immune tolerance
immunity vs tolerance
immunity: Immune activity triggered during infection, in response to a wide diversity of antigens derived from pathogens
tolerance: Tolerance to self antigens expressed in different parts of the body at different times during development, or expressed on neighbouring uninfected cells
types of immune tolerance
Central tolerance
Peripheral tolerance
what: immature lymphocytes undergo a selection process in primary lymphoid organs (eg bone marrow and thymus)
- this is when the lymphocytes are developing
mechanisms operating on mature lymphocytes in the periphery
Somatic recombination: randomly generates a diverse repertoire of antigen receptors in T cells and B cells. Each T or B cell expresses a single population of antigen receptors.
selection
positive selection
negative selection
we keep for lymphocytes with TCRs that
have low to moderate affinity for
self-MHC presenting self peptides
apoptosis for the T cells with receptors
that bind to self peptide MHC complexes with a high affinity
- else they will cause an autoimmune response
insert the photo of the postitive negative selection table
Autoimmune regulator (AIRE)
- this will explain how do we test lymphocytes with the antibodies of cells that are not produced in the thymus (where the cells differentiate and mature)
- the thymus will temporarily express the antigens that are not supposed to be found in the thymus but are found elsewhere
- mutations of the AIRE will cause there to be autoimmune diseases
their both selected by seeing
whether they bind to self peptides
and not foreign peptides
mechanism (reasons for why
we would not choose these cells to become T cells of the body)
Ignorance
Anergy
Deletion
T regs inhibiting immune responses ⭐
the result is that anergised T cells remain unresponseive even if they subsequently are exposed to the MHC receptor again
Tregs are CD4+ CD25+ T cells that
express the transcription factor Foxp3
immune checkpoint
(when there is regulation of the T cell activity when via T regs
similarities and differences
of CTLA4 and CD28 table
Tregs express CTLA4 which inhibits T cell activation by
- binds to on APC
- downregulation of B7 on APC
molecules that could cause issues
Anti-CTLA-4 antibody
- can enhance T cell functions by
- depleting the Tregs
- block the inhibitory effect of CTLA4 on effector T cell
- anti CTLA4 antibody can ultimately cause autoimmune disease
Programmed Cell Death Protein 1 (PD-1)
- Inhibits activation signals from the TCR complex and CD28
- hence it helps to regulate effector T cell function
expression of PD1 and CTLA4 will allow tumour cells to grow
- treated with antibodies that block CTLA-4 and PD-1
- side effect is that the antibodies are not tumour specific
- they could cause destruction of T cells that are good for the body too
insert the table comparing CTLA4 and PD1