Flashcards in Lecture 15: Functional Lymphoid Tissue Deck (50)
Why is lymphoid tissue essential to discrete/diverse lymphocyte development?
gives rise to accurate T and B cell populations
Where is lymphoid tissue?
spread throughout the body in critical areas where large amounts of antigen are encountered (ex: entrance to mucosal areas)
What are 4 main purposes of lymphoid tissue?
1) supports lymphopoiesis
2) supports development of incredibly diverse repertoire of antigen-specific lymphocytes
3) critically important for both central and peripheral tolerance
4) provides sustaining signals for lymphocyte survival
What are the central lymphoid tissues?
thymus and bone marrow
What are the peripheral lymphoid tissues?
lymph nodes, spleen, mucosal associated
How do naive lymphocytes enter the lymph nodes?
via the blood
What are the 4 postulates of the clonal selection hypothesis?
1) Each lymphocyte bears a single type of receptor with unique specificity
2) interaction between foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
3) differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell
4) lymphocytes bearing receptors specific for ubiquitous self molecules are depleted at an early stage in lymphoid cell development and are ABSENT from the repertoire
All lymphocytes develop from _______ _____ _____ ______ _______
HSCs in the bone marrow
What cells in bone marrow are critical for early B cell development?
What is central tolerance?
self reactive B cells die by apoptosis prior to leaving bone marrow
What are the 4 possibilities for B cell development as they see central tolerance?
1) No self reaction
2) Multivalent self (multiple receptors bind) DELETED OR RECEPTOR EDITED
3) Soluble self (bind free floating stuff)
4) low affinity non-cross linking self
Lymphoid follicles and germinal centers are characteristic of _________________
peripheral lymph tissue (lymph nodes)
The thymic cortex contains what kind of cells?
immature T cells, scattered macs
What cells are in the thymic medulla?
mature T cells, DCs, and macs
What happens at Hassall's Corpuscles?
process of synthesis, mobilization, transduction of tissue-specific auto-antigens for immune tolerance (Tregs)
How many T cells do we have and how many are made per day?
Make per day: 50,000
What do T cells rely on for survival?
thymic epithelial cells (IL-7)
When is rate of T-cell production the greatest?
Where do the T cell progenitors enter the thymus?
What is positive selection?
positively selects the T cells that recognize host MHC (determines whether cell will become CD4 or CD8)
What is negative selection and where does it occur?
medulla; negatively selects against those T cells that recognize self antigen too strongly
progression of T cell development in the thymus is dependent on ________ ____________
timely expression of surface and signaling molecules
What happens first, positive or negative selection?
What important group of cells express self peptide on host MHC I and II in negative selection?
Thymic cortical epithelial cells
What level of affinity is positive selection looking for?
some but low affinity for peptide/MHC complex
What is the optimal affinity negative selection is looking for?
low (kills those that have high affinity)
What gene in the TECs is important for allowing them to present host peptides?
AIRE (dont have AIRE, get auto reactivity)
When infection occurs in skin, where do antigens and antigen-binding DCs go?
from the site of infection thru the afferent lymph vessels into draining nodes
What type of lymphatics bring free antigen to the lymph node?
afferent (go to paracortical area of node)