This document focuses on the structure and function of immunoglobulins (antibodies), detailing their glycoprotein composition, chain structure, and regions responsible for antigen binding. It explains the classification of immunoglobulins, the significance of their constant and variable regions, and their effector functions. The presentation also highlights historical experiments that led to the identification of immunoglobulins and their role in the immune response.

1. WELCME
t
My
Presentatin
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2. FINE STRUCTUREFINE STRUCTURE
OFOF
IMMUNOGLOBULIIMMUNOGLOBULI
NNDivya SrivastavaDivya Srivastava
M.Tech Biotechnology 2M.Tech Biotechnology 2NDND
Sem.Sem.
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Immunoglobulin (Ig)
Immunoglobulins are glycoprotein molecules that are produced by
plasma cells in response to an immunogen and which function as
antibodies. The immunoglobulins derive their name from the
finding that they migrate with globular proteins when antibody-
containing serum is placed in an electrical field.

4. INTRODUCTIONINTRODUCTION
 Arne Tiselius and Elvin A. Kabat (1939) immunized a rabit
with the protein ovalbumin, prepared the serum and then
divided the serum into two aliquots.
 Electrophoresis separation of one serum aliquot revealed
four major fraction corresponding to serum: albumin, the ά,
β, and γ globulins.
 Prior to electrophoresis, the other serum aliquot was mixed
with the immunized Ag, allowing the formation of an
immune precipitate that was removed, leaving the remaining
serum proteins which did not react with the Ag.
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 A comparison of the electrophoretic profiles of these two
serum aliquot revealed that there was a significant drop in γ
globulin peak in the aliquot that had been reacted with
antigen.
 Thus the γ globulin fraction was identified as containing
serum Abs which were called Immunoglobulin to distinguish
them from any other proteins that might be contained in the γ
globulin fraction.
 Thus the γ globulin fraction was identified as containing
serum Abs which were called Immunoglobulin to distinguish
them from any other proteins that might be contained in the γ
globulin fraction.

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untreated
treated

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Heavy and Light Chains
All immunoglobulins have a four chain structure as their basic
unit. They are composed of two identical light chains (23kD)
and two identical heavy chains (50-70kD)

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Variable (V) and Constant (C) Regions
When the amino acid sequences of many different heavy
chains and light chains were compared, it became clear that
both the heavy and light chain could be divided into two
regions based on variability in the amino acid sequences.
These are the:
1. Light Chain - VL
(110 amino acids) and CL
(110 amino
acids)
2. Heavy Chain - VH
(110 amino acids) and CH
(330-440
amino acids)

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•Immunoglobulin Domains
•Variable-Region Domains:Variable-Region Domains: 110 or so amino acids of heavy and
light chains varies among Abs of different Ags specificity, called
VH and VL respectively.
•The variable domain is also referred to as the FV region and is
the most important region for binding to antigens.
•To be specific, variable loops of β-strands, three each on the
light (VL) and heavy (VH) chains are responsible for binding to
the antigen. These loops are referred to as the complementarity
determining regions (CDRs).
•The structures of these CDRs have been clustered and classified
by Chothia et al.and more recently by North et al.
•CDRs are also called idiotypes. According to immune network
theory, the adaptive immune system is regulated by interactions
between idiotypes.

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Constant region :
It is the same for all immunoglobulins of the same class but
differs between classes).Heavy chains γ, α and δ have a constant
region composed of three tandem immunoglobulin domains but
also have a hinge region for added flexibility.
Heavy chains μ and ε have a constant region composed of four
domains.
Hinge Region
This is the region at which the arms of the antibody molecule
forms a Y. It is called the hinge region because there is some
flexibility in the molecule at this point. It is proline rich region.

11. Light chains of ImmunoglobulinLight chains of Immunoglobulin
22,000 Da22,000 Da
 There are two types of light chain in humans (as in other
mammals),
 kappa (κ) chain: 60% in human and 95 % in mice
 lambda (λ) chain: 40% in human and 5 % in mice
These chains are called Bence- Jones Proteins and produced by
neoplastic plasma cell as well as multiple myeloma cell.
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12. Five major class of heavy chainsFive major class of heavy chains
55,000 Da55,000 Da
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15. Chemical method to identify basic structureChemical method to identify basic structure
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16. IMMUNOGLOBULIN FRAGMENTS: STRUCTURE/FUNCTIONIMMUNOGLOBULIN FRAGMENTS: STRUCTURE/FUNCTION
RELATIONSHIPSRELATIONSHIPS
 Fab : Digestion with papain breaks the immunoglobulin
molecule in the hinge region before the H-H inter-chain
disulfide bond. This results in the formation of two identical
fragments that contain the light chain and the VH and CH1 domains
of the heavy chain.
 Fc : Digestion with papain also produces a fragment that
contains the remainder of the two heavy chains each containing
a CH2 and CH3 domain. This fragment was called Fc because it was
easily crystallized.
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Immunoglobulin DomainsImmunoglobulin Domains
•βstrand,
•βsheet

18. Unfolded VL region showing 8 antiparallel β-pleated sheets
connected by loops.
NH2
COOH
S S
The Immunoglobulin Fold

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Influenza virus antigen/ antibodyInfluenza virus antigen/ antibody

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GENERAL FUNCTIONS OF IMMUNOGLOBULINS
A. Antigen binding
Immunoglobulins bind specifically to one or a few closely related
antigens. Each immunoglobulin actually binds to a specific antigenic
determinant. Antigen binding by antibodies is the primary function of
antibodies and can result in protection of the host. The valency of
antibody refers to the number of antigenic determinants that an
individual antibody molecule can bind. The valency of all antibodies
is at least two and in some instances more.

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B. Effector Functions
Frequently the binding of an antibody to an antigen has no direct biological
effect. Rather, the significant biological effects are a consequence of
secondary "effector functions" of antibodies. The immunoglobulins
mediate a variety of these effector functions. Usually the ability to carry out
a particular effector function requires that the antibody bind to its antigen.
Not every immunoglobulin will mediate all effector functions. Such
effector functions include:

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1. Fixation of complement - This results in lysis of cells and release of
biologically active molecules .
2. Binding to various cell types - Phagocytic cells, lymphocytes,
platelets, mast cells, and basophils have receptors that bind
immunoglobulins. This binding can activate the cells to perform some
function. Some immunoglobulins also bind to receptors on placental
trophoblasts, which results in transfer of the immunoglobulin across the
placenta. As a result, the transferred maternal antibodies provide
immunity to the fetus and newborn.

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Immunoglobulin Classes andImmunoglobulin Classes and
Biological ActivitiesBiological Activities
5 major classes of secreted antibody

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28. ReferencesReferences
 Litman GW, Rast JP, Shamblott MJ, Haire RN, Hulst M, Roess W,
Litman RT, Hinds-Frey KR, Zilch A, Amemiya CT (January 1993).
"Phylogenetic diversification of immunoglobulin genes and the antibody
repertoire“.
 Johansson SG (2006). "The discovery of immunoglobulin E". Allergy
and asthma proceedings : the official journal of regional and state allergy
societies 27(2 Suppl 1): S3–6.
 Lieber MR, Yu K, Raghavan SC (2006). "Roles of nonhomologous
DNA end joining, V(D)J recombination, and class switch recombination
in chromosomal translocations".
 Immunology - chapter four immunoglobulins structure and function by
Dr. Gene Mayer
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