CHAPTER 22 LYMPHATIC AND IMMUNE SYSTEMS

The lymphatic system consists of:

1. Lymphatic vessels (lymphatics)

2. Lymph (the fluid they contain)

3. Structures and organs that contain lymphatic tissue (which is special reticular

tissue that contains a large number of lymphocytes)

4. Red bone marrow

Functions:

1. Draining excess interstitial fluid from tissue spaces—once interstitial fluid enters lymphatic vessels it is called lymph

2. Transportation of dietary fats---lymphatic vessels pick up lipids and lipid-soluble vitamins as they are absorbed by the GI tract and carry them to the blood

3. Immune responses--lymphatic tissue carries out immune responses, which are highly specific responses to particular invaders or abnormal cells, carried out by lymphocytes.

LYMPHATIC VESSELS AND LYMPH CIRCULATION

Lymphatic vessels begin as one-way vessels called lymphatic capillaries in spaces between cells. These come together to form larger and larger lymphatic vessels. Lymphatic vessels resemble veins in structure, but have thinner walls and more valves. At intervals, they flow through lymph nodes.

Lymph capillaries are found in almost all tissues, but are lacking in avascular tissues, the CNS, part of the spleen, and red bone marrow. They have a slightly larger diameter than blood capillaries and allow interstitial fluid to enter by flowing through spaces between the endothelial cells that form their walls. In the lining of the small intestine, each of the villi contains a special lymph capillary called a lacteal. These absorb fats and because of the fat content their lymph is milky white and is called chyle. (All other lymph is a clear yellowish fluid.)

The flow of lymph is maintained mostly by the squeezing action of skeletal muscles with the valves preventing backflow. Respiratory movements also help maintain lymph flow. This is the same skeletal muscle pump & respiratory pump that aids in venous return.

Remember, fluid filtered from capillaries is mostly reabsorbed, but 10 - 15% of filtered fluid (3 liters/day) must be picked up by the lymphatic system and returned to the bloodstream. Any plasma proteins which have leaked out into tissue spaces are also returned by the lymphatic system.

Lymphatic vessels generally follow superficial veins in the skin. In body cavities, they follow arteries.

Lymph capillaries

¯

Lymphatic vessels (getting larger as they merge)

¯ Through lymph nodes

Lymphatic trunks:

1) Lumbar (R & L)

2) Intestinal (Single)

3) Bronchomediastinal (R & L)

4) Subclavian (R & L)

5) Jugular (R & L)

Combine to form 2 main channels:

1) Thoracic duct

2) Right lymphatic duct

The thoracic duct (left lymphatic duct) begins in the abdominal cavity just in front of vertebra L2 as a dilated area called the cisterna chyli. This is the main collecting duct and receives lymph from:

Left side of head, neck, and chest

Left arm

Entire body below the ribs

The intestinal trunk and right and left lumbar trunks empty into the cisterna chyli. The left bronchomediastinal, subclavian and jugular trunks empty into the thoracic duct in the neck area. The thoracic duct then empties into the left subclavian vein. Length of the thoracic duct is 15-18 inches.

The right lymphatic duct is much shorter (only about 1/2 inch long). It receives lymph from the right bronchomediastinal, subclavian, and jugular trunks and empties into the right subclavian vein.

LYMPHATIC ORGANS AND TISSUES

1. Primary lymphatic organs---sites of production and maturation of B and T lymphocytes

a. Red bone marrow

b. Thymus gland

2. Secondary lymphatic organs---site of most immune responses

a. Lymph nodes

b. Spleen

c. Lymphatic nodules---clusters of lymphatic tissue (mostly lymphocytes) that guard against invaders, numerous in mucous membranes

THYMUS GLAND

Located in the mediastinum and usually consists of 2 lobes, each covered by a capsule. Fibrous extensions of the capsule called trabeculae divide the lobes into lobules. Each lobule has a cortex and a medulla:

1. Cortex---contains large numbers of T cells, scattered dendritic cells, specialized epithelial cells, and macrophages. Immature T cells (pre-T cells) migrate to the cortex from the bone marrow and begin the maturation process. Those T cells that survive move to the medulla. The dendritic cells have long branched projections. Here in the thymus their function is to assist in the maturation of the T cells. The specialized epithelial cells also have long processes, but these surround a group of T cells. These epithelial cells also secrete thymic hormones.

2. Medulla---more mature T cells, widely scattered, as well as more of the same types of cells found in the cortex. Also found are concentric layers of flattened epithelial cells called thymic corpuscles (Hassall’s corpuscles).

Thymic hormones aid in the maturation of T cells and also have other functions in the immune system. One of the thymic hormones (thymosin) seems to be required for other lymphatic organs to develop properly. When fully mature, T cells leave the thymus and travel to other lymphatic tissue.

The gland is large in infants and reaches its maximum size at the age of 10-12 years. After this, it atrophies (shrinks) but continues to function.

LYMPH NODES

Lymph nodes are located along lymphatic vessels and often arranged in groups. Each node is covered by a capsule of dense CT. Inside, the node is divided into compartments by trabeculae extending in from the capsule. The parenchyma (functional tissue) is arranged in a network of reticular fibers and includes:

1. Cortex (outer region) in 2 parts:

a. Outer cortex—closest to capsule—contains clusters of B cells called lymphatic nodules. Primary lymphatic nodules are those that are inactive. Active nodules are participating in an active response and are called secondary lymphatic nodules. In the center of active nodules, B cells are proliferating into plasma cells and secreting antibodies. These areas are called germinal centers. Dendritic cells in the germinal centers act as antigen-presenting cells. Macrophages are also present.

b. Inner cortex--made up of T cells and dendritic cells; no nodules are present

2. Medulla (inner region)---contains B cells, plasma cells, and macrophages embedded in a network of reticular fibers.

Lymph flows through a lymph node in one direction. It enters through afferent lymphatic vessels and flows through irregular channels called sinuses, first in the cortex and then in the medulla. It exits through efferent lymphatic vessels at the hilum. In the sinuses, foreign substances are filtered out of the lymph as they become trapped in a mesh of reticular fibers. Macrophages then destroy some substances by phagocytosis and lymphocytes destroy others by immune responses. As the filtered lymph leaves a node, T cells, plasma cells, and antibodies can go with it.

Metastasis (spread of cancer) frequently occurs in the lymphatic system. Wherever the cancer cells lodge, secondary tumors may develop. The sites are predictable by tracing lymph flow away from the primary tumor.

SPLEEN

Largest mass of lymphatic tissue in the body. It is located in the left hypochondriac region between stomach and diaphragm. It is covered by a capsule of dense CT with smooth muscle.

The stroma consists of reticular fibers and trabeculae from the capsule. The parenchyma consists of:

1. White pulp---lymphocytes and macrophages arranged around central arteries

2. Red pulp---venous sinuses full of concentrated RBC and thin cords of splenic tissue called splenic (Billroth’s) cords.

The spleen DOES NOT filter lymph. Functions:

1. Site of proliferation of B cells into plasma cells (immune responses)

2. Phagocytosis of bacteria

3. Storage of platelets

4. Storage of blood and release on demand by contraction of the smooth muscle of the capsule, which squeezes it out of the red pulp like squeezing a sponge.

5. Phagocytosis of worn-out RBC and platelets

Severe blows to the abdomen may cause a ruptured spleen, which results in severe bleeding. This can rarely be repaired and usually the spleen must be removed. Without a spleen, the susceptibility to infection will be increased, esp. if the splenectomy is done in a child.

LYMPHATIC NODULES

Oval-shaped concentrations of lymphatic tissue, not enclosed by a capsule. These are found in the lamina propria (connective tissue layer) of the mucous membrane of the respiratory, urinary, digestive and reproductive tracts, where they are called mucosa-associated lymphoid tissue (MALT). Large aggregations are found in the appendix and the ileum (Peyer’s patches) and forming the tonsils.

TONSILS

Aggregations of large lymphatic nodules embedded in the mucous membrane forming a ring at the junction of the oral cavity and the pharynx.

1. Pharyngeal tonsil (adenoid)---single and embedded in the posterior wall of the nasopharynx

2. Palatine tonsils---paired and located on each side of the soft palate. These are the ones commonly removed in a tonsillectomy.

3. Lingual tonsils---paired and located at the base of the tongue.

Tonsils protect against invasion by inhalation or ingestion and participate in the immune response.

RESISTANCE TO DISEASE: INNATE DEFENSES

We must constantly defend the body against pathogens (disease-causing organisms) or toxic substances they produce. This is called resistance.

I. NONSPECIFIC RESISTANCE--general defense mechanisms not directed against any particular organism

A. First line of defense: Skin and mucous membranes

1. Mechanical barrier to entry

a. Epidermis--only a few pathogens can penetrate intact epidermis. Broken or

moist skin may allow entry.

b. Mucous membranes--line all body cavities open to the outside. Barrier not as

effective as epidermis but still important.

1) Mucus traps microbes

2) Hairs in nose act as filter

3) Cilia propel mucus containing microbes toward surface

c. Lacrimal apparatus (tears)--wash out microbes & irritants

d. Saliva--washes microbes off teeth & mouth surfaces

e. Flow of urine

f. Defecation and vomiting

2. Chemical protection

a. Sebum--protective film and low pH (3-5)

b. Lysozyme--breaks down some bacteria--found in perspiration, tears, saliva, nasal mucus

c. Gastric juice--acid pH destroys many bacteria & toxins

d. Vaginal secretions--acidic

B. Second line of defense: Antimicrobial substances in deeper tissue and blood

1. Antimicrobial proteins

a. Interferons--produced and released from cells infected with a virus. Interferons can't save the infected cell but diffuse to nearby uninfected cells and help them to defend themselves. Cells with interferon bound to them do not allow replication of a virus. Interferon also helps the body fight certain tumors.

b. Complement system--a group of proteins in blood plasma (produced by the liver). They become activated in a cascade of reactions (one factor activates another which in turn activates another and so on). Activated complement proteins may directly destroy invaders or make them more susceptible to other means of defense.

c. Transferrins---bind to iron and make it unavailable to microbes, interfering with their reproduction.

2. Natural killer cells--a kind of lymphocyte located in the spleen, lymph nodes, bone marrow and blood. These are able to directly attack and kill a variety of infected cells and certain tumor cells. Any body cell displaying abnormal or unusual proteins on its plasma membrane is a target for NK cells. They act in 2 ways:

a. Release of perforins, chemical which punch holes in the plasma membrane of an invader or cell

b. Binding to target cell and releasing molecules that enter and cause the cell to

self-destruct

3. Phagocytosis--ingestion of microbes or any foreign particulate matter by certain white blood cells

a. Phagocytes (phagocytic cells)

1) Neutrophils rush to site of invasion and phagocytize mostly bacteria

2) Eosinophils--phagocytic activity limited to antigen-antibody complexes

3) Monocytes--leave circulating blood and become:

a) Wandering macrophages--travel to a site of invasion more slowly than neutrophils, leave the blood and enter tissues, where they phagocytize bacteria and also clean up debris and dead cells

b) Fixed macrophages--always present in certain tissues and organs attached to CT. They remove microbes, foreign particles and worn out blood cells brought to them by the blood.

b. Phases of phagocytosis

1) Chemotaxis--chemical attraction of phagocytes to the area

2) Adherence--attachment of the cell membrane of a phagocyte to the surface of a microbe or particle of foreign material

3) Ingestion--phagocyte engulfs the microbe and draws it into the cell enclosed in a phagocytic vesicle (phagosome)

4) Digestion and killing--phagocytic vesicle merges with lysosomes inside WBC. Digestive enzymes and lethal oxidants, formed by the phagocyte in a process called the oxidative burst, break down and digest the microbe (most of the time). Some microbes are not easily killed this way. They may kill the phagocyte or survive and multiply inside it. Other microbes have defenses against being phagocytized in the first place.

4. Inflammation--response of the body to tissue damage of any type.

Damage may be due to invading microbes, physical or chemical damage.

a. Signs and symptoms

1) Redness

2) Heat

3) Swelling

4) Pain

5) Loss of function (if severe enough)

b. Functions of the inflammatory response

1) Prepares the site for tissue repair

2) Aids in disposal of foreign material

3) Aids in disposal of microbes & their toxins

4) Prevents spread of microbes

c. Stages of the inflammatory response

1) Vasodilation and increased permeability of blood vessels--occurs immediately after injury. It brings more blood to the area, which permits defensive materials such as antibodies, phagocytes and clotting factors to travel from the blood into injured tissue and helps remove toxic products. Within minutes after an injury, dilation of arterioles and increased permeability of capillaries produce heat, redness, and swelling (edema). Pain can result from injury to nerve fibers, irritation from toxic substances, increased pressure from edema and effects of chemicals produced by damaged cells.

2) Phagocytic migration--within an hour or less numerous phagocytes appear at the scene due to chemotaxis. Neutrophils are first. If the injury is extensive the white count will quickly rise (leukocytosis). Monocytes arrive later and leave blood to become wandering macrophages.

If large numbers of bacteria were in present in the damaged tissue, a fluid called pus may form. It contains dead phagocytes, dead bacteria (and possibly some live ones), and damaged tissue. Pus is sometimes absorbed by the body and sometimes drains to the outside. If it forms deep in tissues and becomes surrounded by a wall of CT, this is an abscess.

3) Repair--after the injured area is cleared of dead tissue and invading microbes, the process of repair can begin.

5. Fever--elevated body temperature

a. Intensifies the effects of interferons

b. Inhibits growth of some microbes

c. Speeds up reactions that aid repair