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)
What attractant brings APCS and antigens to the lymph node?
What is the avenue for lymphocytes to get out of the blood vessels and into the paracortical areas?
high endothelial venules
The precise location of B cells, T cells, macrophages, and DCs in peripheral lymphoid tissue is controlled by ____________
chemokines (produced by stromal cells and bone marrow)
What happens to free antigen that finds its way to the lymph node?
can be captured by macs there and presented directly to follicular B cells, paracortical T cells and passed to follicular DCs
IN THE PARACORTICAL REGION
What are T cells doing in the lymphocyte?
helping B cells get activated
(once activated, T cells and B cells move to border of follcle and T-cell zone)
What cells are found in a primary follicle?
non-activated B cells
What cells are found in a secondary follicle?
B cell differentiating into PCs or memory cells and proliferating
Where are plasma cells longer lived, medullary cord or medullary sinus?
SINUS (on the way to bone marrow or gut)
What does the spleen do?
1) disposes of old RBCS and recycles iron (red pulp)
2) does not receive any afferent lymphatics
3) clears blood borne pathogens (white pulp)
The spleen is involved in immune responses to ________ ________ _________
blood borne pathogens
What comprises the majority of the spleen?
red pulp (site of RBC disposal)
What is the white pulp of the spleen?
lymphocytes surrounding the arterioles running thru the spleen (which drain into marginal sinus)
What is the periarteriolar lymphoid sheath?
PALS; sheath of lymphocytes around arteriole (mainly T cells; follicles with B cells are adjacent)
What is the marginal zone?
surrounds follicle (which neighbors PALS) has macs and B cells
What artery perfuses the spleen?
splenic (branches into many little channels)
What makes up the red pulp?
blood-filled vascular sinusoids (lined by macs which filter out RBCs and opsonized cells/microbes)
Why is it important for the spleen to have fenestrated capillaries?
so it can pull out damaged RBCs
The marginal B cells are sensitive to what kind of pathogens?
bacterial polysaccharides and other circulating peptides
How are blood antigens brought to the marginal sinus?
circulating DCs or sampled by marginal zone macs
What are 2 other important lymphoid functions?
1) peripheral tolerance
2) lymphocyte homeostasis