Lymphatic and Immune Systems

A number of mechanisms operate within the bodies of birds and mammals that either prevent infection or fight infection by foreign particles and cells. Nonspecific immunity refers to mechanisms that are generally effective against a variety of infections. 

Specific immunity refers to  mechanisms that are specific for one type of  infection. Specific immunity is generally acquired after exposure to the infecting particles or cells.

Barriers to Entry

The skin is the main barrier preventing the entry of foreign organisms and particles.

Skin oils weaken or kill bacteria.

Cilia lining the respiratory tract sweep mucus and trapped particles to the throat where they are swallowed.

The low pH of the stomach kills microorganisms.

Tears wash the eyes.

Saliva helps clean teeth, preventing dental caries.

Urine flow prevents colonization of the urinary tract.

Vaginal secretions move microorganisms out of the reproductive tract.

The normal bacterial colonists of the skin, gut, and vagina prevent harmful microorganisms from colonizing the areas.

Inflammatory Reaction

The inflammatory reaction is a local response to injury.

Damaged tissue releases bradykinin, which causes pain and stimulates mast cells to release histamine.

Bradykinin and histamine produce vasodilation, ( increased blood vessel diameter) to increase blood flow to the area.

Bradykinin and histamine also cause increased permeability (allows fluid to leak out). This brings more defensive cells and chemicals to the area.

Neutrophils and monocytes are amoeboid white blood cells (leukocytes) that squeeze out of the capillaries and enter the damaged tissue.

Neutrophils phagocytize foreign material.

Monocytes are transformed into macrophages, which can  phagocytize a large number of viruses and bacteria.

Macrophages release white blood cell growth factor. This hormone stimulates the bone marrow to produce leukocytes (white blood cells).

Basophils that have left the blood vessels to reside in the tissues become mast cells.

Pus is a large # of dead leukocytes that fought infection.

Antibody-Mediated Immunity

Antigens and Antibodies

Antibodies are proteins that protect against foreign invaders, either foreign molecules, viruses, or cells. They are capable of recognizing specific particles due to their shape. Their ability to recognize foreign shapes makes them useful in defending against foreign invaders.

Antigens are molecules that antibodies are capable of recognizing. They are usually a protein or carbohydrate chain. The body can recognize bacteria and viruses as being foreign because they have antigens on their surface which are different than the bodies "self" antigens.

Antibodies are Y-shaped molecules with a constant region and two binding sites that vary from one antibody to the next.

Antibodies fit together with and bind with antigens like a lock and key.

The body does not produce antibodies that bind to its own (self) antigens. Therefore all particles that are bound to antibodies are foreign.

Cells, particles, or molecules that are marked with antibodies:

1. may be phagocytized (engulfed) by neutrophils or macrophages.

2. may agglutinate (clump together) because each antibody is capable of binding to two antigens. If the antigens are chemicals that are dissolved in the body fluids, the clumps of antibody-bound particles will precipitate. Antigens attached to cells will cause the cells to clump together. The clumps are then phagocytized.

3. may activate the complement system (discussed below). The complement system is a system of blood proteins that enhances the elimination of foreign cells or particles.

During our life, we will encounter over 1 million different antigens, so we need at least 1 million different antibodies, one for each kind of antigen.

There are 5 different classes of antibodies (IgA, IgD, IgG, IgH, IgM). One class contains pentamers, another contains dimers.

Antibodies are produced by B lymphocytes.

B Lymphocytes

B lymphocytes (B cells) mature in the bone marrow.

B lymphocytes have receptors (antibodies) attached to their surface which function to detect antigens.

There is only one specific kind of receptor on the surface of a lymphocyte. A single B lymphocyte can therefore detect only one kind of antigen. Our bodies have millions of different kinds of B lymphocytes.

Clonal selection

B cells that encounter the correct antigen with their antibody receptors become activated and begin to divide many times producing plasma cells, which, in turn produce antibodies.

B lymphocyte + antigen ®  more B-cells (called memory B-cells) and plasma cells ®  antibodies

B lymphocyte + incorrect antigen ®  no reaction

Plasma cells produce antibodies that are identical to the receptors on the surface of the B cell that was initially stimulated by antigen.  The antibodies therefore can adhere to the type of invader that initially activated the B cell.

Memory B cells are B cells that are produced as a result of stimulation by the antigen. Because there are now many of these to fight off future infection, they are called memory B cells.

Large numbers of B-cells are found in the lymph nodes and in the spleen.

The Complement System

The complement system consists of a number of different proteins that help defend the body when they are activated.

Each activated complement protein activates many others so that a large number of active proteins are produced.

The following may initially activate the complement system:

Antigen-Antibody interaction

Substances on the capsules or cell walls of microorganisms; substances produced by microorganisms 

Functions of the Complement System:

  1. The activated proteins stimulate mast cells causing inflammation and attract phagocytes (neutrophils, macrophages) to the area.
  2. Complement proteins bind to microorganisms and other particles enhancing their recognition by phagocytes.
  3. Other complement proteins produce holes in bacterial cell walls allowing salts and fluids to enter, rupturing the cell.

It is called complement because it enhances (complements) other immune responses such as the inflammatory reaction and the antibody-mediated response (the proteins bind to microbes that already have antibodies attached, improving recognition by phagocytes).

Some Important Molecules

Interferons

Interferons are proteins produced by virus-infected animal cells that stimulate  other cells to produce substances that interfere with viral replication.

Lysozyme

Lysozyme is an enzyme capable of breaking down the cell walls of gram-positive bacteria. It is found in perspiration, tears, saliva, nasal secretions, and tissue fluids.

Cell-Mediated Immunity

T lymphocytes (T-cells) are lymphocytes that mature in the thymus.

This type of immunity is used to fight cells such as cancer cells, virus-infected cells, single-celled fungi, parasites, and cells of an organ transplant.

T Lymphocytes

Activating T Cells

T cells cannot recognize antigens unless an antigen-presenting cell (usually a macrophage) presents the antigens to them.

The macrophage first engulfs the antigen (or bacterium, virus, etc.) and brings fragments of the foreign antigens to its surface linked to its own (self) antigens.

The "self" antigen is referred to as an "MHC" protein. (MHC = major histocompatibility complex)

If receptors on a virgin T cell match both the self and foreign antigens, the T cell becomes activated and undergoes clonal expansion (cell reproduction) producing the 4 kinds of T cells described below.

Cytotoxic T Cells

Cytotoxic T cells (also called killer T cells) attack antigen-MHC bearing cells that also have foreign antigens. Because MHC is a "self" marker, Cytotoxic T cells attack the body’s own cells that are infected viruses and microorganisms and also cancer cells. Cancer cells are attacked because they have mutated (therefore foreign) antigens.

The cytotoxic T cell releases proteins that penetrate the target cell membrane. Salts and fluid enter through the holes and the cell ruptures.

Helper T Cells

When exposed to an antigen-MHC complex, Helper T cells secrete lymphokines, which enhance the response of other immune cells. For example, they stimulate T cells to clone, macrophages to phagocytize, and B cells to become plasma cells and produce antibodies.

HIV (the virus that causes AIDS) attacks helper T cells as well as others in the immune system. HIV therefore prevents the immune system from becoming activated.

Suppressor T Cells

Suppressor T cells regulate the immune response by suppressing the activity and development of B cells and helper T cells. They do this by secreting inhibitory chemicals in response to declining antigen levels.

Memory T Cells

Memory T cells are T cells that persist after infection. They will secrete lymphokines if the same antigen reenters the body.

Active Immunity

Active immunity is produced in individuals by administering foreign antigens. These antigens may come from weakened or dead microorganisms. This process is called vaccination.

Genetically engineered bacteria are currently being used to produce some antigens. Examples: malaria, hepatitis B.

After exposure to antigens in a vaccine, the level of antibodies in the blood begins to increase after several days, levels off, then declines. After a secondary exposure (called a booster), the level increases rapidly.

Memory B cells and memory T cells allow the individual to be actively immune. If they are exposed to the disease, a rapid immune response will occur because they already have large numbers of the correct B and T cells.

Passive Immunity

Passive immunity occurs when an individual receives antibodies instead of making their own. Passive immunity is short-lived because the person’s B and T cells have not been stimulated to produce antibodies. The immunity lasts only as long as the antibodies they received remain in their bloodstream.

Examples of Passive Immunity

Newborn babies have antibodies they received from their mother.

Breast-fed babies receive antibodies from their mother’s milk.

Allergies

Allergies are due to an overactive immune system.

Basophils that have left the blood vessels to reside in the tissues are called mast cells. They contain antibody receptors to allergens (antigens) and when stimulated, they secrete histamine.

Histamine causes mucus secretion, airway constriction, and inflammation due to blood vessels leaking. Leaky blood vessels cause the tissues to swell.

Allergy shots stimulate the body to produce high levels of antibodies. The antibodies react with the allergens before they have a chance to interact with the mast cells.

Components of the Immune System

Leukocytes

Leukocytes are white blood cells. The following kinds of leukocytes were discussed in this chapter:

basophils (become mast cells)

neutrophils

monocytes (become macrophages)

macrophages

lymphocytes

B cells - mature in bone marrow

T cells - mature in thymus, small intestine, skin

Lymphatic System

Functions of the Lymphatic System

1.  take up excess tissue fluid and return it to the bloodstream

2.  absorb fats at the intestinal villi and transport to the circulatory system

3.  defend against disease

Lymphatic Vessels

Lymphatic vessels are similar to veins, including the presence of valves. They depend on the movement of skeletal muscles to move the fluid inside.

The fluid they contain is called lymph.

They empty into the circulatory system via the thoracic duct and the right lymphatic duct. The thoracic duct is much larger than the right lymphatic duct.

Lymph Nodes

Lymph nodes are small (1-25 mm), spherical or ovoid structures that are connected to lymphatic vessels. They contain open spaces (sinuses), each with many lymphocytes and macrophages.

As lymph passes through, macrophages purify it of infectious organisms and particles.

The structures listed below are groups of nodules that also function to purify lymph:

tonsils - back of mouth

adenoids - back of mouth above the soft palate

Peyer’s patches - intestinal wall

Spleen

The spleen stores blood.

It helps purify blood that passes through it by removing bacteria and worn-out or damaged red blood cells.

Thymus Gland

T lymphocytes mature in the thymus.

Bone Marrow

Macrophages and lymphocytes (B cells and T cells) are produced in the bone marrow. T cells mature in the thymus gland, small intestine, and in the skin.

Autoimmune Diseases

Autoimmune diseases result when the body is attacked by its immune system.

They often appear in individuals that have recovered from other infections. Somehow the body seems to have learned to recognize itself (its own antigens).

Examples

Myasthenia gravis - neuromuscular junctions are weakened

Multiple sclerosis - the myelin sheath of nerve fibers is attacked

Lupus erythematosus

Rheumatoid arthritis - the membranes that surround the joints are attacked

Summary of Leukocytes

Nonspecific response

Basophils - leave the circulatory system to become mast cells; secrete histamine

Neutrophils - participate in inflammatory response; phagocytize

Monocytes - become macrophages which phagocytize; produce white blood cell growth factor

Specific Immune Response

B-lymphocytes

give rise to plasma cells that produce antibodies

give rise to more B lymphocytes (also called memory B lymphocytes)

T-lymphocytes

Cytotoxic T cells - attack cells that bear antigens

Helper T cells - secrete lymphokines which enhances the response of other immune cells

Suppresser T cells - suppress helper T cells and B cells

Memory T cells - remain after the infection and produce the 4 kinds of T cells if activated.

 
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