Transcript Ig, Struction and Function

Immunoglobulin
Structure and Function
By
Associate Lecturer Mortadha H AL-Hussainy
Faculty of Veterinary Medicine
Kufa University
Immunogobulin, Ig
• What is Immunoglobulin?
Immunoglobulin are the critical
ingredients of humoral acquired
immune response.
• The immunoglobulins are a group of
glycoproteins present in the serum and
tissue fluids of all mammals.
Immunoglobulins:Structure and
Function
• Definition: Glycoprotein molecules that are
produced by plasma cells in response to an
immunogen and which function as antibodies
Amount of protein
+
albumin
globulins
α1
α2
β
γ
Immune serum
Ag adsorbed serum
Mobility
General Functions of
Immunoglobulins
• Ag binding
– Can result in protection
– Valence
• Effector functions (Usually require Ag binding)
– Fixation of complement
– Binding to mast cells , macrophages, NK cell
Basic Immunoglobulin Structure
• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous
immunoglobulins
Two Forms of Immunoglobulin
Membrane-bound receptor
Soluble antibody
Immunoglobulin Structure
Disulfide bond
• Variable(V) &
Constant (C)
Regions
– VL & CL
– VH & CH
• Hinge Region
Carbohydrate
CL
VL
CH2
CH1
VH
Hinge Region
CH3
Structural Regions
• hypervariable
region
• also called
Complementarity
Determining
Regions(CDRs),
超变区（ hyper-variable region, HVR),又称互补决定区
(complementary determining region, CDR）
IgG molecule
Used with permission from: Dr. Mike Clark, Immunology
Division, Department of Pathology Cambridge University,
Cambridge, England
Enzymatic Digestion Products
of Immunoglobulins
Immunoglobulin Fragments:
Structure/Function Relationships
• Fab
Papain
– Ag binding
– Valence = 1
– Specificity
determined by VH
and VL
• Fc ( crystallizable)
– Effector functions
Fc
Fab
Domains of Immunoglobulin
Functions of the domains on Ig：
VH, VL — antigen binding sites；
CH1～3, CL — genetic markers of Ig；
CH2(IgG), CH3(IgM) — C1q binding sites；
CH2～CH3(IgG) — binding to placenta；
CH3(IgG) — FcγR binding site；
CH4(IgE) — FcεR binding site.
Function of Immunoglobulins
• Recognition of antigen 识别抗原
• Activation of complement 激活补体
• Opsonization 调理作用
• Antibody-dependent cell-mediated
cytotoxicity,ADCC 抗体依赖性细胞毒作用
• Mediate hypersensitivity type I 超敏反应
Immunoglobulin Classes and
Subclasses
Immunglobulin molecules are divided into
distinct classes and subclasses in terms of
the differences in amino acid sequence of
constant region of heavy chain,
i.e.γ,α,μ,δ,andεchains.
Immunoglobulin Classes of Mammals
•
•
•
•
•
IgG - Gamma (γ) heavy chains
IgM - Mu (µ) heavy chains
IgA - Alpha (α) heavy chains
IgD - Delta (δ) heavy chains
IgE - Epsilon (ε) heavy chains
Five Classes of Immunoglobulin
• IgG has a family of subclass, IgG1, IgG2, IgG3,
IgG4(cattle has no)
• IgA is divided into two subclasses, IgA1 and
IgA2(sheep).
Light Chain Types of Immunoglobulin
• Kappa (κ)
• Lambda (λ)
• All light chains have protein molecular
weights of approximately 23,000 but can
be divided into two distinct types, namely
λchain, κchain, respectively
B Cell Antigen Receptor (BCR)
Ig-α Ig-β
Ig-α Ig-β
IgA
• Structure
– Serum - monomer
– Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory component
Secretory Piece
J Chain
IgA
• Structure
• Properties
– 2nd highest serum Ig
– Major secretory Ig (Mucosal or Local Immunity)
• Tears, saliva, gastric and pulmonary secretions
– Does not fix complement (unless aggregated)
– Binds to Fc receptors on some cells
IgD
• Structure
• Properties
– 4th highest serum Ig
– B cell surface Ig
– Does not bind complement
IgE
• Structure
• Properties
– Least common serum Ig
• Binds to basophils and mast cells (Does not
require Ag binding)
– Allergic reactions
– Parasitic infections (Helminths)
• Binds to Fc receptor on eosinophils
– Does not fix complement