Lecture 2 Immunoglobulin
Objectives; Define secretary IgA Describe structure & functions of IgM Compare the antigenic receptor of B lymphocyte Assess the role of IgE in Atopy Distinguish between Isotype, Allotype & Idiotype Explain Anti-idiotype Ab List the characteristic of specific Immune response Compare between primary & secondary Immune Response
IgA Constitute 15% of total serum Ig Main Ig in the external secretions as saliva tears breast milk Subdivided into IgA1 & IgA2 subclasses It has 2 forms ; 1-Monomeric in the blood 2- dimeric in the external secretions
Dimeric IgA IgA synthesized by plasma cell as monomeric one in the submucosa which will be combine with another monomeric IgA by a polypeptide J chain to form dimeric IgA this will be protected by a secretary piece from the secretary epithelium to form the secretary IgA
Secretory piece( SP):. Produced by mucosa epithelial cells. Secretory IgA (siga). Functions: protect siga, resist proteolysis in extra secretory liquid. J chain IgA SP
Ⅲ. IgA 1. Two types Serum type :monomer Secretary type(siga): dimer 2. Two subclasses:iga1,iga2
Functions of secretary IgA Activation of the complement through the alternative pathway Blocking & Neutrilization opsonization
IgM Constitute 10% of total serum Ig Its molecular weight 900 000 (Heavy) It has 2 forms 1-Monomeric form on the surface of B lymphocytes as antigen Receptor together with IgD 2-pentameric IgM by J chain 5 monomeric connected
Pentameric IgM
IgM has no hinge region replaced by an additional domiain(ch2)---ch3,ch4 Pentameric IgM has 10 FAB so it is the most agglutinating & complement fixing Ab It is the main Ig in the primary immune response It is the 1 st Ig synthetized by the fetus
IgD Very low concentration in the blood less than 1% Short half life 2-3 days Present on the surface of B lymphocyte together with monomeric IgM as a surface antigen receptor of B lymphocyte Immature B cell only IgM on its surface Mature B cell IgM+IgD on its surface
IgD
IgE 0.002 % of serum Ig ( detection by Elisa) In atopic patient the level increase by handreds IgE also called Reagenic or homocytotropic Ab because of its ability of binding to FC receptors on the surface of Mast cells & basophiles
allergen IgE FceRI degranulation inflammation
Functions of IgE Triggering an acute inflammatory reaction Has the ability to bind to FC receptor on eosinophils so important against parasitic infections eosinophils contain granules that realize cat Ionic proteins which are toxic to the parasites
IgE increases in Parasitic infections Atopic patients IL 4 causes switching of Ig to IgE IL 5 causes eosinophilia
allergen IgE FceRI degranulation inflammation
Variants of Ig Isotype all classes,subclasses & forms of Ig which present in normal individual Allotype existence of allelic forms, single a.a. variation in the peptide chain of Ig ( genetic marker) IgG =GM, IgA=AM Idiotype each Ig has its own antigenic determinant area against which an antiidiotype Ab will be formed (Idiotype antiidiotype network)
A.I. vaccine Anti idiotype vaccine Anti idiotype vaccine
Anti idiotype vaccine
Characteristics of sp. Immune respond : 1-Discrimination (distinguish) between self & Foreign Ag Any Ag when reach the lymphoid tissue during pre-natal period suppress any further immunological response to that Ag in future ((self)) _colonel deletion theory _ During embryonic dev. All T & B lymphocytes that carry auto reactive receptors for self Ag ( ( Auto-reactive cells) will be deleted by apoptosis self tolerance
2- specificity Ab react specifically with Ag that causes its production,sometimes can react with similar not identical = cross reaction β- haemolytic streptococci can lead to rheumatic heart dis. Because cross reaction between bacteria Ag & valve tissue in some individuals
3-clonality 8 We have more that 10 T & B lymphocytic clones (group) each clone with different Ag receptor, when the Ag enter the body lymphocytes bearing receptors that fit the epitope best are stimulated to divided (clonal selection theory) this response is called primary immune response
Clonal Selection of B Cells is Caused by Antigenic Stimulation
B lymphocyte development (2)
4-Anamnest response :(memory) The primary I.R. (1 st exposure) a-lag phase (7days) Ab level is zero (time for finding appropriate Ag receptor) depend on nature,routs, immune state b-log phase Ab(mainly IgM) start to appear & increase logarythemly c-plateau phase d-decline phase
Secondary I.R. (2 nd exposure) there is memory cell so no lag phase,ab titer quickly shooting up 10-100 times *There is genetic switching from IgM in the pri. I.R. to IgG in the 2 nd I.R.
Primary I.R. Secondary I.R. * There is lag phase *No lag phase *IgM class *Ab of IgG class *Low affinity Ab *Ab of high affinity *Ab titer is low *The host exposure for the 1 st time so no memory cell *Ab titer decline rapidly *Ab titer is high *Host exposure for the 2 nd time there is memory cell *Ab titer decline slowly
Best example is the vaccination we give booster Doses(multiple doses) to shift the I.R. from primary to secondary I.R.
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