HC28: Pathology of allergy

Classification

Classification is the act of forming a distribution into groups, classes, orders and families according to some common relations or attributes. A classification system is used to:

• Enhanced the quality of communication
  • Especially between experts involved in the field
• Provide a logical structure for categorization
  • For epidemiologic, prognostic or interventional studies
• Assist in the management of individual patients
  • To this extent, categories should be mutually exclusive and predictive of the subsequent behavior of the disease

Conjunctivitis

Conjunctivitis is a type I hypersensitivity reaction. In case of direct hypersensitivity reactions, there is a fast immunological reaction in a sensitive individual, often called an allergy.

Morphology:

Histological images of conjunctivitis are different from most images of type I hypersensitivity reactions:

• Eosinophils are strongly present
• IgE is hard to find in a histological image
• Mast cells are present, but are hard to distinguish

Symptoms:

Conjunctivitis is an ocular allergy caused by pollen release spores. Symptoms are:

• Itching
• Watery discharge
• Redness

The upper ENT may also be involved.

Therapy:

Therapy consists of:

• Antihistamines
• Mast cell stabilizers
• Non-steroidal anti-inflammatory agents

Anti-GBM nephritis

Anti-GBM nephritis is an example of Type II hypersensitivity. GBM stands for glomerular basal membrane. Type II hypersensitivity reactions are mediated by antibodies directed to antigens on the cell-surface in the extracellular matrix. It is caused by cell destruction, an inflammatory reaction or intervention with the normal function. Deposited IgG-antibodies activate the complement system → inflammatory reaction.

Process:

In case of anti-GBM nephritis, the following happens:

1. Anti-GBM antibodies bind to the basal membrane of capillaries
2. Leukocytes (such as neutrophils) are activated and attack the vessel walls → the basal membrane breaks
3. The vessel walls become infected → glomerulonephritis and alveolar capillaritis
   • Capillary loops are destroyed
4. Inflammatory mediators come into Bowman’s space → lining epithelium starts to proliferate → crescent formation
   • Histological images of glomerulonephritis show a crescent

The IgG antibodies work against the alpha-3 chain of collagen type IV, a complement of GBM. The alpha-3 chain is part of the basement membrane in the kidney and the lung. This causes leukocytes to attack the membrane with antigens. Anti-GBM nephritis typically occurs in the kidneys and lungs.

Goodpasture syndrome:

About 50% of anti-GBM nephritis cases occurs without the lungs being involved. In case of Goodpasture-syndrome, both kidneys and lungs are involved. This usually is paired with hemorrhagia (bleeding). The alveolar walls are inflamed and pneumocytes are clearly visible.

Smokers:

Glomerulonephritis typically occurs in smokers → smoking destroys the alveolar epithelia → antibodies travel from the lungs to the kidneys. This can be diagnosed with serology for anti-GBM antibodies.

Fibrinoid necrosis

Fibrinoid necrosis is a type III hypersensitivity reaction. An important difference between type II and III hypersensitivity is that in case of type III the antibodies bind to solubles.

Morphology:

Histological images of fibrinoid necrosis show:

• Fibrine
• Necrosis
• Inflammation

Process:

Fibrinoid necrosis is vasculitis at the level of the glomerular capillary:

1. The capillaries are destroyed → inflammatory mediators are released
2. Fibrin and cytokines leak into Bowman’s space
3. Epithelial cells lining Bowman’s capsule start to proliferate

Asthma

Asthma is a type I hypersensitivity reaction. This reaction is triggered by the binding of an antigen to IgE on the surface of mast cells.

Morphology:

A morphological image of asthma shows:

• Eosinophils
• Lymphocytes
  • Whether they are B- or T-lymphocytes isn’t distinguishable
• Prominent muscle tissue
  • Caused by hyperplasia of smooth muscle cells
• Many mucus producing cells
• Small lumen

In case of allergic rhinitis (hayfever) an infiltrate with granulocytes can be visible → edema. Eosinophils can be distinguishing for the diagnosis of asthma.

Diabetes

Diabetes is an example of type IV hypersensitivity. Cytotoxic T-cells destroy insulin-producing cells in the islets of Langerhans. In a histological image, this is visible as brown spots. There also are infection cells colored for CD8.

Auto-antibodies also are present at one point, but later disappear again.

Systemic Lupus Erythematosus

An example of type III hypersensitivity is Systemic Lupus Erythematosus. SLE is a prototype of a multisystemic disease of autoimmune origin. It is characterized by production of many antibodies by the B-cells. On the face, erythema and butterfly-looking rash is visible.

Lupus nephritis:

60% of SLE patients develop renal involvement during the course of their disease → lupus nephritis. Lupus nephritis is linked with high morbidity rates, especially in case of ESRD. There is a complex relation between diagnosis, pathogenesis and treatment of lupus nephritis.

Classification:

Histopathological characteristics of lupus nephritis can vary considerably → classification of lupus is important for the choice of treatment. The classification system of lupus nephritis is based on the percentage available in the glomeruli:

• If less than 50% of glomeruli are present the classification is acute or chronic
• If more than 50% of glomeruli are present the classification is segmental or global