Immunity Lecture AP Biology, Human Anatomy & Physiology B.Rife SOHI 2001

Immunity Lecture AP Biology, Human Anatomy & Physiology B.Rife SOHI 2001

The Lymphatic System

The lymphatic system is composed of lymph vessels, lymph nodes, and organs. The functions of this system include the absorption of excess fluid and its return to the blood stream, absorption of fat (in the villi of the small intestine) and the immune system function. Lymph forms as blood plasma filters out of the capillaries into the microscopic spaces between tissue cells. This liquid is called interstitial fluid. Much of the interstitial fluid goes back into the blood by the same route it came out (through the capillary membrane). The remainder of the interstitial fluid enters the lymphatic system.

Lymph vessels are closely associated with the circulatory system vessels. Larger lymph vessels are similar to veins. Lymph capillaries are scatted throughout the body. Contraction of skeletal muscle causes movement of the lymph fluid through valves.

Lymph organs include the bone marrow, lymph nodes, spleen, and thymus. Bone marrow contains tissue that produces lymphocytes. B-lymphocytes (B-cells) mature in the bone marrow. T-lymphocytes (T-cells) mature in the thymus gland. Other blood cells such as monocytes and leukocytes are produced in the bone marrow. Lymph nodes are areas of concentrated lymphocytes and macrophages along the lymphatic veins. The spleen is similar to the lymph node except that it is larger and filled with blood. The spleen serves as a reservoir for blood, and filters or purifies the blood and lymph fluid that flows through it. If the spleen is damaged or removed, the individual is more susceptible to infections. The thymus secretes a hormone, thymosin, that causes pre-T-cells to mature (in the thymus) into T-cells. Masses of lymphoid tissue called tonsils are located in a protective ring under the mucous membranes in the mouth and back of the throat. The tonsils serve as the first line of defense from the exterior and as such are subject to chronic infection.

The Immune System

Immunity is the body's capability to repel foreign substances and cells. The nonspecific responses are the first line of defense. Highly specific responses are the second line of defense and are tailored to an individual threat. The immune response includes both specific and nonspecific components. Nonspecific responses block the entry and spread of disease-causing agents. Antibody-mediated (humoral) and cell-mediated responses are two types of specific response. The immune system is associated with defense against disease-causing agents, problems in transplants and blood transfusions, and diseases resulting from over-reaction (autoimmune, allergies) and under-reaction (AIDS).

Inborn immunity is immunity to certain disease (of other species, i.e. canine distemper) is inherited.

Natural immunity is exposure to the causative agent is not deliberate.

Acquired active immunity is when a child develops measles and acquires an immunity to a subsequent infection.

Acquired passive immunity is when a fetus receives protection from the mother through the placenta, or an infant receives protection via the mother’s breast milk.

Artificial immunity is exposure to the causative agent is deliberate.

Artificial active immunity is caused by the injection of the causative agent such as a vaccination against polio.

Artificial passive immunity is caused by the injection of protective material (antibodies) that were developed by another individual’s immune system.

Nonspecific Immunity

Barriers to entry are the skin and mucous membranes. The skin is a passive barrier to infectious agents such as bacteria and viruses. The organisms living on the skin surface are unable to penetrate the layers of dead skin at the surface. Tears and saliva secrete enzymes that breakdown bacterial cell walls. Skin glands (eccrine) secrete chemicals (lysozyme) that retard the growth of bacteria. Mucus membranes lining the respiratory, digestive, urinary, and reproductive tracts secrete mucus that forms another barrier. Stomach acid kills most bacteria swallowed with food. Physical barriers are the first line of defense.

When microorganisms penetrate skin or epithelium lining respiratory, digestive, or urinary tracts, inflammation results. Damaged cells and mast cells, which resemble basophils, release chemical signals such as histamine that increase capillary blood flow into the affected area (causing the areas to become heated and reddened).

The heat makes the environment unfavorable for microbes, promotes healing, raises mobility of white blood cells, and increases the metabolic rate of nearby cells. Capillaries pass fluid into intestitial areas, causing the infected/injured area to swell (edema). Clotting factors trigger formation of many small blood clots. Finally, monocytes and neutrophils (types of white blood cells) clean up dead microbes, cells, and debris. Monocytes develop into macrophages and neutrophils develop into microphages. Both phagocytize bacteria and viruses. Other white blood cells, called natural killer cells, attack cancer cells and virus infected body cells. They have no specificity and no memory.

The inflammatory response is often strong enough to stop the spread of disease-causing agents such as viruses, bacteria, and fungi. The response begins with the release of chemical signals and ends with cleanup by monocytes. If this is not enough to stop the invaders, the complement system and immune response act.

Protective proteins that are produced in the liver include the complement system of proteins. The complement system proteins bind to a bacterium and open pores in its membrane through which fluids and salt move, swelling and bursting the cell. Other complement proteins coat the surfaces of microbes, making them easier for macrophages to engulf. The complement system directly kills microbes, supplements inflammatory response, and works with the immune response. It complements the actions of the immune system. Complement proteins are made in the liver and become active in a sequence (C1 activates C2, etc.).

Interferon is a protein produced by virus-infected cells. Interferon binds to receptors of surrounding noninfected cells, causing them to prepare for possible attack by producing substances that interfere with viral replication. Interferon is specific to the species; therefore, only human interferon can be used in humans.

Specific Immunity

The immune system also generates specific responses to specific invaders. The immune system is more effective than the nonspecific methods, and has a memory component that improves response time when an invader of the same type (or species) is again encountered.

Specific Immunity continued

The humoral (antibody-mediated) immunity system identifies and helps destroy invaders that are in our blood, lymph. Or interstitial fluid, in other words, outside our body cells. But many invaders, including all viruses, enter cells and reproduce there. It is the cell-mediated immunity produced by T cells that battles pathogens that have already entered body cells.

Macrophages are white blood cells that continually search for foreign (nonself) antigenic molecules, viruses, or microbes. When found, the macrophage engulfs and destroys them. Small fragments of the antigen are displayed on the outer surface of the macrophage plasma membrane. Thus the macrophage becomes an antigen-presenting cell (APC).

Helper T cells interact with the APC. All of cell-mediated immunity and much of humoral immunity depend on precise interaction of APC and helper T cells. Helper T cells recognize and bind to the combination of self protein and foreign antigen displayed on an APC. The double recognition system used by helper T cells is like the system banks use for safe-deposit boxes. The activated helper T cells release stimulatory proteins such as interleukin-2. Interleukin-2 stimulates replication of more helper-T cells as well as stimulating the activity of cytotoxic T cells and B cells (the humoral immunity).

Humoral (antibody-mediated) immunity

All lymphocytes that circulate in the tissues arise from primitive cells in the bone marrow called stem cells. The first stage of B-cell development, transformation of stem cells into immature B cells, occurs in the liver and bone marrow before birth but only in the bone marrow in adults. The second stage of B cell development changes an immature B cell into an activated B cell. Once activated by helper T cells (interleukin-2), B cells divide, forming effector B cells or plasma B cells and memory B cells. This dividing into plasma B and memory B cells is known as clonal expansion (clonal selection theory). The initial phase, called the primary immune response, occurs when lymphocytes are first exposed to an antigen and form a clone of effector cells. After the primary immune response, a second exposure to the same antigen elicits a faster and stronger response, called the secondary immune response. During the secondary immune response, the memory B cells bind antigens and are stimulated to quickly produce new effector or plasma B clones and antibodies (without the interaction of the APC and helper T cells).

Plasma B cells make and release between 2000 and 20,000 antibody molecules per second into the blood for the next four or five days. B memory cells live for months or years, and are part of the immune memory system. There are five different classes of circulating antibody proteins or immunoglobulins (Igs). They are IgG, IgM, IgA, IgD, and IGE. The most common type of antibody (IgG) is a Y-shaped protein molecule with two arms. The main role of antibodies in eliminating invading microbes or molecules is to mark the invaders. An antibody marks an antigen by combining with it to form antigen-antibody complex. Binding of antibodies to antigens inactivates antigens by:

1.  Neutralization, which is blocking viral binding sites or coating viral toxins.

2.  Agglutination, which is clumping together viruses, bacteria, or foreign eukaryotic cells (blood). Agglutination makes the cells east for phagocytes to capture.

3.  Precipitation, which is when the antibody molecules link dissolved antigen molecules together.

4.  Activation of complement.

Cell-Mediated Immunity

When T cells leave the thymus th3ey have unique receptors just as B cells do, although they are unable to recognize an antigen present in lymph, blood, or tissues. The antigen must be presented by an APC to a helper T cell. The activated helper T cells release stimulatory proteins such as interleukin-2. Interleukin-2 stimulates replication of more helper-T cells as well as stimulating the activity of cytotoxic T cells. A cell infected with a virus or bacteria will display viral or bacterial antigens on its plasma membrane. Cytotoxic T or Killer T cells recognize the antigens and attach to that cell's plasma membrane. The T cells secrete perforin proteins that punch holes in the infected cell's plasma membrane. The infected cell's cytoplasm leaks out, the cell dies, and is removed by phagocytes. Killer T cells may also bind to cells of transplanted organs. The genetic changes that lead to cancer produce changes in normal body cells. Altered surface molecules stimulate cytotoxic T cells to kill cancer cells. Suppressor T cells regulate cytotoxic T cells. If cytotoxic T cells become to abundant, lymphomas and leukemias may result.

HIV and AIDS

To date, Acquired immunodeficiency syndrome (AIDS) has killed more than 15 million people worldwide, and more than 50 million people worldwide may have contracted human immunodeficiency viruses (HIV). A new infection is believed to occur every 15 seconds, the majority in heterosexuals. HIV infects helper T cells, the type of lymphocyte, which stimulates B Cells to produce antibodies and cytotoxic T cells to destroy virus-infected cells. Macrophages, which present antigens to helper T cells and thereby stimulate them, are also under attack.

The Centers for Disease Control and Prevention (CDC) recognize three stages of HIV infection call category A, B, and C.

During category A stage, the helper T lymphocyte count is 500 per mm3 . For a period of time after the initial infection with HIV, people don’t have any symptoms. Some will have mononucleosis like symptoms of fever, chills, aches, and swollen lymph nodes. Although there are a large number of viruses in the plasma, the HIV blood test is not yet positive because it tests for the presence of antibodies and not for the presence of HIV itself. The person is highly infectious.

Several months to several years after a nontreated infection, the individual will progress to category B in which the helper T lymphocyte count is 200 to 499 per mm3 . During this stage there will be swollen lymph nodes in the neck, armpits, or groin that persist for three months or more. Other symptoms are severe fatigue, unexplained persistent and recurrent fevers, often with night sweats, persistent cough, and persistent diarrhea. When the individual develops non-life threatening but recurrent infection, it is a signal that the disease is progressing.

The majority of infected persons proceed to category C, in which the helper T lymphocyte count is less than 200 per mm3 and the lymph nodes degenerate. The patient, who is now suffering from AIDS, characterized by severe weight loss and weakness due to persistent diarrhea and coughing, will most likely contract an opportunistic infection. Persons with AIDS die from one or more opportunistic diseases and not from the HIV infection itself. The opportunistic diseases include:

Pneumocystis pneumonia, the lungs become useless as they fill with fluid and debris due to an infection.

Mycobacterium tuberculosis, a bacterial infection of the lungs. Of special concern, tuberculosis is spreading into the general population and is multidrug resistant.

Toxoplasmic encephalitis caused by a one-celled parasite that lives in cats and other animals as well as humans. The infection leads to loss of brain cells, seizures or weakness.

Kaposi’s sarcoma, an unusual cancer of blood vessels, which gives rise to reddish purple, spots and sessions on the skin.

Invasive cervical cancer that spreads to nearby tissues.