Comprehensive notes on lymphocytes, thymus, Bursa of Fabricius, and secondary lymphoid tissues (vet physiology)
Hematopoiesis: lineages and the focus on lymphocytes
The bone marrow generates all white blood cells (WBCs) and red blood cells (RBCs) from pluripotent stem cells.
There are three main lineages of blood cells mentioned: erythroid (red blood cells and platelets), myeloid (basophils, eosinophils, etc.), and lymphoid (lymphocytes).
The lecture mainly focuses on lymphocytes (B cells and T cells) and briefly mentions natural killer (NK) cells as another lymphoid-associated population.
The immune system comes online shortly after birth and is most functional in young animals; by puberty, sites of lymphocyte proliferation begin to decrease, and in geriatric animals lymphocyte activity is limited though the basic function remains.
Key terms and concepts
Pluripotent stem cells: can give rise to multiple cell types, but are typically committed to a precursor destined for a specific lineage.
Lymphoid precursors: commit to the lymphoid lineage, which gives rise to B cells, T cells, and NK cells.
Innate vs adaptive immunity:
B and T cells are part of the adaptive (acquired) immune system and are highly specific.
NK cells are part of the innate lymphoid lineages and target infected or cancerous cells.
B cell activating factor (BAFF): a cytokine that stimulates B cell activation.
Intestinal microbiome: gut microbes that influence immune development and B cell activation.
Bursa of Fabricius: a specialized organ in birds adjacent to the cloaca where B cells are trained; its name helped define B cells.
Peyer’s patches: lymphoid tissue in the ileum (ileal Peyer’s patches) that is involved in intestinal immune responses and B cell development in mammals.
IgA, IgG, etc.: antibodies produced by B cells/ plasma cells in response to antigens (not spelled out in detail in this transcript, but relevant to B cell function).
B cells: development, training sites, and activation
Immature B cell development: B cells initially develop in the bone marrow and then migrate to peripheral lymphoid tissues for final maturation.
Two main factors controlling B cell development after leaving the bone marrow:
B cell activating factor (BAFF). This is a cytokine that stimulates B cell activation and maturation.
Intestinal microbiome: gut microbes influence B cell activation and the development of antibodies.
Birds (B cell training):
Bursa of Fabricius is the primary training site for B cells in birds, located next to the cloaca.
Bursaectomy (removal of the bursa at a young age) removes the ability to develop antibodies, showing the critical role of the bursa in B cell training.
Bursa reaches maximum size in young birds and undergoes involution (shrinking) after puberty, being replaced largely by fatty tissue.
Mammals (B cell training):
In mammals, B cells are trained primarily in primary lymphoid tissues (bone marrow and ileal Peyer’s patches) and then in secondary lymphoid tissues (spleen and lymph nodes).
Most B cell training in higher vertebrates happens in secondary lymphoid tissues (spleen and lymph nodes), providing efficient central hubs for antigen encounter.
Ileal Peyer’s patches (IPPs):
In some mammals (e.g., sheep, lambs), IPPs in the ileum are important for antibody production.
Removal of IPPs in young lambs reduces antibody production on challenge, but does not completely abolish it, illustrating redundancy and compensatory mechanisms.
Secondary lymphoid tissues for B cells: spleen and lymph nodes are major sites for B cell activation and antibody production in many mammals.
Birds vs mammals: in birds, B cells are trained in the Bursa of Fabricius; in mammals, B cells are trained largely in primary lymphoid tissue (bone marrow) with additional training in IPPs and other secondary tissues.
T cells: development, training, and selection
T cell development site: thymus, which is located in the upper thorax (near the sternum) across mammals and horses.
Thymus entry point for developing T cells: subcapsular region, where precursors enter the organ via blood-tissue interfaces.
Naive T cells: after initial development, T cells become naive and have not yet been tested for their specific antigen.
Migration within thymus: naive T cells migrate from the outer cortex toward the inner medulla during maturation.
Selection processes (to ensure self-tolerance and antigen specificity):
Positive selection: T cells must be able to recognize self-MHC molecules presenting antigens; otherwise they are eliminated.
Negative selection: T cells that react strongly to self-antigens are eliminated to prevent autoimmunity.
Outcome: functional naive T cells that are non-self reactive are released to the periphery.
Thymus anatomy and aging:
The thymus is encapsulated, with cortex (outer) and medulla (inner).
Hassall’s corpuscles (often called carpuscles in some texts) in the medulla release growth factors that promote ongoing T cell development.
The thymus is largest right after birth and undergoes age-related involution during puberty, progressively shrinking and often becoming difficult to detect in older animals.
Athymic (thymus-free) animals lack T cell–mediated (cell-mediated) immunity, illustrating the essential role of the thymus in T cell development.
Thymus histology and function
Encapsulated lymphoid tissue with lobulated structure; cortex to medulla flow is typical.
Immature T cells proliferate in the cortex and are tested with macrophages and dendritic cells throughout thymic tissue.
Antigen presentation within the thymus is supported by antigen-presenting cells (APCs): macrophages and dendritic cells process antigens and present them to developing T cells to drive selection.
Dendritic cells and macrophages are distributed throughout the thymus to present antigens and help educate T cells.
The thymus contains reticular fibroblasts that maintain the supportive stroma and contribute to the “sponge-like” architecture that permits cell movement and antigen sampling.
Lymphoid tissues: encapsulated vs unencapsulated
Encapsulated lymphoid tissues:
Lymph nodes and spleen are classic encapsulated secondary lymphoid organs with a capsule and trabeculae that organize tissue into functional zones.
The cortex/medulla in thymus is a special case of encapsulated lymphoid tissue; in lymph nodes, the analogous regions are the B cell follicles (often in cortex) and T cell zones (paracortex).
Unencapsulated lymphoid tissues (MALT):
MALT = mucosa-associated lymphoid tissue; includes tissues that line mucosal surfaces and are exposed to external environments.
Examples include tonsils (in horses these are often uncapsulated), Peyer’s patches in the small intestine, and other lymphoid tissues lining mucosal surfaces.
MALT serves as frontline immune tissue in areas exposed to external environment and pathogens.
Lymphoid tissue distribution in horses and other large mammals:
Tonsils in horses are uncapsulated in some regions.
Lymph nodes are widely distributed; many lymphoid centers exist in cervical, abdominal, and other regions.
The spleen is a major secondary lymphoid tissue with splenic cords and sinuses; the architecture supports filtering blood and mounting immune responses.
Lymph flow, lymph nodes, and antigen sampling
Lymphatic flow basics:
Lymph moves through lymphatic vessels via afferent ducts (toward lymph nodes) and efferent ducts (away from lymph nodes).
Lymphatic fluid enters the node via afferent lymphatics and percolates through subcapsular sinuses and cortical/medullary regions, allowing lymphocytes to sample antigens.
Lymph nodes have one-way flow with valves to prevent backflow, ensuring slow percolation for immune sampling.
Subcapsular sinus: entry region where initial antigen sampling occurs.
Chemotaxis: chemokine-guided migration helps B and T cells localize to their respective zones within lymph nodes.
Follicles and immune activation: B cell zones (follicles) and T cell zones (paracortex) separate, but antigens activate both populations to drive clonal expansion.
Plasma cells and antibody production:
B cells differentiate into plasma cells, which produce antibodies within the cords of lymph nodes.
Antibodies help other immune cells recognize and neutralize antigens and can be targeted by T cells for clearance.
Antigen, epitopes, and MHC interactions
Antigen: any substance that can provoke an immune response.
Epitope: the specific part of the antigen that interacts with B cell receptors or T cell receptors (via MHC presentation).
Antigen presentation and APCs: antigen-presenting cells process antigens and present peptide fragments via MHC molecules to T cells; B cells can recognize intact antigens via B cell receptors.
T cell recognition specifics:
T cells typically recognize peptide fragments presented by MHC molecules on APCs.
B cells recognize native, unprocessed antigens on their surface or soluble antigens.
Spleen and systemic immunity
Spleen as a secondary lymphoid organ: filters blood rather than lymph.
Primary function in humans and many animals: immune surveillance and clearance of blood-borne pathogens.
In horses, the spleen has a specialized role as a reservoir for blood to support prolonged aerobic activity; it can release stored blood to sustain high activity and oxygen delivery to muscles during extended exertion.
Lymph flow in the spleen parallels other secondary lymphoid tissues but involves blood-borne antigens rather than lymphatic antigens.
Vaccination and immune response concepts
Vaccination types:
Live (attenuated) vaccines: may elicit strong, long-lasting immunity with fewer boosters because they mimic natural infection (involves active lytic phase in some cases).
Dead (inactivated) vaccines: often require boosters to maintain immunity because they do not replicate.
Rhinovirus example:
Rhinoviruses are classic pathogens studied for respiratory infections; immunity developed after exposure or vaccination can wane, necessitating boosters for some vaccines.
Lytic phase and viral vaccines: the lytic phase is a viral replication step that triggers host cell responses; vaccines can be designed to remove or inactivate this phase to reduce disease while still provoking an immune response.
Practical and ethical considerations in immune function research
Animal models: athymic (thymus-less) animals lack T cell–mediated immunity, illustrating the essential role of the thymus in adaptive immunity.
Immunosuppression and transplantation:
Cyclosporine is an immunosuppressive drug used to reduce graft rejection; it’s effective but expensive and has limitations.
Transplantation raises ethical and practical concerns about immune compatibility and long-term management.
Critical thinking about immune development:
Even when a primary organ (e.g., IP patches or bursa) is removed or damaged, other tissues often compensate, leading to partial rather than complete loss of function.
This highlights redundancy and plasticity in the immune system and has real-world implications for breeding, management, and disease resistance in animals.
Age-related decline in immune function:
In aging animals, lymphoid organs undergo involution and reduce output and activity, contributing to decreased immune responsiveness.
Summary of key relationships and concepts
Lymphocytes (B and T cells) are central to adaptive immunity; NK cells participate in innate lymphoid responses.
B cells mature and are activated in bone marrow and peripheral/secondary lymphoid tissues; birds rely on Bursa of Fabricius for B cell training, whereas mammals rely more on bone marrow and other primary/secondary tissues (e.g., IP patches, spleen, lymph nodes).
T cells mature in the thymus and undergo rigorous selection (positive and negative) to ensure self-tolerance and appropriate antigen specificity.
Lymphoid tissue organization (encapsulated vs unencapsulated) and the architecture of lymph nodes and spleen enable efficient sampling and mounting of immune responses.
Antigen interactions involve epitopes, MHC presentation, and APCs; B and T cells recognize antigens through different yet complementary mechanisms.
Vaccination strategies exploit differences between live and dead vaccines and leverage the immune system’s capacity to generate memory responses, with boosters often required for non-replicating vaccines.
The spleen’s role as a blood filter and reservoir supports systemic immunity and, in some species like horses, contributes to rapid physiological responses during exercise.
Ethical considerations in immune research include the use of animal models, transplantation challenges, and balancing immune competence with welfare.
main types of peripheral lymphoid tissue: encapsulated and unencapsulated (MALT)
primary lymphoid tissues involved in lymphocyte development (bone marrow for B cells, thymus for T cells)
Key terms to review: BAFF, Bursa of Fabricius, Peyer’s patches, Hassall’s corpuscles, subscapular region, germinal centers, afferent/efferent lymphatics, sinuses, plasma cells, and APCs (macrophages and dendritic cells).