Immunology and Serology Antibody Immunoglobulins

1. J O A N N A I S M Y N A M E
CHAPTER 4
ANTIBODY STRUCTURE AND FUNCTION

2. IMMUNOGLOBULINS
• are glycoproteins found in the serum portion of the
blood
• Composed of 82% - 96% polypeptide and 2% - 14%
carbohydrate
• Humoral branch of the immune response
• Primary role is antigen recognition and in biological
activities related to immune response and
complement activation
• Has five major classes (IgG, IgM, IgA, IgD, IgE)

3. IMMUNOGLOBULIN: TERAPEPTIDE
STRUCTURE
•

4. IMMUNOGLOBULIN: TERAPEPTIDE
STRUCTURE

5. PAPAIN CLEAVAGE

6. PEPSIN DIGESTION

7. NATURE OF LIGHT CHAINS
• Bence-Jones Proteins
• Kappa (Є)
• Lambda (λ)
• Constant region
• is the C-terminal end and contains similar amino acids for each
class of antibody.
• Variable region
• includes 110-130 amino acids of the light and heavy chains,
and is responsible for binding to antigen. This part of the
antibody shows variations in amino acids when the specificity of
the antibody for antigen is changed.

8. HEAVY CHAIN SEQUENCING
•

9. • Isotype
• Unique amino acid sequence that is common to all
immunoglobulin molecules of a given class in a species
• Allotype
• Found in the constant region and are inherited in simple
Mendelian fashion
• Occur four in IgG subclasses, in one IgA subclss and in the
kappa light chain
• Idiotype
• Found in the amino-terminal ends of both L and H chains
• Essential to the formation of the antigen-binding site
• Together they serve as antigen-recognition unit
ANTIGENIC PROPERTIES OF
ANTIBODIES

10. ANTIGENIC PROPERTIES OF
ANTIBODIES

11. HINGE REGION
• flexible amino acid stretch in the central part of the
heavy chains of the IgG and IgA immunoglobulin
classes, which links these 2 chains by disulfide bonds
• High content of proline and hydrophobic residues
• Flexibility assists inititiation of the complement cascade
• rich in cysteine and proline amino acids, extremely
variable in amino acid sequence,
• no resemblance to any other immunoglobulin region
• Gamma, delta and alpha chains have hinge region
• Mu and epsilon chains do not have hinge region

12. CARBOHYDRATE FUNCTIONS
•

13. 3D ANTIBODY STRUCTURE

14. 3D ANTIBODY STRUCTURE
• Basic four-chain structure is folded into compact
globular subunits
• Intrachain of disulfide bonds stabilize globular
regions
• Beta-pleated sheet
• Within each regions or domains, polypeptide chain is folded
back and forth on itself
• Immunoglobulin Fold
• Cylindrical structure produced when folded domains of the
H chains line up with those of the L chains

15. 3D ANTIBODY STRUCTURE
• Hypervariable regions
• Strategic locations wherein antigen binds to a small number
of amino acid and then captured within the barrel
• Comparisons of the amino acid sequences of the variable
regions of immunoglobulins show that most of the variability
resides in three regions called the hypervariable regions
• Complementarity-determining regions (CDRs)
• found in both the H and the L chains
• Occur as loops in the folds of ariable regions
• Antigen binds in the middle of CDRs

16. TYPES OF IMMUNOGLOBULIN
• IgG
• Structure:
• All IgG's are monomers (7S immunoglobulin). The subclasses
differ in the number of disulfide bonds and length of the hinge
region.
• Properties
• most versatile immunoglobulin because it is capable of carrying
out all of the functions of immunoglobulin molecules.
a) IgG is the major Ig in serum - 75% of serum Ig is IgG
b) IgG is the major Ig in extra vascular spaces

17. SUBCLASSES
• a) IgG1 - Gamma 1 heavy chains
• 67%
• b) IgG2 - Gamma 2 heavy chains
• 22%
• c) IgG3 - Gamma 3 heavy chains
• 7%
• Largest hinge region
• d) IgG4 - Gamma 4 heavy chains
• 4%

18. TYPES OF IMMUNOGLOBULIN
• c) Placental transfer - IgG is the only class of Ig that crosses the
placenta. Transfer is mediated by a receptor on placental
cells for the Fc region of IgG. Not all subclasses cross equally
well; IgG2 does not cross well.
• d) Fixes complement - Not all subclasses fix equally well; IgG4
does not fix complement
• e) Binding to cells - Macrophages, monocytes, PMNs and
some lymphocytes have Fc receptors for the Fc region of IgG.
Not all subclasses bind equally well; IgG2 and IgG4 do not
bind to Fc receptors. A consequence of binding to the Fc
receptors on PMNs, monocytes and macrophages is that the
cell can now internalize the antigen better. The antibody has
prepared the antigen for eating by the phagocytic cells. The
term opsonin is used to describe substances that enhance
phagocytosis. IgG is a good opsonin. Binding of IgG to Fc
receptors on other types of cells results in the activation of
other functions.

19. FUNCTIONS OF IMMUNOGLOBULIN G
1. Providing immunity for the newborn because IgG
can cross the placenta
2. Fixing complement
3. Coating antigen for enhanced phagocytosis
(Opsonization)
4. Neutralizing toxins and virus
5. Participating in agglutination and precipitating
reactions

20. TYPES OF IMMUNOGLOBULIN
• IgM
• Structure:
• IgM normally exists as a pentamer (19S immunoglobulin) but it
can also exist as a monomer. In the pentameric form all heavy
chains are identical and all light chains are identical. Thus, the
valence is theoretically 10. IgM has an extra domain on the mu
chain (CH4) and it has another protein covalently bound via a S-
S bond called the Joining chain or J chain. This chain functions
in polymerization of the molecule into a pentamer.
• macroglobulin

21. FUNCTIONS
• 1. Complement fixation
• 2. Agglutination
• 3. Opsonization
• 4. Toxin Neutralization

22. TYPES OF IMMUNOGLOBULIN
• Properties:
• a) IgM is the third 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 . Thus, IgM antibodies are very good in
clumping microorganisms for eventual elimination from the
body.
• e) IgM binds to some cells via Fc receptors.

23. TYPES OF IMMUNOGLOBULIN
• f) B cell surface Ig
• Surface IgM exists as a monomer and lacks J chain but it has an
extra 20 amino acids at the C-terminus to anchor it into the
membrane.
• Cell surface IgM functions as a receptor for antigen on B cells.
Surface IgM is noncovalently associated with two additional
proteins in the membrane of the B cell called Ig-alpha and Ig-
beta. These additional proteins act as signal transducing
molecules since the cytoplasmic tail of the Ig molecule itself is too
short to transduce a signal. Contact between surface
immunoglobulin and an antigen is required before a signal can
be transduced by the Ig-alpha and Ig-beta chains.
• In the case of T-independent antigens, contact between the
antigen and surface immunoglobulin is sufficient to activate B
cells to differentiate into antibody secreting plasma cells.
However, for T-dependent antigens, a second signal provided by
helper T cells is required before B cells are activated.

24. TYPES OF IMMUNOGLOBULIN
• IgA
• Structure:
• Dimer
• When IgA is found in secretions is also has another protein
associated with it called the secretory piece or T piece; sIgA is
sometimes referred to as 11S immunoglobulin. Unlike the
remainder of the IgA which is made in the plasma cell, the
secretory piece is made in epithelial cells and is added to the
IgA as it passes into the secretions). The secretory piece helps
IgA to be transported across mucosa and also protects it from
degradation in the secretions.

25. SUBCLASSES
• a) IgA1 - Alpha 1 heavy chains
• predominant IgA subclass found in serum. Most lymphoid
tissues have a predominance of IgA-producing cells.
• b) IgA2 - Alpha 2 heavy chains
• the heavy and light chains are not linked with disulfide, but
with noncovalent bonds. In secretory lymphoid tissues (e.g.,
gut-associated lymphoid tissue, or GALT), the share of IgA2
production is larger than in the non-secretory lymphoid
organs

26. TYPES OF IMMUNOGLOBULIN
•

27. TYPES OF IMMUNOGLOBULIN
• Properties:
• 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.

28. E N D
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