Exam 2: Dr. Pinchuk Development of T Lymphocytes Flashcards
What do T cells derive from?
Bone marrow stem cells
Look at figure of T cell lineage
Look at figure of T cell lineage
Where are TCR genes rearranged?
Thymus (antigen-independent)
What are the 2 lineages of T cells?
The majority are α:β and the minority are γ:δ
What do T cells undergo?
Positive and negative selection (both are α:β only)
What do B cells derive from?
Bone marrow stem cells
Where do BCR genes rearrange?
Bone marrow (antigen-independent)
What do B cells undergo?
Somatic hypermutation (antigen-dependent)
Describe the thymus
Primary lymphoid organ
T cell development only
Blood is the only route to enter and leave
What are the T cells that leave the thymus like?
Naive
When is the thymus most active?
When you are very young
What is the thymus fully developed?
At birth
What happens to the thymus with increasing age?
Atrophies with thymocytes replaced by fat (involution)
How long does it take for involution of thymus to be complete?
30 years
Do involution or thymectomy compromise T cell immunity in adults?
No
What is DiGeorge’s syndrome?
Genetic disease where the thymus fails to develop
What are the 2 major signals for T cell lineage commitment?
IL-7 and Notch-1
Look at T cell lineage and T cell selection in the thymus figures
Look at T cell lineage and T cell selection in the thymus figures
What is positive selection?
Selection of T cells that can recognize peptides presented by a self-MHC molecules
Small population of T cells is signaled to mature further, leaving the vast majority go double-poisitve cells to die by apoptosis
Control expression of the CD4 or CD8 co-receptor
What is negative selection?
Deletion of T cells whose antigen receptors bind too strongly to the complexes of self-peptides and self-MHC molecules presented
What can negative selection not eliminate?
T cells whose receptors are specific for self-peptides that are present only in tissues other than the thymus
What does autoimmune regulatory (AIRE) transcription factor cause?
Several hundred of other tissue specific genes to be transcribed by a subpopulation of the thymus epithelial cells
What does AIRE gene mutation cause?
Autoimmune polyglandular syndrom type I or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
Because of the AIRE gene, what do APCs in the thymus do?
Express and present many peptides derived from nonthymic tissues
What is the major mechanism of immunological tolerance in the thymus?
Negative selection
What are mechanisms that contribute to immunological central self-tolerance?
Negative selection in the bone marrow and thymus
Expresson of tissue-specific proteins in the thymus
What are mechanisms that contribute to immunological peripheral self-tolerance?
No lymphocyte access to some tissue
Suppression of autoimmune response by regulatory T cells
Induction of anergy in auto-reactive B and T cells
What are mechanisms of malignant transformations and generation of lymphomas?
High division rate of maturing lymphocytes
Activity of DNA recombination mechanisms responsible for generating antigen receptor diversity
What is the immunological analysis of XLSCID in basset hounds?
Roles of IL-2 in T cell proliferation in the thymus and proliferation and differentiation in the secondary lymphoid organs
Roles of IL-4 in differentiation of B cells and Th2 cells
Roles of IL-7 in the development of lymphoid progenitor cells in the bone marrow
