Blood Cells and Hematopoiesis

• Blood cells are initially produced in the yolk sac during the embryonic stage.
• The spleen, lymph nodes, and liver take over blood cell production as development progresses.
• Bone marrow eventually becomes the primary site for hematopoiesis.
• The final stages of cell differentiation can occur in other organs.
• Red bone marrow is a loose collection of cells where hematopoiesis occurs.
• Yellow bone marrow is a site of energy storage composed largely of fat cells.
• B cells undergo nearly all of their development in the red bone marrow.
• Immature T cells (thymocytes) mature mostly in the thymus gland after leaving the bone marrow.

Thymus

• The thymus is a bilobed organ located between the sternum and the aorta of the heart.
• Connective tissue holds the lobes together and forms a capsule around them.
• Trabeculae, extensions of the connective tissue capsule, divide the thymus into lobules.
• The cortex is the outer region of the thymus containing many thymocytes, epithelial cells, macrophages, and dendritic cells.
• The medulla is where thymocytes migrate before exiting the thymus.
• The medulla contains fewer thymocytes, epithelial cells, and dendritic cells than the cortex.

Immune System and Aging

• Immunosenescence is the loss of immune function with age.
• Thymic involution, the shrinking of the thymus gland, is a major cause of age-related immune deficiencies.
• Thymic involution begins at birth, with a tissue loss of about 3% per year, slowing to 1% after 35-45 years.
• Complete loss of thymic epithelial tissue and thymocytes would theoretically occur at about 120 years of age.
• Thymic involution has been observed in all vertebrate species with a thymus gland.
• Studies show that transplanted thymic grafts involute according to the donor's age, implying a genetic program.
• The thymic microenvironment loses thymic epithelial cells due to decreasing expression of the FOXN1 gene with age.
• Sex hormones like estrogen and testosterone can enhance thymic involution.
• Hormone changes in pregnant women cause temporary thymic involution that reverses after lactation.
• Potential therapies include thymic transplants and gene therapies to target gene expression.

Secondary Lymphoid Organs

• Lymphocytes mature in primary lymphoid organs but mount immune responses from secondary lymphoid organs.
• Naïve lymphocytes are immunologically functional but haven't encountered an antigen yet.
• Lymphocytes circulate in blood, lymph, and concentrate in secondary lymphoid organs: lymph nodes, spleen, and lymphoid nodules.
• Lymphoid follicles, with B cell-rich and T cell-rich areas, are present.
• Reticular fibers with fixed macrophages provide an internal structure.
• Germinal centers are sites of rapidly dividing and differentiating B lymphocytes.
• High endothelial venules allow cells from the blood to directly enter these tissues.

Lymph Nodes

• Lymph nodes remove debris and pathogens from the lymph, acting as "filters."
• Bacteria infecting interstitial fluid are taken up by lymphatic capillaries and transported to lymph nodes.
• Dendritic cells and macrophages internalize and kill pathogens.
• Lymph nodes mediate adaptive immune responses via T cells, B cells, and accessory cells.
• Bean-shaped lymph nodes are surrounded by a connective tissue capsule and divided into compartments by trabeculae.
• Reticular fibers laid down by fibroblasts provide structural support.
• Afferent lymphatic vessels serve as the major routes into the lymph node.
• Efferent lymphatic vessels serve as the routes for cells and lymph fluid to leave the lymph node.
• Lymph enters the lymph node via the subcapsular sinus, which contains dendritic cells, macrophages, and reticular fibers.
• Lymphoid follicles within the cortex consist of germinal centers of rapidly dividing B cells surrounded by T cells and accessory cells.
• The medulla contains medullary cords of B cells and plasma cells, and medullary sinuses where lymph collects before exiting.

Spleen

• The spleen is a major secondary lymphoid organ, about 12 cm long, attached to the stomach.
• The spleen is fragile without a strong capsule and is dark red due to extensive vascularization.
• The spleen filters the blood, removing microbes and other materials, including dying red blood cells.
• It functions as the location of immune responses to blood-borne pathogens.
• Trabeculae of connective tissue divide the spleen.
• Splenic nodules contain red pulp (mostly red blood cells) and white pulp (resembles lymphoid follicles).
• The splenic artery splits into arterioles (surrounded by white pulp) and sinusoids upon entering the spleen.
• Blood collects in venous sinuses and leaves via the splenic vein.
• Red pulp consists of reticular fibers, fixed and free macrophages, and blood cells.
• White pulp surrounds a central arteriole and consists of germinal centers of dividing B cells surrounded by T cells and accessory cells.
• Red pulp primarily functions as a filtration system of the blood, using nonspecific immune responses.
• White pulp is where adaptive T and B cell responses are mounted.

Lymphoid Nodules

• Lymphoid nodules have a simpler structure without a surrounding fibrous capsule.
• Nodules are located in the respiratory and digestive tracts, areas exposed to environmental pathogens.
• Tonsils are lymphoid nodules in the pharynx, important for immunity to oral pathogens.
• The pharyngeal tonsil, when swollen, is referred to as the adenoid.
• Tonsils lack a complete capsule, and the epithelial layer invaginates to form tonsillar crypts.
• Tonsillar crypts accumulate materials taken into the body and encourage pathogens to penetrate tissues.
• Tonsils help children develop immunity to common environmental pathogens.
• Tonsils are often removed in children with recurring throat infections.
• Mucosa-associated lymphoid tissue (MALT) consists of lymphoid follicles associated with mucous membrane epithelia.
• MALT makes up dome-shaped structures underlying the mucosa of the gastrointestinal tract, breast tissue, lungs, and eyes.
• Peyer’s patches, a type of MALT in the small intestine, are important for immune responses against ingested substances.
• Peyer's patches contain M (microfold) cells that sample material from the intestinal lumen and transport it to nearby follicles for adaptive immune responses.
• A similar process occurs in the appendix involving MALT, where a blockage triggers inflammation leading to appendicitis.
• Bronchus-associated lymphoid tissue (BALT) consists of lymphoid follicular structures along the bifurcations of the bronchi.
• BALT, along with tonsils, are effective against inhaled pathogens.