Transcript immunoglobulin

IMMUNOLOGY
Immunoglobulin
Chen Weilin, Ph.D
Institute of immunology, ZJU
immunoglobulin
1. Introduction
2. the basic structure of immunoglobulins
3. Fuction of immunoglobulins
4. the structures and properties of
immunoglobulin classes
5. Monoclonal antibody
immunoglobulin
Introduction
Immunoglobulins (Ig)
- Glycoprotein molecules which are produced by
plasma cells in response to an immunogen and
which function as antibodies. The immunoglobulins
derive their name from the finding that when
antibody-containing serum is place in an electrical
field the antibodies, which were responsible for
immunity, migrated with the globular proteins
- secreted Ig(sIg) ; membrane Ig(mIg)
immunoglobulin
Introduction
immunoglobulin
Introduction
Antibody(Ab)
- Serum protein formed in response to
immunization; antibodies are generally defined
in terms of their specific binding to the
immunizing antigen.
immunoglobulin
basic structure of the immunoglobulins
immunoglobulin
basic structure of the immunoglobulins
1.Heavy Chain and Light Chain
heavy chain (H chain)
50-75Kd 450-550aa
isotype:IgM,IgD,IgA,IgE,IgG
H chain: μ
δ
α ε γ
light chain (L chain)
25Kd
214aa
classes of L chain: κ λ
immunoglobulin
basic structure of the immunoglobulins
2.variable region and constant region
variable region(V region)
Light Chain - VL (110 aa)
Heavy Chain - VH (110 aa)
HRV(hypervariable region)
CDR(complementarity-determining region)
FR(framework region)
immunoglobulin
basic structure of the immunoglobulins
CDR binds with epitope of antigen
immunoglobulin
basic structure of the immunoglobulins
2.variable region and constant region
constant region(C region)
Light Chain - CL (110 aa)
Heavy Chain - CH (330-440 aa)
CH1, CH2, CH3,( CH4)
immunoglobulin
basic structure of the immunoglobulins
3. Hinge Region
- between the CH1 and CH2 region of the H chain
- be made of cysteine and proline residues
cysteine:be involved in formation of interchain
disulfide bonds
proline residues:prevent folding in a globular
structure
- flexibility: allow the two Fab arms to open;
close to accommodate binding to epitope;
be cleaved by proteases.
- IgM and IgE have no hinge region
immunoglobulin
Domains of immunoglobulin
Domains
- 3D images of the immunoglobulin molecule shows
that it is not straight as depicted in Figure. Rather, it
is folded into globular regions each of which
contains an intra-chain disulfide bond. These
regions are called domains.
1. Light Chain Domains - VL and CL
2. Heavy Chain Domains - VH, CH1,CH2, CH3 (or CH4)
immunoglobulin
Domains of immunoglobulin
immunoglobulin
Domains of the Ig
immunoglobulin
immunoglobulin
Immunoglobulin fragments
immunoglobulin
J chain and SP
Joining chain
-J chain
a ploypeptide chain
Join the units together
immunoglobulin
J chain and SP
Secretory piece
-SP,SC
immunoglobulin
Function of immunoglobulins
Functions of V regions
- recognition and binding to antigen
- HVR (CDR)
- neutralization of toxins; immobilization
of microorganisms; neutralization of
viral activity
immunoglobulin
Function of C regions (Fc portion)
1. Activation of complement: IgM,
IgG1,3; IgA
2. Binding to Fc receptor of cell
• opsonization, enhancement of Ag uptake by DC and
M
• ADCC
• Participation in type I hypersensitivity
3. Passage through the placenta (IgG)
and mucosa (sIgA)
immunoglobulin
Opsonization of antibody
immunoglobulin
Antibody-dependent cellmediated cytotoxicity (ADCC)
immunoglobulin
IgG
a) IgG is the major Ig in serum - 75% of serum Ig
b) IgG is the major Ig in extra vascular spaces
c) Fixes complement - Not all subclasses fix equally
well; IgG4 does not fix complement
d) Binding to cells - Macrophages, monocytes, PMN's
and some lymphocytes have Fc receptors for the Fc
region of IgG.
immunoglobulin
IgM
a) IgM is the 3rd most common serum Ig.
b) IgM is the first Ig to be made by the fetus and the
first Ig to be made by a virgin B cells when it is
stimulated by antigen.
c) As a consequence of its pentameric structure, IgM
is a good complement fixing Ig. Thus, IgM antibodies
are very efficient in leading to the lysis of
microorganisms
d) As a consequence of its structure, IgM is also a
good agglutinating Ig .
e) IgM binds to some cells via Fc receptors.
immunoglobulin
IgA
a) IgA is the 2nd most common serum Ig.
b) IgA is the major class of Ig in secretions –
tears, saliva, colostrum, mucus. Since it is
found in secretions secretory IgA is
important in local (mucosal) immunity.
c) Normally IgA does not fix complement,
unless aggregated.
d) IgA can binding to some cells - PMN's and
some lymphocytes.
immunoglobulin
IgA
immunoglobulin
IgD
a) IgD is found in low levels in serum; its role
in serum uncertain.
b) IgD is primarily found on B cell surfaces
where it functions as a receptor for
antigen. IgD on the surface of B cells has
extra amino acids at C-terminal end for
anchoring to the membrane. It also
associates with the Ig-alpha and Ig-beta
chains.
c) IgD does not bind complement.
immunoglobulin
IgE
a) IgE is the least common serum Ig
since it binds very tightly to Fc
receptors on basophils and mast cells
even before interacting with antigen.
b) Involved in allergic reactions
c) IgE also plays a role in parasitic
helminth diseases
d) IgE does not fix complement
immunoglobulin
Monoclonal antibody