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year 2 - endocrine > Immunology of endocrine disease > Flashcards

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
Q

Environmental triggers like infection and other inflammatory stimuli promote the influx of what into tissue and so what implication may this have

A

promote the influx of lymphocytes into issues and the activation of self reactive T cells resulting in tissue injury

26
Q

HLA-B27 mutation associated with what autoimmune disease

A

Ankylosing spondylitis

27
Q

How may infections contribute to onset of autoimmunity

A

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
Q

How may drugs contribute to onset of autoimmunity

A

Molecular mimicry

Genetic variation in drug metabolism

29
Q

How may UV radiation contribute to onset of autoimmunity

A

Trigger skin inflammation

Modify self antigen

30
Q

Define autoimmune polyendocrine syndromes

A

group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance

31
Q

Autoimmune polyendocrine syndromes frequently include what conditions (4)

A

alopecia - hair loss
vitiligo - pale white patches on skin due to lack of melanin
Coeliac disease - gluten intolerance
autoimmune gastritis

32
Q

What do autoimmune polyendocrine syndromes involve

A

Circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs
–>eventually leading to organ failure

33
Q

Causes of autoimmune polyendocrine syndromes (2)

A

Genetic predispositon
+
Enviromental factors

34
Q

Name the 3 classes of autoimmune polyendocrine syndromes (rare)

A

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
Q

Describe autoimmune Polyendocrine Syndrome (APS) Type 1

  • autosomal dominant or recessive
  • what age group does it affect
  • mutation of what autoimmune regulator gene
A

autosomal recessive
affects children
mutation of AIRE gene –. dysfunctional Treg cells –> systemic autoimmunity

36
Q

To diagnose autoimmune Polyendocrine Syndrome (APS) Type 1, at least 2 of 3 of what conditions must be present during childhood

A

Chronic mucocutaneous candidiasis

Hypoparathyroidism

Primary adrenal insufficiency (Addison’s disease)

37
Q

To diagnose autoimmune Polyendocrine Syndrome (APS) Type 2, at least 2 of 3 of what endocrinopathies must be present

A

Type 1 diabetes
Autoimmune thyroid disease
Addison’s disease

38
Q

X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) is characterised by what 3 autoimmune conditions

A

neonatal type 1 diabetes

Autoimmune enteropathy with intractable diarrhoea and malabsorption

Dermatitis - eczema

39
Q

People with X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX) have high levels of what in their blood (2)

A

Eosinophils

IgE

year 2 - endocrine (21 decks)

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