Immunology of endocrine disease Flashcards

1
Q

List some organ specific autoimmune disease

A

Type 1 DM
Hashimoto’s disease
Grave’s disease

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2
Q

List some non-organ specific autoimmune disease

A

Systelic lupus erythematous
Diffuse scleroderma
Polymyositis

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3
Q

Autoimmune disease occurs when what process breaks down

A

Self tolerance - immune system is usually specifically unreactive (tolerant) to self antigens

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4
Q

Properties of non-organ specific autoimmune diseases (3)

A

Affect multiple organs

Associated with autoimmune responses against self-antigens distributed all throughout body

Often attack intracellular molecules involved in transcription and translation

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5
Q

Properties of organ specific autoimmune disease (2)

A

Restricted to one organ

Typically affects endocrine glands

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6
Q

What self antigen is attacked in Addison’s disease

A

21-hydroxylase

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7
Q

Almost all types of autoimmune diseases are more common in women, except what

A

Ankylosing spondylitis

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8
Q

Define tolerogens

A

Antigens that induce tolerance of the immune system

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9
Q

Define self tolerance

A

Tolerance to self antigens; fundamental property of immune system to be unresponsive to a harmless antigen

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10
Q

Multifactorial aetiology of autoimmune disease

  • genetic (1)
  • environmental (4)
A

Genetic factors
-mutation of HLA gene

Environmental factors

  • hormones
  • infection
  • iatrogenic (drugs)
  • UV radiation
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11
Q

What is the human leukocyte antigen (HLA) complex

A

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)

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12
Q

To avoid autoimmune disease, T and B cells that have high affinity to self antigens are eliminated or suppressed by what mechanisms

A

Central tolerance

Peripheral tolerance

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13
Q

Central tolerance occurs where (2)

Peripheral tolerance occurs where (2)

A

Generative (PRIMARY) lymphoid organs

  • Thymus
  • Bone marrow

Secondary lymphoid organs

  • spleen
  • lymph nodes
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14
Q

What is peripheral tolerance

A

Secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs (thymus and bone marrow)

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15
Q

What is central tolerance

A

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

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16
Q

Mechanisms of central tolerance

A

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
17
Q

Mechanisms of peripheral tolerance (3)

A

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

18
Q

Name some antigen presenting cells

A

Dendritic cells

Macrophages

19
Q

Treg cells develop from what

A

CD4+ T cells

20
Q

Overcoming peripheral tolerance is a contributing factor to the process of autoimmunity; in what ways is peripheral tolerance overcome (3)

A

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

21
Q

Breakdown of peripheral tolerance is more likely to happen when what is present

A

Inflammation/tissue injury due to increased activity of proteolytic enzymes –> increased protein breakdown –> high concentrations of peptides being presented to responsive to T cells

22
Q

How may self antigens bypass previously established tolerance

A

May be altered by viruses, free radials or radiation

23
Q

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

A

Molecular mimicry

24
Q

What is epitope spreading

A

Once peripheral tolerance has broken down, continuous inflammation can allow presentation of further peptides and local tissue damage accelerates so immune response broadens

25
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
26
HLA-B27 mutation associated with what autoimmune disease
Ankylosing spondylitis
27
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
28
How may drugs contribute to onset of autoimmunity
Molecular mimicry | Genetic variation in drug metabolism
29
How may UV radiation contribute to onset of autoimmunity
Trigger skin inflammation | Modify self antigen
30
Define autoimmune polyendocrine syndromes
group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance
31
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
32
What do autoimmune polyendocrine syndromes involve
Circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs -->eventually leading to organ failure
33
Causes of autoimmune polyendocrine syndromes (2)
Genetic predispositon + Enviromental factors
34
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
35
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
36
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)
37
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
38
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
39
People with X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) have high levels of what in their blood (2)
Eosinophils | IgE