The Lymphatic System

Components of the Lymphatic System

• Lymph is recovered fluid.
• Lymphatic vessels transport lymph.
• Lymphatic tissues are composed of lymphocyte and macrophage aggregates that populate many organs.
• Lymphatic organs have a high concentration of defense cells.
• Lymphatic organs are separated from surrounding tissues by connective tissue capsules.

Mechanisms of Lymph Flow

• Lymph flows under forces similar to venous return, but without a pump like the heart.
• Lymph flows at a lower pressure and slower speed than venous blood.
• Rhythmic contractions of lymphatic vessels move lymph.
  • Stretching of vessels stimulates contraction.
• Skeletal muscle pump aids lymph flow.
• Arterial pulsation rhythmically squeezes lymphatic vessels.
• The thoracic pump aids flow from the abdominal to the thoracic cavity.
• Valves prevent backward flow.
• Rapidly flowing blood in subclavian veins draws lymph into it.
• Exercise increases lymphatic return.

Lymphatic Cells

• Natural killer (NK) cells are large lymphocytes that attack and destroy bacteria, transplanted tissue, host cells infected with viruses, or cells which have become cancerous.
  • NK cells are responsible for immune surveillance.
• T lymphocytes (T cells) mature in the thymus.
• B lymphocytes (B cells) activation causes proliferation and differentiation into plasma cells that produce antibodies.
• Macrophages are large, avidly phagocytic cells of the connective tissue.
  • Macrophages develop from monocytes.
  • Macrophages phagocytize tissue debris, dead neutrophils, bacteria, and other foreign matter.
  • Macrophages process foreign matter and display antigenic fragments to certain T cells, thereby alerting the immune system to the presence of the enemy.
  • Macrophages are antigen-presenting cells (APCs).
• Dendritic cells are branched, mobile APCs found in the epidermis, mucous membranes, and lymphatic organs.
  • Dendritic cells alert the immune system to pathogens that have breached their surface.
• Reticular cells are branched stationary cells that contribute to the stroma of a lymphatic organ.
  • Reticular cells act as APCs in the thymus.

Lymphatic Organs

• Lymphatic organs have well-defined anatomical sites.
  • These organs have a connective tissue capsule that separates the lymphatic tissue from neighboring tissues.
• Primary lymphatic organs include red bone marrow and the thymus.
  • These are the sites where T and B cells become immunocompetent, enabling them to recognize and respond to antigens.
• Secondary lymphatic organs include lymph nodes, tonsils, and the spleen.
  • Immunocompetent cells populate these tissues.

Red Bone Marrow

• Red bone marrow is involved in hemopoiesis (blood formation) and immunity.
  • It is a soft, loosely organized, highly vascular material.
  • Red bone marrow is separated from osseous tissue by the endosteum of bone.
  • As blood cells mature, they push their way through the reticular and endothelial cells to enter the sinus and flow away in the blood stream.

Lymph Node

• Lymph nodes are the most numerous lymphatic organs.
  • There are about 450 in a typical young adult.
  • They cleanse the lymph and act as sites for T and B cell activation.
• Lymph nodes have an elongated, bean-shaped structure with a hilum.
• The nodes are enclosed in fibrous capsules with trabeculae that divide the interior into compartments.
  • The stroma is made of reticular fibers and reticular cells.
• Parenchyma is divided into the cortex and medulla.
  • There are germinal centers where B cells multiply and differentiate into plasma cells.
• Several afferent lymphatic vessels lead into the node along its convex surface.
• Lymph leaves the node through one to three efferent lymphatic vessels that leave the hilum.

Lymph Node Locations

• Cervical lymph nodes are found in deep and superficial groups in the neck.
  • They monitor lymph coming from the head and neck.
• Axillary lymph nodes are concentrated in the armpit.
  • They receive lymph from the upper limb and female breast.
• Thoracic lymph nodes are located in the thoracic cavity, embedded in the mediastinum.
  • They receive lymph from the mediastinum, lungs, and airway.

Lymphadenopathy

• Lymphadenopathy is a collective term for all lymph node diseases.

Lymphadenitis

• Lymphadenitis is characterized by swollen, painful nodes that are responding to a foreign antigen.

Lymph Nodes and Metastatic Cancer

• Lymph nodes are common sites for metastatic cancer.
  • These nodes are swollen, firm, and usually painless.
• Metastasis is the phenomenon in which cancerous cells break free from the original, primary tumor and establish new tumors.
  • Metastasizing cancer cells can easily enter the lymphatic vessels.
  • They tend to lodge in the first lymph node they encounter.
  • They multiply there and eventually destroy the node.
  • Cancers tend to spread to the next node downstream.
  • Treatment of breast cancer may involve lumpectomy, mastectomy, and removal of nearby axillary nodes.

Tonsils

• Tonsils are patches of lymphatic tissue located at the entrance to the pharynx.
  • They guard against ingested or inhaled pathogens.
  • Tonsils are covered with epithelium and have deep pits called tonsillar crypts, which are lined with lymphatic nodules.
  • Tonsillitis and tonsillectomy relate to tonsils.
• Three main sets of tonsils include:
  • Palatine tonsils: a pair found at the posterior margin of the oral cavity, most often infected.
  • Lingual tonsils: a pair at the root of the tongue.
  • Pharyngeal tonsil (adenoid): a single tonsil on the wall of the nasopharynx.

Defenses Against Pathogens

• Pathogens are environmental agents capable of producing disease.
  • These include infectious organisms, toxic chemicals, and radiation.
• Three lines of defense against pathogens:
  • The first line of defense consists of external barriers, such as skin and mucous membranes.
  • The second line of defense includes several nonspecific defense mechanisms.
    • These mechanisms include leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever.
    • Also, they are effective against a broad range of pathogens.
  • The third line of defense is the immune system.
    • Also, it defeats a pathogen and leaves the body with a 'memory' so it can defeat it faster in the future.

Nonspecific Resistance and Immunity

• Nonspecific resistance guards equally against a broad range of pathogens.
  • Its effectiveness does not depend on prior exposure.
  • Includes skin and mucous membranes, leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever.
• Immunity is a specific defense because it results from prior exposure to a pathogen.
  • It usually provides future protection only against that particular one.

Neutrophils

• Neutrophils wander in connective tissue to kill bacteria.
  • They use phagocytosis and digestion and produce a cloud of bactericidal chemicals.
• A killing zone is created, which is degranulation.
  • Lysosomes discharge into tissue fluid.
  • Respiratory burst: Neutrophils rapidly absorb oxygen and create toxic chemicals like O₂, H₂O₂, and HClO.
  • Kill more bacteria with toxic chemicals than phagocytosis.

Eosinophils

• Eosinophils are found especially in the mucous membranes.
• They stand guard against parasites, allergens (allergy-causing agents), and other pathogens.
• Eosinophils kill tapeworms and roundworms by producing superoxide, hydrogen peroxide, and toxic proteins.
• They promote the action of basophils and mast cells.
• Eosinophils phagocytize antigen-antibody complexes.
• They limit the action of histamine and other inflammatory chemicals.

Basophils

• Basophils secrete chemicals that aid the mobility and action of WBCs and other leukocytes.
  • Leukotrienes activate and attract neutrophils and eosinophils.
  • Histamine is a vasodilator that increases blood flow, which speeds delivery of leukocytes to the area.
  • Heparin inhibits the formation of clots and would impede leukocyte mobility.
• Mast cells also secrete these substances and are a type of connective tissue cell similar to basophils.

Lymphocytes

• There are three basic categories of lymphocytes.
• Circulating blood contains 80% T cells, 15% B cells, and 5% NK cells.
• Also, they have many diverse functions.

Monocytes

• Monocytes emigrate from the blood into the connective tissue and transform into macrophages.
• The macrophage system includes all the body's avidly phagocytic cells, except leukocytes.
  • Wandering macrophages actively seek pathogens and are widely distributed in loose connective tissue.
  • Fixed macrophages phagocytize only pathogens that come to them.
    • Microglia: in the central nervous system.
    • Alveolar macrophages: in the lungs.
    • Hepatic macrophages: in the liver.

Passive and Active Immunity

• Natural active immunity results from one's own antibodies or T cells produced as a result of infection or natural exposure to an antigen.
• Artificial active immunity results from one's own antibodies or T cells produced as a result of vaccination against disease.
  • A vaccine consists of dead or attenuated (weakened) pathogens that stimulate the immune response without causing the disease.
  • Booster shots are periodic immunizations to stimulate immune memory to maintain a high level of protection.
• Natural passive immunity is temporary immunity that results from antibodies produced by another person.
  • A fetus acquires antibodies from its mother through the placenta or milk.
• Artificial passive immunity is temporary immunity that results from the injection of immune serum (antibodies) from another person or animal.
  • This is a treatment for snakebites, botulism, rabies, tetanus, and other diseases.

Lymphocytes Overview

• Lymphocytes are major cells of the immune system.
  • Includes lymphocytes, macrophages, and dendritic cells.
• Primarily, lymphocytes are concentrated in strategic places such as lymphatic organs, skin, and mucous membranes.
• Three categories of lymphocytes includes natural killer (NK) cells, T lymphocytes (T cells), and B lymphocytes (B cells).
• Natural killer (NK) cells are responsible for the immune survelliance.

Cellular Immunity

• Cellular (cell-mediated) immunity is a form of specific defense in which T lymphocytes directly attack and destroy diseased or foreign cells.
  • The immune system remembers the antigens and prevents them from causing disease in the future.
• Involves four classes of T cells:
  • Cytotoxic T (T𝒸) cells (killer T cells (T8, CD8, or CD8+)): the 'effectors' of cellular immunity.
  • Helper T (Tₕ) cells (T4, CD4, CD4+): help promote T cell and B cell action and nonspecific resistance.
  • Regulatory T (Tᵣ) cells (T-regs): inhibit multiplication and cytokine secretion by other T cells limiting the immune response.
  • Memory (Tₘ) cells: descend from the cytotoxic T cells which are responsible for memory in cellular immunity.
• Both cellular and humoral immunity occur in three stages: recognition, attack, and memory.
• Immunity is thought of as the 'three Rs of immunity': recognize, react, and remember.

Five Classes of Antibodies

• Named for the structure of their C region:
  • IgA - exists as a monomer in plasma, but as a dimer in mucus, saliva, tears, milk, and intestinal secretions.
    • Prevents pathogen adherence to epithelia penetrating underlying tissues.
    • Provides passive immunity to newborns.
  • IgD - monomer; found as B cell transmembrane antigen receptor.
    • Thought to function in B cell activation by antigens.
  • IgE - monomer; transmembrane protein on basophils and mast cells.
    • Stimulates release of histamine and other chemical mediators of inflammation and allergy.
    • Attracts eosinophils to parasitic infections and produces immediate hypersensitivity reactions.
  • IgG - monomer and constitutes 80% of circulating antibodies.
    • Crosses placenta to fetus, secreted in secondary immune response, complement fixation.
  • IgM - pentamer in plasma and lymph.
    • Secreted in primary immune response, agglutination, complement fixation.

Humoral Immunity - Memory

• Primary immune response: an immune reaction brought about by the first exposure to an antigen.
  • The appearance of protective antibodies is delayed for 3 to 6 days while naïve B cells multiply and differentiate into plasma cells.
  • As plasma cells produce antibodies, the antibody titer (level in the blood plasma) rises in about 10 days before soon declining, showing that IgM appears first on the rise.
    • IgG levels rise as IgM declines, but IgG titer drops to a low level within a month.
  • Primary response leaves one with an immune memory of the antigen.
    • During clonal selection, some of the clones become memory B cells, which is found mainly in germinal centers of the lymph nodes.
    • Can mount a very quick secondary response.
• Secondary (anamnestic) response: if re-exposed to the same antigen, plasma cells will form within hours.
  • IgG titer will rise sharply and peaks in a few days, leaving little chance to exert a noticeable effect on the body. The result is no illness. -Low levels of IgM are also secreted and quickly declines.
  • IgG remain elevated for weeks to years, conferring long lasting protection.
• Notably, memory does not last as long in humoral immunity as in cellular immunity.

Autoimmune Diseases

• Autoimmune diseases are failures of self-tolerance.
• Consist of an immune system fails to distinguish self-antigens from foreign ones.
  • Produces autoantibodies that attack the body's own tissues.
• Three reasons why self-tolerance exist:
  • Cross-reactivity: some antibodies against foreign antigens react to similar self-antigens.
    • Rheumatic fever has streptococcus antibodies which also react with heart valves.
  • Abnormal exposure has a blood-testes barrier isolates sperm from blood.
    • Some of our native antigens are not exposed to blood. -Changes in structure of self-antigens are caused by viruses and drugs which change the structure of self-antigens and cause the immune system to perceive them as foreign.
• With self-reactive T cells, not all are eliminated in the thymus and are normally kept in check by regulatory T (Tᵣ) cells.

Immunodeficiency Diseases

• When the immune system fails to react vigorously enough, can lead to Severe Combined Immunodeficiency Disease (SCID). -Hereditary lack of T and B cells with this diseases, leading to a vulnerability to opportunistic infection and must live in protective enclosures.