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ANTIBODY DIVERSITY
CONSTRUCTION OF LIGHT CHAIN AND
HEAVY CHAIN VARIABLE REGIONS
* Light chain
* Constructed from 2 segments
* 1 (V) segment
* 1 (J) segment
* Heavy chain
* Constructed from 3 segments
* 1 (V) segment
* 1 (D) segment
* 1 (J) segment
SOMATIC RECOMBINATION
* Performed by enzymes with cut and rejoin DNA
* Recombination-activating genes 1 & 2 (RAG1 & RAG2)
* Directed by
* Recombination signal sequences (RSS)
* Recombination signal sequences
* Recognition sites for enzymes
* Recombination occurs between different types
* 9 / 12 / 7
* 9 / 23 / 7
* Mechanism follows the 12/23 rule
* Ensures segments joined in correct order
MECHANISMS OF GENETIC DIVERSITY
IN V-REGION OF IMMUNOGLOBULINS
* Random combination of
* V and J segments in light chain genes
* V, D and J segments in heavy chain genes
* Addition of P (palindromic) and N (non-templated)
nucleotides at junctions of gene segments during
recombination
* Junctional diversity
* Association of H and L chains in different
combinations
CLASSES, SUBCLASSES AND PHYSICAL
PROPERTIES OF IMMUNOGLOBULINS
Subclasses are numbered according to plasma concentration
Classes Subclasses
IgG IgG1, IgG2, IgG3, IgG4
IgA IgA1, IgA2
IgM
IgD
IgE
FUNCTIONS AND PROPERTIES OF
ANTIBODY
* Neutralization
* Direct inactivation of pathogen or toxin thereby preventing its
interaction with human cells
* Opsonization
* Coating of pathogens for more efficient phagocytosis
* Activation of complement
* More efficient phagocytosis
* Direct killing
IgM ANTIBODY OF THE IMMUNE
RESPONSE
* First isotype produced in primary response
* May or may not be produced in secondary response
* Produced before B cells undergo somatic hypermutation
* Occurs as pentamer with J chain
* Found primarily in blood and lymph
* Multiple binding sites confers high avidity and
compensates for low affinity of monomers
* Highly effective in complement activation
* Functions as rheumatoid factor
IgG ANTIBODY OF THE IMMUNE
RESPONSE
* Second isotype produced in primary response
* Primary isotype of
* Secondary immune response
* Memory immune response
* Represents approximately 75% of total serum IG
* Four subclassses (1-4)
* Different effector functions
* Transported across placenta
* Functions as rheumatoid factor
IgA ANTIBODY OF THE IMMUNE
RESPONSE
* Two subclasses (IgA1 and IgA2) and two forms
(monomeric and dimeric)
* Monomeric
* Located in blood and extracellular spaces
* Predominately IgA1
* Ratio of IgA1 to IgA2 is 10:1
* Functions as rheumatoid factor
* Dimeric
* Located in mucous membranes and secretions
* Predominately IgA2
* Ratio of IgA2 to IgA1 is 3:2
* J chain like IgM
IgE AND IgD ANTIBODIES OF THE
IMMUNE RESPONSE
* IgE
* Binds with high affinity to receptors on mast cells, basophils and
activated eosinophils
* Longer half-life when cell bound
* Initiates a strong inflammatory reaction to parasites
* Involved in allergic reactions
* IgD
* Antigen receptor on mature B-cells
* No other known function

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Immunochemistry figures

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  • 9. CONSTRUCTION OF LIGHT CHAIN AND HEAVY CHAIN VARIABLE REGIONS * Light chain * Constructed from 2 segments * 1 (V) segment * 1 (J) segment * Heavy chain * Constructed from 3 segments * 1 (V) segment * 1 (D) segment * 1 (J) segment
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  • 11. SOMATIC RECOMBINATION * Performed by enzymes with cut and rejoin DNA * Recombination-activating genes 1 & 2 (RAG1 & RAG2) * Directed by * Recombination signal sequences (RSS) * Recombination signal sequences * Recognition sites for enzymes * Recombination occurs between different types * 9 / 12 / 7 * 9 / 23 / 7 * Mechanism follows the 12/23 rule * Ensures segments joined in correct order
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  • 15. MECHANISMS OF GENETIC DIVERSITY IN V-REGION OF IMMUNOGLOBULINS * Random combination of * V and J segments in light chain genes * V, D and J segments in heavy chain genes * Addition of P (palindromic) and N (non-templated) nucleotides at junctions of gene segments during recombination * Junctional diversity * Association of H and L chains in different combinations
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  • 20. CLASSES, SUBCLASSES AND PHYSICAL PROPERTIES OF IMMUNOGLOBULINS Subclasses are numbered according to plasma concentration Classes Subclasses IgG IgG1, IgG2, IgG3, IgG4 IgA IgA1, IgA2 IgM IgD IgE
  • 21.
  • 22. FUNCTIONS AND PROPERTIES OF ANTIBODY * Neutralization * Direct inactivation of pathogen or toxin thereby preventing its interaction with human cells * Opsonization * Coating of pathogens for more efficient phagocytosis * Activation of complement * More efficient phagocytosis * Direct killing
  • 23.
  • 24. IgM ANTIBODY OF THE IMMUNE RESPONSE * First isotype produced in primary response * May or may not be produced in secondary response * Produced before B cells undergo somatic hypermutation * Occurs as pentamer with J chain * Found primarily in blood and lymph * Multiple binding sites confers high avidity and compensates for low affinity of monomers * Highly effective in complement activation * Functions as rheumatoid factor
  • 25. IgG ANTIBODY OF THE IMMUNE RESPONSE * Second isotype produced in primary response * Primary isotype of * Secondary immune response * Memory immune response * Represents approximately 75% of total serum IG * Four subclassses (1-4) * Different effector functions * Transported across placenta * Functions as rheumatoid factor
  • 26. IgA ANTIBODY OF THE IMMUNE RESPONSE * Two subclasses (IgA1 and IgA2) and two forms (monomeric and dimeric) * Monomeric * Located in blood and extracellular spaces * Predominately IgA1 * Ratio of IgA1 to IgA2 is 10:1 * Functions as rheumatoid factor * Dimeric * Located in mucous membranes and secretions * Predominately IgA2 * Ratio of IgA2 to IgA1 is 3:2 * J chain like IgM
  • 27.
  • 28. IgE AND IgD ANTIBODIES OF THE IMMUNE RESPONSE * IgE * Binds with high affinity to receptors on mast cells, basophils and activated eosinophils * Longer half-life when cell bound * Initiates a strong inflammatory reaction to parasites * Involved in allergic reactions * IgD * Antigen receptor on mature B-cells * No other known function