Immune5&6 - Autoimmunity

Question 1

3 general features of autoimmune diseases

Clinical Patterns
Types of Autoantibodies
Triggers

Answer 1

1. ) Clinical Patterns - organ or non-organ specific
   - antigens in one organ/tissue or throughout the body
   - usually type 2 (antibody mediated) or type 4 (T cell driven) hypersensitivty reactions
2. ) Types of Autoantibodies - primary or secondary
   - primary directly drives the disease (anti-TSHR in graves disease), secondary is more common but doesn’t drive the disease itself (anti-nuclear in SLE)
3. ) Triggers - genetic and environmental factors
   - environmental: hormones, infections, drugs

Question 2

3 environmental factors triggering autoimmunity

Hormones
Infections x3
Drugs

Answer 2

1.) Hormones - autoimmune disease are more common in women of child bearing ages (80%)

2. ) Infections - microbial antigens can mimic self antigens with similar structures
   - S.pyogenes M protein in rheumatic fever
   - Campylobacter jejuni glycoproteins in GB syndrome
   - Coxsakieviruse B4 nuclear protein in type 1 DM
3. ) Drugs
   - D-penicillamine (RA) –> SLE, MG, glomerulonephritis
   - methyldopa (antihypertensive) -> haemolytic anaemia
   - hydralazine, procainamide, isoniazid can all –> SLE

Question 3

5 theurapeutic strategies for autoimmune diseases

Plasmapheresis
Immunosuppressive Drugs
Monoclonal Antibodies
Anti Inflammatory Drugs
Replacement Therapy

Answer 3

1. ) Plasmapheresis - removes the autoantibodies
   - used in Grave’s, myasthenia gravis, Goodpasture’s
2. ) Immunosuppressive Drugs - ↓autoreactive T cells
   - methotrexate (anti-metabolite), ciclosporin (anti T-cell), azathioprine (anti-proliferative), cyclophosphamide (cytotoxic)
3. ) Monoclonal Antibodies - can directly target the autoantibodies and autoreactive T cells
   - Tu = tumour regulator, Lim = immune modulator
   - Xi - chimeric (25% mice), u = 100% human, zu = 95%
4. ) Anti Inflammatory Drugs - reduces tissue damage
   - NSAIDs, prednisolone etc.
5. ) Replacement Therapy - replace whats missing
   - e.g. replace T3/T4 in hashimoto’s disease
   - organ transplant if complete organ failure

Question 4

4 criteria for the diagnosis of an autoimmune disease

Answer 4

1. ) Presence of autoantibodies or autoreactive T cells
   - should be found at the site of tissue damage
   - levels should correlate with disease severtiy
2. ) Transfer of autoantibody/autoreactive T cells to a healthy host induces the autoimmune disease
   - most common during pregnancy where antibodies are passed onto the fetus and last roughly 6 months
   - common for SLE, myasthenia gravis, Grave’s disease, haemolytic anaemia, thrombocytopenia

3.) Immunomodulatory Therapy is Effective

4. ) Familiy History - can be triggered by genetic factors
   - 8x ↑risk w/ an affected sibling (30x w/ identical twin)
   - diseases are often associated with MHC variants

Question 5

8 organ specific autoimmune diseases

(clinical outcome, autoantibody/self-antigen, hypersensitivity reaction, treatment)

Grave's Disease
Hashimoto's Disease
Type 1 Diabetes Mellitus
Addision's Disease
Myasthenia Gravis
Multiple Sclerosis
Goodpasture's Disease
Pernicious Anaemia

Answer 5

1. ) Grave’s Disease - hyperthyroidism
   - anti-TSHR (I) antibodies binds to the TSH receptor
   - type 2 hypersensitivity
   - treatment: anti-thyroid drugs (carbimazole) /plasmapheresis/thyroidectomy
2. ) Hashimoto’s Disease - hypothyroidism
   - anti-TPO (II) antibodies (thyroid peroxidase)
   - type 4 hypersensitivity
   - treatment: replacement therapy (T3/T4), levothyroxine
3. ) Type 1 Diabetes Mellitus - hyperglycaemia
   - self antigen are the pancreatic islet cells
   - type 4 hypersensitivity
   - treatment: replacement therapy (insulin)
4. ) Addision’s Disease - adrenal insufficiency
   - self antigen is steroid-21 hydroxylase (adrenal cortex)
   - type 2/4 hypersensitivity
   - treatment: replacement therapy (steroid hormones)
5. ) Myasthenia Gravis - skeletal muscle weakness
   - anti-AChR (I) antibdoies bind to the ACh receptor
   - type 2 hypersensitivity
   - treatment: AChEi/immunosuppresive drugs
6. ) Multiple Sclerosis - demyelinating disease
   - self antigen is the myelin sheath
   - type 4 hypersensitivity
   - treatment: anti-inflammatory drugs/MABs
7. ) Goodpasture’s Disease - glomerulonephritis
   - anti-GBM antbodies bind to the glomerular/alveolar basement membrane
   - type 2 hypersensitivity
   - treatment: plasmapheresis/cytotoxic drugs/dialysis
8. ) Pernicious Anaemia - vitB12 deficiency
   - anti-gastric parietal cell (II) antibodies bind to parietal cells, ↓production of intrinsic factor
   - type 2 hypersensitivity
   - treatment: replacement therapy (vitB12)

Question 6

4 non-organ specific autoimmune diseases

(clinical outcome, autoantibody/self-antigen, hypersensitivity reaction, treatment)

SLE
Rheumatoid Arthritis
Autoimmune Haemolytic Anaemia
Sjogren’s Syndrome

Answer 6

1. ) SLE - multisystem disease
   - anti-nuclear (II) antibodies bind to dsDNA
   - type 3 hypersensitivity
   - treatment: immunosuppressants/MABs
2. ) Rheumatoid Arthritis - inflammatory arthritis
   - anti-RF (II) antibodies bind to rheumatoid factor
   - type 3/4 hypersensitivity
   - treatment: immunosuppressants/MABs
3. ) Autoimmune Haemolytic Anaemia - anaemia
   - self antigens are RBC antigens
   - type 2 hypersensitivity
   - treatment: anti-inflammatories/splenectomy
4. ) Sjogren’s Syndrome - dry eyes, mouth, and arthritis
   - self antigen are nuclear antigens
   - type 4 hypersensitivity
   - treatment: eye drops etc.

Question 7

4 features of rheumatoid arthritis

Pathophysiology
Articular Symptoms
Non-Articular Symptoms
Treatment

Answer 7

1.) Pathophysiology - autoantibodies to the Fc portion of IgG (rheumatoid factor) and citrullinated cyclic peptide

2. ) Articular Symptoms - persistent synovitis –>chronic symmetrical polyarthritis with systemic inflammation
   - ↑inflammatory cells (T/B cells) –> ↑TNF-a –> ↑IL-6 leads to synovitis and joint destruction
3. ) Non-Articular Symptoms
   - lungs: pleural effusion, interstitial lung disease, small airway disease, nodules, caplan syndrome
   - lymphadenopathy, Sjogrens syndrome, pericarditis
4. ) Treatment - immunosuppressants/MABs
   - blockage of TNF-a and IL-6