Development of Immune Cells Flashcards
What are APCs and granulocytes?
APCs:
Dendritic= initiates T cell response
Follicular dendritic cells
Macrophage= effector phase of cell mediated immunity
Granulocytes: neutro/baso/eosinophils, mast cells, NK
Draw a diagram to show the lymphoid lineage
Describe the fate of non specific immune cells after generation in bone marrow
Granulocytes + monocytes circulate in blood, recruited at infection sites.
Resident APCs (DCs and macrophages) stationed at skin, airways, gut etc to detect invaders
Outline the maturation process of lymphocytes
ie- what type of lymphocytes end up maturing?
Only lymphocytes w Ag receptors that recognise Ags mature= positive selection
Lymphocytes w receptors that don’t recognise Ags die by apoptosis=death by neglect
Lymphocytes w Ag receptors that recognise self Ags too strongly are eliminated =negative selection, (prevents AI)
Describe the concept of self tolerance
What happens if there is a failure of self tolerance?
T and B Ag receptors are randomly generated:
-Self reactive lymphocytes produced
Mechanisms that prevent response to self Ags=self tolerance
We have lymphocytes specific to self Ags that are trained to recognise, but not respond.
Failure of this= AI
Describe the mechanism of CENTRAL self tolerance in T cells
Occurs in thymus, clonal deletion of certain immature T cells
A pool of thymocytes express CD4 and CD8 (double positive). Then selected and tested:
-Cells don’t recognise antigen =death by neglect
-Recognise antigens too strongly =apoptosis
-Weakly recognise self Ag =positive selection
What is the involvement of Treg cells in central self tolerance?
Treg cells prevent autoimmunity in periphery
Treg cells are generated from thymocytes that encounter self Ags. Thymocytes with high affinity for self-antigens differentiate into Treg cells.
Treg will become either CD8 or CD4:
-If they recognise self Ag displaced by MHCI = CD8
-If recognise self Ag displaced by MHCII = CD4
What is PERIPHERAL self tolerance in T cells and where does it take place?
Occurs in in peripheral tissues and lymphoid organs (spleen, lymph nodes).
Some self reactive T cells escape central tolerance, so this aims to eliminate mature T cells recognising Self Ags
Describe a mechanism of peripheral tolerance in T cells
ANERGY:
For a self reactive T cell to get activated no suficiente to just recognise Ag- it also needs:
Costimulation= present infection
Cytokine stimulation (become Th1 or Th2)
If none of above, self T cell gets anergic, unable to react to Ag
Anergic cells have signalling blocked, so die due to stunted activation= deletion (apoptosis)
What is central tolerance in B cells?
Occurs in bone marrow, kills or alters immature B cells that recognise self Ags via:
Apoptosis/negative selection: if recognise too strongly
Anergy: if insuficinet bonding= reduced receptor expression = functional inactivation
Rearrange Ig receptor light chain= different Ag receptor specificity so tested again (receptor editing)
What is peripheral tolerance in B cells?
Occurs in the lymph nodes and spleen, eliminates mature B cells that recognise self Ags via:
deletion (by apoptosis)
Anergy
Blockade activation by inhibitory receptors
Suppression by Treg cells
Expand on the concept of receptor editing in B cell central tolerance?
Immature B cells that recognise self Ags strongly in bone marrow can change their Ag receptor specificity para ya no recognise self Ags strongly
They do this by rearranging genes for the light chain of the Ig receptor
