Immunology of endocrine disease

Question 1

List some organ specific autoimmune disease

Answer 1

Type 1 DM
Hashimoto’s disease
Grave’s disease

Question 2

List some non-organ specific autoimmune disease

Answer 2

Systelic lupus erythematous
Diffuse scleroderma
Polymyositis

Question 3

Autoimmune disease occurs when what process breaks down

Answer 3

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

Question 4

Properties of non-organ specific autoimmune diseases (3)

Answer 4

Affect multiple organs

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

Often attack intracellular molecules involved in transcription and translation

Question 5

Properties of organ specific autoimmune disease (2)

Answer 5

Restricted to one organ

Typically affects endocrine glands

Question 6

What self antigen is attacked in Addison’s disease

Answer 6

21-hydroxylase

Question 7

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

Answer 7

Ankylosing spondylitis

Question 8

Define tolerogens

Answer 8

Antigens that induce tolerance of the immune system

Question 9

Define self tolerance

Answer 9

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

Question 10

Multifactorial aetiology of autoimmune disease

• genetic (1)
• environmental (4)

Answer 10

Genetic factors
-mutation of HLA gene

Environmental factors

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

Question 11

What is the human leukocyte antigen (HLA) complex

Answer 11

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)

Question 12

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

Answer 12

Central tolerance

Peripheral tolerance

Question 13

Central tolerance occurs where (2)

Peripheral tolerance occurs where (2)

Answer 13

Generative (PRIMARY) lymphoid organs

• Thymus
• Bone marrow

Secondary lymphoid organs

• spleen
• lymph nodes

Question 14

What is peripheral tolerance

Answer 14

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

Question 15

What is central tolerance

Answer 15

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

Question 16

Mechanisms of central tolerance

Answer 16

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

Question 17

Mechanisms of peripheral tolerance (3)

Answer 17

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

Question 18

Name some antigen presenting cells

Answer 18

Dendritic cells

Macrophages

Question 19

Treg cells develop from what

Answer 19

CD4+ T cells

Question 20

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

Answer 20

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

Question 21

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

Answer 21

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

Question 22

How may self antigens bypass previously established tolerance

Answer 22

May be altered by viruses, free radials or radiation

Question 23

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

Answer 23

Molecular mimicry

Question 24

What is epitope spreading

Answer 24

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

Question 25

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

Answer 25

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

Question 26

HLA-B27 mutation associated with what autoimmune disease

Answer 26

Ankylosing spondylitis

Question 27

How may infections contribute to onset of autoimmunity

Answer 27

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

Question 28

How may drugs contribute to onset of autoimmunity

Answer 28

Molecular mimicry

Genetic variation in drug metabolism

Question 29

How may UV radiation contribute to onset of autoimmunity

Answer 29

Trigger skin inflammation

Modify self antigen

Question 30

Define autoimmune polyendocrine syndromes

Answer 30

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

Question 31

Autoimmune polyendocrine syndromes frequently include what conditions (4)

Answer 31

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

Question 32

What do autoimmune polyendocrine syndromes involve

Answer 32

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

Question 33

Causes of autoimmune polyendocrine syndromes (2)

Answer 33

Genetic predispositon
+
Enviromental factors

Question 34

Name the 3 classes of autoimmune polyendocrine syndromes (rare)

Answer 34

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

Question 35

Describe autoimmune Polyendocrine Syndrome (APS) Type 1

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

Answer 35

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

Question 36

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

Answer 36

Chronic mucocutaneous candidiasis

Hypoparathyroidism

Primary adrenal insufficiency (Addison’s disease)

Question 37

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

Answer 37

Type 1 diabetes
Autoimmune thyroid disease
Addison’s disease

Question 38

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

Answer 38

neonatal type 1 diabetes

Autoimmune enteropathy with intractable diarrhoea and malabsorption

Dermatitis - eczema

Question 39

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

Answer 39

Eosinophils

IgE