Structural Biology and Functions【医疗课件】.pptVIP

Why do antibodies need an Fc region? Detect antigen Precipitate antigen Block the active sites of toxins or pathogen-associated molecules Block interactions between host and pathogen-associated molecules The (Fab)2 fragment can - Inflammatory and effector functions associated with cells Inflammatory and effector functions of complement The trafficking of antigens into the antigen processing pathways but can not activate 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 Structural Biology and Functions of Immunoglobulins Section 3 ?Dr. Colin R.A. Hewitt 2003-2004 Monomeric IgM IgM only exists as a monomer on the surface of B cells Cm4 contains the transmembrane and cytoplasmic regions. These are removed by RNA splicing to produce secreted IgM Monomeric IgM has a very low affinity for antigen Cm4 Cm3 Cm2 Cm1 N.B. Only constant heavy chain domains are shown Cm3 binds C1q to initiate activation of the classical complement pathway Cm1 binds C3b to facilitate uptake of opsonised antigens by macrophages Cm4 mediates multimerisation (Cm3 may also be involved) Cm4 Cm3 Cm2 Cm1 N.B. Only constant heavy chain domains are shown Polymeric IgM IgM forms pentamers and hexamers C C C C C C Multimerisation of IgM Cm4 Cm3 Cm2 C C Cm4 Cm3 Cm2 C C Cm4 Cm3 Cm2 C C Cm4 Cm3 Cm2 C C Cm4 Cm3 Cm2 C C s s s s s s C C s s 1. Two IgM monomers in the ER (Fc regions only shown) 2. Cysteines in the J chain form disulphide bonds with cysteines from each monomer to form a dimer 3. A J chain detaches leaving the dimer disulphide bonded. 4. A J chain captures another IgM monomer and joins it to the dimer. 5. The cycle is repeated twice more 6. The J chain remains attached to the IgM pentamer. Antigen-induced confor