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IMMUNOGLOBULINS 2

IMMUNOGLOBULINS 2

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Published by: rednri on Jan 11, 2011
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04/26/2013

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IMMUNOGLOBULINS: ISOTYPES, ALLOTYPES AND IDIOTYPESI.
 
ISOTYPES
A.
 
Definition
- Isotypes are antigenic determinants that characterize classes and subclasses of heavychains and types and subtypes of light chains
.
 If human IgM is injected into a rabbit the rabbit will recognize antigenic determinants on the heavy chain and light chain and make antibodies to them
.
If that antiserumis absorbed with human IgG the antibodies to the light chaindeterminants and any determinants in common between human IgM and IgG will be removed and the resultingantiserum will be react only with human IgM
.
Indeed, the antibodies will only react with the constant region of theµ chain
.
 
A
ntibodies to the variable region are rare perhaps because only a few copies of each different variableregion are represented in the IgM and thus effective immunization does not occur
.
The determinants that arerecognized by such antibodies are called isotypic determinants and the antibodies to those determinants are calledanti-isotypic antibodies
.
Each class, subclass, type and subtype of immunoglobulin has its unique set of isotypicdeterminants
.
 B
.
 
Location
- Heavy chain isotypes are found onthe Fc portion of the constant region of themolecule while light chain isotypes are found inthe constant region
.
The location of isotypicdeterminants is illustrated in Figure 1
.
 C
.
 
Occurrence
- Isotypes are found in
ALL
 NORM
AL
individuals in the species
.
The prefixIso means same in all members ofthe species
.
 Some individuals with immunodeficiencies maylack one or more isotypes but normalindividuals have all isotypes
.
 D
.
 
Importance
-
A
ntibodies to isotypes are usedfor the quantitating Ig classes and subclasses invarious diseases, in the characterization of B cellleukemia and in the diagnosis of variousimmunodeficiency diseases
.
  
II.
 
ALLOTYPES
A.
 
Definition
-
A
llotypes are antigenic determinants specified by allelic forms of the Ig genes
.
 
A
llotypes represent slight differences in the amino acid sequences in the heavy or light chains of different individuals
.
Even a single amino acid difference can give rise to an allotypic determinant, although in many casesthe several amino acid substitutions have occurred
.
 
A
llotypic differences are detected by using antibodies directed against allotypic determinants
.
These antibodiescan be prepared by injecting the Ig from one person into another
.
In practice however we obtain anti-allotypeantisera from women who have had multiple pregnancies or from people who have received blood transfusions orfrom some patients with rheumatoid arthritis
.
 B
.
 
Location
- In man the allotypic differences arelocalized to the constant region of the heavy and light chains as illustrated in the Figure 2
.
 C
.
 
Occurrence
- Individual allotypes are found inindividual members of a species
.
 
A
ll allotypes are not found in allmembers of the species
.
The prefix
A
llomeans different in individuals of a species 
 
D
.
 
H
uman IgAllotypesNomenclature
- Human Igallotypes are named on the basis of the heavy or light chain on which it is located
.
Thus, an allotype on a Gamma 1 heavy chain is given the name: G1m(3)
.
 
A
n allotype on a Kappa light chain is given the name: Km(1)
.
Table 1 lists some human allotypes
.
 
 Table1 Human allotypes 
 
Chain
 
 
Domain
 
 
Allotype
 
 
AminoAcid
 
 
Position
 
 
IgG1
 
 
C
H1
 
 
G1m(f)=(3)
 
 
Arg
 
 
214
 
 
C
H1
 
 
G1m(z)=(17)
 
 
Lys
  
 
C
H1
 
 
G1m(a)=(1)
 
 
Arg,Asp,Glu,Leu
 
 
355-358
 
 
 
light chain
 
 
C
L
 
 
Km(1)
 
 
Val,Leu
 
 
153,191
 
 
C
L
 
 
Km(3)
 
 
Ala,Val
 
 
153,191
 
AdaptedfromStites
etal 
.
,BasicandClin
.
Immunol
.
,3rdEd
.
,Table7-8
E
.
 
Genetics
  1
.
 
C
odominant autosomal genes
-
A
llotypes that represent amino acid substitutions at the same position ina heavy or light chain  (eg
.
G1m(3) and G1m(17) or Km(1) and Km(3) are inherited as codominant autosomal genes
.
eg
.
 
Km(1)/Km(3) X Km(1)/Km(1)
 

Km(1)/Km(1)andKm(1)/Km(3)
 2
.
 
Allelic Exclusion
-
A
lthough in a heterozygote both alleles are expressed, any individual Ig molecule willonly have one allotype
.
This is because an individual B cell can only expresses one allele
.
This is calledallelic exclusion
.
 
A
llotypes that represent amino acid substitutions at different locations in a molecule (eg
.
 G1m(1) and G1m(17)) can be found on the same molecule
.
 eg
.
In a G1m(1,17) individual both allotypes can be on the same heavy chain
G1m (17) Gm1 (1)| |214 355-358
F
.
 
Importance
 1
.
 
Monitoring bone marrow grafts
- Bone marrow grafts that produce a different allotype from the recipient can be used to monitor the graft 
.
 2
.
 
F
orensic medicine
- Km and Gmallotypes are detectable in blood stains and semen and are useful inforensic medicine
.
 3
.
 
Paternity testing
- The immunoglobulin allotypes are one of the characteristics used in legal casesinvolving paternity
.
 

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