1. Humoral Immunity & Immunoglobulin Structure and Function
Immunology Unit
Dept. of Pathology

2. Humoral (Antibody-Mediated) Immunity
+ Involves production of antibodies against foreign antigens.
+ Antibodies are produced by a subset of lymphocytes called B cells.
+ B cells that are stimulated will actively secrete antibodies and are called plasma cells.

3. + Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells.
+ Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before
they enter cells.
+ Also cause certain reactions against transplanted tissue.

9. Structure of Immunoglobulins
Domains are folded, compact, protease resistant structures Fc
Fab
Light chain C
domains
k or l CL VL S
CH3
CH2
CH1 VH S
Heavy chain C
domains
a, d, e, g, or m
F(ab)2

10. Antibody + complement- mediated
Healthy E. coli
Electron micrographs of the effect of antibodies and complement upon bacteria
Antibody + complement- mediated
damage to E. coli

11. (although there are allotypes)
Structure and function of the Fc region
CH3
CH2
IgA IgD IgG
CH4
CH3
CH2
IgE IgM
The hinge region is replaced by an additional Ig domain
Fc structure is common to all specificities of antibody within an ISOTYPE
(although there are allotypes)
The structure acts as a receptor for complement proteins and a ligand for cellular binding sites

12. N.B. Only constant heavy chain domains are shown
Monomeric IgM
IgM only exists as a monomer on the surface of B cells
Monomeric IgM has a very low affinity for antigen
Cm4
Cm3
Cm2
Cm1
N.B. Only constant heavy chain domains are shown
IgM forms pentamers and hexamers

13. Multimerisation of IgM
Cm4
Cm3
Cm2 C
Cm4
Cm3
Cm2 C
Cm4
Cm3
Cm2 C s s C C C C s
Cm4
Cm3
Cm2 C s
Cm4
Cm3
Cm2 C

14. IgM facts and figures Heavy chain: m - Mu Half-life: 5 to 10 days
% of Ig in serum: 10
Serum level (mgml-1):
Complement activation: ++++ by classical pathway
Interactions with cells: Phagocytes via C3b receptors Epithelial cells via polymeric Ig receptor
Transplacental transfer: No
Affinity for antigen: Monomeric IgM - low affinity - valency of Pentameric IgM - high avidity - valency of 10

15. IgD facts and figures ??IgD & IgM ?? Heavy chain: d - Delta
Half-life: 2 to 8 days
% of Ig in serum: 0.2
Serum level (mgml-1):
Complement activation: No
Interactions with cells: T cells via lectin like IgD receptor
Transplacental transfer: No
??IgD & IgM ??

16. IgA dimerisation and secretion
IgA is the major isotype of antibody secreted at mucosal surfaces
Exists in serum as a monomer, but more usually as a J chain- linked dimer, that is formed in a similar manner to IgM pentamers. S C S C J C s
IgA exists in two subclasses
IgA1 and IgA2

17. IgA facts and figures Heavy chains: a1 or a2 - Alpha 1 or 2
Half-life: IgA days IgA days
Serum levels (mgml-1): IgA IgA
% of Ig in serum: IgA IgA
Complement activation: IgA1 - by alternative and lectin pathway IgA2 - No
Interactions with cells: Epithelial cells by pIgR Phagocytes by IgA receptor
Transplacental transfer: No

18. its role in protecting against parasitic infections
IgE facts and figures
Heavy chain: e - Epsilon
Half-life: days
Serum level (mgml-1):
% of Ig in serum:
Complement activation: No
Interactions with cells: Via high affinity IgE receptors expressed by mast cells, eosinophils, basophils and Langerhans cells Via low affinity IgE receptor on B cells and monocytes
Transplacental transfer: No
its role in protecting against parasitic infections
IgE is also closely linked with allergic diseases

19. IgG facts and figures The neonatal Fcg receptor may be responsible!
Heavy chains: g 1 g 2 g3 g4 - Gamma 1 - 4
Half-life: IgG days IgG days IgG days IgG days
Serum level (mgml-1): IgG IgG IgG IgG
% of Ig in serum: IgG IgG IgG IgG
Complement activation: IgG IgG IgG IgG4 No
Interactions with cells: All subclasses via IgG receptors on macrophages and phagocytes
Transplacental transfer: IgG IgG IgG IgG4 ++
The neonatal Fcg receptor may be responsible!

20. Fcg receptors Receptor Cell type Effect of ligation
FcgRI Macrophages Neutrophils,
Eosinophils, Dendritic cells Uptake, Respiratory burst
FcgRIIA Macrophages Neutrophils,
Eosinophils, Platelets Langerhans cells Uptake, Granule release
FcgRIIB1 B cells, Mast Cells No Uptake, Inhibition of stimulation
FcgRIIB2 Macrophages Neutrophils,
Eosinophils Uptake, Inhibition of stimulation
FcgRIII NK cells, Eosinophils, Macrophages, Neutrophils Mast cells Induction of killing (NK cells)

21. Antibody Dependent Cell Mediated Cytotoxicity (ADCC)
Target cell is covered with antibodies, leaving Fc portion sticking outwards.
Natural killer and other nonspecific cells that have receptors for Fc region are stimulated to kill targeted cells.
Target organism is lysed by substances secreted by attacking cells.
Used to destroy large organisms that cannot be phagocytosed.