AUTOIMMUNE DISEASES

Question 1

Autoreactive B cells and autoantibodies

Answer 1

Directly cytotoxic, Activation of complement, Interfere with normal physiological function

Question 2

Autoreactive T cells

Answer 2

Directly cytotoxic, Inflammatory cytokine production.
General inflammation and end-organ damage
Characteristic exacerbation and remission. Organ specific or systemic, common for overlap.

Question 3

innate

Answer 3

macrophages, dendritic cells, mast cells, neutrophils complement. Pattern recognition

Question 4

Adaptive

Answer 4

T an B cells.
Specific. Strong memory and amplification. Slow response but lasts longer. Can’t function without innate system as need dendritic cells to present to T cells. They then activate innate cells to cause inflammation with innate support. Lots of cross talk.

Question 5

Autoimmunity:

Answer 5

Theoretical concept. Genetically determined. Inherent to immune system

Question 6

Autoimmune diseases:

Answer 6

Distinct autoimmune processes. Distinct clinical entities. Environmental factors acting on favorable genetic background. Breakdown of self-tolerance

Question 7

Class 2 MHC

Answer 7

may shape the T cells repertoire: predisposing to autoimmunity. Class 1 on ALL cells of body.
MHC TYPE 2 PREDISOPOSED TO AUTOIMMUNE DISEASES.

Question 8

causes of autoimmune disease

Answer 8

May arise due to failure of central/peripheral tolerance. Most common genetic susceptibility is in the HLA region. Other associations: F>F, increasing age and environmental triggers eg infection, trauma-tissue damage and smoking. Lifelong chronic.

Question 9

Rheumatoid Arthritis

Answer 9

an example of how many complex factors are needed to bring about autoimmune inflammation

Question 10

Rheumatoid factor (RF)

Answer 10

Antibody (IgM, IgG or IgA) directed against the Fc portion of IgG
Commonly found in rheumatoid arthritis but not diagnostic of the diseases (sensitivity and specificity around 70%)
Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections). High titters may be pathogenic in vasculitis

Question 11

ACPA

Answer 11

more specific (95%) for RA then RF. Similar sensitivity to RF. Useful prognostic marker. ACPA positive patients tend to have more severe and erosive disease 
Treatment: supportive, immunosuppression and preventative

Question 12

Systemic Lupus Erythematosus

Answer 12

Photosensitive malar rash, multiple mouth ulcers, arthralgia, alopecia, left pleural effusion. In SLE the immune system forms antibodies against proteins and DNA in the nuclei of cells. Anti-nuclear antibodies and their antigens form immune complexes that bind to complement and cause inflammation in any tissue. Causes Lupus nephritis where immune complexes are deposited in glomerulus  renal scarring and failure. Lung: Pleurisy / Pleural Effusion. Brain: Cerebral Lupus, seizures, strokes etc

Question 13

ANCA Vasculitis: 3Forms

Answer 13

Microscopic Polyangiitis (MPA), Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosus with Polyangiitis (EGPA)
All forms have polyangiitis: Inflammation of small blood vessels causing inflammation and damage in skin, kidney, lung, gut
Some forms also have granulomata: Destructive masses of chronic inflammatory tissue. Tend to affect upper airways and lung. May cavitate.
Testing: Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
Treatment: Immunosuppression

Question 14

Raynaud’s Phenomenon

Answer 14

Primary Raynaud’s: Common in young women, Runs in families, ANA negative, Fairly harmless
Secondary Raynaud’s: ANA positive, May be associated with scleroderma (also SLE and other diseases)

Question 15

Scleroderma

Answer 15

Main features: Autoimmunity leads to ischaemia and fibrosis. Raynaud’s phenomenon, skin thickening and tightening in fingers and face
Internal organ involvement: Fibrosis may also affect lungs, gut, kidneys
Testing: Anti-Nuclear Antibodies (looking for anti-centromere or anti-Scl-70 antibodies)
Treatment: Immunosuppression – but often poor response

Question 16

Organ specific

Answer 16

Affect a single organ. Autoimmunity restricted to autoantigens of that organ. Overlap with other organ specific diseases. Autoimmune thyroid disease is typical.
Examples: Hashimotos thyroiditis, Graves’ disease, Myaesthenia gravis and pernicious anaemia

Question 17

Systemic

Answer 17

Affect several organs simultaneously. Autoimmunity associated with autoantigens found in most cells of body. Overlap with other non-organ specific diseases. Connective tissue diseases are typical.
Examples: SLE, ANCA Vasculitis and scleroderma,