ANTIBODIES AND
IMMUNOGLOBULINS
DR.NASRIN NAHAR
MBBS, BCS,MD(MICROBIOLOGY)
LECTURER
SHER-E-BANGLA MEDICAL COLLEGE
BARISHAL
DEFINITIONS
• Antibodies are specific glycoprotein produced by plasma cells in
response to a specific antigen and capable of reacting with that
antigen.
• Immunoglobulin structurally similar animal proteins that may or may
not be endowed with antibody activity.
• Non functional immunoglobulins are produced in multiple myeloma (plasma cell
cancer).
• These immunoglobulins can not bind with specific antigen and are not antibodies.
Thus all antibodies are immunoglobulin but all immunoglobulin are not
antibodies however, the terms are used interchangeably.
STRUCTURE OF IMMUNOGLOBULIN
STRUCTURE OF IMMUNOGLOBULIN
EFFECTOR FUNCTION OF ANTIBODY
NUTRALIZATION
OPSONIZATION
ADCC
IMMUNOGLOBULIN G
Most abundant class in serum (13.5mg/ml)(75%)
Consists of two γ H chain and two κ or λ L chain
Molecular formula γ2κ2 or γ2λ2)
γ H chain contain one variable and three constant
domain (Cγ1, Cγ2, Cγ3 ) - involved in the different
effector functions
Produced during secondary immune responses
Subclasses
• Four subclasses, distinguished by differences in H chain
sequence
• Numbered according to decreasing serum concentrations
• IgG1- 60-70%
• IgG2- 14-20%
• IgG3- 4-8%
• IgG4- 2-6%
Biologic activities
1. activate the classical complement pathway
2. bind to macrophage and neutrophils for enhanced phagocytosis
3. bind to NK cells for antibody-dependent cytotoxicity (ADCC).
4. enables it to cross the placenta (IgG is the only class of antibody that
can cross the placenta and enter the fetal circulation)
IMMUNOGLOBULIN M
• Is the first antibody produced during primary immune
response.
• Also first antibody produced by neonates in certain
infection.
• Approximately 9% of the serum antibodies (1.5 mg/ml).
• Present as receptor (monomer) on B cell surface.
• Secreted from plasma cell as pentamer.
• Each pentamer contains a J (Joining) chain - a polypeptide
linked with Carboxyl- Terminal end of  H chain
• J chain is required for polymerization of monomer to form
pentamer IgM before secretion.
BIOLOGIC ACTIVITIES
Complement activation-
• Most efficient in activating complement
Complement activation requires close proximity of 2 Fc
regions. Pentavalent IgM fulfills that need
Neutralization of virus-
• less IgM than IgG is required to neutralize viral infectivity
• Most efficient in agglutination and other antibody functions.
IMMUNOGLOBULIN A
Main class of Ab in the secretion (both external and internal body
fluids)
• Present in blood as monomer.
• Present in secretion (Milk, colostrum, tear, saliva, mucous of GIT, RT
and genital tract) as dimer.
• Secretory IgA is a dimer and has 4 Fab sites.
• polymerized by a polypeptide chain called J-Chain (MW 15000)
• Function of J-Chain is to Polymerization of IgA.
• It has a secretory component.
SECRETORY COMPONENT
• produced by epithelial cells of mucous membrane.
• responsible for transporting polymeric IgA across the cell
membranes into the mucous secretions.
• It masks Hinge region from protease cleavage in Protease-
rich mucosal environment.
BIOLOGIC ACTIVITIES
IgA plays important role in mucosal immunity provide first line of
defense specially against
• Salmonella
• Vibrio
• N. gonorrhoeae
• Polio
• Influenza
• Rota virus
BIOLOGIC ACTIVITIES
• Breast milk contains secretory IgA and protect the
newborn against infection during the first month of life
• Binds to bacterial and viral antigen and prevent attachment
to mucosal cells
IgA cannot bind to complements
IMMUNOGLOBULIN E
Present in extremely low concentration due to
 short half life of two days
slow rate of synthesis and
rapid binding to mast cell and basophil
BIOLOGIC ACTIVITIES
• It participates in host defences against certain parasites.
• This is a major defense against helminths
 Strongyloides
Ascaris
Trichinella
Hookworm
BIOLOGIC ACTIVITIES
BIOLOGIC ACTIVITIES
• Mediates type 1 hypersensitivity
(anaphylactic) reaction
• The Fc portion of IgE can bind to mast
cells and basophils where it mediates
many allergic reactions.
• Cross linking of cell-bound IgE by antigen
triggers the release of vasodilators for an
inflammatory response
IMMUNOGLOBULIN D
• Present in minute concentrations in blood and other body
fluids.
• Commonly found on the surface of B-lymphocytes (along with
monomeric IgM) as a B-cell receptor.
ISOTYPES AND ALLOTYPES
• Isotypes are antigenic determinants that are
defined by their Fc regions. For example, the
different antibody classes are different
isotypes; the constant regions of their H
chains are different.
• while allotype is an antigenic determinant
specified by the allelic forms of the
immunoglobulin genes. Allotype antibodies
might be of the same isotype but have
additional features that vary among
individuals. For example, γ heavy chain
contains an allotype called Gm, which varies
by 1or2 amino acids between individuals.
CLASS SWITCHING
CLASS SWITCHING
Certain cytokines Of T helper cells influence B cells to switch to one isotype
or another
• If B cells exposed to an environment rich in IL-4 and IL-5, they switch
isotype from IgM to IgE appropriate for protection against worms
If there is INF γ around, B cells switch to produce IgG 3, that work against
bacteria or viruses
Or if TGF β is present during class switching, change from IgM to IgA
appropriate for the common cold
• Once a B cell has class switched a certain H chain gene, it can no longer
make that class of H chain, as the intervening DNA is excised
SOMATIC HYPERMUTATION
MONOCLONAL ANTIBODIES
• Antibodies having single specificity produced from a single clone of B cell
are referred as Mono clonal antibodies (MAbs).
• In 1975, Georges Köhler and Cesar Milstein devised a method for
preparing monoclonal antibody, which quickly became one of
immunology’s key technologies. The significance of the work by Köhler and
Milstein was acknowledged when each was awarded a Nobel Prize.
• Group of antibodies having different specificity produced from different
clone of B cell is referred as polyclonal antibodies.
FORMATION OF MONOCLONAL ANTIBODY
USE
• Mainly monoclonal antibodies applied in two fields namely,
• I. Diagnostic Field
• II. Therapeutic Field
ANTIBODY AND IMMUNOGLOBULIN.pptx

ANTIBODY AND IMMUNOGLOBULIN.pptx

  • 1.
    ANTIBODIES AND IMMUNOGLOBULINS DR.NASRIN NAHAR MBBS,BCS,MD(MICROBIOLOGY) LECTURER SHER-E-BANGLA MEDICAL COLLEGE BARISHAL
  • 2.
    DEFINITIONS • Antibodies arespecific glycoprotein produced by plasma cells in response to a specific antigen and capable of reacting with that antigen. • Immunoglobulin structurally similar animal proteins that may or may not be endowed with antibody activity. • Non functional immunoglobulins are produced in multiple myeloma (plasma cell cancer). • These immunoglobulins can not bind with specific antigen and are not antibodies. Thus all antibodies are immunoglobulin but all immunoglobulin are not antibodies however, the terms are used interchangeably.
  • 3.
  • 4.
  • 8.
  • 9.
  • 10.
  • 11.
  • 15.
    IMMUNOGLOBULIN G Most abundantclass in serum (13.5mg/ml)(75%) Consists of two γ H chain and two κ or λ L chain Molecular formula γ2κ2 or γ2λ2) γ H chain contain one variable and three constant domain (Cγ1, Cγ2, Cγ3 ) - involved in the different effector functions Produced during secondary immune responses
  • 16.
    Subclasses • Four subclasses,distinguished by differences in H chain sequence • Numbered according to decreasing serum concentrations • IgG1- 60-70% • IgG2- 14-20% • IgG3- 4-8% • IgG4- 2-6%
  • 17.
    Biologic activities 1. activatethe classical complement pathway 2. bind to macrophage and neutrophils for enhanced phagocytosis 3. bind to NK cells for antibody-dependent cytotoxicity (ADCC). 4. enables it to cross the placenta (IgG is the only class of antibody that can cross the placenta and enter the fetal circulation)
  • 18.
    IMMUNOGLOBULIN M • Isthe first antibody produced during primary immune response. • Also first antibody produced by neonates in certain infection. • Approximately 9% of the serum antibodies (1.5 mg/ml). • Present as receptor (monomer) on B cell surface. • Secreted from plasma cell as pentamer. • Each pentamer contains a J (Joining) chain - a polypeptide linked with Carboxyl- Terminal end of  H chain • J chain is required for polymerization of monomer to form pentamer IgM before secretion.
  • 19.
    BIOLOGIC ACTIVITIES Complement activation- •Most efficient in activating complement Complement activation requires close proximity of 2 Fc regions. Pentavalent IgM fulfills that need Neutralization of virus- • less IgM than IgG is required to neutralize viral infectivity • Most efficient in agglutination and other antibody functions.
  • 20.
    IMMUNOGLOBULIN A Main classof Ab in the secretion (both external and internal body fluids) • Present in blood as monomer. • Present in secretion (Milk, colostrum, tear, saliva, mucous of GIT, RT and genital tract) as dimer. • Secretory IgA is a dimer and has 4 Fab sites. • polymerized by a polypeptide chain called J-Chain (MW 15000) • Function of J-Chain is to Polymerization of IgA. • It has a secretory component.
  • 22.
    SECRETORY COMPONENT • producedby epithelial cells of mucous membrane. • responsible for transporting polymeric IgA across the cell membranes into the mucous secretions. • It masks Hinge region from protease cleavage in Protease- rich mucosal environment.
  • 23.
    BIOLOGIC ACTIVITIES IgA playsimportant role in mucosal immunity provide first line of defense specially against • Salmonella • Vibrio • N. gonorrhoeae • Polio • Influenza • Rota virus
  • 24.
    BIOLOGIC ACTIVITIES • Breastmilk contains secretory IgA and protect the newborn against infection during the first month of life • Binds to bacterial and viral antigen and prevent attachment to mucosal cells IgA cannot bind to complements
  • 25.
    IMMUNOGLOBULIN E Present inextremely low concentration due to  short half life of two days slow rate of synthesis and rapid binding to mast cell and basophil
  • 26.
    BIOLOGIC ACTIVITIES • Itparticipates in host defences against certain parasites. • This is a major defense against helminths  Strongyloides Ascaris Trichinella Hookworm
  • 27.
  • 28.
    BIOLOGIC ACTIVITIES • Mediatestype 1 hypersensitivity (anaphylactic) reaction • The Fc portion of IgE can bind to mast cells and basophils where it mediates many allergic reactions. • Cross linking of cell-bound IgE by antigen triggers the release of vasodilators for an inflammatory response
  • 29.
    IMMUNOGLOBULIN D • Presentin minute concentrations in blood and other body fluids. • Commonly found on the surface of B-lymphocytes (along with monomeric IgM) as a B-cell receptor.
  • 31.
    ISOTYPES AND ALLOTYPES •Isotypes are antigenic determinants that are defined by their Fc regions. For example, the different antibody classes are different isotypes; the constant regions of their H chains are different. • while allotype is an antigenic determinant specified by the allelic forms of the immunoglobulin genes. Allotype antibodies might be of the same isotype but have additional features that vary among individuals. For example, γ heavy chain contains an allotype called Gm, which varies by 1or2 amino acids between individuals.
  • 32.
  • 36.
    CLASS SWITCHING Certain cytokinesOf T helper cells influence B cells to switch to one isotype or another • If B cells exposed to an environment rich in IL-4 and IL-5, they switch isotype from IgM to IgE appropriate for protection against worms If there is INF γ around, B cells switch to produce IgG 3, that work against bacteria or viruses Or if TGF β is present during class switching, change from IgM to IgA appropriate for the common cold • Once a B cell has class switched a certain H chain gene, it can no longer make that class of H chain, as the intervening DNA is excised
  • 37.
  • 39.
    MONOCLONAL ANTIBODIES • Antibodieshaving single specificity produced from a single clone of B cell are referred as Mono clonal antibodies (MAbs). • In 1975, Georges Köhler and Cesar Milstein devised a method for preparing monoclonal antibody, which quickly became one of immunology’s key technologies. The significance of the work by Köhler and Milstein was acknowledged when each was awarded a Nobel Prize. • Group of antibodies having different specificity produced from different clone of B cell is referred as polyclonal antibodies.
  • 40.
  • 41.
    USE • Mainly monoclonalantibodies applied in two fields namely, • I. Diagnostic Field • II. Therapeutic Field