IMMUNOGLOBULINS: STRUCTURE & FUNCTION

DR. CROSDALE O. PUGHIKUMO

MBBS, PGDM, FMCPath (Haem), MSc.

COLLEGE OF HEALTH SCIENCES

NIGER DELTA UNIVERSITY

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 INTRODUCTION

 Immunoglobulins (Igs) are a group of plasma proteins produced by plasma

cells and mature B cells in response to immunogens.
 Plasma cells are terminally differentiated B cells.
 An antibody (Ab) is an Ig molecule with specifity for an epitope of the
molecules that make up antigens (Ags).
 Antibodies bind Antigens non-covalently to immobilise (agglutination), disarm
them or opsonize them for destruction by the RES or other components of the
immune system like cytotoxic T-cells.
 Antibodies are the key players in humoral immunity.

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 Structure of Immunoglobulins

 Igs are heterodimeric proteins composed of 4 polypeptide chains; 2 identical

heavy and 2 identical light chains.
 The heavy (H) chains carry covalently attached oligosaccharide groups
 The light (L) chains are non-glycosylated .
 H & L are joined by disulphide bonds located in a flexible region
of the heavy chain known as the hinge region.

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 Structure of Igs contd

 Most species produce 2 major classes of light chains, kappa (κ) and lambda
(λ).
 The kappa genes are encoded on chromosome 2
 While lambda genes are encoded on chromosome 22.
 In naturally occurring Abs, the light chains in a given antibody are always the
same, either both k or both λ.
 There are 5 types of heavy chains and all of them are encoded on
chromosome 14.

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Structure of Immunoglobulins contd

 Each immunoglobulin molecule has 4 domains:

 2 variable domains (VH, VL)
 2 constant domains (CH, CL)
 The variable domains are attached to the constant domains. 
 The variable domains vary in their amino acid sequence from one antibody
molecule to another. This is the basis for the diversity of the immune system.
 Fab is formed where a VH and a VL come together.
 These parts vary widely among different antibodies.

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 Structure of Immunoglobulins contd

 The variable domains are created by a series of gene rearrangement events

and can then be subjected to somatic hypermutation after exposure to
antigen.
 Each variable domain can be split into:
 3 regions of sequence variability termed the complementarity-determining
regions (CDRs).
 and 4 regions of relatively constant sequence termed the framework regions.
 The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to
form the antigen-binding site

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 Proteolytic Treatment of Immunoglobulins

 Proteolytic treatment with the enzyme papain cleaves the immunoglobulin

molecule into 3 fragments of approximately the same size.
 2 of these, called fragment antigen binding (Fab), retain the ability to bind
antigens.
 The 3rd, known as fragment crystallizable (Fc) is responsible for biological
effector functions like complement fixation, binding to macrophages, natural
killer cells and neutrophils.
 Treatment with the enzyme pepsin results in a divalent fragment called
F(ab‘)2, consisting of two Fab fragments that are joined by disulfide bonds
and several Fc fragments.

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 Immunoglobulin structure contd.

 The CH domains can be switched to alter effector function while maintaining

antigen specificity.
 Each heavy chain type defines the class of Ig: IgM, IgG, IgA, IgD, and IgE
isotypes.
 IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its
own biologic properties.
 IgA also has 2 subclasses, IgA1 and IgA2.

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 IgG

 It is the commonest, contributing about 80% to serum Ig.

 Subdivided into 4 classes: IgG1-4.
 IgG1 & IgG3 are very efficient in complement binding.
 It is present in serum and the ECF.
 It is capable of crossing the placental barrier.
 It is the major Ig of the secondary immune response.

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 Ig A

 The secretory component (SC) enhances resistance to enzymatic degradation.

 Secretory IgA dimers are present in saliva, GI secretions, tears, mucus, and
the respiratory (RT)

 More IgA is produced daily than all the other isotypes combined.

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 Ig D

 It has a monomeric structure.

 Displayed mainly on the surface of B cells.

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 Ig E

 It is mostly adsorbed onto the surfaces of mast cells, monocytes, and

eosinophils.
 Basophils and mast cells have specific receptors (FcR, CD23) for the Fc
portion of free Ig E molecules.
 Cross-linking of Ig E mast cells activates the release of histamine & other
vaso-active substances, pro-inflammatory mediators causing immediate
hypersensitivity reactions.

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General features of immunoglobulins

 The effector functions of the antibody like placental transport or antigen-

dependent cellular toxicity (ADCC)are determined by the
constant region of the heavy chain.
 Igs are the main thrust of the humoral response.
 A clone of Igs are produced in response to antigenic stimulation.

 Secretion of heavy amounts of Igs is the pathogenetic basis in diseases like

Multiple Myeloma and Waldenstrom’s Macroglobulinaemia.

 In some immunologic disorders, Igs bind to blood cells causing agglutination

(CHAD) or lysis following complement fixation or delayed elimination in the RES.

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THANK YOU FOR
ASSIMILATING SO MUCH!

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