ANTIBODY

Ig G AND IgA

PRESENTED BY
SYED.KHAJA.ALI UDDIN
M.S.D(ENDODONTICS)
 INTRODUCTION
 Antibodies (also known as immunoglobulins, abbreviated Ig)
are gamma globulinproteins that are found in blood or
other bodily fluids of vertebrates, and are used by the immune
system to identify and neutralize foreign objects, such
as bacteria and viruses.
 They are typically made of basic structural units—each with
two large heavy chains and two small light chains—to form,
 For example, monomers with one unit, dimers with two units
or pentamers with five units.
 Antibodies are produced by a kind of white blood cell called a
plasma cell.
 Though the general structure of all antibodies is very similar.
 A small region at the tip of the protein is extremely variable,
allowing millions of antibodies with slightly different tip
structures, or antigen binding sites, to exist.
 This region is known as the hypervariable region. Each of
these variants can bind to a different target, known as
an antigen.
 This huge diversity of antibodies allows the
immune system to recognize an equally wide
variety of antigens. The unique part of the
antigen recognized by an antibody is called
the epitope
 These epitopes bind with their antibody in a highly specific
interaction, called induced fit, that allows antibodies to identify
and bind only their unique antigen in the midst of the millions
of different molecules that make up an organism.

  Recognition of an antigen by an antibody tags it for attack by

other parts of the immune system. Antibodies can also
neutralize targets directly by, for example, binding to a part of
a pathogen that it needs to cause an infection
 Surface immunoglobulin (Ig) is attached to the membrane of
the effector B cells by its transmembrane region, while
antibodies are the secreted form of Ig and lack the trans
membrane region so that antibodies can be secreted into the
bloodstream and body cavities.

 As a result, surface Ig and antibodies are identical except for

the transmembrane regions.

 Therefore, they are considered two forms of antibodies:

soluble form or membrane-bound form
 Isotopes
 Antibodies can come in different varieties known as
isotypes or classes.

 In placental mammals there are five antibody isotypes known

as IgA, IgD, IgE, IgG and IgM.


 They are each named with an "Ig" prefix that stands for
immunoglobulin, another name for antibody, and differ in their
biological properties, functional locations and ability to deal
with different antigens,
 STRUCTURE OF ANTIBODY
 Antibodies are heavy (~150 kDa) globular plasma proteins.

 They have sugar chains added to some of their amino acid

residues.In other words, antibodies are glycoproteins.

 The basic functional unit of each antibody is an immunoglobulin

(Ig) monomer(containing only one Ig unit); secreted antibodies can
also be dimeric with two Ig units as with IgA,.
 The Ig monomer is a "Y"-shaped molecule that consists of
four polypeptide chains; two identical heavy chains and two
identical light chains connected by disulfide bonds.

  Each chain is composed of structural

domains called immunoglobulin domains.

 These domains contain about 70-110 amino acids and are

classified into different categories (for example, variable or
IgV, and constant or IgC) according to their size and function. 
 Heavy chain
 There are five types of mammalian Ig heavy chain denoted by
the Greek letters : α, δ, ε, γ, and μ.

 The type of heavy chain present defines the class of antibody;

these chains are found in IgA, IgD, IgE, IgG, and IgM
antibodies, respectively.

 Distinct heavy chains differ in size and composition; α and γ

contain approximately 450 amino acids, while μ and ε have
approximately 550 amino acids.
 Light chain
 In mammals there are two types of immunoglobulin light
chain, which are called lambda (λ) and kappa (κ). A light chain
has two successive domains.

 one constant domain and one variable domain. The

approximate length of a light chain is 211 to 217 amino acids.
  Each antibody contains two light chains that are always
identical; only one type of light chain, κ or λ, is present per
antibody in mammals. Other types of light chains, such as the
iota (ι) chain, are found in lower vertebrates.
 FUNCTIONS OF ANTIBODIES
 ACTIVATED B CELLS differentiate

 Antibody producing cell memory cell

 Plasma cell which survive for years

to remember the antigen
and respond faster upon
the second exposure.
 At the prenatal and neonatal stages of life, the presence of
antibodies is provided by passive immunization from the
mother.

 Early endogenous antibody production varies for different

kinds of antibodies, and usually appear within the first years of
life.

 Since antibodies exist freely in the bloodstream, they are said

to be part of the humoral immune system.
 Circulating antibodies are produced by clonal B cells that
specifically respond to only one antigen (an example is
a virus capsid protein fragment).
 Antibodies contribute to immunity in three ways,

 1- They prevent pathogens from entering or damaging cells by

binding to them.

 2-They stimulate removal of pathogens by macrophages and other

cells by coating the pathogen.

 3- They trigger destruction of pathogens by stimulating

other immune responses such as the complement pathway.
 Activation of complement
 Antibodies that bind to surface antigens on, for example, a
bacterium attract the first component of the complement
cascade with their Fc region and initiate activation of the
"classical" complement system. 
 This results in the killing of bacteria in two ways.
 First, the binding of the antibody and complement molecules
marks the microbe for ingestion by phagocytes in a process
called opsonization.
 These phagocytes are attracted by certain complement
molecules generated in the complement cascade. Secondly,
some complement system components form a membrane
attack complex to assist antibodies to kill the bacterium
directly.
 The Fab portion of the antibody binds to epitopes on the
"foreign" cell.

 The NK cell then binds to the Fc portion of the antibody.

 The NK cell is then able to contact the cell and release pore-

forming proteins called perforins, proteolytic enzymes called
granzymes, and chemokines.
 Granzymes pass through the pores and activate the enzymes
that lead to apoptosis of the infected cell by means
of destruction of its structural cytoskeleton proteins and
by chromosomal degradation.

 As a result, the cell breaks into fragments that are

subsequently removed by phagocytes.

 Perforins can also sometimes result in cell lysis.

 Ig G
 Immunoglobulin G (IgG) are antibody molecules. Each IgG
is composed of four peptide chains -- two heavy chains γ and
two light chains. Each IgG has two antigen binding sites. Other
Immunoglobulins may be described in terms of polymers with
the IgG structure considered the monomer.

 IgG consitutes 75% of serum immunoglobulins in

humans. IgG molecules are synthesized and secreted
by plasma B cells.
 Functions
 IgG antibodies are predominantly involved in the secondary
immune response (the main antibody involved in primary
response is IgM).

 The presence of specific IgG generally corresponds to maturation

of the antibody response.

 IgG is the only isotype that can pass through the human placenta,

thereby providing protection to the fetus in utero.

 Along with IgA secreted in the breast milk, residual IgG

absorbed through the placenta provides
the neonate with humoral immunity before its own immune
system develops.
 IgG can bind to many kinds of pathogens, for
example viruses, bacteria, and fungi, and protects the body against
them by agglutination and immobilization complement activation
(classical
pathway), opsonization for phagocytosis and neutralization of their
toxins.

 It also plays an important role in Antibody-dependent cell-

mediated cytotoxicity(ADCC) and Intracellular antibody-mediated
proteolysis, in which it binds to TRIM21(the receptor with greatest
affinity to IgG in humans) in order to direct marked virions to
the proteasome in the cytosol.

 IgG is also associated with Type II and Type III Hypersensitivity

 IgG antibodies are large molecules of about
150 kDa composed of 4 peptide chains.

 It contains 2 identical heavy chains of about 50 kDa and 2

identical light chains of about 25 kDa, thus tetrameric
quaternary structure.
 The two heavy chains are linked to each other and to a light
chain each by disulfide bonds.

 The resulting tetramer has two identical halves which together

form the Y-like shape. Each end of the fork contains an
identical antigen binding site.
 Subclasses
 There are four IgG subclasses (IgG1, 2, 3 and 4) in humans,
named in order of their abundance in serum (IgG1 being the
most abundant).

Crosses placenta Complement Binds to Fc

 easily activator receptor on
Name Percent
phagocytic
cells
IgG1 66% yes (1.47)† second highest high affinity

IgG2 23% no (0.8)† third highest extremely low

affinity
IgG3 7% yes (1.17)† highest high affinity
IgG4 4% yes (1.15)† no intermediate
affinity
 Ig A
 Immunoglobulin A (IgA) is an antibody that plays a critical
role in mucosal immunity.

 More IgA is produced in mucosal linings than all other types

of antibody combined, between 3 and 5gm is secreted into the
intestinal lumen each day.
  This accumulates to 75% of the total immunoglobulin
produced in the entire body.
 IgA has two subclasses (IgA1 and IgA2) and can exist in a
dimeric form called secretory IgA(sIgA).

 In its secretory form, IgA is the main immunoglobulin found

in mucous secretions, including tears, saliva, colostrum and
secretions from the genito-urinary tract, gastrointestinal
tract , prostate and respiratory epithelium .

 It is also found in small amounts in blood

 . The secretory component of sIgA protects the immunoglobulin
from being degraded by proteolytic enzymes, thus sIgA can
survive in the harsh gastrointestinal tract environment and
provide protection against microbes  that multiply in body
secretions.

  IgA is a poor activator of the complement system,

and opsonises only weakly. Its heavy chains are of the type α.
 IgA1 vs. IgA2
 It exists in two isotypes, IgA1 (90%) and IgA2 (10%).
 IgA1 is found in serum and made by bone marrow B cells.

 In IgA2, the heavy and light chains are not linked

with disulfide but with with noncovalent  bonds.

 IgA2 is made by B cells located in the mucosae and has been

found to secrete into colostrum, maternal milk, tears  and saliva.
 Serum vs. secretory IgA

 It is also possible to distinguish forms of IgA based upon their

location - serum IgA vs. secretory IgA.

 One of these is the J chain (joining chain), which is

a polypeptide  of molecular mass 15kD, rich with cysteine  and
structurally completely different from other immunoglobulin
chains.
This chain is formed in the IgA-secreting cells.
 STRUCTURE OF IgA
 Serum IgA 
Exists as monomer or dimer 
80% in monomer form, 20% in dimer form monomer is ~ 160,000
D.

 In dimer, the two monomers are held together by the J chain, dimer
(~415,000 )
 STRUCTURE OF IgA
 Secretory IgA 
Exists primarily as a dimer .The two monomers are held together
with a 15,000 D J chain. 


In addition, secretory IgA contains an extra polypetpide (170,000 D)

which is termed the secretory component.

 The secretory component (or piece) is synthesized by mucosal

epithelial cells and is derived from the poly-Ig-receptor. 


When the IgA is released into the lumen of the mucosa, the secretory
component is covalently linked to the Fc of the IgA and is wrapped
around the Fc portion of the IgA dimer.
 Due to the huge surface area of the body covered by mucosa,
the combined quantities of serum and secretory IgA make
this the most abundant in the human body.

 IgA also is the predominant class of Ig found in seromucous

secretions, saliva, tracheobronchial secretions, colostrum,
milk, and genitourinary secretions. 


Ig in colostrum does not enter baby’s circulation but protects

GI tract and perhaps respiratory tract from pathogens.
 IgA activity
 The high prevalence of IgA in mucosal areas is a result of a
cooperation between plasma cells  that produce polymeric IgA
(pIgA),

 mucosal epithelial cells that express an immunoglobulin

receptor called the polymeric Ig receptor (pIgR). pIgA is
released from the nearby activated plasma cells and binds to
pIgR.

 This results in transportation of IgA across mucosal epithelial

cells and its cleavage from pIgR for release into external
secretions
 In the blood, IgA interacts with an Fc receptor called FcαRI ,
which is expressed on immune effector cells, to initiate
inflammatory reactions.Ligation of FcαRI by IgA containing
immune complexes causes 

 antibody-dependent cell-mediated cytotoxicity  (ADCC) ,

degranulation of eosinophils  and basophils, 
 phagocytosis by monocytes, macrophages, neutrophils and eosino
phils, and triggering of respiratory burst activity
by polymorphonuclear leukocytes.
 Transport

 Polymeric IgA (mainly the secretory dimer) is produced

by plasma cells in the lamina propria adjacent to mucosal
surfaces.

 It binds to the polymeric immunoglobulin receptor on the

basolateral surface of epithelial cells and is taken up into the
cell via endocytosis.
 The receptor-IgA complex passes through the cellular
compartments before being secreted on the luminal surfaces of
the epithelial cells, still attached to the receptor. 

 Proteolysis of the receptor occurs and the dimeric IgA

molecule, along with a portion of the receptor known as
the secretory component, are free to diffuse throughout the
lumen.

 In the gut, it can bind to the mucus layer on top of the

epithelial cells to form a barrier capable of neutralizing threats
before they reach the cells.
 Pathology
 Decreased or absent IgA, termed selective IgA deficiency, can be
a clinically significant  immunodeficiency.

Neisseria gonorrhœae (which causes gonorrhea) releases a

protease which destroys IgA
THANK U ALL