Question

1. Please briefly explain the following. a.) Discuss the sequence of events in the B-cell response to a thymus-dependent antigen. b.) Discuss the structure and function of class I and II MHC molecules. c.) Discuss the development of T cells in the thymus.

Answer 1

Answer (a)

• Activation of B cells by soluble antigen or thymus dependent antigen requires the involvement of T helper cells.
• Activation of B cells require binding of antigen to B cell membrane bound immunoglobulin receptors (mIgs).
• Antigen crosslinks mIg, generating signal1 which leads to increased expression of class II MHC and costimulatory B7.
• Antigen, internalized by receptor mediated endocytosis and degraded to peptides.
• Processed peptides are bound by class II MHC on B cells membrane.
• This interaction activates T helper cell.
• Interaction of CD40 (present on B cell membrane) and CD 40 L (present on T helper cells) provides signal 2 for B cell activation.
• Interaction between B7 of B cell membrane and CD28 present on T helper cell membrane provide co-stimulation to the T helper cell.
• In the presence of signal, B cell begins to express receptors for cytokines (IL-2, IL-4 ,IL-5 etc).
• Binding of cytokines (Released by T helper cell) to the cytokine receptor of B cells promotes differentiation of B cells.

Answer (b)

MHC molecules

Structure of MHC molecules

• Class I MHC has -chain and 2 microglobulin and class II is a hetrodimer of and chain.
• 1 and 2 domains of chain forms the polymorphic region of class I MHC molecule and 1 and 1 forms the polymorphic region of class II MHC molecules.
• 3 region of class I forms the binding site for T cell Co-receptor of CD8 cells and
• 2 region of Class II forms the binding sites for T cell co-receptor of CD4 cells.
• Both types of membrane glycoproteins (class I and class II MHC) function as highly specialized antigen-presenting molecules.

Function

• The class I and class II MHC molecules present antigen to T cells.
• Antigen recognition is mediated by or T cell antigen receptors (TCR).
• T cells recognize only peptides combined with MHC molecules.
• Class I molecules present processed endogenous antigen to CD8 T cells.
• Class II molecules present processed exogenous antigen to CD4 cells.
• Class I MHC molecules presents peptide of 8-10 amino acids.
• Class II molecules molecules bind and present longer peptide of 13-18 aminoacids.

Answer (c)

• Development or maturation of T cells occurs in the thymus.
• The progenitor T cells (Pro-T cells) migrate from the bone marrow into the thymus under the influence of chemotactic factors that are secreted by the thymic epithelial cells.
• In the thymus, developing T cells, known as thymocytes, proliferate and differentiate.
• Pro-T cell lacks the CD4 and CD8 co-receptors.