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