❑ Immunoglobulin(Ig)/antibody(Ab):

➢ Glycoprotein molecules that are produced by

plasma cells in response to an immunogen and
which function as antibodies, mostly albumin

Amount of protein
associated with γ fraction.

globulins
❑ But γ-globulin and Ig are not synonymous.
➢ Ig is a functional term
➢ γ-globulin is physical term.
- Mobility +

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General Functions of Immunoglobulin

❑ Antigen(Ag) binding
➢ Ig binds to a specific antigenic determinant

❑ Effector functions
➢ Complement activation
➢ Binding to various cells such as phagocytic cells, lymphocytes, mast
cells: antibody-mediated phagocytosis or antibody-dependent cell-
mediated cytotoxicity (ADCC).

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 Two Forms of Ig
1. Membrane Ig, mIg
It confers antigenic specificity on B cells.

mIg
2. Secreted Ig, SIg
➢It can circulate in the blood and serve as
the effectors of humoral immunity by
searching out and neutralizing antigens or
marking them for elimination.

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SIg
Basic Structure
1. four chains (H2L2): Y shape
two identical light chains (L): 23 kDa
two identical heavy chains (H): 53-75 kDa

2. Disulfide bonds and such noncovalent interactions

as salt linkages, hydrogen bonds and
hydrophobic bonds to form heterodimer (H-L).

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 1. Variable region (V): VL&VH
2. Constant region (C): CL&CH
3. Hinge region: flexibility

Hinge Light Chain:

region
– VL (110 aa) + CL (110 aa)
Heavy Chain:
– VH (110 aa) + CH1-CH3 (or CH4) (330-440 aa)

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Structural Regions

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Immunoglobulin Classes and Subclasses
❑ In terms of the differences in amino acid sequence of constant
region of heavy chain, immunglobulin molecules are divided into 5
classes:
– IgG, IgA, IgM, IgD and IgE

➢ Heavy chain: ➢ Alpha(α)

➢ Gamma(γ)
– 5 types: γ,α,μ,δ and ε. ➢ Delta(δ)
➢ Mu(μ)
➢ Epsilon(ε)

➢ Light chains
– 2 types: κ and λ.
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Five classes of immunoglobulins

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• Igs are named as per their heavy chain type as IgA , IgG , IgD , IgM & IgE

• The L and H chains are subdivided into variable and constant regions

• L chain consists of one variable(VL) and one constant (CL) domain or

region

• Most H-chains consist of one variable(VH) and 3 constant(CH-1,CH-2 &

CH-3) domains

• IgG & IgA have 3 CH domains whereas IgM & IgE have 4

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• Each Ig molecule has hinge region between CH-1 & CH-2, which
allows better fit with the antigen surface.

• The variable regions of both L & H chains have 3 extremely variable

amino acid sequences at the amino terminal end called hypervariable
region

• Enzyme(papain) digestion splits the Ig molecule into 2 fragments

named as Fab (Fragment for antigen binding) and Fc (crystallizable
fragment)

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• Hypervariable region: also called Complementarity Determining
Regions (CDRs)

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 IgG

IgG1, IgG2, IgG4 IgG3

➢ It is the most abundant class in serum, constitutes about 80% of the total
serum Ig.

➢ 4 subclasses, IgG1, IgG2, IgG3, and IgG4.

➢ All IgG's are monomers. The subclasses differ in the number of disulfide
bonds and length of the hinge region.
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Functions of IgG
1. Major Ig in extravascular spaces.

2. Placental transfer: IgG is the only class of Ig that crosses the placenta.

3. Complement activation.

4. Binding to cells - Macrophages, monocytes, PMNs (polymorphonuclear

leukocyte), and some lymphocytes have Fc receptors for the Fc region of IgG.

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 Fc receptor
• Fc receptor: protein found on the surface of certain
cells (including natural killer cells, macrophages,
neutrophils, and mast cells).

• Fc receptors bind to antibodies that are attached to

infected cells or invading pathogens.

• Their activity stimulates phagocytic or cytotoxic cells

to destroy microbes, or infected cells by antibody-
mediated phagocytosis or antibody-dependent cell-
mediated cytotoxicity.
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IgA
❑IgA occurs in 2 forms:
➢Secretory IgA
➢Serum IgA

❑Secretory IgA is a dimeric molecule formed by 2 monomer units, joined together

at their carboxy terminals by a protein termed J-chains

❑2nd highest serum Ig

❑Mw 170kD, t ½ 6d

Secretory Piece J Chain

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IgA functions
• Major secretory Ig (Mucosal or Local Immunity)

• Found in the body secretions: tears, breast milk, saliva, mucus of

the bronchial, genitourinary, and digestive tract

• IgA is the most predominant antibody in the colostrum, the initial

secretion from the mother’ breast after a baby is born.

• Does not activate complement (unless aggregated)

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• Binds to Fc receptors on some cells

• Secretory IgA prevents attachment of bacteria and viruses to

mucous membranes and helps protect mucous surface from
antigenic attack

• Prevents access of foreign substances to circulation

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IgM

Structure
The largest Ig composed of 5 Y-
shaped units held together by a J
polypeptide chain.
1. Pentamer
2. Extra domain (CH4)
3. J chain

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• The natural blood group antibodies, anti-A & anti-B are IgM

• IgM present on the surface of B lymphocytes is monomer, where it

functions as an antigen binding receptor for antigen recognition

• IgM can be produced by fetus in certain infections.

• Waldenstorm’s macroglobulinaemia : It is a malignant disease of

lymphoid elements, characterized by high serum concentrarion of IgM

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Functions of IgM
• 3rd highest serum Ig.

• IgM cannot traverse blood vessels, hence it is restricted to the

blood stream.

• 1st Ig produced in a primary response to an antigen and serve as

first line of defense.

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• A good complement activation Ig. Thus, IgM is the most effective in
leading to the lysis of microorganisms.

• Binds to Fc receptors.

• Activate complement, promotes phagocytosis & causes lysis of antigenic

cells(bacteria)

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IgD

• Structure
• Monomer
• Tail piece

Tail Piece

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IgD
❑Properties

• 4th highest serum Ig, its role in serum uncertain.

•
• B cell surface Ig.

• Does not bind complement.

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IgE

• Structure
• Monomer
• Extra domain (CH4)

CH4

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IgE
❑Function
• Least common serum Ig

• Allergic reactions
✓ Binds to basophils and mast cells (Does not require Ag binding)

• Parasitic infections (Helminths)

✓ Binds to Fc receptor on eosinophils

• no complement activation.

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• IgE is responsible for anaphylactic(immediate) type of
hypersensitivity & allergy.

• Its main activity is mediated by mast cells or basophils

• Defends against worm infections by causing release of enzymes from

eosinophils

• Main host defense against parasites like helminths

• Provides protection in the disease schistomiasis

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Major functions of immunoglobulins
Immunoglobulin Major Functions

IgG Main antibody in the secondary response. Opsonizes bacteria, Fixes complement,
neutralizes bacterial toxins and viruses and crosses the placenta.

Secretory IgA prevents attachment of bacteria and viruses to mucous membranes.

IgA Does not fix complement.

Produced in the primary response to an antigen. Fixes complement. Does not cross
IgM the placenta. Antigen receptor on the surface of B cells.

IgD Uncertain. Found on the surface of many B cells as well as in serum.

IgE Mediates immediate hypersensitivity Defends against worm infections. Does not fix
complement.
 Fibrinogen
• Also called clotting factor1

• Constitutes 4-6% of total protein

• Precipitated with 1/5 th saturation with ammonium sulphate

• Large asymmetric molecule

• Highly elongated with axial ratio of 20:1

• Imparts maximum viscosity to blood

• Synthesized in liver

• Made up of 6 polypeptide chains

• Chains are linked together by S-S linkages

• Amino terminal end is highly negative due to the presence of

glutamic acid

• Negative charge contributes to its solubility in plasma and

prevents aggregation due to electrostatic repulsions between the
fibrinogen molecules.
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Abnormal Proteins
1) Bence – Jone’s proteins
❑Abnormal proteins- monoclonal light chains
❑Present in the urine of a patient suffering from multiple myeloma (50% of patients)
❑Molecular weight 45,000
❑Identified by heat coagulation test
❑Best detected by zone electrophoresis and immunoelectrophoresis

2)Cryoglobulins
❑These proteins coagulate when serum is cooled to very low temperature
❑Commonly monoclonal IgG or IgM or both
❑Increased in rheumatoid arthritis, multiple myeloma, lymphocytic leukemia, lymphosarcoma
and systemic lupus erythematosus
Hypergammaglobulinemia

1)Polyclonal
❑ Chronic infections
❑ Chronic liver diseases
❑ Sarcoidosis
❑ Auto immune diseases

2) Monoclonal
❑ Multiple myeloma
❑ Macroglobulinaemia
❑ Lymphosarcoma
❑ Leukemia
❑ Hodgkin’s disease
Hypoproteinemia
❑ Decease in total protein concentration
➢ Hemodilution- Both Albumin and globulins are decreased, A:G ratio remains
same, as in water intoxication

❑ Hypoalbuminemia- low level of Albumin in plasma

Causes-
➢ Nephrotic syndrome
➢ Protein losing enteropathy
➢ Severe liver diseases
➢ Mal nutrition or malabsorption
➢ Extensive skin burns
➢ Pregnancy
➢ Malignancy
Clinical Significance of Plasma proteins
❑ Hyperproteinemia- Levels higher than 8.0gm/dl
Causes-
➢ Hemoconcentration- due to dehydration, albumin and globulin both are
increased. Albumin to Globulin ratio remains same.
➢ Causes- Excessive vomiting
➢ Diarrhea
➢ Diabetes Insipidus
➢ Pyloric stenosis or obstruction
➢ Diuresis
➢ Intestinal obstruction
Transport proteins
Name Compounds transported
Albumin Fatty acids, bilirubin, hormones, calcium, heavy
metals, drugs etc.

Prealbumin-(Transthyretin) Steroid hormones thyroxin, Retinol

Retinol binding protein Retinol (Vitamin A)
Thyroxin binding protein(TBG) Thyroxin
Transcortin(Cortisol binding protein) Cortisol and corticosteroids
Haptoglobin Hemoglobin
Hemopexin Free haem
Transferrin Iron
HDL(High density lipoprotein) Cholesterol (Tissues to liver)
LDL(Low density lipoprotein) Cholesterol(Liver to tissues)
THANK YOU

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