IMMUNOGLOBULIN

S

Dr. Humera Kausar

2014

Immunology lecture # 5

Antibodies

� Proteins that recognize and bind to a particular antigen with very high specificity.

� Made in response to exposure to the antigen.

� Each antibody has at least two identical sites that bind antigen: Antigen binding sites.

Antibody Structure

An antibody molecule is composed of two identical heavy chains (H) and two identical light chains (L), each with a variable region (V) & constant region (C).

45 kDa

50 kDa

100kDa

Immunoglobulins are glycoproteins made up of: - Four polypeptide chains (IgG): a- Two light (L) polypeptide chains b- Two heavy (H) polypeptide chains - The four chains are linked by disulfide bonds

- Terminal portion of L-chain contains part of antigen binding site

- Terminal portion of H-chain participate in antigen binding site - H-chains are distinct for each of the five Immunoglobulins

- The other (Carboxyl) terminal portion forms Fc fragment

Antibody Structure

Antibody Structure

Fine Structure of Antibody

Five classes of Antibodies:

* IgG IgM IgA IgD IgE

Immunoglobulin Classes

I. IgG� Structure: Monomer� Percentage serum antibodies: 80%� Location: Blood, lymph, intestine� Half- l i fe in serum: 23 days� Complement Fixation: Yes� Placental Transfer: Yes� Known Functions: Enhances phagocytosis,

neutralizes toxins and viruses, protects fetus and newborn.

IgG ---- BIOLOGICAL ACTIVITY

IgG1, IgG3 & IgG4 readily cross the placenta and play an important role in protecting the developing fetus.

IgG3 is the most effective complement activator, followed by IgG1, IgG2 is less efficient and IgG4 is not able to activate complement at all.

IgG ---- BIOLOGICAL ACTIVITY

IgG1 and IgG3 bind with high affinity to Fc receptor on phagocytic cells and mediate opsonization.

IgG4 has an intermediate affinity for Fc receptors, and IgG2 has an extremely low affinity.

Immunoglobulin Classes

II. IgM� Structure: Pentamer� Percentage serum antibodies: 5-10%� Location: Blood, lymph, B cell surface

(monomer)� Half- l i fe in serum: 5 days� Complement Fixation: Yes� Placental Transfer: No� Known Functions: First antibodies produced

during an infection. Effective against microbes and agglutinating antigens.

1st Ig class produced in primary response to an antigen and also 1st Ig to be synthesized by the neonate.

More efficient than IgG at activating complement.

Secreted by plasma cells as a pentamer. plays an important accessory role as a secretory immunoglobulin.

Five monomer units are held together by disulfide bonds that link their carboxyl-terminal heavy chain domains.

IgM --------- BIOLOGICAL ACTIVITY

Each IgM pentamer contains additional Fc linked polypeptide called J-Chain, which is –S-S- bonded to the carboxyl-terminal cystein residue of two of the ten µ chains.

J-Chain required for polymerization of monomers to form pentameric IgM.

J-Chain is added just before secretion of the pentamer.

Presence of J-Chain allows IgM to bind to receptors on secretory cells, which transport it across epithelial lining to enter the external secretions that bathe mucosal surface.

Immunoglobulin ClassesIII. IgA� Structure: Dimer� Percentage serum antibodies: 10-15%� Location: Secretions (tears, saliva, intestine,

milk), blood and lymph.� Half- l i fe in serum: 6 days� Complement Fixation: No� Placental Transfer: No� Known Functions: Localized protection of

mucosal surfaces. Provides immunity to infant digestive tract.

Major Secretory Ig, present in saliva, tears, milk, and mucus of bronchial, genitourinary & digestive tracts.

Secretory IgA consists of a dimer or tetramer, a j-chain polypeptide and a polypeptide chain called secretory component.

IgA ---- BIOLOGICAL ACTIVITY

J-Chain polypeptide in IgA is identical to that

found in pentameric IgM & serves similar

function in facilitating the polymerization of

both serum IgA and secretory IgA.

Secretory component (70 kDa) consists of 5

Ig like domains.

IgA --- BIOLOGICAL ACTIVITYDomains of secretory polypeptide binds to the

domains of IgA dimer and stabil ized by a disulf ide

bond.

Every day , a human secretes 5 to 15 g of

secretory IgA in to mucous secretions.

Immunoglobulin Classes

IV. IgD� Structure: Monomer� Percentage serum antibodies: 0.2%� Location: B-cell surface, blood, and lymph� Half- l i fe in serum: 3 days� Complement Fixation: No� Placental Transfer: No� Known Functions: In serum function is unknown.

On B cell surface, init iate immune response.

Major membrane bond immunoglobulin expressed by mature B cells.

I ts role in the physiology of B cells is under investigation.

No biological effector function has been identif ied for IgD.

Immunoglobulin Classes

V. IgE� Structure: Monomer� Percentage serum antibodies: 0.002%� Location: Bound to mast cells and basophils

throughout body. Blood.� Half-l i fe in serum: 2 days� Complement Fixation: No� Placental Transfer: No� Known Functions: Allergic reactions. Possibly

lysis of worms.

IgE mediate the immediate hypersensit ivity reaction / allergic reaction.

Ragweed pollen is a potent inducers of this class of Ab.

IgE binds to Fc receptors on the membranes of Basophils and t issue mast cells.

Cross linkage of receptor bound IgE molecules by Ag (allergens) induces Basophils & mast cells to translocate their granules to the plasma membranes & release contants to the extracellular enviornment (degranulation).

AntibodiesFunction

Protective outcomes of antibody-antigen binding› Neutralization

Prevents toxin from interacting with cell

› Immobilization and prevention of adherence Antibody bonding to cellular

structures to interfere with function› Agglutination and precipitation

Clumping of bacterial cells by specific antibody

Bacteria more easily phagocytized

Protective outcomes of antibody-antigen binding› Opsinization

Coating of bacteria with antibody to enhance phagocytosis

› Complement activation Antibody bonding triggers classical

pathway› Antibody-dependent cellular

cytotoxicity Multiple antibodies bind a cell which

becomes target for certain cells

AntibodiesFunction

 پیدا سے مٹی تمہیں نے جس ہے وہی ااس اور دیا کر مقرر وقت ایک پھر کیابھی پھر تم ہے مقرر مدت ایک کےہاں

ہو کرتے )2( شکَعام ٴلن ا ُة َر ۡو ُس