Autoimmunity

Question 1

How are autoreactive t and b cells selected against?

Answer 1

In the bone marrow autoreactive B cells will be rearranged in the germinal centres
T cells will be negatively selected in the thymus
These are both central tolerance

Question 2

What role does CTLA-4 play in tolerance?

Answer 2

This has a role in peripheral tolerance and it negatively regulates expansion of cells. Defects in this pathway are associated with aggressive lymphoproliferative disease

Question 3

What role do CD4 cells play in tolerance?

Answer 3

They are T regulatory cells and suppress auto-reactive cells through the release of cytokines

Question 4

What is the cause of autoimmune disease?

Answer 4

It is multifactorial and caused by both gene defects and environmental factors

Question 5

How can infectious agents cause autoimmune disease?

Answer 5

It may activate the immune system or alter a self peptide causing an autoimmune reaction

Question 6

What is the pathogenesis behind RA?

Answer 6

CD4 t cells recognise citrullinated peptides and cause immune attack. Citrullination is promoted by smoking.

Question 7

When is it normal for the body to produce autoantibodes?

Answer 7

During an infection but this is usually self limiting and T regs usually censor this

Question 8

Why can epstein barr virus cause autoantibodies to be produced?

Answer 8

This is because when infected cells are killed both self and viral proteins are taken up by dendritic cells and presented to CD4 cells

Question 9

What are the four criteria to prove that an autoantibody is associated with the pathogenesis of a disease?

Answer 9

Reproduction of the disease after transfer of the antibodies
Induction of a lesion similar to the disease after immunisation with the antigen
Isolation of the autoantibody from a typical lesion
Correlation of the antibody levels with disease activity

Question 10

What are the four main mechanisms that autoantibodies produce disease through?

Answer 10

• Complement dependent lysis e.g. paroxysmal nocturnal haemoglobinuria mediated by IgM antibodies
• Opsonisation and destruction by phagocytes, mechanism of most forms of haemolytic anaemia
• Immune complexes forming in the intravascular or extravascular spaces e.g. glomerulonephritis in SLE
• Receptor blockade stopping normal ligands from forming e.g. myasthenia gravis

Question 11

What is the pathogenesis of RA?

Answer 11

Citrullinated self-peptides are the autoantigens and cause immune reaction. This causes release of Il-1 and TNF alpha, this is the basis for infliximab therapy which is a TNF alpha blocker

Question 12

What are the main lab tests for RA?

Answer 12

Rheumatoid factor (against fc of IgG)
anti CCP antibodies (Anti-citrullinated protein antibody)

Question 13

What are the lab investigations of lupus?

Answer 13

Antinuclear antibodies

double stranded DNA antibodies (important for predicting disease severity)

Question 14

What are the two main classifications of scleroderma?

Answer 14

Limited (crest syndrome)
Diffuse
Both have lots of GIT involvement

Question 15

What does CREST in crest syndrome stand for?

Answer 15

Calcinosis (of skin)
Raynauds phenomenon
Esophageal dysmotility
Sclerodactyly
Telangectasias

Question 16

What is Sjogren’s syndrome?

Answer 16

It is a relatively common autoimmune disease that causes exocrinopathy. This manifests as dry eyes and dry mouth

Question 17

What is anti-phospholipid syndrome?

Answer 17

Occurs in patients with lupus by also people who do not fit the criteria for lupus.
Causes lots of thrombi from the antibodies

Question 18

What are the three main types of vaculitis and how does the lab test for it?

Answer 18

The main types are:

• large vessel affecting e.g. giant cell arteritis
• medium sized vessels - classic polyarteritis nodosa
• small vessels - ANCA associated

The lab tests involve ANCA (antineutrophil cytoplasmic antibody) which can ditinguish between different kinds however positive ANCA is also seen in other conditions such as infection

Question 19

What is cryptoglobinaemia?

Answer 19

Presence of immunoglobulins that precipitate on cooling. Obstruction of small blood vessels that can lead to ischaemia and infarction of the tissues they supply

Question 20

What is polymyositis?

Answer 20

Inflammatory muscle disease that majority of which have at least one autoantibody

Question 21

How can autoantibodies affect the thyroid?

Answer 21

Can either stimulate causing hyperthyroidism (Graves) or block the TSH receptor causing hypothyroidism (hashimotos)

Question 22

What is the cause of type 1 diabetes mellitus?

Answer 22

Autoimmune attack of the beta cells in the pancreatic islets of langerhans

Question 23

What is the main cause of addisons in the western world?

Answer 23

Autoantibodies against 21-hydroxylase

Question 24

What are pemphigus and pemphigoid?

Answer 24

Pemphigus - IgG Autoantibodies directed against intercellular desmosomes in the epidermis causing blisters
Pemphigoid - IgG directed against the epidermal basement membrane causing tense blisters

Question 25

What is myesthenia gravis?

Answer 25

Autoantibodies against the nicotinic acetylcholine receptors
This is easily fatiguable
Majority of patients have hyperplastic thymus and benefit from thyroidectomy

Question 26

What is Lambert-eaton syndrome?

Answer 26

Autoantibodies against pre synaptic voltage gated sodium channels
Usually paraneoplastic

Question 27

What is guillian barre?

Answer 27

Guillain-Barré syndrome (GBS) is an acute or sub-acute ascending motor polyneuropathy and radiculopathy, with patchy sensory loss. This occurs as peripheral nerve myelin sheaths become inflamed, typically following infection with Campylobacter jejuni.
This causes autoantibodies to form