Autoimmunity Flashcards
B Cell Self Tolerance:
B cells develop their specific antibodies in bone marrow (which 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 will happen:
1) Clonal deletion – the cells die and are never released into circulation
2) Clonal anergy – the cells are made inactive so that they can be released but make to response to antigens
These 2 processes act as a test for B cells before they are released into circulation to ensure to autoantibodies are released
T-cell self tolerance:
T-cells leave marrow as pro-thymocytes
They travel to thymus where they become thymocytes
These thymocytes then undergo a complex process to deveop their TcR and mature into CD4 or CD8 cells within the thymus gland.
The eventual TcR must be specific for foreign-antigen and self-MHC.
If they recognise self-antigen, they can cause autoimmune disease and are released. If they cannot recognise self-MHC molecules then they are not useful as T cells
This happens via a process called T-cell education
T-Cell Education process
1) Thymocytes start by arranging proteins to form random TcRs.
- –At this stage T cells express both CD4 and CD8 - so they differentiate into either one or the other
2) Thymocytes 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 cant recognise it they are destroyed
3) Thymocytes meet dendritic cells in the thymus, that present them with self antigens . If the thymocyte:
- - Can recognise self antigen –> destroyed
- - Cant recognise self antigen –> allowed to pass out of thymus and become full T-cells
Type 1 diabetes:
Type 1 diabetes:
Type 1 diabetes: (AI)
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.
Graves Disease:
Graves Disease: antibodies specific to thyroid stimulating hormone (TSH) receptors stimulate those receptors, leading to hyperthyroidism.
Systemic Lupus Erythematosus (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
Myasthenia Gravis:
antibodies specific to cholinergic receptors on muscles bind to the receptors preventing them from 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 Syndrome
antibodies specific to a type of collage in the glomerular basement membrane in the kidneys and lungs lead to inflammation and destruction of the basement membrane leading to pulmonary hemorrhage and kidney failure.
Autoimmune Thrombocytopenia (ITP)
Autoimmune Thrombocytopenia (ITP): antibodies bind to platelets and act as opsonins, resulting in them being consumed by phagocytes. This leads to a profound thrombocytopenia.
Pernicious Anaemia
Pernicious 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.
