Chapter 22

The Lymphatic System

 

Lecture Outline

INTRODUCTION

•      The ability to ward off the pathogens that produce disease is called resistance.

•      Lack of resistance is called susceptibility.

•      Resistance to disease can be grouped into two broad areas.

•      Nonspecific resistance to disease includes defense mechanisms that provide general protection against invasion by a wide range of pathogens.

•      Immunity involves activation of specific lymphocytes that combat a particular pathogen or other foreign substance.

•      The body system that carries out immune responses is the lymphatic system.

Chapter 22
The Lymphatic System

•      Resistance is the ability to ward off disease

–   lack of resistance is termed susceptibility

•      Nonspecific resistance to disease

–   general defensive mechanisms effective on a wide range of pathogens (disease producing microbes)

•      Specific resistance or immunity is ability to fight a specific pathogen

–   cell-mediated immunity

–   antibody-mediated immunity

LYMPHATIC SYSTEM STRUCTURE AND FUNCTION

•      The lymphatic system consists of a fluid called lymph flowing within lymphatic vessels, several structures and organs that contain lymphatic tissue (specialized reticular tissue containing large numbers of lymphocytes), and bone marrow, which is the site of lymphocyte production (Figure 22.1).

•      Interstitial fluid and lymph are very similar.

•      Their major difference is location.

•      The lymphatic system functions to drain interstitial fluid, return leaked plasma proteins to the blood, transport dietary fats, and protect against invasion by nonspecific defenses and specific immune responses.

Lymphatic System

•       Organs, vessels and a fluid called lymph

–    similar to interstitial fluid

•       Organs involved

–    red bone marrow

–    thymus

–    spleen

–    lymph nodes

–    diffuse lymphatic tissue

•    tonsils, adenoids & peyers patches

Functions of the Lymphatic System

•      Draining excess interstitial fluid & plasma proteins from tissue spaces

•      Transporting dietary lipids & vitamins from GI tract to the blood

•      Facilitating immune responses

–   recognize microbes or abnormal cells & responding by killing them directly or secreting antibodies that cause their destruction

Lymphatic Vessels and Lymph Circulation

•      Lymphatic vessels begin as blind-ended lymph capillaries in tissue spaces between cells (Figure 22.2).

•      Interstitial fluid drains into lymphatic capillaries, thus forming lymph.

•      Lymph capillaries merge to form larger vessels, called lymphatic vessels, which convey lymph into and out of structures called lymph nodes (Figure 22.1).

Lymphatic Vessels & Circulation

•      Capillaries that begin as
closed-ended tubes found
in spaces between cells

•      Combine to form lymphatic
vessels

–   resemble veins with thin
walls & more valves

•      Fluid flows through lymph

     nodes towards large veins

     above the heart

–   lymph emptied into bloodstream

Lymphatic Capillaries

•      Lymphatic capillaries have a slightly larger diameter than blood capillaries and have overlapping endothelial cells which work as one-way valves for fluid to enter the lymphatic capillary.

•      Anchoring filaments attach endothelial cells to surround tissue (Figure 22.2).

•      A lymphatic capillary in the villus of the small intestine is the lacteal. It functions to transport digested fats from the small intestine into blood.

Lymphatic Capillaries

•      Found throughout the
body except in Avascular
tissue (cartilage, epidermis
& cornea)

•      Structure is designed to let
tissue fluid in but not out

–   anchoring filaments keep tube
from collapsing under outside pressure

–   overlapping endothelial cells open when tissue pressure is high (one-way valve)

Lymph Trunk and Ducts

•      The principal lymph trunks, formed from the exiting vessels of lymph nodes, are the lumbar, intestinal, bronchomediastinal, subclavian, and jugular trunks (Figure 22.3).

•      The thoracic duct begins as a dilation called the cisterna chyli (Figure 22.4) and is the main collecting duct of the lymphatic system.

•      The thoracic duct receives lymph from the left side of the head, neck, and chest, the left upper extremity, and the entire body below the ribs.

•      It drains lymph into venous blood via the left subclavian vein.

Lymph Trunks & Ducts

•       Vessels unite to form trunks & thoracic ducts

•       Right side head, arm & chest empty into right lymphatic duct and rest of body empties into thoracic duct

•       Lymph is dumped directly into left & right subclavian veins

 

Right Lymphatic Duct (Figure 22.3)

•      The right lymphatic duct drains lymph from the upper right side of the body.

•      It drains lymph into venous blood via the right subclavian vein.

Formation and Flow of Lymph

•      Interstitial fluid drains into lymph capillaries.

•      The passage of lymph is from arteries and blood capillaries (blood) to interstitial spaces (interstitial fluid) to lymph capillaries (lymph) to lymphatic vessels to lymph trunks to the thoracic duct or right lymphatic duct to the subclavian veins (blood) (Figure 22.4).

•      Lymph flows as a result of the milking action of skeletal muscle contractions and respiratory movements.

•      It is also aided by lymphatic vessel valves that prevent backflow of lymph.

•      An excessive accumulation of interstitial fluid may be caused by an obstruction to lymph flow (Clinical Application).

Formation & Flow of Lymph

•       Fluid & proteins escaping from vascular capillaries is collected by lymphatic capillaries & returned to the blood

•       Respiratory & muscular pumps promote flow of lymphatic fluid

•       Lymphatic vessels empty into subclavian veins

Lymphatic Organs and Tissues

Lymphatic Organs & Tissues

•      Widely distributed throughout the body

•      Primary lymphatic organs

–   provide environment for stem cells to divide & mature into B and T lymphocytes

•   red bone marrow gives rise to mature B cells

•   thymus is site where pre-T cells from red marrow mature

•      Secondary lymphatic organs & tissues

–   site where most immune responses occur

•   lymph nodes, spleen & lymphatic nodules

Thymus Gland Figure 22.5

•      Large organ in infants (70 g) but atrophied as adult (3 g)

•      2 lobed organ located in mediastinum

•      Capsule & trabeculae divide
it into lobules

•      Each lobule has cortex &
medulla

•      Cortex

–   tightly packed lymphocytes &
macrophages

•      Medulla

–   reticular epithelial cells produces thymic hormones

–   Hassall’s corpuscles

Thymus Gland

•       Large organ in infants (70 g) but atrophied as adult (3 g)

•       2 lobed organ located in mediastinum

•       Capsule & trabeculae divide
it into lobules

•       Each lobule has cortex &
medulla

•       Cortex

–    tightly packed lymphocytes &
macrophages

•       Medulla

–    reticular epithelial cells produces thymic hormones

–    Hassall’s corpuscles

Lymph Nodes - Overview

•       Lymph nodes are encapsulated oval structures located along lymphatic vessels (Figures 22.1a and 22.6).

•       They contain T cells, macrophages, follicular dendritic cells, and B cells.

•       Lymph enters nodes through afferent lymphatic vessels, is filtered to remove damaged cells and microorganisms, and exits through efferent lymphatic vessels.

•       Foreign substances filtered by the lymph nodes are trapped by nodal reticular fibers.

•       Macrophages then destroy some foreign substances by phagocytosis and lymphocytes bring about the destruction of others by immune responses.

•       Lymph nodes are the site of proliferation of plasma cells and T cells.

•       Knowledge of the location of the lymph nodes and the direction of lymph flow is important in the diagnosis and prognosis of the spread of cancer by metastasis; many cancer cells are spread by way of the lymphatic system, producing clusters of tumor cells where they lodge. (Clinical Application)

Lymph Nodes

•       Flow is in one direction

–    afferent vessels lead in

–    sinuses lead to efferent vessels that exit at hilus

•       Only nodes filter lymph

 

Lymph Nodes

•       Bean-shaped organs, up to 1 inch long, located along lymphatic vessels

–    scattered throughout body but concentrated near mammary glands, axillae & groin

•       Stroma is capsule, trabeculae & reticular fibers

•       Parenchyma is divided into 2 regions:

–    cortex

•    lymphatic nodules with germinal centers containing dendritic cells

–   antigen-presenting cells and macrophages

•    B cells proliferate into antibody-secreting plasma cells

–    medulla

•    contains B cells & plasma cells in medullary cords

Metastasis Through Lymphatic System

•      Characteristic of malignant tumors

•      Spread of disease from one organ to another

–   cancer cells travel via blood or lymphatic system

–   cells establish new tumors where lodge

•      Secondary tumor sites can be predicted by direction of lymphatic flow from primary site

•      Cancerous lymph nodes are firm, enlarged and nontender -- infected lymph nodes are not firm and are very tender

 

 

Spleen Figure 22.7

•       5 inch organ between stomach & diaphragm

•       Hilus contains blood & lymphatic vessels

•       Stroma consists of capsule, trabeculae, fibers & fibroblasts

•       Parenchyma consists of white pulp and red pulp

–    white is lymphatic tissue (lymphocytes & macrophages) around branches of splenic artery

–    red pulp is venous sinuses filled with blood & splenic tissue (splenic cords)

Spleen

•      The red pulp consists of venous sinuses filled with blood and splenic cords consisting of RBCs, macrophages, lymphocytes, plasma cells, and granulocytes.

•      Macrophages remove worn-out or defective RBCs, WBCs, and platelets.

•      The spleen stores blood platelets in the red pulp.

•      The red pulp is involved in the production of blood cells during the second trimester of pregnancy.

Clinical Application

•      The spleen is often damaged in abdominal trauma.  A splenectomy may be required to prevent excessive bleeding.

Lymphatic Nodules

•      Concentrations of lymphatic tissue not surrounded by a capsule scattered throughout connective tissue of mucous membranes

–   mucosa-associated lymphoid tissue (MALT)

•      Peyer’s patches in the ileum of the small intestine

•      Appendix

•      Tonsils form ring at top of throat - Figure 23.2

–   adenoids (pharyngeal tonsil)

–   palatine tonsils (on each side wall)

–   lingual tonsil in the back of the tongue

DEVELOPMENT OF THE LYMPH TISSUES

•      Lymphatic vessels develop from lymph sacs, which develop from veins. Thus, they are derived from mesoderm.

•      Lymph nodes develop from lymph sacs that become invaded by mesenchymal cells (Figure 22.8).

Developmental Anatomy

•       Begins to develop by 5th
week

•       Lymphatic vessels develop
from lymphatic sacs that
arise from veins

•       Jugular sac & cisterna chyli
form thoracic duct

•       Sacs develop into lymph nodes

•       Spleen develops in gastric mesentery

•       Thymus is outgrowth of 3rd pharyngeal pouch

NONSPECIFIC RESISTANCE: INNATE DEFENSES

First Line of Defense: Skin and Mucous Membranes

•       Nonspecific resistance refers to a wide variety of body responses against a wide range of pathogens (disease producing organisms) and their toxins.

•       Mechanical protection includes the intact epidermis layer of the skin (Figure 5.1), mucous membranes, the lacrimal apparatus, saliva, mucus, cilia, the epiglottis, and the flow of urine. Defecation and vomiting also may be considered mechanical processes that expel microbes.

•       Chemical protection is localized on the skin, in loose connective tissue, stomach, and vagina.

•       The skin produces sebum, which has a low pH due to the presence of unsaturated fatty acids and lactic acid.

•       Lysozyme is an enzyme component of sweat that also has antimicrobial properties.

•       Gastric juice renders the stomach nearly sterile because its low pH (1.5-3.0) kills many bacteria and destroys most of their toxins; vaginal secretions also are slightly acidic.

Skin & Mucous Membranes

•      Mechanical protection

–   skin (epidermis) closely packed, keratinized cells

•   shedding helps remove microbes

–   mucous membrane secretes viscous mucous

•   cilia & mucus trap & move microbes toward throat

–   washing action of tears, urine and saliva

•      Chemical protection

–   sebum inhibits growth bacteria & fungus

–   perspiration lysozymes breakdown bacterial cells

–   acidic pH of gastric juice and vaginal secretions destroys bacteria

Second Line of Defense: Internal Defenses

•      The second line of defense involves internal antimicrobial proteins, phagocytic and natural killer cells, inflammation, and fever.

Internal Defenses

•      Antimicrobial proteins discourage microbial growth

–   interferons

 

–   complement proteins

 

–   transferrins

 

Antimicrobial Proteins

•      Body cells infected with viruses produce proteins called interferons (IFNs).

–   Once produced and released from virus-infected cells, IFN diffuses to uninfected neighboring cells and binds to surface receptors, inducing uninfected cells to synthesize antiviral proteins that interfere with or inhibit viral replication.

–   INFs also enhance the activity of phagocytes and natural killer (NK) cells, inhibit cell growth, and suppress tumor formation; they may hold promise as clinical tools in AIDS and cancer treatment once they are more fully understood.

Antimicrobial Proteins

•      A group of about 20 proteins present in blood plasma and on cell membranes comprises the complement system

–   when activated, these proteins “complement” or enhance certain immune, allergic, and inflammatory reactions.

Natural Killer Cells & Phagocytes

•      NK cells kill a variety of microbes & tumor cells

–   found in blood, spleen, lymph nodes & red marrow

–   attack cells displaying abnormal MHC antigens

•      Phagocytes (neutrophils & macrophages)

–   ingest microbes or particulate matter

–   macrophages developed from monocytes

•   fixed macrophages stand guard in specific tissues

–  histiocytes in the skin, kupffer cells in the liver, alveolar macrophages in the lungs, microglia in the brain & macrophages in spleen, red marrow & lymph nodes

•   wandering macrophages in most tissue

Phagocytosis

•      Phagocytes are cells specialized to perform phagocytosis and include neutrophils and macrophages.

–   The four phases of phagocytosis include chemotaxis, adherence, ingestion, digestion and killing. (Figure 22.9).

–   After phagocytosis has been accomplished, a phagolysosome (Figure 22.9) is formed.

–   The lysosome in the phagolysosome, along with lethal oxidants produced by the phagocyte, quickly kills many types of microbes.

•      Some of the reasons why a microbe may evade phagocytosis include: capsule formation, toxin production, interference with lysozyme secretion, and the microbe’s ability to counter oxidants produced by the phagocytes.

Phagocytosis

•       Chemotaxis

–    attraction to chemicals from damaged tissues, complement proteins, or microbial products

•       Adherence

–    attachment to plasma membrane of phagocyte

•       Ingestion

–    engulf by pseudopods to form phagosome

•       Digestion & killing

–    merge with lysosome containing digestive enzymes & form lethal oxidants

–    exocytosis residual body

 

 

Inflammation

•      Damaged cell initiates

•      Signs of inflammation

–   redness

–   heat

–   swelling

–   pain

–   Loss of function may be a fifth symptom, depending on the site and extent of the injury.

•      Function is to trap microbes, toxins or foreign material & begin tissue repair

Stages of Inflammation

•       The three basic stages of inflammation are vasodilation and increased permeability of blood vessels, phagocyte migration, and tissue repair (Figure 22.10).

•       Vasodilation & increased permeability of vessels

–    caused by histamine from mast cells, kinins from precursors in the blood, prostaglandins from damaged cells, and leukotrienes from basophils & mast cells

–    occurs within minutes producing heat, redness & edema

–    pain can result from injury, pressure from edema or irritation by toxic chemicals from organisms

–    blood-clotting factors leak into tissues trapping microbes

•       Phagocyte emigration

–    within an hour, neutrophils and then monocytes arrive and leave blood stream (emigration)

•       Tissue repair

Abscesses and Ulcers

•      Pus is dead phagocytes, damaged tissue cells & fluid

•      Abscess is accumulation of pus in a confined space not open to the outside

–   pimples & boils

•      Ulcer is an open sore

•      People with poor circulation (diabetics with advanced atherosclerosis)

–   stasis ulcers in tissues of legs due to poor oxygen & nutrient supply to tissues

Fever

•      Abnormally high body temperature that occurs because the hypothalamic thermostat is reset

•      Occurs during infection & inflammation

–   bacterial toxins trigger release of fever-causing cytokines such as interleukin-1

•      Benefits

–   intensifies effects of interferons, inhibits bacterial growth, speeds up tissue repair

Review

•      Table 22.1 summarizes the components of nonspecific resistance.

SPECIFIC RESISTANCE: IMMUNITY

•      Immunity is the ability of the body to defend itself against specific invading agents.

–   bacteria, toxins, viruses, cat dander, etc.

•      Differs from nonspecific defense mechanisms

–   specificity----recognize self & non-self

–   memory----2nd encounter produces even more vigorous response

•      Antigens are substances recognized as foreign by the immune responses.

•      The branch of science that deals with the responses of the body when challenged by antigens is called immunology.

Maturation of T Cells and B Cells

•      Both T cells and B cells derive from stem cells in bone marrow (Figure 22.11).

•      B cells complete their development in bone marrow (Figure 22.11).

•      T cells develop from pre-T cells that migrate to the thymus.

•      Before T cells leave the thymus or B cells leave bone marrow, they acquire several distinctive surface proteins; some function as antigen receptors, molecules capable of recognizing specific antigens (Figure 22.12).

Maturation of T and B Cells

•       T cell mature in thymus

–    cell-mediated response

•    killer cells attack antigens

•    helper cells costimulate T and B cells

–    effective against fungi, viruses, parasites, cancer, and tissue transplants

•       B cells in bone marrow

–    antibody-mediated response

•    plasma cells form antibodies

–    effective against bacteria

Types of Immune Response

•      Cell-mediated immunity (CMI) refers to destruction of antigens by T cells.

–   particularly effective against intracellular pathogens, such as fungi, parasites, and viruses; some cancer cells; and foreign tissue transplants.

–   CMI always involves cells attacking cells.

•      Antibody-mediated (humoral) immunity (AMI) refers to destruction of antigens by antibodies.

–   works mainly against antigens dissolved in body fluids and extracellular pathogens, primarily bacteria, that multiply in body fluids but rarely enter body cells.

•      Often a pathogen provokes both types of immune response.

APCs and MHC-II

Antigens

•       Molecules or bits of foreign material

–