Self recognition and autoimmune disease Flashcards
autoimmune diseases
components of the specific immune system start to recognise self-antigens
type I diabetes
antibodies to islet cells (insulin producing cells in the pancreas) lead to destruction of those cells, and the loss of the ability of the pancreas to produce insulin.
grave’s disease
antibodies specific to thyroid stimulating hormone (TSH) receptors stimulate those receptors, leading to hyperthyroidism.
SLE
autoantibodies against various body tissues lead to antibody-antigen complexes activating the complement system causing inflammation and damage to tissues throughout the body (such as the skin, joints, kidneys, heart and lungs).
myasthenia gravis
antibodies specific to cholinergic receptors on muscles bind to the receptors preventing them being activated by the neurotransmitter acetylcholine. This leads to progressive muscle weakness.
pemphigus
antibodies specific to desmoglein, a protein that holds skin cells together bind to that protein and act as opsonins to destroy it. This results in skin cells separating from each and large fluid filled blisters to form.
goodpastures
antibodies specific to a type of collage in the the glomerular basement membrane in the kidneys and lungs lead to inflammation and destruction of the basement membrane leading to pulmonary haemorrhage and kidney failure.
ITP
antibodies bind to platelets and act as opsonins, resulting in them being consumed by phagocytes. This leads to a profound thrombocytopenia.
pernacious anaemia
: antibodies specific to intrinsic factor (a molecule essential for the absorption of vitamin B12 in the intestine) block the function of intrinsic factor, preventing B12 from being absorbed. This leads vitamin B12 deficiency and a megaloblastic anaemia.
autoimmune haemolytic anaemia
: antibodies specific red blood cells activate complement on the red blood cell membrane. The complement activation leads to lysis of the red blood cells, resulting in anaemia.
what mechanism exists to prevent T and B cells from autoimmunity
B cell self tolerance
T cell self tolerance
what is b cell self tolerance?
B cells develop their specific antibodies in the bone marrow.
The bone marrow contains no pathogenic material, but is full of self-antigens.
If the developing B cell creates antibodies that match antigens in the bone marrow environment (self-antigens), one of two things happen:
Clonal deletion: the cells die and are never released into the circulation (if high affinity)
Clonal anergy: the cells are made inactive so that they can be released but make no response to antigens (if low affinity)
The acts as a means for testing B cells before they are released to ensure they do not contain antibodies that could be active against self.
peripheral tolerance:
if encounter self-antigens they undergo anergy or apoptosis or inhibitory receptors to prevent b cell activation
what is t cell self tolerance?
t cells leave the bone marrow as ‘pro thymocytes’
they travel to the thymus and become ‘thymocytes’ and then undergo a complex process to develop their TcR and mature into CD4/CD8 in the thymus gland
TcR must be specific for foreign antigen and self MHC
if they recognise self antigen they can cause autoimmune disease. if they cannot recognise self MHC molecules they are usless.
t cell education
Thymocytes start by arranging proteins to form random TcRs.
At first the T cells express CD4 and CD8. The first step is to stop expressing one of these, so that they become either CD4 or CD8 cells.
The second step is to meet cortical epithelial cells in the thymus, that present them with MHC proteins. If the thymocyte can recognise the MHC protein, they go to the next step. If they can’t recognise it, they are destroyed.
The third step is to meet dendritic cells in the thymus, that present them with self-antigens. If the thymocyte can recognise the self-antigen, they are destroyed. If they can’t recognise it, they are allowed to pass out of the thymus and become fully fledged T cells.
*CD4 and CD8 are presented with self peptides. if they bind to it they are selectively removed (negative selection). ones that do not recognise are allowed to enter the circulation
what is immune tolerance?
the mechanism by which the immune system prevents reacting against its self
two types
central tolerance: this happens during lymphocyte development to prevent a rection to self antigens
peripheral tolerance: after lymphocytes mature and enter the periphery (circulation)
peripheral tolerance
after central tolerance, not all autoreactive T cells are deleted (about 2/3 are) so peripheral tolerance is needed to get the 1/3
anergy: unresponsive
ACID: activation induced cell death
immunological ignorance: leave the auto T cells and hop ehtye may never come into cnotact with their auto antigen
sequestria: prevent antigen contact (e.g BBB)
