The lymphatic system.

•           Consists of lymphatic vessels and organs.

•           Four main functions:

•           Lymphatic capillaries absorb excess interstitial fluid and return it to the bloodstream.

•           Lymphatic capillaries called lacteals in the small intestine absorb dietary fats and transport them to the bloodstream.

•           Production, maintenance, and distribution of lymphocytes in the body.

•           Helps in defense against pathogens.

Lymphatic vessels.

•           Carry a fluid called lymph.

•           Begin as blind-ended lymphatic capillaries in the tissues.

•           The anatomy of the larger lymphatic vessels is similar to that of cardiovascular veins, including the presence of valves.

•           Valves prevent lymph from flowing backward.

•           The movement of lymph is largely dependent on skeletal muscle contraction.

Lymphatic organs.

•           Two types: primary and secondary.

•           Primary lymphatic organs: red bone marrow, thymus.

•           Secondary lymphatic organs: lymph nodes, spleen, tonsils.

The Primary Lymphatic Organs

Red bone marrow.

•           The site of blood cell production.

•           In children, most bones have red marrow; only a few do in adults.

•           B cells (B lymphocytes) mature here.

Thymus.

•           Bilobed; in the thoracic cavity superior to the heart.

•           It is largest in children and shrinks as we age.

•           Maturation of T cells

The Secondary Lymphatic Organs

Spleen.

•           Filters blood.

•           In the upper left region of the abdominal cavity.

•           Has a thin outer capsule, so can rupture from trauma.

Lymph nodes.

•           Found along the lymphatic vessels.

•           Filter lymph.

•           Connective tissue forms a capsule around it and divides it into compartments.

•           Filled with macrophages that engulf pathogens and debris.

•           Also houses lymphocytes, which fight infections and cancer cells.

•           Named for their location: common in the neck, armpit, and groin.

Lymphatic nodules.

•           Concentrations of lymphoid tissue that don’t have a capsule.

Tonsils are located in the pharynx.

•           Have the same function as lymph nodes; fight infections that come in through the nose and mouth.

Peyer patches.

•           Found in the intestinal walls and the appendix.

•           Fight infections that come in via the digestive tract.

Immunity—killing or removing foreign substances, pathogens, and cancer cells from the body.

There are two branches of our immune system: innate and adaptive.

•           Innate—fully functional without previous exposure to a pathogen.

•           Adaptive—is initiated when exposed to a pathogen.

Innate (nonspecific) immune defenses include:

•           Physical and chemical barriers.

•           The inflammatory response.

•           Protective proteins.

Innate defenses have no recognition of a pathogen, and no memory**.**

Physical and Chemical Barriers

First line of defense against pathogens.

•           Barriers to entry: physical and chemical.

•           Physical: skin and mucous membranes.

•           The skin has lots of keratin, so is tough; also, exfoliation carries microbes away from the body.

•           Mucous membranes have ciliated cells; the cilia sweep away mucus with entrapped pathogens.

•           Chemical:

•           Acidic secretions of sebaceous glands weaken, kill bacteria on the skin.

•           Sweat, saliva, and tears have lysozyme—an antibacterial enzyme.

•           Chemical barriers, continued.

•           The acidic pH of the stomach inhibits or kills bacteria.

•           Normal flora (microbes that usually reside in the mouth and intestine) prevent potential pathogens from taking up residence.

•           Chronic use of antibiotics can make one susceptible to infection by killing off the normal flora.

Inflammatory response.

•           Second line of defense against pathogens.

•           Employs mainly neutrophils and macrophages to engulf pathogens.

•           Four hallmark symptoms: redness, heat, swelling, and pain.

•           Chemicals such as histamine, released by damaged tissue cells and mast cells, cause the capillaries to dilate and become more permeable.

•           Four hallmark symptoms: redness, heat, swelling, and pain, continued.

•           Excess blood flow causes the skin to redden and become warm.

•           Increased temperature inhibits growth of pathogens.

•           Increased blood flow brings white blood cells to the area.

•           Increased permeability of capillaries allows fluids and proteins to escape into the tissues.

•           Blood clot prevents blood loss.

•           Excess fluid in the area (swelling) presses on nerve endings, causing pain.

Inflammatory response

•           WBCs move out of the bloodstream into the surrounding tissue.

•           Neutrophils are first; they phagocytize debris, dead cells, and bacteria.

•           Can usually localize any infection and keep it from spreading.

•           If die off in great quantities, they become a yellow-white substance called pus.

•           If neutrophils become overwhelmed, they secrete cytokines—chemicals that attract more WBCs.

•           Monocytes that come to the area become macrophages—powerful phagocytes.

Protective proteins.

•           Complement system—several plasma proteins designated by the letter C and a number.

•           Are involved in and amplify the inflammatory response.

•           Some bind to mast cells, triggering histamine release.

•           Others attract phagocytes to the scene.

•           Some form a membrane attack complex that produces holes in the surface of bacteria; fluids enter the bacterial cells and they burst.

•           Interferons.

•           Chemicals produced by cells that are infected with viruses as a warning to other cells.

•           Bind to receptors of noninfected cells, causing them to produce substances that interfere with viral replication.

Adaptive defenses

•           Come into play when innate (nonspecific) defenses have failed to prevent an infection.

•           Provide some protection against cancer.

•           Respond to antigens (immune system recognizes as foreign).

•           Fragments of bacteria, viruses, molds, and parasitic worms can all be antigenic.

•           Abnormal plasma membrane proteins produced by cancer cells may also be antigens.

•           The immune system is able to distinguish ‘self’ (our cells) from ‘nonself’ (pathogens).

How Adaptive Defenses Work

Depend on the action of B cells (B lymphocytes) or T cells (T lymphocytes).

•           B cells and T cells have specific antigen receptors (plasma membrane proteins that bind to particular antigens).

•           Each lymphocyte has only one type of receptor.

•           The receptor and antigen fit together like a lock and key.

There are two pathways of adaptive immunity: cell-mediated and antibody-mediated.

•           In cell-mediated immunity, T cells kill cells that are presenting a specific “foreign” antigen.

•           In antibody-mediated immunity (also called humoral immunity), B cells produce antibodies that bind to free antigens in body fluids.

T Cells and Cell-Mediated Immunity

T-cell receptor (TCR)—unique receptor on the surface of each T cell.

•           B cells also have unique receptors, but unlike B cells, T cells are unable to recognize an antigen without help; it must be displayed to them by an antigen-presenting cell (APC) such as a macrophage.

•           After phagocytizing a pathogen, APCs travel to the

T cells in a lymph node or the spleen.

•           APCs break the ingested pathogen apart in a lysosome.

•           A piece of the pathogen is then displayed in the groove of a major histocompatibility complex (MHC) protein on the cell’s surface. The two classes of MHC proteins are called MHC I and MHC II.

•           Human MHC II proteins are called human leukocyte antigens (HLAs).

•           Found on all body cells.

•           There are three general groups of HLAs (HLA-A, HLA-B, and HLA-DR), each with a number of protein variations.

•           Each person has a unique combination of HLAs.

•           HLAs of identical twins, however, are identical.

Clonal Expansion.

•           Many copies of the activated T cell are produced.

•           Occurs when a macrophage presents an antigen to a T cell that has the specific TCR that will bind this particular antigen.

•           This activates the T cell, causing it to undergo clonal expansion.

•           Some T cells become cytotoxic T cells, and some will become helper T cells.

Cytotoxic T cell.

•           Has storage vacuoles that contain perforins

•           After binding to a virus-infected cell or tumor cell, it releases perforins, which punch holes in the plasma membrane, forming a pore.

•           Responsible for cell-mediated immunity.

Helper T cells.

•           Secrete cytokines that enhance the response of all types of immune cells.

•           B cells cannot be activated without T-cell help.

•           The human immunodeficiency virus (HIV), which causes AIDS, infects helper T cells, thus inactivating the immune response.

B Cells and Antibody-Mediated Immunity

B-cell receptors (BCR)—protein receptors on B cells.

•           An antigen binds to the BCR on only one type of B cell.

•           That one B cell then produces copies of itself—this group of identical B cells is called a clone.

B Cells Become Plasma Cells and Memory B Cells

During clonal expansion, cytokines secreted by helper T (TH) cells stimulate B cells to clone

•           Most of the cloned B cells become plasma cells, which produce large numbers of antibodies that bind to the antigen that initiated this whole process.

•           Some B cells become memory cells, which become active in future encounters of this same antigen

•           Confer immunity to that antigen.

Structure of an antibody.

•           Y-shaped protein with two arms.

•           Each arm has a “heavy” (long) polypeptide chain and a “light” (short) polypeptide chain.

•           These chains have constant regions, located at the trunk of the Y, where the sequence of amino acids is fixed.

•           Antibodies are classified by the structure of its constant region.

•           The variable regions form an antigen-binding site; their shape is specific to a particular antigen.

•           The antigen combines with the antibody at the antigen-binding site in a lock-and-key manner.

•           Antibodies may consist of single Y-shaped molecules, called monomers, or may be paired together in a dimer.

•           Some are pentamers—clusters of five Y-shaped molecules linked together.

Classes of Antibodies

There are five classes of circulating antibodies: IgG, IgM, IgA, IgD, IgE.

•           IgG—the major type in blood; smaller numbers are found in lymph and interstitial fluid.

•           Bind to pathogens, toxins.

•           Crosses the placenta from mother to fetus; confers temporary immune protection.

•           IgM—pentamers; the first antibodies produced by a newborn.

•           The first to appear in blood after an infection begins and the first to disappear when the infection is over.

•           Activate the complement system.

•           IgA—monomers or dimers containing two Y-shaped structures.

•           Main type of antibody found in body secretions: saliva, tears, mucus, and breast milk.

•           Bind to pathogens so they can’t reach the bloodstream.

•           IgD—antigen receptors on immature B cells.

•           IgE—prevent parasitic worm infections.

•           Can also cause allergic responses.

•           Can be brought about naturally through an infection or artificially through medical intervention.

•           There are 2 types of acquired immunity: active and passive.

Active immunity.

•           The individual’s body makes antibodies against a particular antigen.

•           Can happen through natural infection or through immunization involving vaccines.

•           Contain antigens from the pathogen or the pathogens themselves (treated so they can no longer cause disease).

•           The first exposure to an antigen produces a primary response; second exposure a secondary response.

•           Depends on memory lymphocytes and sometimes booster shots.

Passive immunity.

•           An individual is given antibodies to combat a disease; since not produced by the individual’s plasma cells, passive immunity is temporary.

•           That is, newborn infants are passively immune to some diseases because IgG antibodies have crossed the placenta from the mother’s blood.

•           Breast-feeding prolongs this natural passive immunity because IgG and IgA antibodies are present in mother’s milk.

•           That is, can also receive antibodies by injection.

Hypersensitivity reactions—when the immune system overreacts and causes harm to the body.

•           That is, allergies, receiving an incompatible blood type, tissue rejection, or autoimmune disease.

Allergies

•           Hypersensitivity to allergens such as pollen, food, or animal hair, which would normally be harmless.

•           Immediate allergic response—occurs within seconds of contact with the antigen.

•           Caused by IgE antibodies attached to receptors on mast cells and basophils, which release histamine when they bind allergens.

•           When pollen is an allergen, histamine stimulates the mucous membranes of the nose and eyes to release fluid (runny nose and watery eyes—hay fever).

•           With asthma, airways constrict, resulting in wheezing.

•           Food allergies—nausea, vomiting, diarrhea.

•           **Anaphylactic shock—**an immediate allergic response.

•           Occurs when the allergen enters the bloodstream.

•           Characterized by a sudden and life-threatening drop in blood pressure due to increased permeability of the capillaries by histamine.

•           Taking epinephrine can counteract this reaction.

•           **Delayed allergic responses—**initiated by memory T cells at the location of contact with the allergen.

•           That is, poison ivy.

Tissue Rejection

Rejection of transplanted tissue results because the recipient’s immune system recognizes that the transplanted tissue is not “self”.

•           Cytotoxic T cells attack the transplanted tissue.

•           Can be controlled with immunosuppressive drugs and by transplanting organs that have the same MHC proteins in the donor and recipient.

•           Some immunosuppressive drugs act by inhibiting the production of cytokines.

•           Xenotransplantation—transplanting organs from an animal.

•           Some organs can be grown in a lab.

Severe Combined Immunodeficiency Disease

Severe combined immunodeficiency disease.

•           Both antibody- and cell-mediated immunity are inadequate or lacking.

•           A minor infection can be fatal.

•           Treated with bone marrow transplant or gene therapy.

Acquired Immune Deficiency

Acquired immune deficiencies can be caused by infections, chemical exposure, or radiation.

•           Acquired immunodeficiency syndrome (AIDS) results from infection with the human immunodeficiency virus (HIV).

•           AIDS patients are more susceptible to infections and have a higher risk of cancer.

Autoimmune disease.

•           Cytotoxic T cells or antibodies attack the body’s own cells as if they were foreign.

•           Involves both genetic and environmental factors.

•           Sometimes follows an infection.

•           That is, rheumatic fever—antibodies induced by a streptococcal bacterial infection of the throat also react with heart muscle.

•           Damages the heart muscle and valves.

•           That is, rheumatoid arthritis—antibodies against joints.

Systemic lupus erythematosus (SLE).

•           Usually just called ‘lupus’.

•           Various symptoms: facial rash, fever, joint pain.

•           Damage to the central nervous system, heart, and kidneys can be fatal.

•           Produce high levels of anti-DNA antibodies.

•           All human cells (except red blood cells) contain DNA, so the symptoms of lupus can be exhibited throughout the body.

Multiple Sclerosis.

•           T cells attack the myelin sheath covering nerve fibers, causing central nervous system dysfunction, double vision, and muscular weakness.

•           MS may not be an autoimmune disease, because a specific antigen has not been identified.

•           Treatments for all of these diseases are drugs designed to decrease the immune response.