Immunology

Question 1

Amyloidosis— Definition, Physical and Chemical Nature, Biochemical Forms,.

Answer 1

Definition: Amyloidosis is a condition associated with a no. of inherited and inflammatory conditions in which there is deposition of predominantly extracellular fibrillar proteins, which cause tissue damage and functional compromise.

Physical nature: can be viewed by:

1) EM= All types of amyloid look the same under EM. Appear as continuous non branching fibrils of 7.5-10nm diameter
2) X-Ray Crystallography/Infrared spectroscopy= Amyloid shows a Cross- beta-pleated sheet conformation. Responsible for Congo red Staining and apple birefringence of amyloid

Chemical Nature: 95% fibril proteins and 5% P component (may be GAGs/proteoglycan etc)

Biochemical Forms of Amyloid:

1. Major Forms
   i) AL - Ig light chain/Amino terminal part of Ig light chain or both- Produced by monoclonal plasma cells- Seen in plasma cell tumors
   ii) AA - Derived from SAA protein produced in liver. Acute phase protein which increases in acute inflammation. Hence seen in chronic inflammatory conditions.
   iii) A-Beta - Derived by proteolysis of Amyloid precursor protein (APP). It’s a transmembrane protein. Seen in Alzheimer’s disease.

Question 2

Classification of Amyloidosis.

Answer 2

Clinicopathological Classification:

1. Generalized/Systemic
   i) Primary
   ii) Secondary (Reactive systemic)
   iii) Hemodialysis associated
2. Localised
   i) Endocrine - Thyroid Ca and Type 2 DM
   ii) Senile cerebral (Alzheimer’s)
3. Hereditary
   i) Familial Mediterranean fever
   ii) Familial Amyloidotic Polyneuropathy
   iii) Senile Systemic

Question 3

Define & classify hypersensitivity reactions.

Answer 3

HSR is a pathological, excessive and injurious immune response to antigen leading to tissue injury, disease or sometimes death in a sensitized individual.

• Occurs in sensitised individuals
• Nature of antigen may be Exogenous or Endogenous
• Usually associated with susceptibility genes
• Results from imbalance between control and effector mechanism

Classification: Gel and Coombs classification according to time taken for the HS reaction to occur and the type of mediator

• Type I: Within minutes. IgE mediated
• Type II: 5-8 hours. IgG (rarely IgM) mediated. Can cause either complement mediated lysis or ADCC.
• Type III: 2-8 hours. Immune complex mediated.
• Type IV/ Delayed Type: 24 - 72 hours. CD4+ T cell mediated