The lymphatic system consists of 2 parts: a meandering network of lymphatic vessels and various lymphoid organs scattered throughout the body. Lymphatic vessels transport fluids that have escaped the blood system back to the blood, and the lymphatic organs house phagocytic cells and lymphocytes which function in body defense and resistance.

Lymphatic vessels form a one-way network from capillaries to collecting vessels (which have valves) to trunks to ducts in which fluid flows toward the heart. The right lymphatic duct and the thoracic duct empty lymph fluid into the blood vascular system in the neck.

At intervals along the lymphatic vessels, lymph flows through the lymph nodes. Each lymph node has a fibrous capsule, a cortex (containing lymphocytes for the immune response) and a medulla (containing mostly macrophages which engulf bacteria, viruses, and foreign material and may initiate an immune response).

Spleen – site for lymphocyte proliferation, destroys aged red blood cells, stores and releases the breakdown products of hemoglobin, site of rbc production in the fetus, stores and releases blood in times of demand.

Thymus – During youth it functions in T cell development.

Tonsils and Peyer’s Patches – Defend against pathogens attacking via the respiratory and digestive tracts.

Maintaining homeostatis requires ways to continually defend against the activities of disease-producing organisms, or their toxins. The ability to ward off disease through our defenses is called resistance.

Nonspecific resistance comprises defenses that provide a general response against invasion by a wide range of pathogens. Specific resistance, or immunity, involves the production of a defense to a specific pathogen by producing specific antibodies or activation of specific T cells.

Unbroken skin and mucous membranes are the first line of defense by providing a mechanical barrier to pathogens. Periodic shedding of epidermal cells helps remove microbes at the skin surface. The mucous on mucous membranes is viscous and traps microbes. The mucous membrane of the respiratory tract has cilia which propels dust and microbes toward the throat.

Tears keep microbes from settling on the eye surface. Saliva dilutes microbes and washes them from surface of teeth and mouth. Urine cleans the urethra. Defecation and vomiting may also be considered mechanical processes which aid in the removal of microbes.

Chemicals also contribute to the resistance of skin and mucous membranes. Sebum forms a protective film over skin surface and contains unsaturated fatty acids which inhibit the growth of some bacteria and fungi. The acidity of the skin also discourages microbe growth.

Lysozyme destroys the cell walls of some bacteria. It is found in perspiration, tears, saliva, nasal secretions, and tissue fluids. Gastric juice also destroys many bacteria and toxins.

Interferon is produces and released by virus-infected cells. It diffuses to uninfected cells, binds to surface receptors, and induces cells to synthesize proteins that interfere with viral replication. Thus it is an important defense against many viruses. There are 2 varieties: Type I (includes alpha and beta interferon) and Type II (gamma interferon – produced by lymphocytes and macrophages). While all interferons inhibit viral replication each type has other special abilities. Type I inhibits cell growth and suppresses tumor formation. Type II (gamma) interferon enhances cell-killing activity of phagocytes and natural killer cells.

Complement is a group of plasma proteins that, once activated by a cascade mechanism, enhance immune, allergic, and inflammatory reactions. The total system is comprised of 11 proteins. Two separate pathways initiate the complement cascade, joining into a common pathway at the level of C3. The classical pathway is triggered by immune complexes (a conglomeration of specific antibodies and pathogens). The alternative pathway is triggered by certain polysaccharides in the cell walls of some yeasts and bacteria. Once the complement cascade is initiated it provides defense by three mechanisms.

Natural Killer cells (NK cells) are lymphocytes that have the ability to kill a wide variety of infectious microbes and tumor cells with no prior activation required. They are present in the spleen, lymph nodes, bone marrow, and blood. They kill cells by binding to them and releasing perforin, which causes cytolysis.

Phagocytosis is accomplished by neutrophils and macrophages. When an infection occurs both cell types migrate to the infected area. Monocytes from the blood enlarge and develop into highly phagocytic macrophages, called wandering macrophages. Other macrophages are fixed in place and located in the skin, liver, lungs, brain, spleen, lymph nodes, and bone marrow. All the macrophages spread throughout the body is called the reticuloendothelial system. The process of phagocytosis has three phases: chemotaxis (chemical attraction of phagocytes to an area), adherence (attachment of cell membrane of phagocyte to the surface of the microbe or foreign material), and ingestion. Phagocyte lysosomes contain lethal oxidants such as superoxides which destroy the ingested microbe.

When cells are damaged, the response to tissue damage is called inflammation. The signs are redness, pain, heat, and swelling. Inflammation attempts to prevent microbial spread to other areas, mobilizes the body to fight the potential infection, and prepares the site for tissue repair.

Three stages are vasodilation, phagocyte migration, and repair. Vasodilation allows more blood to flow through the damaged area and permits defensive materials in the blood to enter the injured area. It also helps remove toxic products released by invading organisms and dead cells. Phagocyte migration occurs in as little as two minutes in response to chemotaxic substances. Neutrophils arrive first and monocytes follow. Neutrophils predominate in the early stages, but tend to die off rapidly. Macrophages are more phagocytic and engulf damaged tissue, worn-out neutrophils, and invading microbes. Fever intensifies the effect of interferons, inhibits growth of some microbes and speeds by body reactions that aid in repair.

Specificity – ability to distinguish self from non-self and also to generate a response to a specific pathogen

Memory – previously encountered pathogens are recognized and a second encounter prompts an even more vigorous response.

Any chemical substance that when introduced into the body is recognized as foreign is known as an antigen. Antigens have two important characteristics: immunogenicity (ability to provoke an immune response) and reactivity (ability to react specifically with the antibodies or cells produced by the immune response). Antigens are usually proteins, but some large polysaccharides can be antigens. A microbe will usually have several substances associated with it that is antigenic. Specific portions of antigen molecules trigger immune responses. These regions are called antigenic determinants or epitopes. One antigenic molecule may have several different antigenic determinants. Our immune system has the ability to recognize and bind to at least a billion different antigenic determinants.

The cells that carry out the immune response are the lymphocytes (B and T cells) and the antigen presenting cells (macrophages). Lymphocytes develop from stem cells in the bone marrow. B cells complete their development in the marrow. T cells are released in an immature state and migrate to the thymus where they develop immunocompetence (the ability to carry out an immune response upon activation). B and T cells have distinctive cell surface proteins that identify them. B cells have antibodies on their surface that function as antigen receptors. T cells also have antigen receptors. In addition T cells are subdivided into 2 groups: T helper cells (initiate immune responses, have CD4 molecules on cell surface) and cytotoxic T cells (effector cell of immune response, have CD8 molecules on cell surface).

Unique self-identifying proteins exist on cells of our body. These are known as the major histocompatibility complex (MHC) or human leukocyte associated antigens (HLA). There are two categories: Class I molecules are found on all body cells except rbc’s and function in self/non-self recognition; Class II molecules appear only on the surface of immunocompetent cells (T, B APC’s) and function to regulate the immune response.

Cell-mediated response – CD8 cells proliferate and these cytotoxic T cells directly attack the invading antigen. It is primarily responsible for defense against intracellular pathogens (viruses while inside of host cells), fungi, parasites, and cancer cells. Cytotoxic T cells also attack foreign tissue transplants.

Humoral response – mediated by antibodies produced by plasma cells which develop from B cells. It is primarily responsible for defense against bacteria and other soluble antigens.

Usually both parts of the immune response are stimulated although one or the other may be primarily responsible for resolution of infection.

Macrophages activate T helper cells.

T helper cells activate the humoral and cell-mediated immune responses.

When bacteria (for example) invade the body, the macrophage will nonspecifically phagocytize some of the bacteria. Inside the macrophage, the bacteria will be broken down by lysosomal enzymes. A small piece of the bacteria (an antigenic determinant) will be placed on the macrophage cell surface complexed with class II MHC proteins. In this form the macrophage "presents" the antigen to the helper T cell and helper T cell activation takes place. Two signals cause this to happen: the binding of antigen on the macrophage surface by the T helper cell and the secretion of a substance called interleukin 1 from the macrophage. As a result of these two things, the T helper cell is stimulated: it divides many times, and it becomes ready to "help" the B cells.

For the B cell to become activated, it needs two signals: to bind the antigen simultaneously with T helper cells (which "cross-links" the antigen) and interleukin 2 (secreted by T helper cells). Only the B cell that is specific for the invading antigen will be stimulated to divide. The antibody that will eventually be produced by the humoral immune response is the antigen receptor on the B cell.

The B cell becomes activated, which means that it divides many times so there will be many B cells that will become mature. After a few rounds of cell division some of the B cells become plasma cells. Plasma cells are antibody factories. They have lost their antigen receptors because they no longer need to communicate with other cells. Their job is to produce and secrete large amounts of antibody which will circulate in the blood and tissue fluid. The B cells which do not become plasma cells become memory cells. They "deactivate" and remain on alert for the same antigen to invade later. If the same antigen ever comes back these memory cells quickly activate, divide, and become plasma cells. This is the secondary response and the antibody is produced much faster than the initial primary response.

Once the antibody is secreted it can bind to the invading antigen. This can have several consequences. The resulting antigen-antibody complexes may trigger complement. Neutralization is the clumping of antigen together preventing the pathogen from attacking cells. The main consequence is opsonization: the marking of the antigen for phagocytosis and subsequent destruction by macrophages.

14. Describe antibody structure and function.
Antibodies are manufactured and released by plasma cells (which develop from B cells). They can bind specifically to the antigenic determinant that triggered its production. Another name for antibody is immunoglobulin. The monomeric form of an antibody is slightly Y shaped. One end is the variable region which is where antigen binds. The other end is the constant region which identifies the class of the antibody.

The class of the antibody identifies its special abilities and functions:

IgM - appears first in the primary response; pentamer; can trigger complement;

can clump the antigens together (agglutination)

IgG - most abundant; enhances phagocytosis; can trigger complement; can cross

the placenta

IgA - occurs as a dimer; found in body secretions (along mucous membranes of

respiratory and digestive tracts and in breast milk)

IgD - part of the antigen receptor on B cells

IgE - located on the surface of mast cells and basophils; binding to antigen causes

mast cell/basophil degranulation (an allergy attack)

It occurs in the same pattern as humoral immunity. Macrophages present antigen to T helper cells which proliferate and activate cytotoxic T cells by secreting interleukin 2.

Cytotoxic T cells (CD 8) recognize foreign antigens in association with class I MHC proteins on the surface of body cells infected with viruses, cancers, and any other non-self cells (transplants, fungi). The cytotoxic T cells are each specific for one antigenic determinant. After recognizing the antigenic determinant that a cytotoxic T cell is specific for, the cytotoxic T cell binds to that cell and secretes a highly toxic substance that destroys the cell. Like the humoral response, some cytotoxic T cells will become memory cells that will recognize the same antigenic determinant and attack quickly if it ever returns.