SCIDImmunology

Introduction

Hematopoiesis in bone marrow:• 2-5 x 10⁸ of WBCs are

generated/hour• 1 x 10¹⁰ of RBCs are

generated/hour

T-Cells• Development of T-lymphocytes:Production bone marrow (immature cells)Migration thymus gland (triple negative), no

TCR, no CDsThymic cortex, present TCR + both CD4 & CD8Thymic medulla, differentiate to T-helper (with CD4) or

T-cytotoxic (with CD8)

TCR

• T-cell receptor: α and β (95%), γ and δ• The carboxyl-terminus is anchored through membrane.• The N-terminus has a groove between the two chains to

accommodate the binding of small antigenic peptides (9-11 amino acids).• Antigen presenting cells (APC), such as macrophages, B-

lymphocytes and dendritic cells hydrolyze antigens to be carried on MHC molecules and presented to T-cells.

T-Cell Selection• T-cells selection for self-tolerance by exposure to MHC I

& II antigens:• TCR recognize MHC with low affinity Positive• TCR cannot recognize MHC No positive• TCR recognize MHC with high affinity Negative

(autoimmunity)

B-Cells• Development of B-lymphocytes:Produced & mature in bone marrowSecreted in the central sinus to encounter first antigen exposure to develop specificity.Maturation: express IgM & IgD receptors.• IgD will be lost upon exposure to antigens.• IgM receptors are released upon activation and act as antibodies.• After antigen recognition and binding, a signal transduction is carried by

(Ig-α, Ig-β, CD19 & CD21) which activates the cell.B-lymphocytes with high affinity to self-antigen are either deleted (clonal

deletion) or inactivated in the periphery (clonal anergy).Tolerating cells are allowed to leave the bone marrow.