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What is hematopoiesis?
The process by which all red and white blood cells develop from a pluripotent hematopoietic stem cell (HSC).
Where does hematopoiesis occur in adult vertebrates?
In the bone marrow.
What are the two major types of progenitor cells that HSCs differentiate into?
Common myeloid progenitor cells and common lymphoid progenitor cells.
What do common myeloid progenitor cells give rise to?
Red blood cells, platelets, and myeloid cells (granulocytes, monocytes, macrophages, and some dendritic cells).
What do common lymphoid progenitor cells give rise to?
Lymphocytes (T and B), innate lymphoid cells, and some dendritic cells
Where does hematopoiesis begin during fetal development?
In the yolk sac.
Where do mature HSCs seed late in fetal development?
The bone marrow.
Why are lymphoid organs necessary for an immune response to occur?
Antigens must meet lymphocytes with matching antigen receptors within lymphoid organs.
What are the two categories of lymphoid organs?
Primary lymphoid organs and secondary lymphoid organs.
What is the function of primary lymphoid organs?
They regulate the production and differentiation of lymphocytes, and self-reactive cells are removed.
What is the function of secondary lymphoid organs?
They are the tissues where antigen processing occurs and lymphocytes respond to antigen.
Name the primary lymphoid organs
Thymus, Bursa (birds only), Peyer's patches (ruminants), and bone marrow.
Name the secondary lymphoid organs.
Tonsils, spleen, lymph nodes, Peyer's patches, and bone marrow.
Which organs perform both primary and secondary lymphoid functions?
Peyer's patches and bone marrow.
What do B lymphocytes develop in contact with in the bone marrow?
Stromal cells.
What is the role of stromal cells in the bone marrow?
They facilitate HSC proliferation, direct migration, and stimulate differentiation.
In young ruminants, what acts as a primary lymphoid organ for B cells?
Ileal Peyer's patches.
What happens to ileal Peyer's patches as animals reach sexual maturity?
They regress.
In which species is the Bursa of Fabricius found?
only in birds
Where is the Bursa of Fabricius located?
Just above the cloaca.
What is the function of the Bursa of Fabricius?
It is the source of B cells.
What happens if a neonatal bird undergoes bursectomy?
Antibody production is prevented.
Where are Peyer's patches located?
In the walls of the small intestine.
What are the two types of Peyer's patches?
Ileal and jejunal.
Which Peyer's patches regress at around sexual maturity?
Ileal Peyer's patches.
Which Peyer's patches are present throughout life?
Jejunal Peyer's patches.
In Group 1 mammals (ruminants and possibly pigs), which Peyer's patches are primary lymphoid organs?
Ileal Peyer's patches (in young animals).
In Group 1 mammals, which Peyer's patches are secondary lymphoid organs?
Jejunal Peyer's patches.
In Group 2 mammals (other species), what is the classification of all Peyer's patches?
All are secondary lymphoid organs.
Where do T cells develop initially?
In the bone marrow.
Where do T cells migrate to achieve full maturity?
The thymus.
What is the structure of the thymus?
Bilobed, located behind the breastbone (sternum) in most species.
What drives positive and negative selection of T cells in the thymus?
TCR affinity of binding with MHC-peptides.
What is positive selection of T cells?
Stimulating the remaining T cells.
What is negative selection of T cells?
Eliminating self-reactive T cells.
What happens if a neonate undergoes thymectomy?
Cell-mediated immunity is prevented (T cells are absent).
What happens to lymphocytes in secondary lymphoid organs?
They encounter antigens, become activated, undergo clonal expansion, and differentiate into effector cells.
What are the three main secondary lymphoid organ areas?
Lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT) — Peyer's patches.
How are secondary lymphoid organs connected to each other?
Via the blood and lymphatic circulatory systems.
What are lymphatics?
Open-ended vessels that return extravascular fluid from tissues to the heart.
How many afferent (inflowing) lymphatic vessels connect to each lymph node?
Multiple.
How many efferent (outflowing) lymphatic vessels connect to each lymph node?
One.
What are lymph nodes and the spleen considered?
The most highly organized secondary lymphoid organs.
What do lymph nodes filter?
Lymphatic fluid.
What is the major site of B cell responses in the lymph node?
The cortex.
What are primary follicles?
Follicles in the cortex in the absence of antigenic stimulation
What are secondary follicles?
Follicles that exhibit a germinal center (with dark and light zones) upon infection or vaccination; they produce antibodies.
What is the paracortex inhabited mainly by?
T cells.
What is the medulla rich in?
Antigen-processing cells, dendritic cells (DCs), and macrophages.
How does the lymph node structure of pigs differ from other species?
Pigs have an inverted (inside-out) structure: cortex at the center of the nodule and medulla towards the periphery.
How do naive lymphocytes enter the lymph node in all species?
Via blood.
How do primed lymphocytes enter the lymph node?
Via afferent lymphatics.
How do lymphocytes leave the lymph node in pigs?
Through high endothelial venules.
How do lymphocytes leave the lymph node in other species?
Through efferent lymphatics that drain into the thoracic duct
Where is the spleen located?
In the left cranial abdomen, dorsal to the stomach/rumen-reticulum and caudal to the diaphragm.
What does the spleen filter?
Antigens from the blood.
What is the function of the red pulp in the spleen?
Red cell storage and hematopoiesis.
What is the function of the white pulp in the spleen?
Lymphoid tissue.
Where do T cells form in the spleen?
Peri-arteriolar lymphoid sheaths (PALS).
Where do B cells form in the spleen?
Follicles containing germinal centers (which produce antibodies).
Where are macrophages and DCs located in the spleen?
In the marginal zone surrounding the white pulp.
What is the function of MALT?
An important layer of defense against infection at mucosal and epithelial layers; organizes responses to antigens that enter mucosal tissues.
What does GALT stand for?
Gut-associated lymphoid tissue.
What is an example of GALT?
Peyer's patches in the ileum and jejunum.
In which species are ileal Peyer's patches primary organs?
Young ruminants and pigs.
If antigen enters through the blood, which major lymphoid organ responds?
The spleen.
If antigen enters through the skin/tissues, which major lymphoid organ responds?
The draining lymph node.
If antigen enters through the gastrointestinal or respiratory mucosa, which major lymphoid organ responds?
Tonsils and Peyer's patches (MALT).
What is the main function of the spleen?
Filters blood-borne antigens.
What is the main function of draining lymph nodes?
Filters tissue-derived antigens.
What is the main function of tonsils and Peyer's patches (MALT)?
Filters mucosal antigens.
Where are antibodies primarily produced during a primary response?
Lymph nodes and spleen.
Where are antibodies primarily produced during a secondary response?
Bone marrow.
During a primary response to intravenous (i/v) vaccination, what are the primary sites of antibody production?
Spleen and lymph nodes.
During a secondary (boost) response to intravenous (i/v) vaccination, what are the primary sites of antibody production?
Bone marrow and spleen.
When a vaccine with an oil-based adjuvant is administered intramuscularly (i/m), what are the major sites of antibody production?
granuloma (formed at the injection site) and bone marrow.