Presentation on theme: "Humoral Immunity & Immunoglobulin Structure and Function Immunology Unit Dept. of Pathology."— Presentation transcript:
Humoral Immunity & Immunoglobulin Structure and Function Immunology Unit Dept. of Pathology
Humoral () Immunity 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.
+ 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.
CLCL VLVL S S S S S S S S CH3CH3 CH2CH2 CH1CH1 VHVH Fc Fab F(ab) 2 Domains are folded, compact, protease resistant structures Structure of Immunoglobulins Light chain C domains or Heavy chain C domains or
Antibody + complement- mediated damage to E. coli Healthy E. coli Electron micrographs of the effect of antibodies and complement upon bacteria
Structure and function of the Fc region CH3CH3 CH2CH2 IgA IgD IgG CH4CH4 CH3CH3 CH2CH2 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
Monomeric IgM IgM only exists as a monomer on the surface of B cells Monomeric IgM has a very low affinity for antigen C4C4 C3C3 C2C2 C1C1 N.B. Only constant heavy chain domains are shown IgM forms pentamers and hexamers
C C C C C C Multimerisation of IgM C4C4 C3C3 C2C2 C C C4C4 C3C3 C2C2 C C C4C4 C3C3 C2C2 C C C4C4 C3C3 C2C2 C C C4C4 C3C3 C2C2 C C ss ss ss C C ss
IgM facts and figures Heavy chain: - Mu Half-life: 5 to 10 days % of Ig in serum:10 Serum level (mgml -1 ): 0.25 - 3.1 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 2 Pentameric IgM - high avidity - valency of 10
IgD facts and figures ??IgD & IgM ?? Heavy chain: - Delta Half-life: 2 to 8 days % of Ig in serum:0.2 Serum level (mgml -1 ): 0.03 - 0.4 Complement activation:No Interactions with cells: T cells via lectin like IgD receptor Transplacental transfer: No
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. J C C S S S S C C S S S S C C ss IgA exists in two subclasses IgA1 and IgA2
IgA facts and figures Heavy chains: 1 or 2 - Alpha 1 or 2 Half-life: IgA1 5 - 7 days IgA2 4 - 6 days Serum levels (mgml -1 ): IgA1 1.4 - 4.2 IgA2 0.2 - 0.5 % of Ig in serum:IgA1 11 - 14 IgA2 1 - 4 Complement activation:IgA1 - by alternative and lectin pathway IgA2 - No Interactions with cells: Epithelial cells by pIgR Phagocytes by IgA receptor Transplacental transfer: No
IgE facts and figures its role in protecting against parasitic infections IgE is also closely linked with allergic diseases Heavy chain: - Epsilon Half-life: 1 - 5 days Serum level (mgml -1 ): 0.0001 - 0.0002 % of Ig in serum:0.004 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
IgG facts and figures Heavy chains: 1 2 3 4 - Gamma 1 - 4 Half-life: IgG1 21 - 24 days IgG2 21 - 24 days IgG3 7 - 8 days IgG4 21 - 24 days Serum level (mgml -1 ): IgG15 - 12IgG2 2 - 6 IgG3 0.5 - 1IgG4 0.2 - 1 % of Ig in serum:IgG145 - 53IgG2 11 - 15 IgG3 3 - 6IgG4 1 - 4 Complement activation:IgG1+++ IgG2 + IgG3 ++++ IgG4 No Interactions with cells: All subclasses via IgG receptors on macrophages and phagocytes Transplacental transfer: IgG1++IgG2 + IgG3 ++IgG4 ++ The neonatal Fc receptor may be responsible!
Fc receptors ReceptorCell typeEffect of ligation Fc RI Macrophages Neutrophils, Eosinophils, Dendritic cells Uptake, Respiratory burst Fc RIIA Macrophages Neutrophils, Eosinophils, Platelets Langerhans cells Uptake, Granule release Fc RIIB1 B cells, Mast CellsNo Uptake, Inhibition of stimulation Fc RIIB2 Macrophages Neutrophils, Eosinophils Uptake, Inhibition of stimulation Fc RIII NK cells, Eosinophils, Macrophages, Neutrophils Mast cellsInduction of killing (NK cells)
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.