Insulitis is the
manifestation of the autoimmune attack against beta cells
Insulitis is a
hallmark of T1D
insulitis is characterised by
the presence of immune and inflammatory cells within the pancreatic islets
definition of insulitis
the presence of a predominately lymphocytic (B and T cells) infiltration of the islets of langerhans.
- consists of at least 15 CD45+ cells
- present in a minimum of three islets
while both T and B cells are reported in insulitis lesions, which cells are the predominant population
cytotoxic CD8 T cells
CD8 T cells are though to target B cells which
express elevated levels of HLA class I molecule e.g. MHC 1
hyper expression of MHC I (HLA class I molecule)
may be associated with viral infections implicated in the development of t1DM
when a CD8 T cells recognises a B cell over expressing MHC 1receptors
cytotoxic killing via apoptosis
hyper expression of HLA molecules is another
key feature in the pathology of T1D- represents chronic inflammatory state
immune cells infiltrate islets in a
non-uniform fashion
when lymphocytes infiltrate
decrease in Beta cells mass and lesions in pancreas
which immune cells ae present wishing insulitis infilitration
- CD8 (which do killing)
- CD4 (in lesser amounts)
- CD20 B cells
- CD68+ macrohages
what is a marker stain for all lymphoctes
CD45
CD68 is a
glycoprotein found on the surface of macrophages
CD20 is a
glycoprotein found on the surface of B cells
CD4 is a
glycoprotein found on the surface of T helper cells
CD8 is a
glycoprotein found on the surface of cytoxic T cells
CD45
a marker for all lymphocytes
HLA class 1 molecules is a
genome complex which encodes MHC I
HLA class 2 molecules is a
genome complex which encodes MHC II
immunostains targets
CD glycoproteins e.g. CD8/ CD4
which types of cells are present in the highest concentration in T1D
CD8 T cells
which cells are present the lowest conc in T1D
CD4 t cells
as insulin content decreases
mean number of immune cells increases and then at a set point decreases to 0
once insulin is gone
immune cells go back to where they came from 9therefore present in patients with newly diagnosed diabetes)
both …. are involved in b cell destruction
by themselves- not strong enough
insulin-speciifc autoantibodies (produced by bc els)
are present in children with T1D before the age of 5
islet autoantibodies are
a differential diagnosis marker for T1D
IAAs arise from
auto reactive B cells and CD4 T cell iteraction
CD4 T cells and other immune cells
provide “help” to B cells and stimulate antibody production, as well as promote responses by effector CD8 T cells, and stimulate islet-resident macrophages.
auto reactive CD4 T cells
- represent an active area of research and clinical interest for therapies. Developing antigen-specific tolerance-promoting methods to inhibit autoreactive CD4 T cells is an idea
CD45
CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes