Immunoglobulin
IMMUNOLOGY
immunoglobulin
1. Introduction
2. the basic structure of immunoglobulins
3. Fuction of immunoglobulins
4. the structures and properties of
immunoglobulin classes
5. Monoclonal antibody
IntroductionImmunoglobulins (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
IntroductionAntibody(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 immunoglobulinsimmunoglobulin
basic structure of the immunoglobulins1.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 immunoglobulins2.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
immunoglobulin
basic structure of the immunoglobulins
CDR binds with epitope of antigen
basic structure of the immunoglobulins2.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 immunoglobulins3. 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 immunoglobulinDomains - 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 immunoglobulinimmunoglobulin
immunoglobulin
Domains of the Ig
immunoglobulin
Immunoglobulin fragmentsimmunoglobulin
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 immunoglobulinsimmunoglobulin
Functions of V regions - recognition and binding to antigen - HVR (CDR) - neutralization of toxins;
immobilization of microorganisms; neutralization
of viral activity
Function of C regions (Fc portion)
1. Activation of complement: IgM, IgG1,3; IgA2. Binding to Fc receptor of cellopsonization, enhancement of Ag
uptake by DC and M ADCC Participation in type I hypersensitivity3. Passage through the placenta (IgG) and mucosa (sIgA)
immunoglobulin
immunoglobulin
Opsonization of antibody
immunoglobulin
Antibody-dependent cell-mediated cytotoxicity (ADCC)
IgGimmunoglobulin
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.
IgMimmunoglobulin
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.
IgAimmunoglobulina) 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
IgDimmunoglobulina) 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.
IgEimmunoglobulin
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