Antigen

ANTIGEN

• An antigen is a molecule that induces an immune response in

the body and helps in production of antibody or activate cells.
• Also called as immunogen.
• Any substance that is foreign and doesn't belong to the host
and satisfies two distinct immunologic properties-
o Immunogenicity
o Antigenicity.

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 Origin of antigen

Exogenous antigens
• Antigens that have entered the body from the outside.
E.g. By inhalation , ingestion , or injection .

Endogenous antigens
• Antigens that have been generated within previously normal cells
as a result of normal cell metabolism , or because of viral or
intracellular bacterial infection
 Immunogenicity
• Ability of an antigen to induce immune response in the body
(both humoral and/or cell mediated).
o B cells + antigen → effector B cells (plasma cell) + memory
B cells
o T cells + antigen → effector T cells (helper T cell or
cytotoxic T cell) + memory T cells

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 Antigenicity (immunological reactivity)
• Ability of an antigen to combine specifically with the final
products antibodies and/or T cell-surface receptors.

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 ANTIGEN AND HOST RELATIONSHIP

• Based on the antigen-host relationship, antigens can

be grouped into two groups:
o Self or auto antigens
o Non-self or foreign antigens

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 FACTORS INFLUENCING IMMUNOGENICITY

• Size of the antigen

• Chemical nature of the antigen
• Susceptibility of antigen to tissue enzymes
• Foreignness to the host
• Genetic factor
• Optimal dose of antigen
• Route of antigen administration:
• Repeated Number of doses of antigens
• Multiple antigens:
• Effect of prior administration of antibody:
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Antibody
ANTIBODY

• Humoral basis of immunity

• Secreted by plasma cell
• Present on B cell membrane
• React with antigen - specifically
observable
 Antibody or immunoglobulin
• Specialized glycoprotein, produced from activated B cells
(plasma cells) in response to an antigen.
• Capable of combining with the antigen that triggered its
production.
• By electrophoresis, the serum proteins are separated into four
fragments- albumin, globulin α, β and γ.
• Antibodies are located in the γ-globulin fraction; because they
immunologically react with the antigen; they were given the
name as immunoglobulin.
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 Antibody or immunoglobulin
• Both the terms, immunoglobulin (Ig) and antibody are used
interchangeably; representing the physiological &functional
properties of same molecule respectively.
• Immunoglobulin (Ig) constitutes 20-25 per cent of total serum
proteins.
• There are five classes (or isotypes) of immunoglobulins
recognised-IgG, IgA, IgM, IgD and IgE.

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 STRUCTURE OF ANTIBODY

• An antibody molecule is a ‘Y-shaped’

heterodimer; composed of four
polypeptide chains.
• Two identical light (L) chains, and Two
identical heavy (H).
• Each H and L chain comprises of two
regions- variable and constant region and
this is called Two Fab and One Fc

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ANTIBODY STRUCTURE
 STRUCTURE OF ANTIBODY (cont..)

• H and L chain:
o All four H and L chains are bound to
each other by disulfide bonds, and
by noncovalent interactions such as
salt linkages, hydrogen bonds, and
hydrophobic bonds.
o All the chains have two ends- an
amino terminal end (NH3) and a
carboxyl terminal end (COOH).
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 STRUCTURE OF ANTIBODY (cont..)

• There are five classes of H chains and two classes of light

chains. Immunoglobulin class Heavy chain type
IgG γ(gamma)
IgA α (alpha)
IgM µ(mu)
IgD δ(delta)
IgE ε(epsilon)

• L chains are of two types- kappa (κ) and lambda (λ).

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 Variable and Hyper variable region

• Represents the antigen binding site of

the antibody.
• Within the variable region, there are
some zones (hot spots) that show
relatively higher variability in the amino
acid sequences.
• Called as hypervariable regions or
complementarity determining regions
(CDRs).
• Form the antigen-binding site. 16
 Constant regions

• Constant region
o Constitutes the remaining part of an Ig
molecule other than that of variable
region.
o The amino acid sequence of constant
region shows uniform pattern.
o A single antibody molecule has two
identical heavy chains and two identical
light chains; H2L2.
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 FUNCTIONS OF IMMUNOGLOBULINS

• Antigen binding (by Fab region)

o Protection of the host.
o Interaction with the antigen.
o Valency of an antibody refers to the number of Fab regions it
possesses. Thus, a simple monomeric antibody molecule has
a valency of two.

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 IMMUNOGLOBULIN CLASSES

• Based on five types of heavy chains, there are five classes

of immunoglobulins (lgG, IgA, IgM, IgD and IgE).

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 Immunoglobulin G (IgG)

• Constitutes about 70-80% of total Igs of the body.

• IgG has maximum daily production.
• Longest half-life of 23 days.
• Highest serum concentration.
• Level raised - chronic malaria, kala azar,
myeloma, 20 infections.
• IgG has four subclasses- IgG1, IgG2, IgG3
and IgG4
• Called General purpose antibody 20
 Functions of IgG

• IgG can cross placenta - hence provide immunity to the fetus

and new born- Natural passive immunity
• Complement fixing and Phagocytosis
• Mediates precipitation and neutralization reactions.
• IgG plays a major role in neutralization of toxins as it can easily
diffuse into extravascular space.
• IgG is raised after long time following infection and represents
chronic or past infection (recovery).
• Coagglutination
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 Immunoglobulin M (IgM)

• Among all Igs, IgM has highest molecular weight due to polymer of
five peptide subunits, and hence called millionaire molecule.
• Present only in intravascular compartment, not in body fluids or
secretions.
• 5-8% of serum immunoglobulin
• Half-life of 5 days
• lgM – Earliest immunoglobulin to be synthesised

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 Immunoglobulin M (IgM)

• IgM exists in both monomeric and

pentameric forms:
o When present as membrane-bound
antibody on B cells, it exists in
monomeric form.
o When present in secreted form, it is
pentameric in nature

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 Functions of IgM

• Presence in serum - recent infection or Acute infection

• Complement fixing and Acts as an opsonin
• Protection against intravascular organisms
• Mediate agglutination
• Not transported across placenta
• lgM in fetus/newborn - indicates intrauterine infections-
Fetal immunity
• Short lived, disappear earlier than lgG
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 Immunoglobulin A (IgA)

• IgA is the second most abundant class of Ig next to IgG, constituting

about 10-15% of total serum Ig.
• Half-life of 6-8 days
• Major immunoglobulin – colostrum, saliva, tears
• Exists in both monomeric (Serum IgA) and dimeric forms (Secretory
IgA).
• IgA exists in two isotypes:
o IgA1
o IgA2
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 Serum IgA and Secretory IgA

• Secretory IgA; two IgA monomeric units joined

by a J chain.
• Secretory component Location-Predominant
antibody found in body secretions like milk,
saliva, tears, intestinal & respiratory tract
mucosal secretions.
• Dimeric secretory lgA - synthesised by plasma
cells, mucosal/glandular epithelial cells
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 Function of secretory IgA
• Role in local immunity or mucosal immunity against respiratory and
intestinal pathogens
• Resistant to digestive enzymes
• Inhibit adherence of organism to mucosa activates - alternate
complement pathway
• Promotes phagocytosis and intracellular killing of microorganisms
• Effective against bacteria like Salmonella, Vibrio, Neisseria, and viruses
like polio and influenza.
• Breast milk is rich in secretory IgA and provides good protection to the
immunologically immature infant gut.
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 Immunoglobulin E (IgE)

• Lowest serum concentration.

• Shortest half life.
• Minimum daily production.
• Only heat labile antibody (inactivated at 56º C in one hour).
• Has affinity for the surface of tissue cells (mainly mast cells)
of the same species (homocytotropism).
• Extravascular in distribution.
• Mediator of type I hypersensitivity reactions
• IgE is elevated in helminthic infections. 28
 Immunoglobulin D (IgD)

• IgD is found as membrane Ig on the surface of inactivated B cells

and acts as a B cell receptor along with IgM.
• Has the highest carbohydrate content among all the Igs.
• Resembles lgG structurally
• Concentration-3 mg/100 ml serum intravascular
• No other function is known for IgD so far.

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 Properties of various immunoglobulins

Property IgG IgA IgM IgD IgE

Usual form Monomer Monomer,dimer Monomer,Penta Monomer Monomer
mer
Valency 2 2 or 4 2 or 10 2 2
Other chains None J chain, J chain None None
secretory
component
Subclasses G1, G2, G3, G4 A1, A2 None None None
Molecular weight (kDa) 150 150-600 900 150 190
Serum level mg/mL 9.5–12.5 IgA1- 3.0 1.5 0.03 0.0003
IgA2 - 0.5

% of total serum Ig 75–85% 10–15% 5–10% 0.3% 0.019%

Half-life, days 23* 6 5 3 2.5
Daily production mg/kg 34 24 3.3 0.4 0.0023

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 Properties of various immunoglobulins

Property IgG IgA IgM IgD IgE

Intravascular distribution 45% 42% 80% 75% 50%
(%)
Sedimentation coefficient 7 7 19 7 8
Complement activation
Classical ++ (IgG3>1>2) – +++ – –
Alternate - + - - -
Binds to Fc receptors of ++ - ? ** - -
phagocytes
Placental transfer Yes (except IgG2) - - - -
Mediates coagglutination Yes (except IgG3) - - - -
Mucosal transport - Yes - - -
Mast cell degranulation - - - - yes
Marker for B cells - - + + -
Heat stability + + + + -
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