NEET MDS Lessons
General Pathology
IMMUNO PATHOLOGY
Abnormalities of immune reactions are of 3 main groups
- Hypersensitivity,
- Immuno deficiency,
- Auto immunity.
Hypersensitivity (ALLERGY)
This is an exaggerated or altered immune response resulting in adverse effects
They are classified into 4 main types.
I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.
Clinical situations
I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.
2. Local (atopic) allergy.
- Allergic rhinitis (hay fever)
- Asthma
- Urticaria.
- Food allergies.
2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.
The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell.
Clinical situations
- Haemolytic anemia.
- Transfusion reaction
- Auto immune haemolytic anemia.
- Haemolysis due to some drugs like Alpha methyl dopa
Drug induced thrombocytopenia (especially sedormid).
Agranulocytosis due to sensitivity to some drugs.
Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.
3. Type III. (Immune complex disease). Circulating immune complexes especially
small soluble complexes tend to deposit in tissues especially kidney, joints, heart and
arteries.
These then cause clumping of platelets with subsequent release of histamine. and
serotonin resulting in increased permeability. Also, complement activation occurs which
being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to
release of lysosmal enzymes
Clinical situations
- Serum sickness.
- Immune complex glomerulonephritis.
- Systemic lupus erythematosus.
- Allergic alveolitis.
- Immune based vasculitis like
- Drug induced vasculitis.
- Henoch – Schonlein purpura
4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by
cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.
Clinical situations
I. Caseation necrosis in tuberculosis.
2. Contact dermatitis to
- Metals.
- Rubber.
- Drugs (topical).
- Dinitrochlorbenzene (DNCB).
5. Type V. (stimulatory) This is classed by some workers separately and by other with
cytotoxic type (Type II) with a stimulatory instead of toxic effect
Clinical Situations :
LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)
Lupus erythematosus
- chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin and other systems.
- pathogenesis: light and other external agents plus deposition of DNA (planted antigen) and immune complexes in the basement membrane.
Histology:
- basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia) are vacuolated (liquefactive degeneration)
- thickening of lamina densa as a reaction to injury.
- immunofluorescent studies reveal a band of immunofluorescence (band test) in involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
- lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.
Parathyroid hormone
Parathyroid hormone (PTH) is a polypeptide (84 amino acid residues) secreted by the chief cells of the parathyroid glands (four glands: two in each of the superior and inferior lobes of the thyroid; total weight 120 mg).
The main action of PTH is to increase serum calcium and decrease serum phosphate.
Its actions are mediated by the bones and kidneys -
In bone, PTH stimulates osteoclastic bone resorption and inhibits osteoblastic bone deposition. The net effect is the release of calcium from bone.
In the kidney, PTH has the following effects:
- Increases calcium reabsorption.
- Decreases phosphate reabsorption.
- Increases 1-hydroxylation of 25-hydroxyvitamin D (i.e. activates vitamin D).
PTH also increases gastrointestinal calcium absorption.
Psoriasis
1. Characterized by skin lesions that appear as scaly, white plaques.
2. Caused by rapid proliferation of the epidermis.
3. Autoimmune pathogenesis; exact mechanism is unclear.
Lysosomal (lipid) storage diseases
- Genetic transmission: autosomal recessive.
- This group of diseases is characterized by a deficiency of a particular lysosomal enzyme. This results in an accumulation of the metabolite, which would have otherwise been degraded by the presence of normal levels of this specific enzyme.
Diseases include:
Gaucher’s disease
(1) Deficient enzyme: glucocerebrosidase.
(2) Metabolite that accumulates: glucocerebroside.
(3) Important cells affected: macrophages.
Tay-Sachs disease
(1) Deficient enzyme: hexosaminidase A.
(2) Metabolite that accumulates: GM2 ganglioside.
(3) Important cells affected: neurons.
(4) Symptoms include motor and mental deterioration, blindness, and dementia.
(5) Common in the Ashkenazi Jews.
Niemann-Pick disease
(1) Deficient enzyme: sphingomyelinase.
(2) Metabolite that accumulates: sphingomyelin.
(3) Important cells affected: neurons.
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,
Cardiac tamponade
A. Caused by accumulation of fluid in the pericardium. This severe condition can quickly impair ventricular filling and rapidly lead to decreased cardiac output and death.
1. Signs and symptoms include:
a. Hypotension.
b. Jugular venous distention.
c. Distant heart sounds.