Primary Lymphatic Organs

The primary lymphoid organs, also referred to as central lymphoid/lymphatic organs, are the tissues responsible for the production of lymphoid cells from progenitor cells, incuding the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow and the thymus. In the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, hematopoietic stem cells progress to become oligopotent progenitors (in the case of lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes, the common lymphoid progenitor). B lymphocytes B lymphocytes B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells stay and undergo processes for differentiation before migrating to the secondary lymphoid organs (such as lymph nodes). The progenitor cells that are to become T lymphocytes T lymphocytes T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells proceed to the thymus for further maturation.

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Overview

Immune system

  • The immune system provides defense (immunity) against invading pathogens ranging from viruses to parasites. The components of the immune system are interconnected by blood and the lymphatic circulation.
  • 2 overlapping lines of defense:
    • Innate immunity (nonspecific), involving the following cells:
      • Natural killer cells
      • Monocytes/macrophages
      • Dendritic cells
      • Neutrophils, basophils, eosinophils
      • Tissue mast cells
    • Adaptive immunity (based on specific antigen recognition) involves the following cells:
      • T and B lymphocytes B lymphocytes B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells (derived from lymphoid organs)
      • Antigen-presenting cells

Lymphatic system

The lymphatic system (lymph vessels, lymph fluid, and lymphoid organs) is part of the body’s immune system.

  • Lymphoid organs:
    • Primary: 
      • Locations where lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes develop from progenitor cells (initial formation)
      • Include the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow and thymus
    • Secondary: 
      • Sites where lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes undergo activation, proliferation, and additional maturation
      • Include the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, lymph nodes, and MALT (i.e., tonsils)
  • Lymphatic vessels and ducts:
    • A network, similar to the blood vessels, that extend throughout the human body.
    • Connect lymphoid organs and transport interstitial fluid (lymph) 
    • Play crucial roles in immune response and fluid balance
Anatomy of the lymphatic system

Anatomy of the lymphatic system:
Includes the primary ( bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, thymus) and secondary ( spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, lymph nodes, and MALT) lymphoid organs
Lymphatic vessels convey lymph to the larger lymphatic vessels in the torso, transporting fluid back to the venous circulation.

Image: “Anatomy of the Lymphatic System” by OpenStax. License: CC BY 4.0

Bone Marrow

Anatomy

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones marrow is the spongy tissue found in the medullary canals of long bones and cavities of the cancellous bones. 

  • Red bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow:
    • Hematopoietic/blood-forming
    • Located in flat bones ( skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull, sternum, vertebrae, scapulae, and pelvic bones) and epiphysis of long bones (femur, tibia, humerus)
  • Yellow bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow:
    • Nonhematopoietic
    • Located in diaphysis of long bones
Red and yellow marrow portions of the bone

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones marrow:
Cross section showing the red and yellow marrow of the bone

Image: “619 Red and Yellow Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones Marrow” by OpenStax College. License: CC BY 3.0

Main Functions

  • Primary site of blood cell formation (by the 5th month of gestation)
  • Breakdown of old RBCs (into bilirubin, iron, globin) via macrophages and reuse of iron
  • Storage of fat through adipocytes

Structures

  • Hematopoietic:
    • Hematopoietic stem cells (HSCs) are multipotent cells with the ability to self-renew and differentiate to all hematopoietic lineage cells.
    • HSCs → multipotent progenitor cells (MPPs) → oligopotent progenitors:
      • Common lymphoid progenitor cells (CLPs)
      • Common myeloid progenitor cells (CMPs)
    •  CMPs and CLPs develop into lineage-restricted progenitors and, through stages, eventually become effector cells or differentiated cells:
      • CMP → granulocytes, monocytes, megakaryocytes, erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes
      • CLP → lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes (T progenitor cells go to the thymus)
  • Nonhematopoietic: structures that provide a microenvironment that supports the differentiation of hematopoietic cells and proliferation of blood cells:
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones cells
    • Marrow stroma
    • Sinusoids

Thymus

Anatomy

  • Encapsulated bilobed primary lymphoid organ 
  • Located in the anterosuperior mediastinum Mediastinum The mediastinum is the thoracic area between the 2 pleural cavities. The mediastinum contains vital structures of the circulatory, respiratory, digestive, and nervous systems including the heart and esophagus, and major thoracic vessels. Mediastinum and Great Vessels
  • Development and growth:
    • Arises from the 3rd and 4th pharyngeal pouches (endoderm)
    • Thymic lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes arise from the mesoderm.
    • 12 g at birth, reaches maximum weight at puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty (30–40 g)
    • After puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty, it undergoes involution (lymphoid parenchyma is replaced by adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue).

Main function

The main function of bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow is to act as the site of T-cell differentiation and maturation (from the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, progenitor cells go to the thymus).

General structure

  • With dense connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue capsule
  • Divided into 2 asymmetrical lobes (right is larger):
    • Each lobe of the thymus has smaller lobules separated by trabeculae (fibrous septa extending from the outer capsule).
    • Each lobule contains a:
      • Cortex
      • Medulla

Functional regions

  • Cortex:
    • Outer part of the lobule (dark)
    • Area where the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow–derived cells (CD4–, CD8–) enter.
    • Contains dense groups of developing immature T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells/thymocytes (with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables sizes and rare mitoses)
  • Medulla: 
    • Lighter-staining central area of the lobule
    • Loosely arranged
    • As T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells mature, they migrate from the cortex toward the medulla.
    • Contains:
      • Mature lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes (less numerous)
      • Hassall’s, or thymic, corpuscles: whorls of squamous-appearing epithelial cells (remnants of degenerating cells and cytokeratins) 
  • The corticomedullary junction contains antigen-presenting cells, dendritic cells, and macrophages.

Vasculature

  • Arterial blood supply is from the internal thoracic arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
  • Venous blood drains into the brachiocephalic and internal thoracic veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins.
  • Blood vessels enter and exit the thymus through trabeculae.
  • The thymus contains only efferent lymphatics that end up carrying the mature lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes from the thymus.

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Clinical Relevance

  • Acute lymphoblastic leukemia Acute Lymphoblastic Leukemia Acute lymphoblastic leukemia/lymphoma (ALL/LBL) are hematologic malignancies characterized by the uncontrolled proliferation of lymphoid precursor cells. Acute lymphoblastic leukemia/lymphoma, the most common forms of cancer affecting children, show the presence of increased lymphoblasts. Acute Lymphoblastic Leukemia: hematologic malignancy with uncontrolled proliferation of lymphoid precursor cells. Acute lymphoblastic leukemia Acute Lymphoblastic Leukemia Acute lymphoblastic leukemia/lymphoma (ALL/LBL) are hematologic malignancies characterized by the uncontrolled proliferation of lymphoid precursor cells. Acute lymphoblastic leukemia/lymphoma, the most common forms of cancer affecting children, show the presence of increased lymphoblasts. Acute Lymphoblastic Leukemia/lymphoma (ALL/LBL), the most common form of cancer affecting children, is characterized by increased lymphoblasts. The disease causes replacement of normal marrow by lymphoblasts, which eventually go into circulation and infiltrate other organs. Clinical presentation consists of fatigue, bleeding, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and infections that are related to the anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and lack of functional WBCs. Diagnosis is by peripheral blood smear and bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow biopsy examination showing lymphoblasts. Management is mainly chemotherapy administered in phases. 
  • Thymoma: rare thymic neoplasm often discovered incidentally on imaging. Thoracic symptoms occur because of effects on the adjacent organs (can cause shortness of breath, cough, phrenic nerve palsy, superior vena cava syndrome). The most common paraneoplastic syndrome associated with a thymoma is myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis.
  • DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome: condition caused by a microdeletion at location q11.2 of chromosome 22. In DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome, there is defective development of the 3rd and 4th pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia, respectively). Conotruncal anomalies present as congenital heart defects. Diagnosis is via clinical findings, laboratory tests (showing reduced T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells and low calcium), echocardiography, and genetic analysis. Treatment can include calcium supplementation, prophylactic antibiotics, surgery, and thymus or hematopoietic cell transplantation. 

References

  1. Haynes, B.F., Soderberg, K.A., Fauci, A.S. (2018). Introduction to the immune system. In: Jameson, J., et al. (Eds.), Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=192284326
  2. Mescher, A.L. (Ed.). (2018). The immune system & lymphoid organs. In: Junqueira’s Basic Histology: Text and Atlas, 15th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2430&sectionid=190282111
  3. Scoville, S., Caligiuri, M.A. (2021). The organization and structure of lymphoid tissues. In: Kaushansky, K., et al. (Eds.), Williams Hematology, 10th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2962&sectionid=252523494

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