1. Immunoglobulins: Structure and Function

2. Immunoglobulins:Structure and Function
Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies
Immune serum
Ag adsorbed serum 1 2   + -
albumin
globulins
Mobility
Amount of protein

3. General Functions of Immunoglobulins
Ag binding
Can result in protection
Valency
Effector functions
Fixation of complement
Binding to various cells
Usually requires Ag binding

4. Basic Immunoglobulin Structure
Immunoglobulins - heterogeneous
Myeloma proteins - homogeneous immunoglobulins

5. Immunoglobulin Structure
CH1 VL CL VH
CH2
CH3
Hinge Region
Carbohydrate
Disulfide bond
Heavy & Light Chains
Disulfide bonds
Inter-chain
Intra-chain

7. Immunoglobulins (Ig) are
glycoproteins made up of light (L) and
heavy(H) polypeptide chains. The
simplest antibody molecule has a Y
shape and consists of four polypeptide
chains:two H chains and two L chains.
The four chains are linked by disulfide
bonds.

8. Immunoglobulin Structure
CH1 VL CL VH
CH2
CH3
Hinge Region
Carbohydrate
Disulfide bond
Variable & Constant Regions
VL & CL
VH & CH
Hinge Region

9. Of the five Ig classes or isotypes
H chains are distinct for each
Of the five Ig classes or isotypes
and are designated γ α μδ ε for the respective classes
of Ig, namely IgG IgA IgM
IgD IgE.

10. Human Immunoglobulin Classes
IgG - Gamma () heavy chains
IgM - Mu () heavy chains
IgA - Alpha () heavy chains
IgD - Delta () heavy chains
IgE - Epsilon () heavy chains

11. Designated κ and λ and only one type is found in Ig.
L chains are one of two types
Designated κ and λ and only
one type is found in Ig.

12. Human Immunoglobulin Light Chain Types
Kappa ()
Lambda ()

13. L and H chains are subdivided into
variable and constant regions.The regions
are composed of three-dimensionally folded,
repeating segments called domains. An L
chain consists of one variable (VL) and one
constant (CL) domain.Most H chains consist
of one variable (VH) and three constant(CH)
domains.(IgG and IgA have three CH
domains,whereas IgM and IgE have four.)

14. Immunoglobulin Structure
CH1 VL CL VH
CH2
CH3
Hinge Region
Carbohydrate
Disulfide bond
Domains
VL & CL
VH & CH1 - CH (or CH4)
Oligosaccharides

15. for antigenbinding ,whereas the constant
The various regions are responsible
for antigenbinding ,whereas the constant
regions are responsible for various
biologic functions eg, complement
activation and binding to cell surface
receptors.

16. and H chains have three extremely variable (“hypervariable”) amino
The variable regions of both L
and H chains have three extremely
variable (“hypervariable”) amino
acid sequence at the amino-
terminal end that form the antigen-
binding site.

19. Structure of the Variable Region
Hypervariable (HVR) or complimentarity determining regions (CDR)
Framework regions
FR1
FR2
FR3
FR4
HVR1
HVR2
HVR3
Variability Index 25 75 50
100
Amino acid residue
150

20. Immunoglobulin Fragments: Structure/Function Relationships
Papain Fc
Fab
Fab
Ag binding
Valence = 1
Specificty determined by VH and VL Fc
Effector functions

21. Immunoglobulin Fragments: Structure/Function Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc Receptors

22. Immunoglobulin Fragments: Structure/Function Relationships
Pepsin
Fc Peptides
F(ab’)2
Fab
Ag binding Fc
Effector functions
F(ab’)2

23. IgG
Structure
Monomer (7S)
IgG1, IgG2 and IgG4
IgG3

24. IgG Structure Properties Major serum Ig
Major Ig in extravascular spaces
The only antibody to cross the placental
Fixes complement
Binds to Fc receptors
Phagocytes - opsonization
NK cells – ADCC
Binds to SPA

25. IgM Structure Pentamer (19S)
composed H2L2 units plus one molecule of
J chain
Extra domain (CH4)
C4
J Chain

26. Fixation of C1 by IgG and IgM Abs
C1r
C1s
C1q
No activation
Activation

27. IgM Structure Properties 3rd highest serum Ig
First Ig made by fetus and B cells
Produced early in the primary response
The most efficient Ig
Fixes complement
Tail Piece
Agglutinating Ig
Binds to Fc receptors
B cell surface Ig

28. B Cell Antigen Receptor (BcR)

29. IgA Structure Serum - monomer Secretions (sIgA)
Dimer (11S), sIgA molecule consists of two H2L2 units plus one molecule each of J chain and secretory component(SC or SP)
J Chain
Secretory Piece

30. Origin of sIgA: The SP is a polypeptide synthesized by epithelial cells that provides for IgA passage to the mucosal surface. It also protests IgA from being degraded in the intestinal tract. Y Y Y

31. IgA Properties 2nd highest serum Ig
Major secretory Ig ( saliva, tears, respiratory, intestinal, and genital
tract secretions.)
Does not fix complement unless aggregated
Binds to Fc receptors on some cells

32. IgD
Structure
Monomer
Tail piece
Tail Piece

33. IgD Structure Properties 4th highest serum Ig B cell surface Ig
Does not bind complement

34. IgE
Structure
Monomer
Extra domain (CH4)
C4

35. IgE Structure Properties Least common serum Ig Allergic reactions
Parasitic infections
Does not fix complement