Immunology of endocrine disease Flashcards
List some organ specific autoimmune disease
Type 1 DM
Hashimoto’s disease
Grave’s disease
List some non-organ specific autoimmune disease
Systelic lupus erythematous
Diffuse scleroderma
Polymyositis
Autoimmune disease occurs when what process breaks down
Self tolerance - immune system is usually specifically unreactive (tolerant) to self antigens
Properties of non-organ specific autoimmune diseases (3)
Affect multiple organs
Associated with autoimmune responses against self-antigens distributed all throughout body
Often attack intracellular molecules involved in transcription and translation
Properties of organ specific autoimmune disease (2)
Restricted to one organ
Typically affects endocrine glands
What self antigen is attacked in Addison’s disease
21-hydroxylase
Almost all types of autoimmune diseases are more common in women, except what
Ankylosing spondylitis
Define tolerogens
Antigens that induce tolerance of the immune system
Define self tolerance
Tolerance to self antigens; fundamental property of immune system to be unresponsive to a harmless antigen
Multifactorial aetiology of autoimmune disease
- genetic (1)
- environmental (4)
Genetic factors
-mutation of HLA gene
Environmental factors
- hormones
- infection
- iatrogenic (drugs)
- UV radiation
What is the human leukocyte antigen (HLA) complex
a set of cell surface proteins essential for the acquired immune system to recognise foreign molecules from self antigens coded for by the human leukocyte antigen (consists of a family of genes that code for the HLA complex)
is the human version of the major histocompatibility complex (MHC)
To avoid autoimmune disease, T and B cells that have high affinity to self antigens are eliminated or suppressed by what mechanisms
Central tolerance
Peripheral tolerance
Central tolerance occurs where (2)
Peripheral tolerance occurs where (2)
Generative (PRIMARY) lymphoid organs
- Thymus
- Bone marrow
Secondary lymphoid organs
- spleen
- lymph nodes
What is peripheral tolerance
Secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs (thymus and bone marrow)
What is central tolerance
also known as negative selection, is the process of eliminating any developing T or B lymphocytes that have receptors specifically reactive to self antigens at an early stage
Mechanisms of central tolerance
B cell tolerance (in bone marrow)
-those with high affinity to self antigens undergo negative selection and are eliminated via apoptosis
T cell tolerance (in thymus)
- T cells undergo positive and negative selection
- those that have low affinity to self antigens go on to differentiate into single positive CD4 or CD8 T lymphocytes
- some CD4+ T cells with moderate affinity for self antigens receive a survival signal (+ve selection) and differentiate into T regulatory cells
Mechanisms of peripheral tolerance (3)
Anergy (a state of inactivation in which the lymphocytes remain alive but are unable to respond to antigen)
Treg suppression - block activation of lymphocytes
Apoptosis - induce death of these lymphocytes
Name some antigen presenting cells
Dendritic cells
Macrophages
Treg cells develop from what
CD4+ T cells
Overcoming peripheral tolerance is a contributing factor to the process of autoimmunity; in what ways is peripheral tolerance overcome (3)
Inappropriate access of self-antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the ways in which self-molecules are presented to the immune system
Breakdown of peripheral tolerance is more likely to happen when what is present
Inflammation/tissue injury due to increased activity of proteolytic enzymes –> increased protein breakdown –> high concentrations of peptides being presented to responsive to T cells
How may self antigens bypass previously established tolerance
May be altered by viruses, free radials or radiation
Apart of overcoming peripheral tolerance, there’s another immunopathological mechanism that can contribute to autoimmune disease which involves structural similarity between self antigens and antigens of microbes - what is this called
Molecular mimicry
What is epitope spreading
Once peripheral tolerance has broken down, continuous inflammation can allow presentation of further peptides and local tissue damage accelerates so immune response broadens
Environmental triggers like infection and other inflammatory stimuli promote the influx of what into tissue and so what implication may this have
promote the influx of lymphocytes into issues and the activation of self reactive T cells resulting in tissue injury
HLA-B27 mutation associated with what autoimmune disease
Ankylosing spondylitis
How may infections contribute to onset of autoimmunity
Molecular mimicry
Up-regulation of co-stimulation - microbes can activate antigen presenting cells to express co-stimulators so when they present self antigens, the self reactive T cells are activated rather than rendered tolerant
Antigen breakdown and presentation changes
How may drugs contribute to onset of autoimmunity
Molecular mimicry
Genetic variation in drug metabolism
How may UV radiation contribute to onset of autoimmunity
Trigger skin inflammation
Modify self antigen
Define autoimmune polyendocrine syndromes
group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance
Autoimmune polyendocrine syndromes frequently include what conditions (4)
alopecia - hair loss
vitiligo - pale white patches on skin due to lack of melanin
Coeliac disease - gluten intolerance
autoimmune gastritis
What do autoimmune polyendocrine syndromes involve
Circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs
–>eventually leading to organ failure
Causes of autoimmune polyendocrine syndromes (2)
Genetic predispositon
+
Enviromental factors
Name the 3 classes of autoimmune polyendocrine syndromes (rare)
Autoimmune Polyendocrine Syndrome (APS) Type 1
Autoimmune Polyendocrine Syndrome (APS) Type 2 - more common than type 1
X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) - extremely rare
Describe autoimmune Polyendocrine Syndrome (APS) Type 1
- autosomal dominant or recessive
- what age group does it affect
- mutation of what autoimmune regulator gene
autosomal recessive
affects children
mutation of AIRE gene –. dysfunctional Treg cells –> systemic autoimmunity
To diagnose autoimmune Polyendocrine Syndrome (APS) Type 1, at least 2 of 3 of what conditions must be present during childhood
Chronic mucocutaneous candidiasis
Hypoparathyroidism
Primary adrenal insufficiency (Addison’s disease)
To diagnose autoimmune Polyendocrine Syndrome (APS) Type 2, at least 2 of 3 of what endocrinopathies must be present
Type 1 diabetes
Autoimmune thyroid disease
Addison’s disease
X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) is characterised by what 3 autoimmune conditions
neonatal type 1 diabetes
Autoimmune enteropathy with intractable diarrhoea and malabsorption
Dermatitis - eczema
People with X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) have high levels of what in their blood (2)
Eosinophils
IgE
