Antibody (immunoglobulin)

Antibody
(Immunoglobulin)
M. KAMIL KHAN
MICROBIOLOGIST
1

Main contents
• Introduction to Antibody
• Antibody Structure
• Types of Antibody
• Function of Immunoglobulin
• Mechanisms or Action of Immunoglobulin (on board)
• Antibody Diversity (on board)
• Kinetics of Antibody
2

Introduction to Antibody
• Glycoprotein that is produced by B cell when it is in active
form i.e. plasma cells in against presence of an antigen.
• Also present on B cell surface.
• Gamma globulin in nature and also called immunoglobulin
(Ig) that form 20% of the total plasma proteins.
• Also the part of humoral immune system.
• Antibodies enter almost all the tissues of the body.
• After antigen captured by the membrane-bound antibody on
B cell then B cell get activated, differentiate into plasma
cells, which secrete a soluble form of antibody that
circulates through the bloodstream to recognize and bind to
antigen and induces its synthesis.
• Present in the blood serum, tissue fluids, and mucosal
surfaces of vertebrate animals.
3

Types of Antibody
• There are Five types of antibodies:
1. IgG (Ig gamma)
2. IgM (Ig mu).
3. IgA (Ig alpha)
4. IgD (Ig delta)
5. IgE (Ig epsilon)
4

1. Immunoglobulin gamma (IgG)
• IgG forms 75% of the antibodies in the body.
• Present in blood plasma and tissue fluids.
• Acts against bacteria and viruses by opsonizing the invaders and
neutralizing toxins.
• Activate classical complement pathway.
• The first ig that can be passes from mother to child through placenta and
provide natural immunity in uterus.
• There are four human IgG subclasses i.e. IgG1, IgG2, IgG3 and IgG4.
• They are vary chemically in their heavy chain composition and the
number and arrangement of inter chain disulfide bonds.
• About 65% of the total serum IgG is IgG1 and 23% is IgG2.
• IgG2 antibodies are opsonic and develop in response to toxins.
• IgG1 and IgG3, upon recognition of their specific antigens, bind to Fc
receptors expressed on neutrophils and macrophages that increase
phygocytosis.
• IgG4 antibodies function as skin-sensitizing immunoglobulin.
5

2. Immunoglobulin mu (IgM)
• Immunoglobulin or IgM accounts for about 10%.
• It is usually a polymer of five monomeric units (pentamer), each
composed of two heavy and light chains.
• The monomers are arranged in a pin-wheel array with the Fc ends in the
center, held together by disulfide bonds and a special J (joining) chain.
• IgM is the first immunoglobulin made during B-cell maturation and are
expressed on B cells, serving as the antibody component of the BCR.
• Although most IgM appears to be pentameric, around 5% or less of
human serum IgM exists in a hexameric form but lack J chain.
• IgM tends to remain in the bloodstream where it agglutinates (or
clumps) bacteria, activates complement by the classical pathway and
enhances the ingestion of pathogens by phagocytic cells.
• Hexameric IgM activates complement more effectively as compare to
pentameric form.
• the lipopolysaccharides of G-ve bacteria may directly stimulate B cells
to form hexameric IgM without a J chain.
7

3. Immunoglobulin Alpha (IgA)
• IgA, accounts for about 15% of the immunoglobulin pool.
• Some IgA is present in the serum as a monomer.
• IgA mostly secreated from mucous where it is a dimer held together
by a J chain.
• IgA, when transported from the mucus-associated lymphoid tissue to
mucosal surfaces, acquires a protein called Secretory IgA (sIgA).
• Secretory IgA is also found in saliva, tears, and breast milk.
• In these fluids sIgA plays protect surface tissues against infectious
microorganisms by the formation of an immune barrier. For example,
in breast milk sIgA helps protect nursing newborns.
• In the intestine, sIgA attaches to viruses, bacteria, and protozoan
parasites such as Entamoeba histolytica.
• This prevents pathogen adherence to mucosal surfaces and invasion of
host tissues, a phenomenon known as immune exclusion . 9

• sIgA binds to antigens within the mucosal layer of the small
intestine; subsequently the antigen-sIgA complexes are excreted
through the adjacent epithelium into the gut lumen.
• This rids the body of locally formed immune complexes and
decreases their access to the circulatory system.
• SIgA also plays a role in the alternative complement pathway.
10

4. Immunoglobulin delta (IgD)
• Found in trace amounts in blood serum.
• It has a monomeric structure similar to that of IgG.
• Do not fix complement and cannot cross the placenta, but they are
abundant in combination with IgM on the surface of B cells and
thus are part of the B cell receptor complex.
• Therefore their function is to signal the B cell to start antibody
production upon antigen binding.
11

5. Immunoglobulin Epsilon (IgE)
• IgE makes up only a small percent of the total immunoglobulin pool.
• The classic skin-sensitizing and anaphylactic antibodies belong to this
class.
• The Fc portion of IgE can bind to special Fc receptors on mast cells,
eosinophils, and basophils.
• When two IgE molecules on the surface of these cells are cross-linked
by binding to the same antigen, the cells degranulate and release
histamine and other pharmacological mediators of inflammation.
• It also stimulates large number of eosinophilia in the gut which aid in
the elimination of helminthic parasites.
• Thus although IgE is present in small amounts, this class of antibodies
has potent biological capabilities
12

Antibody Structure
• Molecular weight is 1,50,000 to 9,00,000.
• Formed by two pairs of chains i.e. one pair of heavy or
long chains consists of about 400 or 440 amino acids
having 50,000 to 70,000 Da MW and one pair of light or
short chains consists of about 200 or 220 amino acids
having 25000 Da MW.
• Actually, each antibody has two halves, which are
identical and are held together by disulfide bonds (S–S).
• Each half of the antibody consists of one heavy and light
chain.
• The two chains in each half are also joined by disulfide
bonds (S– S) which allow the movement of amino acid
chains.
13

• In each antibody, the light chain is parallel to one
end of the heavy chain.
• The light chain and the part of heavy chain parallel
to it form one arm while the remaining part of the
heavy chain forms another arm.
• Both the heavy and light chains contain several
homologous units of about 100 to 110 amino acids.
Within each unit, called a domain, disulfide bonds
form a loop of approximately 60 amino acids.
• A hinge joins both the arms.
• The four chains are arranged in the form of a
flexible “Y” with a hinge region. This hinge allows
the antibody molecule to be more flexible,
adjusting to the different spatial arrangements of
epitopes or antigenic determinants of antigens.
15

• The light chain may be either of two distinct forms called
kappa and lambda which can be distinguished by the
amino acid sequence of the constant portion of the chain
• The B cell will contain either kappa or lambda light
chains, but never both.
• Within the light chain variable (V) domain are
hypervariable regions, or complementarity determining
regions (CDRs),that differ in amino acid sequence more
frequently than the rest of the variable domain.
• The amino-terminal domain of the heavy chain has a
pattern of variability similar to that of the variable (V)
region of the kappa chain and the variable region of the
lambda chain domains, and is termed the VH domain
while the other domain constant.
• The constant domains of the heavy chain form the
constant (CH) region in which the amino acid sequencing
determines the classes of heavy chains.
16

• In humans there are five classes of heavy chains i.e. gamma (G), alpha (A),
mu (M), delta (D) and epsilon (E).
• The properties of these heavy chains determine, respectively, the five
immunoglobulin (Ig) classes—IgG, IgA, IgM, IgD, and IgE.
• There are variants of immunoglobulins that can be classified as
(1) Isotypes are the variations in the heavy chain constant regions associated
with the different classes that are normally present in all individuals.
Therefore there are five isotypes corresponding to the five antibody classes.
(2) Allotypes are the genetically controlled, allelic forms of immunoglobulin
molecules that are not present in all individuals but arise by genetic
recombination
(3) Idiotypes are individual, specific immunoglobulin molecules that differ in
the hypervariable region of the Fab portion due to mutations that occur
during B cell development
These variations of immunoglobulin structure reflect the diversity of antibodies
generated by the immune response.
• Each chain (light and heavy) of the antibody includes two regions:
1. Constant region.
2. Variable region. 17

• Constant region: in which the amino acids are similar in
number present in all the antibodies of each type called as
constant region or Fc (Fragment crystallizable) region.
Thus, the identification and the functions of different types
of immunoglobulin depend upon the constant region. This
region binds to the antibody receptor situated on the surface
of the cell membrane. It also causes complement fixation
and called the complement binding region.
• Variable Region: that is smaller as compared to constant
region in which amino acids are different in number and
placement (sequence) in each antibody called variable
region or antigen-binding region or Fab (Fragment antigen
binding) region. This region enables the antibody to
recognize the specific antigen and to bind itself with the
antigen. The amino acid in variable region folded together
the light and heavy chain, that form the antigen-binding
sites.
19

Function of Immunoglobulin
1. IgA plays a role in localized defense mechanism in external
secretions like tear.
2. IgD is involved in recognition of the antigen by B-
lymphocytes.
3. IgE is involved in allergic reactions.
4. IgG is responsible for complement fixation.
5. IgM is also responsible for complement fixation.
• As there are 2 end of the immunoglobulin which has a
unique role i.e. The Fab region is concerned with binding to
antigen, while the Fc region binds to Fc receptors found on
various cells of the immune system, or the first component
of the classical complement system.
20

• The binding of an antibody to an antigen usually does not
cause destruction of the antigen or of the microorganism, cell,
or agent to which it is attached.
• Rather the antibody serves to mark and identify the nonself
agent as a target for immunological attack and to activate
nonspecific immune responses that can destroy the target.
• At the fab antibody site, specific amino acids contact the
antigen’s epitope or haptenic groups and form multiple
noncovalent bonds between the antigen and amino acids of
the binding site.
• Because binding is due to weak, noncovalent bonds such as
hydrogen bonds and electrostatic attractions, the antigen’s
shape must exactly match that of the antigen-binding site.
• If the shape of the epitope and binding site are not truly
complementary, the antibody will not effectively bind the
antigen.
21

• Phagocytes have Fc receptors for immunoglobulin on
their surface, so bacteria that are covered with
antibodies are better targets for phagocytosis by
neutrophils and macrophages.
• This is termed opsonization.
• Other cells may kill antibody-coated cells through a
process called antibody-dependent cell mediated
cytotoxicity.
• Immune destruction also is promoted by antibody-
induced activation of the classical complement
system.
23

Kinetics of Antibody
• The synthesis and secretion of antibody can also be
evaluated with respect to time.
• Monomeric IgM serves as the B-cell receptor for
antigen, and pentameric IgM is secreted after B-cell
acti-vation.
• Furthermore, under the influence of T-helper cells
(responding to other stimuli), the IgM-secreting
plasma cells may stop producing and secreting IgM
in favor of another antibody class (IgG, IgA, IgE, for
example). This is known as class switching.
• These events take time to unfold. 24

The Primary Antibody Response When a individual is exposed to an
antigen (for example, an infection or vaccine), there is an initial lag
phase, or latent period, of several days to weeks before an antibody
response is mounted.
• During this latent period no antibody can be detected in the blood
Once B cells have differentiated into plasma cells, antibody is secreted
and can be detected.
• This explains why antibody-based HIV tests, for example, are not
accurate until weeks after exposure.
• The antibody titer, which is a measurement of serum antibody
concentration (the reciprocal of the highest dilution of an antiserum
that gives a positive reaction in the test being used), then rises
logarithmically to a plateau during the second, or log, phase.
• In the plateau phase the antibody titer stabilizes.
• This is followed by a decline phase, during which anti-bodies are
naturally metabolized or bound to the antigen and cleared from the
circulation. During the primary antibody response, IgM appears first,
then IgG, or another antibody class.
• The affinity of the antibodies for the antigen’s determinants is low to
moderate during this primary antibody response.
25

The Secondary Antibody Response The primary
antibody response primes the immune system so
that it possesses specific immunological memory
through its clones of memory B cells.
Upon secondary antigen challenge, as occurs when an
individual is re-exposed to a pathogen or receives a
vaccine booster, B cells mount a heightened
secondary, or anamnestic [Greek anamnesis,
remembrance], response to the same antigen
Compared to the primary antibody response, the
secondary antibody response has a shorter lag
phase and a more rapid log phase, persists for a
longer plateau period, attains a higher IgG titer, and
produces antibodies with a higher affinity for the
antigen.
27

Antibody (immunoglobulin)

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