Immunology

IMMUNOLOGYImmunoglobins

Dr. HUDA IBRAHIM Lec.no.4

Teaching Objectives

1. To discuss the general properties of all immunoglobulins 2. To describe the basic structure of immunoglobulins 3. To define immunoglobulin hypervariable regions


4. To define immunoglobulin classes and subclasses, types and subtypes 5. To understand the effector functions of antibodies. 6. To describe the structures and properties of immunoglobulin classes .

Immunoglobulins

Humoral basis of immunity – 19th century.Introduction of an Ag into an animalAbs appeared in the serum & body fluidsImmune seraAbs react with Ag in a specific & observable manner.

Distribution of Major Human Ig

Electrophoresis of human serum separated serum proteins into 2 major components : 1. Soluble Albumins 2. Insoluble Globulins - ,  & Ab activity - γ globulin fraction of serum proteins.

Igs are synthesized mainly by the plasma cells. Constitutes 20-25% of total serum proteins.

Structure of an Ig

Glycoproteins.2 pairs of polypeptide chains – 2 light (L) chains & 2 heavy (H) chains.“L” chain – smaller chain - low molecular wt (25,000)“H” chain – larger chain - high molecular wt (50,000)


Structure of an Ig

Structure

L chain attached to H chain by disulphide & non- covalent bonds.L chains : 2 forms – kappa () & lambda ()Each molecule of Ig can have either  or , but never both. This can gives the basis of the types of Ig.Minor differences in amino-acid sequences give rise to subtypes.

H chains : structurally & antigenically distinct for each class .This can gives the basis of Ig classes(isotypes) 5 classes of Igs – IgG, IgA, IgM, IgD & IgE.IgG & IgA have subclasses.

H chain

H chain designated by Greek letter.
Ig class
H chain
Ig G
 Ig M
 Ig A
 Ig D
 Ig E


Structure

Light chain – 2 regions Constant (CL ) Variable (VL ) C – terminal N - terminal

Structure

H chain also divided into VH & CH regions; the CH region is further divided into CH1, CH2 & CH3. Regions also called as DOMAINS : - globular in shape - stabilized by intrachain disulphide bonds Ag binding sites are located in the variable domains.

Hypervariable regions

Amino acid sequence in the variable region of L & H chains are not uniformly variable.Consists of some highly variable(hypervariable) & some relatively invariable zones.Highly variable zones actually make contact with the epitope on an Ag and are called as Complementarity Determining Regions (CDRs)3 CDRs – each made up of 9 -12 amino acids. CDR3 is the longest & most variable of the three.

Dr Ekta, Microbiology, GMCA

Fragments of Ig
Fab – Ag binding.Fc fragmentComposed of carboxy terminal of H chain.Determines the biological properties of Ig molecule.Receptors for Fc portion expressed by – mononuclear cells neutrophils phagocytosis NK cells tumour cell killing eosinophils & mast cell degranulation mast cells

Effector functions of antibodies

There are two sites at which pathogens may be located: 1. Extracellular sites 2. Intracellular sites Antibodies are effective against extracellular pathogens and function in three major ways: 1. Neutralization a. Antibodies may bind to bacterial toxins b. Antibodies may bind to molecules that viruses and bacteria use to attach to cells to gain entry for infection.


2. Opsonization An antibody facilitates uptake by phagocyte 3. Complement activation It should be noted that antibodies in each class can have different sites of action and are not equally effective in neutralization, opsonization, and complement activation.

Ig G

Major serum IgConstitutes 75% of total Igs.4 subclasses found in humans – IgG1, IgG2, IgG3 & IgG4, each having a distinct type of gamma chain.Major Ab of secondary response, found both in serum & body fluids.Participates in complement fixation, opsonzation precipitation & neutralization of viruses & toxinsAnother name is opsonin..


Ig M
5-8 % of serum Igs. Short lived Abs. Pentameric structure. Predominant Ab in primary immune response. Earliest Ab to be synthesized by the fetus. Confined to the intravascular pool due to its large size. Not transported across placenta. Present on surface of B lymphocytes as monomer

Ig A

2nd most abundant, constitutes 10-13 %.Major Ig in the colostrum, saliva, tears & other body fluids.Occur in 2 forms : IgA1 & IgA2.Secretory IgA is always in dimeric form – composed of 2 basic chain units, a J chain & the secretory component.Secretory component helps to transport the dimer from the submucosa to the mucosal cell surface.Secretory component protects IgA from proteolytic digestion and denaturation.

Dr Ekta, Microbiology, GMCA

Ig D
Resembles Ig G structurally. Occurs along with Ig M on the surface of B cells Very susceptible to proteolytic attack.

Ig E

Present in very low levels in serum. Found on the surface of mast cells & basophils which have specific receptors for the Fc portion of IgE. Chiefly produced in the linings of respiratory & intestinal tracts. Responsible for anaphylactic type of hypersensitivity. Defense against parasitic infections.