Autoimmunity Flashcards
Describe three (3) mechanisms of peripheral T-cell tolerance (3)
Anergy (functional unresponsiveness), clonal deletion via activation-induced cell death, suppression (via T-regs)
Name the immune cells that are important in peripheral self-tolerance (1)
Tregs
Autoimmunity is associated with a loss of tolerance to self-antigens. Outline three (3) examples of possible ways that self-tolerance can be lost (3)
Loss of “sequestered antigen”/Immune privileged site; viral or drug induced altered self-antigen, T-reg depletion or functional deficit; molecular mimicry (cross-reactive immunity to self)
Name two (2) HLA types that put people at risk for autoimmune diseases (1), and explain why HLA type may be important in AI (1)
HLA DR 2, 3, 4, 5, and HLAB27. HLA molecules present specific Ags and these HLA types can present certain self-Ags.
Describe the mechanism of platelet destruction in autoimmune thrombocytopaenia highlighting the main immune cells and process involved (3)
Binding of antibody to membrane-bound antigen on platelets, opsonisation – antibody coated target cell – recruitment of neutrophils and monocytes – phagocytosis with platelet destruction (usually occurs in spleen) (3)
Name two (2) examples of autoimmune conditions that are the result of self-reactive antibodies binding to self-activation and causing activation of with complement and/or FcR-mediated activation of phagocytic and NK cells (2) (
(Any 2) Autoimmune haemolytic anaemia or thrombocytopaenia, Goodpasture’s syndrome, ARF, grave’s disease, myasthenia gravis.
Aberrant immune complex clearance is a key part of the pathogenesis of systemic lupus. Name three (3) of the main target organs commonly affected (1½)
Skin, kidney, joints, and vessels (any 3)
Outline the immune processes resulting in Type 1 Diabetes (2)
Autoimmune disease (0.5) Lack of Insulin (0.5) caused by destruction of insulin- secreting β- cells (0.5) in pancreas (0.5)
Name the effector cells that are responsible for the tissue damage that results in Type 1 Diabetes (1)
Tissue damage caused by autoreactive CD4+/ T Helper cells (0.5) and CD8+/ Cytotoxic T cells (0.5) / or T cell mediated tissue damage due to Type IV hypersensitivity reactions (DTH).
Name two (2) self-antigens that are recognized by immune cells that leads to Type 1 Diabetes (1)
Pancreatic Beta-cell hormone proinsulin/insulin and/or glutamic acid decarboxylase (GAD) and/or pancreatic islet cell antigen (IA2) (1)
Name the HLA background of a person that gives rise to about a 20-fold increase in Type 1 Diabetes (½)
DR3/DR4
Name the pancreatic cell type that is the target of the immune onslaught in type 1 IDDM [1]
Islet beta-cells [that produce insulin]
State the main immune effector cell responsible for the destruction of B-cells in the onset of type 1 diabetes mellitus (1)
CD8 T-cells
State which cells are responsible for the autoreactivity in Type I diabetes, and name their target cells (1)
T cells, Beta cells
Name the cell type that gives rise to the Hypersensitivity reaction that leads to Diabetes Type 1 (½)
T cells
a) Provide two (2) alternative names for this type of hypersensitivity reaction (1)
Delayed Type Hypersensitivity (DTH) or Type IV (1)
“Insulitis” is a term that refers to infiltration of pancreatic -cells by which component of the immune response? (1)
Cell mediated immunity or T-cells
Name two (2) self-antigens that are recognized in Diabetes Type 1 (1)
Pancreatic Beta-cell hormone proinsulin/insulin and/or glutamic acid decarboxylase (GAD) and/or pancreatic islet cell antigen (IA2) (1)
Define the immunological process leading to the pathology in type 1 diabetes mellitus, and list the cellular effector cells that are responsible for the tissue damage (5)
Chronic autoimmune insulitis: T-cell infiltration of pancreatic Beta cells leading to inflammation and their destruction via delayed type hypersensitivity (DTH) (CD4+ effect) and cytotoxicity (CD8+ effect).
Describe the immunopathogenesis of Type 1 diabetes (3)
Genetic predisposition
Lack of immunoregulation
Autoreactive T lymphocytes recognising beta cell peptides become activated, expand clonally, and undergo an inflammatory cascade
Result is beta cell destruction by effector cells
List three essential components that interact together to cause diabetes mellitus type 1 (autoimmune diabetes mellitus) (3x2 = 6)
Genetic background - includes HLA type (DR3/4 and DQ tissue type).
Environmental trigger - usually virus infection
Failure of immune regulation- Regulatory T-cells (Treg)
Name and explain two mechanisms that are responsible for normal immune tolerance which are presumed to be defective in type 1 IDDM [2x1.5 = 3] (NB)
“Central tolerance” - the complete deletion of putative auto-reactive T-cells in the thymus.
“Peripheral tolerance” - holding potentially auto-reactive T-cells in check either by clonal deletion, induction of anergy, or by Regulatory T-cells (Treg).
State which immune regulatory system fails to the development of Diabetes Type 1 (½)
Peripheral Tolerance/CD4+ Regulatory T cells
State which cells are normally responsible for inhibition of autoreactivity and name two (2) of the soluble factors by which they mediate this inhibition (1½)
Tregs & TGFb, IL-10, IDO, ICOS
Type 1 IDDM is considered an autoimmune disorder. Outline two observations in support of this statement [2+2]
Serum autoantibodies (2) are frequently detected and can antedate clinical disease for years: these include anti-islet cell (ICA) Ab’s, anti-GAD, or anti-insulin Ab’s (1 each)
Pathological/histological finding of “insulitis, i.e. islet cell inflammation and destruction of -cells by T-cells, in the absence of clear cut evidence of infection of the pancreas.
List two findings that support the contention that diabetes mellitus type 1 is an autoimmune disease (2x2 = 4)
Autoantibodies are present: anti-Insulin, islet cell AB’s (ICA), Glutamic acid decarboxylase (GAD), IA-2.
Islet cell infiltration by T-cells in the absence of detectable infection
Loss of Treg cells that suppress autoreactivity.
Type 1 IDDM is strongly linked to HLA (human leukocyte antigen) region genes.
Which HLA region genes have the association? [1]
The HLA class 2 region, HLA –DR (and HLA –DQ) has the strongest linkage.
Provide an explanation for an immune mechanism that may be involved to explain the HLA association with disease development [1+2]
Class 2 HLA molecules dictate the strength of an immune response (hence they are referred to as IR genes). Diabetic patients presumably have HLA –DR or DQ molecules that can present self-peptides in an immunogenic manner that elicits a robust immune response, which includes auto-reactivity.
State the HLA background that results in a 20-fold increased risk of Diabetes Type 1 (½)
DR3/DR4 (½)
