Biochemistry
Lecture 5.5
Humoral Immunity
IMMUNOGLOBULINS Ig
(ANTIBODIES)
Structure of Immunoglobulins
Disulfide bond
Carbohydrate
CL
VL
CH2
CH1
VH
Hinge Region
CH3
Oligosaccharides
Carbohydrate
CHO
CHO
Fc
Fab - fragment
antigen binding
Fc - fragment
crystallisable
Fc effector
functions. Fc
interacts with
innate effector
mechanisms and
greatly amplifies
them
Immunoglobulins are
Bifunctional Proteins
- 1 x (Fab)2 & 1 x Fc
- 2 x Fab 1 x Fc
Detect antigen
Precipitate antigen
Consequences of antibody-antigen
binding
A. Viral Inhibition: virus preventing it from attaching to cell
B. Neutralization: make toxins unable to bind to cells
C. Opsonization: antibodies bind to antigen and facilitate
attachment of phagocytic cells
D. and E. Agglutination and Precipitation: antibodies bind to
antigen and get them into clumps, then one big mouthful
for phagocyte
F. Phagocytosis: Fc portion of antibody encourages
phagocytosis
Complement Activation: binding of antigen to antibody can
trigger one pathway of complement cascade
Classes of immunoglobulins
(depend on H chain)
MONOMER
PENTAMER
MONOMER
MONOMER WHEN
ACTING AS B-CELL
RECEPTOR FOR ANTIGEN
DIMER
MONOMER
IgG
(Monomeric)
IgG1, IgG2 and IgG4
IgG3
Major serum Ig
Major Ig in extravascular spaces 70-80% of total serum
antibody
Half-life in serum 23 days
Placental transfer (IgG2)
Fixes complement (IgG4)
Binds to Fc receptors (IgG2, IgG4)
Phagocytes - opsonization
Serum monomer
Secretions (sIgA) - major secretory Ig (Mucosal or Local Immunity)
10-15 % of total serum antibody (if mucous membranes and body secretions
included, percentage is much higher)
Half-life in serum 6 days
Tears, saliva, gastric and pulmonary secretions
Dimer: J chain; Secretory component
Does not fix complement (unless aggregated)
Binds to Fc receptors on some cells
IgD (Monomer)
IgE (Monomer)
Plasma cells can secrete IgM, IgG, IgA, IgE (all but IgD)
Memory cells display IgG, IgA, IgE, alone or combined with
IgM. These are usually higher affinity than the orginal B-cell
clone because of affinity maturation via somatic cell mutation
Ig-
Ig-
Ig-
Ig-
CELLULAR IMMUNITY
TCR Structure
The variable domains in both chains contain three
hypervariable regions which are equivalent to CDRs present in
Ab light and heavy chains.
Transmembrane domains of both chains contain positively
charged amino acid residues
The most TCRs interact with peptide antigens presented by
MHC molecules.
Certain T cells react with nonpeptide antigens
(carbohydrate and lipids)
In contrast to TCR, TCR exhibits limited diversity
The T cells react with antigen (e.g. phospholipid antigen of
Mycobacterium tuberculosis) that is neither processed or
presented in the context of a MHC molecule.
TCRa
peptide & lipid
No
Yes
Yes
No
Low
Yes
Single receptor
recognizes
an alteration in selfMHC molecules induced
because of association
with foreign antigen.