negative selection?
→If binding of TCR to antigen is weak then it doesn’t pose danger
→If binding is strong then may indicate autoimmunity then reprogrammed for apoptosis
What happens with self-reactive cells in negative selection?
→go through further TCR rearrangements (second chance)
→preserves cost
How does the thymus represent different antigens from parts of the body?
→transcription activator gene which can induce expression of other tissue specific proteins
→ AIRE (Autoimmune Regulator)
→negative selection
Define promiscuous gene expression
→enables generation of self-antigens
→Ectopic Gene Expression in the Thymic Medullary Stroma
Where do T Regs accumulate?
→Hassall corpuscles and later migrate to different tissues
What is the main role of TRegs?
→dampen T cell response
What do single positive cells express before they leave the thymus?
→CD25 and Foxp3
What is a definitive marker of TRegs?
→Foxp3
→Also expresses CD25
When do Tcells become effector Tcells?
→encounter specific antigen,
→they get activated
When do Tcells apoptosis in circulation?
→If they don’t find the target
At what stage is TCRbeta selected?
→selected with an invariant pTa chain at the DN3 stage
At what stage is TCRalpha selected?
→selected with pre-existing TCRb chain at the DP stage
What is the result of CD4 or CD8 cell TCR stimulation?
→activation energy
