Presentation on theme: "Humoral Immunity & Immunoglobulin Structure and Function"— Presentation transcript:
1 Humoral Immunity & Immunoglobulin Structure and Function Immunology UnitDept. 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, beforethey enter cells.+ Also cause certain reactions against transplanted tissue.
9 Structure of Immunoglobulins Domains are folded, compact, protease resistant structuresFcFabLight chain Cdomainsk or lCLVLSCH3CH2CH1VHSHeavy chain Cdomainsa, d, e, g, or mF(ab)2
10 Antibody + complement- mediated Healthy E. coliElectron micrographs of the effect of antibodies and complement upon bacteriaAntibody + complement- mediateddamage to E. coli
11 (although there are allotypes) Structure and function of the Fc regionCH3CH2IgA IgD IgGCH4CH3CH2IgE IgMThe hinge region is replaced by an additional Ig domainFc 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 IgMIgM only exists as a monomer on the surface of B cellsMonomeric IgM has a very low affinity for antigenCm4Cm3Cm2Cm1N.B. Only constant heavy chain domains are shownIgM forms pentamers and hexamers
13 Multimerisation of IgM Cm4Cm3Cm2CCm4Cm3Cm2CCm4Cm3Cm2CssCCCCsCm4Cm3Cm2CsCm4Cm3Cm2C
14 IgM facts and figures Heavy chain: m - Mu Half-life: 5 to 10 days % of Ig in serum: 10Serum level (mgml-1):Complement activation: ++++ by classical pathwayInteractions with cells: Phagocytes via C3b receptors Epithelial cells via polymeric Ig receptorTransplacental transfer: NoAffinity 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: 0.2Serum level (mgml-1):Complement activation: NoInteractions with cells: T cells via lectin like IgD receptorTransplacental transfer: No??IgD & IgM ??
16 IgA dimerisation and secretion IgA is the major isotype of antibody secreted at mucosal surfacesExists in serum as a monomer, but more usually as a J chain- linked dimer, that is formed in a similar manner to IgM pentamers.SCSCJCsIgA exists in two subclassesIgA1 and IgA2
17 IgA facts and figures Heavy chains: a1 or a2 - Alpha 1 or 2 Half-life: IgA days IgA daysSerum levels (mgml-1): IgA IgA% of Ig in serum: IgA IgAComplement activation: IgA1 - by alternative and lectin pathway IgA2 - NoInteractions with cells: Epithelial cells by pIgR Phagocytes by IgA receptorTransplacental transfer: No
18 its role in protecting against parasitic infections IgE facts and figuresHeavy chain: e - EpsilonHalf-life: daysSerum level (mgml-1):% of Ig in serum:Complement activation: NoInteractions 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 monocytesTransplacental transfer: Noits role in protecting against parasitic infectionsIgE 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 - 4Half-life: IgG days IgG days IgG days IgG daysSerum level (mgml-1): IgG IgG IgG IgG% of Ig in serum: IgG IgG IgG IgGComplement activation: IgG IgG IgG IgG4 NoInteractions with cells: All subclasses via IgG receptors on macrophages and phagocytesTransplacental 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 burstFcgRIIA Macrophages Neutrophils,Eosinophils, Platelets Langerhans cells Uptake, Granule releaseFcgRIIB1 B cells, Mast Cells No Uptake, Inhibition of stimulationFcgRIIB2 Macrophages Neutrophils,Eosinophils Uptake, Inhibition of stimulationFcgRIII 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.