T1 L12 and L13: Autoimmune diseases

Question 1

What are some peripheral tolerance mechanisms?

Answer 1

• Immunological hierarchy: CD4 T-cells won’t be activated unless an antigen is present
• Antigen segregation: Physical barriers (immunological privilege)
• Peripheral anergy: Weak signally without co-stimulation causes T-cells to become unresponsive
• Regulatory T-cells: They suppress immune responses
• Cytokine deviation: Change in T-cell phenotype may reduce inflammation
• Clonal exhaustion: Apoptosis post-activation

Question 2

What is autoimmune thrombocytopaenia?

Answer 2

Autoimmune destruction of platelets

Question 3

What is Grave’s disease?

Answer 3

Autoimmune hyperthyroidism

Causes: Goitre, Grave’s ophthalmopathy

Question 4

What is myasthenia gravis?

Answer 4

Muscle weakness and fragility because the body produces antibodies against ACh receptors

Question 5

What is spontaneous urticaria?

Answer 5

Constant manifestations of hives and swelling because IgG causes mast cell degranulation

Question 6

What is Hashimoto’s thyroditis?

Answer 6

Autoimmune hypothyroidism because there is destruction of the thyroid

Question 7

What is multiple sclerosis?

Answer 7

Demyelination of nerve fibres causing weakness

Question 8

What is autoimmune polyglandular syndrome, candidiasis and ectodermal dystrophy (APACED)?

Answer 8

The body forms antibodies to IL-17 which is important against fungi at mucosal surfaces and a mutation to AIRE which regulates the immune system by encouraging negative selection.

These people becomes very prone to developing fungal infections

associated diseases: T1 diabetes, vitiligo, alopecia, autoimmune renal disease

Question 9

What is DiGeorge syndrome?

Answer 9

A microdeletion on chromosome 22 that causes a failed migration of the 3rd/4th brachial arches during development and result in:

• Absent parathyroids (low calcium, tetany)
• Cleft palate
• Congenital heart defects
• Thymic aplasia (low T-cell number, immunodeficiency)

Clinical presentation: Any of above in isolation, mild SCID, autoimmunity

Question 10

What is Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)?

Answer 10

X-linked mutation affecting the FoxP3 gene

Prevents production of: CD4, CD15, FoxP3, and Treg cells

Key features: Inflammatory bowel disease, dermatitis, organ-specific autoimmunity

Question 11

What is the HLA system?

Answer 11

The human leukocyte antigen (HLA) system (the major histocompatibility complex [MHC] in humans) is an important part of the immune system and is controlled by genes located on chromosome 6

There is a strong association between the expression of HLA molecules and some autoimmune diseases

Question 12

What is Coeliac disease?

Answer 12

An inflammatory disease of the small bowel

It had characteristics of an autoimmune disease but is usually triggered by ingestion of gluten

Clinical presentation: malabsorption (loose stool, weight loss, vitamin deficiency, anaemia, poor growth in children)

Most people affected present HLA-DQ2 and HLA-DQ8 or both

Question 13

What is the role of the HLA is Coeliac disease?

Answer 13

Dietary gliadin (wheat, rye, and barley) is degraded by gut tissue transglutamine 2 enzymes which produces gliadin peptides

HLA-DQ2/8 molecules can present the gliadin peptides to T-cells if these appropriate receptors are present which causes tissue damage

Question 14

What is molecular mimicry?

Answer 14

Explains how some infections can lead to autoimmune disease

There are similarities between the host and the infection

Question 15

Give some examples of molecular mimicry

Answer 15

Autoimmune haemolysis after mycoplasma pneumoniae infection
-Mycoplasma antigen has homology to ‘I’ antigen on red blood cells so IgM antibody to mycoplasma can cause haemolysis

Rheumatic fever after a streptococcal infection
-Anti-streptococcal antibodies believed to cross with connective tissue

Question 16

What is the link between T1 diabetes and Coxsackie virus infection?

Answer 16

The virus causes a strong immune response and pancreatitis in mice

Protein 2C from Coxsackie virus has homology with GAD so there is possible molecular mimicry

Question 17

Which systems does Systemic lupus erythematosis (SLE) affect?

Answer 17

Skin
-Causes lupine rash, photosensitivity, hives 
Serositis
-Pleurisy, pleural effusion, pericarditis
Renal
Nephritis
Pulmonary fibrosis
Joint pain
Autoimmune cytopenia's

Question 18

How is indirect immunofluorescence used to detect antibodies in the blood?

Answer 18

Detection antibodies labelled with fluorescent markers are added to a sample of patient serum, if positive, it will become fluorescent under the microscope

Eg. T1 diabetes but replaced recently by using specific islet cell antigens

Question 19

What is pemphigoid?

Answer 19

A blistering disorder

Question 20

What is the function of intrinsic factor?

Answer 20

It’s a co-factor that helps vitamin B12 absorption in the terminal ilium

Question 21

What is pernicious anaemia?

Answer 21

Autoimmune destruction of gastric parietal cells so no intrinsic factor can be secreted

Question 22

What is plasmapheresis?

Answer 22

A method of removing blood plasma from the body by withdrawing blood, separating it into plasma and cells, and transfusing the cells back into the bloodstream