Question

Describe the cellular interactions involved in T cell selection (positive and negative) in the thymus. Include a description of an experiment that helped to sort out how this process works.

Describe the cellular interactions involved in T cell and/or B cell activation in a lymph node.

Answer 1

·T cell belong to group of cell called Lymphocytes (WBCs). There are two type of Lymphocytes : B Lymphocytes & T Lymphocytes.

·B Lymphocytes oversee humoral immunity & T Lymphocytes oversee cell mediated immunity.

·Immature lymphocytes released from bone marrow are identical .

·It will differentiate into B cells or T cells depends on where in the body these cells become immunocompetent.

·If they mature in Bone marrow they are called B cells and if they mature in Thymus they are called T cells.

Positive Selection: ( means positive selection of those thymocytes whose receptor bind with MHC molecules)

·T cell precursors present in the thymus. No surface receptor present at this stage, so no cell recognition.

·Now rearrangement of TCR genes will occur resulting in formation of immature thymocyte. Lot of thymocytes will be produced.

·Thymocytes have different kind of molecules like CD4, CD3, CD8 & T cell receptor.

·Now selection will be done on the basis of MHC molecule which are presented on APC.

·Only those thymocytes which interact with MHC-I or MHC-II will survive other will die by neglect.

·Thus positive selection is MHC detection based on Non self-peptide.

Negative Selection: ( means removes thymocytes that are capable of strongly binding with "self" MHC peptides)

·Again a MHC detection but based on Self peptide detection.

·Thymocytes recognize self-peptide and bind eagerly with it.

·Death of cells with high affinity receptors for Self MHC or Self MHC+ antigen

·It ensures Self-tolerance in thymocytes.

Experiment brief:

Positive selection was demonstrated in radiation chimeras, mice whose hematopoietic cells was destroyed by irradiation and replaced by hematopoietic cells from another mouse strain. Positive selection was confirmed further by experiment done in an MHC^{a x b} thymectomized mouse where thymus was removed in young mouse and transplanted with MHC^a thymus and MHC^axb bone marrow Negative selection was demonstrated in mice expressing an endogenous Superantigen.

B & T cells in Lymph nodes:

·Antigen presentation resulting in T cell activation.

·CC Chemokine Receptor CCR7 & CXCR5 expression

·Migration of activated T cells to edge of follicle.

·B cells present antigen to activated T helper cells.

·Antigen uptake and processing , B cell activation.

·CCR7 expression and migration of activated B cells to edge of follicle

·T:B cell interaction & B cell differentiation.

·Immunoglobulin secretion , isotope switching.

·Germinal Center Reaction: Affinity maturation, long lived plasma cells, isotype switching, memory B cells