The immune system is a network of interacting cellular and soluble components. It’s function is to distinguish entities the body as “self” or “none-self” and to eliminate those that are none-self. Microorganisms are the main non self-entities but neoplasms, transplants, and certain foreign substances (for example some toxins) are also important. To accomplish its tasks, the immune system has evolved two mechanisms: non-specific immunity and specific immunity which are linked to and influence each other.
Non-Specific (Innate) Immunity
This type of immunity is present at birth and does not require a previous encounter with the offending substance and does not develop memory. Innate immunity includes barriers such as the skin and chemical protection, such as gastric acid. There are two cellular components: 1) the phagocytic system whose function is to ingest and digest invading organisms. 2) natural killer “NK” cells, whose function is to kill some tumors, microorganisms, and virus infected cells. The soluble components consist of complement proteins, acute phase reactants, and the cytokines. (Phagocytes include neutraphils and monocytes in the blood, and macrophages in the tissue. Macrophages are widely distributed throughout the body and are strategically located at the interfaces of tissues with blood or tributary spaces).
Cytokines are secreted by monocytes and lymphocytes in response to interaction with a specific antigen (Ag), a nonspecific Ag, or a nonspecific soluble stimulus (e.g. endotoxin). Cytokines affect the magnitude of inflammatory or immune responses.
Specific (Adaptive) Immunity
Specific immunity has the hallmarks of learning, adaptability, and memory. The cellular component is the lymphocyte and immunoglobulin (Igs) are the soluble components. Lymphocytes are divided into two subsets: thymus derived (T cell) and bone marrow derived (B cell). Because the number of Ag's is potentially infinite, this specialization would seem to place an undo burden on the immune system. This dilemma is solved by the ability of the lymphocytes' Ag-receptor genes to combine in potentially infinite arrangements.
The lymphatic system consists of fluid called lymph, the lymphatic vessels contain it, several structures contain lymphatic tissues, several organs, and the stem cells of the red bone marrow that produce lymphocytes. The lymph is essentially the same as interstitial fluid but flowing within lymphatic vessels. Lymphatic tissues are considered specialized form of reticular connective tissue that contains large numbers of lymphocytes.
Our environment presents numerous dangers toward our health including pathogens and tissue trauma. Our ability to neutralize the activity of pathogens and toxins produced by them, as well as the ability to repair tissue damage due to trauma, is critical to our homeostasis. The ability to ward off disease is called resistance. Resistance can be grouped into two areas nonspecific resistance and immunity.
Nonspecific resistance refers to the defense mechanisms that provide general protection against a wide variety of pathogens including bacteria and viruses. Such characteristics as the chemical barriers presented by the skin and mucous membranes, anti-microbial chemicals, nonspecific phagocytes, inflammation, and fever all contribute to our nonspecific resistance.
Immunity is a system of cooperating cells and chemical agents that act to defend against specific pathogens or foreign matter. The body system most responsible for immunity is the lymphatic system.
Function of Lymphatic System
The lymphatic system drains the interstitial fluid, transports dietary lipids, and carries out immune functions.
Anatomy of the Lymphatic System
Lymph nodes draining the superficial areas of the head and the face are located slightly inferior the ear both anteriorly and posteriorly, and inferior to the mandible. The primary lymphatic organs are the red bone marrow and the thymus gland. Secondary lymphatic organs include the lymph nodes and the spleen. Lymphatic nodules, which are not surrounded by a capsule and thus not considered a discrete organ, are also typically considered a part of the secondary lymphatic organs. The two major collecting ducts of the lymphatic system are the thoracic duct and the right lymphatic duct.
Lymphatic fluid is produced as excess blood plasma that is not returned into the capillary system. Approximately 3 liters drain into the lymphatic capillaries per day. Lymphatic capillaries form blind ends in the tissue with large fenestrations. Lymphatic vessels contain one-way valves similar to those of veins. Like veins, the thin walled lymphatic vessels are easily collapsed by local skeletal muscle contractions milking fluid toward the lymphatic ducts and ultimately back to the subclavian veins.
The thymus gland is located in the mediastinum, just superior to the heart and inferior to the thyroid gland. Pre T cells migrate from the red bone marrow to the thymus gland where they accumulate in the medulla. These cells proliferate and develop into mature T cells in the thymus. The thymus also produces thymus hormones thought to be involved in T cell maturation.
Lymph flows through a lymph node in one direction entering through an efferent lymphatic vessel to flow into the sinuses. Lymph flows through the sinuses passing first through the cortex and then the medulla to exit through an efferent lymphatic vessel. T cells are found aggregated in the outer layers of the follicles of the cortex. B cells are clustered in the germinal centers deep in each follicle.
The spleen is located between the stomach and the diaphragm in the left hypochondriac region. The spleen does not filter lymph but does contain masses of white pulp, lymphatic tissues composed of primarily B cells. Its immune function is to provide a site of B cell's proliferation. The principle function of the spleen is the phagocytosis of bacteria and damaged erythrocytes in the red pulp tissue.
The epidermis of the skin is composed of many layers of densely packed, keratinized cells that provide little space for microbial invasion. Shedding the outer most layer also helps to remove microbes from the skin surface. Mucous membranes secrete mucous, a slightly viscous fluid that will trap many microbes and foreign particles. The mucus membrane of the nose contains mucous coated hairs that add additional filtering. The mucus membranes of the upper respiratory track include ciliated cells that propel mucous to the throat for swallowing. Microbes and foreign particles trapped in the mucous are carried along to be delivered to the stomach.
Sebaceous glands of the skin secrete sebum that forms a protective film on the surface of the skin. The acidity of sebum inhibits the growth of many pathogenic bacteria. Perspiration not only helps flush microbes from the surface skin, but also contains lysozyme which can break down the cells walls of many bacteria. Both mucous and perspiration contain immunoglobulins.
Interferons are proteins produced and released by cells invaded by viruses. Interferon diffuses to neighboring cells and binds to surface receptors. Interferon activates the uninhibited cells to produced antiviral proteins that can inhibit viral infection.
Complement is a group of about 20 plasma proteins that enhance immune or inflammatory reactions. Complement may be activated by the classical pathways or the alternative pathway. A plasma protein termed C3 will respond to antigen antibody complexes to begin a cascade effect in the complement proteins in the classical pathway. C3 can also respond to certain polysaccharides on the surface of microbes in the alternative pathway.
Once activated, complement enhances inflammation by acting as a vasodilator causing mast cells to release histamine, and attacking phagocytes to the area of infection. In addition, complement produces opsonization to promote phagocytosis. Complement can also kill microbes directly by forming a membrane attack complex (MAC) that produces cytolysis.
Natural killer cells have the ability to attack a variety of pathogens unlike T cells, which are specialized for specific pathogens. Natural killer cells do not mature in the thymus and do not have antigen receptors in the plasma membranes.
Two major phagocytes are neutrophils and macrophages. Both are relatively generalized phagocytes that can attack a variety of pathogens (neutrophils work best against bacteria). Macrophages develop from monocytes. Phagocyte activity begins with chemotaxis, the attraction of phagocytes by chemical messages, followed by adherence. Adherence occurs when the phagocyte attaches it’s plasma membrane to the microbe or the foreign material to be ingested. Following adherence, ingestion begins by endocytosis.
Inflammation produces redness, swelling, heat, and pain at the site of infection or injury. The swelling and redness are produced by vasodilatation at the site. The increased pressure produced by the edema following vasodilatation is responsible for the pain, and the heat is due to a respiratory burst of activity of phagocytes and repair cells in the area. The principle chemicals responsible for inflammation are histamine, kinins, luekotrienes,complement, and prostaglandins.
Immunity demonstrates two properties that are absent in nonspecific resistance; specificity and memory. Specificity is due to responses by the immune system to particular antigens and memory allows for more rapid, virulent response to a second encounter with the same pathogen.
Immunocompetence is the maturation of B and T cells such that they carry out immune responses if properly stimulated. The B and T cells develop distinctive surface proteins, some of which serve as antigen receptors. Antigens are large, complex molecules, typically proteins, that the immune system will recognize as foreign to the body, they have two characteristics: 1) they will provoke a immune response (immunogenicity), 2) they will react with produced antibodies (reactivity).
Immune responses are either cell mediated or antibody mediated (humeral). Activated T cells produce a cell-mediated response proliferating into several classes of T cells, including the cytotoxic T cell, which actively attacks antigens. The cell-mediated responses are effective against intracellular pathogens, some cancer cells, and foreign tissue transplants. The antibody-mediated response is produced by activated B cells that proliferate to produce antibodies. Helper T cells enhance the activation of both the cell-mediated and antibody-mediated responses. Antibody-mediated responses work well against antigens dissolved in the body fluids and extracellular antigens.
Complete antigens are chemicals that produce immunogenicity and reactivity. Partial antigens (haptens) produce reactivity but not immunogenicity. Many allergic reactions are due to partial antigens. An epitope is the specific portion of the antigen that triggers the immune response.
The major histocompatibility complex (MHC) is a group of glycoproteins unique to each individual. The MHC is built into the plasma membrane of all the body cells except the erythrocytes. This specialized MHC is found on the surface of antigen presenting cells such as T cells. The immune system recognizes the presence of the MHC as an identifier or “self” so that the cells of your body are not attacked by your immune system.
Although B cells can respond to antigens found in the fluids of the body, T cells must be presented with an antigen associated to its MHC. Antigen presenting occurs when a phagocytic cell ingests an antigen and displays it on it’s plasma membrane along with MHC that phagocytic cells will have on it’s membrane. This presentation can act to trigger the T cell response. After a macrophage ingests an antigen, the antigen is broken into peptide fragments by digestive enzymes. At the same time, the macrophage produces MHC on it endoplasmic reticulum and packages it into vesicles at the Golgi apparatus. Vesicle containing MHC and the peptide fragments of the antigen fuse, allowing the MHC and peptides to bond. The vesicles carry the MHC-antigen complex to the plasma membrane where they are presented. The four type of T cells are:
1) Cytotoxic T cell: it causes death of foreign cells by releasing perforin and lymphotoxin; releases cytokines to attract macrophages.
2) Upper T cell: cooperates with B cells to enhance antibody production and secretes interleukin II which stimulates B and T cell proliferation.
3) Suppressor T cell: regulates immune response by producing cytokines and inhibit the proliferation of T cells.
4) Memory T cell: remains in lymphoid tissue to enhance secondary response.
B-cells typically remain in the lymphatic system and become activated when they come in contact with their antigen. B cells have the capability of producing and presenting the MHC-antigen complex. Helper T cells that recognize the MHC-antigen complex provide costimulation to enhance the proliferation and specialization of B cells. Activated B cells produce a clone of plasma B cells that rapidly produce and release antibodies. Activated B cells that do not become plasma B cells remain in the lymphoid tissue as memory B cells to provide an enhanced secondary response.
Although the different classes of antibodies (immunoglobins) have certain specialization, their common actions include:
- neutralizing antigens
- immobilization of bacteria
- agglutination and precipitation of antigen
- activation of complement
- enhancement of phagocytosis
- rovision of fetal immunity
When a cell becomes cancerous, it will often display tumor antigens, molecules that are rarely displayed on the surface of normal cells. The immune system can often recognize a tumor antigens as “non-self” and produce a response. T cells, macrophages, and natural killers cells are the most common agents to resist cancer.
One of the cardinal characteristics of the immune system is its memory for antigens that have triggered an immune response previously. The primary response occurs when the immune system recognizes an antigen for the first time. At the initial contact, there will only be a few immune cells specialized to respond, so the virulence of the response is delayed until these immune cells can divide and produce large numbers of cells capable of producing resistance. At the second contact, large numbers of memory cells (memory T and memory B cells) will be found in the body, remaining from the initial response. With large numbers of responding cells available, the speed and efficiency of the immune response is greatly elevated.
Lymph nodes, also known as lymph glands, are masses of lymph tissue covered by a fibrous capsule. They range up to .8 inches (2cm) in size and contain sinuses (spaces) where many scavenging white blood cells, known as macrophages, ingest bacteria and other foreign matter and debris. The lymph from most tissues or organs crosses one or more lymph nodes to be filtered before draining into the venous bloodstream. Swollen lymph nodes often indicate disease. Lacrimal glands produce tears that contain a protective enzyme. Tonsils and andenoids produce antibodies against ingested or inhaled organisms. Some types of lymphocytes mature in and are then stored in the spleen, the largest of the lymph organs. Acid and enzymes secreted in the stomach destroy ingested organisms. Clusters of lymph tissue, called Peyer’s patches, are found in the lower part of the small intestine. The lymphocytes begin life as stem cells in the bone marrow. Also generated here are monocytes, largest of the white blood cells. These migrate from the blood and the connective tissues where they develop into scavenger cells called macrophages that ingest bacteria and dead cells. Popliteal lymph nodes drain excessive lymph from the legs and feet.
1. Describe the function of the immune system.
2. Describe the two mechanisms of immunity.
3. What is the difference between resistance and immunity?
4. What is the difference between innate and adaptive immunity?
5. What is the difference between a lymph node and a lymph nodule?
6. What is lymph?
7. Describe specificity and memory? Why are they important?
8. What is the difference between an antigen and a hapten?
9. Describe the difference between cellular and humeral immune responses.
10. Describe the major components of the immune system and their roles.