Immunoglobulins. (Ig)

 These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or  immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)

Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).

Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.

Characteristics of Immunoglobulin subclasses

I. Ig G:

(i) Predominant portion (80%) of Ig.

(ii) Molecular weight 150, 000

(iii) Sedimentation coefficient of 7S.

(iv) Crosses placental barrier and to extra cellular fluid.

• (v) Mostly neutralising effect. May be complement fixing.

(vi) Half life of 23 days.

2.IgM :

(i) Pentamer of Ig.

(ii) Molecular weight 900, 000

(iii) 19S.

(iv) More effective complement fixation and cells lysis

(v) Earliest to be produced in infections.

(vi) Does not cross placental barrier.

(vii) Halflife of 5 days.

3. Ig A :

• Secretory  antibody. Found in intestinal, respiratory secretions tears, saliva and urine also.
• Secreted  usually as a dinner with secretory piece.
• Mol. weight variable (160,000+)
• 7 S to 14 S.
• Half life of 6 days.

4.Ig D :

• Found in traces.
• 7 S.
• Does not cross placenta.

5. Ig E

• Normally not traceable
• 7-8 S (MoL weight 200,000)
• Cytophilic antibody, responsible for some hypersensitivity states,

Nephrolithiasis, urolithiasis

Formation of calculi (calcium stones) in the kidney (nephrolithiasis) or urinary tract (urolithiasis).
Commonly associated with hyperparathyroidism.
Signs and symptoms 

urinary tract obstruction, severe pain, and pyelonephritis.

Note: an enlarged prostate can also cause urinary tract obstruction in males.

Bacillus anthrax
 - large Gram (+) rods that produce heat resistant spores; Clostridia and Bacillus species are the two bacterial spore formers; they do not form spores in tissue; produces a powerful exotoxin.
 - contracted by direct contact with animal skins or products  
 
 - four forms of anthrax are recognized → cutaneous (MC), pulmonary, oraloropharyngeal, and gastrointestinal.
 - cutaneous anthrax (90 to 95% of cases) occurs through direct contact with infected or contaminated animal products.
 - lesions resemble insect bites but eventually swell to form a black scab, or eschar, with a central area of necrosis ("malignant pustule").

Bullous and Vesicular Disease
1. There are many diseases characterized by the presence of vesicles and bullae filled  fluid.
2. In pemphigus vulgaris, large, flaccid bullae filled with fluid occur on the skin and within the oral mucosa.
 - immunologic disease with IgG antibodies against the intercellular attachment sites between keratinocytes (type II hypersensitivity).
 - the vesicle in pemphigus vulgaris has a suprabasal location (just above the basal cell layer and resembling "tombstones")
 - scattered keratinocytes in the fluid as a result of acantholysis.
 - Nikolsky's sign is where the epidermis slips when touched with the finger.
 - fatal disease if left untreated (systemic corticosteroids)
3. Bullous pemphigoid is an immunologic vesicular disease whose vesicle are in a subepidermal location.
 - circulating IgG antibody against antigens in the basement membrane (type II hypersensitivity).
4. Dermatitis herpetiformis is an immunologic vesicular lesion characterized by the presence of IgA immune complexes (type III hypersensitivity) at the tips of the dermal papilla at the dermal/epidermal junction producing a subepidermal vesicle filled with neutrophils.
 - strong association with gluten-sensitive enteropathy, or celiac disease. 

Huntington’s disease
a. Causes dementia.
b. Genetic transmission: autosomal dominant.
c. Characterized by the degeneration of striatal neurons, affecting cortical and basal ganglia function.
d. Clinically, the disease affects both movement and cognition and is ultimately fatal.

Pemphigus
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against hemidemosomal attachment of epidermis cells.
3. Histologically characterized by acantholysis, in which epidermal cells appear to detach and separate from each other, as seen by Tzanck smears.
4. Can be life-threatening if untreated.
5. A positive Nikolsky sign is observed.
Because of sloughing of the epidermis, a red blister forms after pressure is applied to affected skin.
6. Treatment: corticosteroids.