The Immune System of Horses
The immune system consists of a network of white blood cells, antibodies, and other substances that fight off infections and reject foreign proteins. In addition, the immune system includes several organs. Some, such as the thymus gland and the bone marrow, are the sites where white blood cells are produced. Others, including the spleen, lymph nodes, and liver, trap microorganisms and foreign substances and provide a place for immune system cells to collect, interact with each other and with foreign substances, and generate an immune response.
The primary role of the immune system is to defend the body against foreign invaders or abnormal cells that invade or attack it. To do this, the immune system must distinguish between “self” and “non-self.” By recognizing invading microorganisms (such as viruses), chemical agents, or other foreign substances that are “non-self,” a body can protect itself from attack. Substances that stimulate an immune response in the body are called antigens. Antigens may be contained within or on bacteria, viruses, other microorganisms, or cancer cells. Antigens may also exist on their own—for example, as pollen or food molecules. A normal immune response consists of recognizing a foreign antigen, mobilizing forces to defend against it, and attacking it.
There are three lines of defense against invaders: physical barriers, nonspecific (or innate) immunity, and specific (or adaptive) immunity. Nonspecific and specific immunity involve various white blood cells.
Specialized Cells and Molecules of the Immune System
The first lines of defense against invaders are mechanical or physical barriers. These include the skin, the cornea of the eye, and the membranes lining the respiratory, digestive, urinary, and reproductive tracts. As long as these barriers remain unbroken, many invaders cannot penetrate them. However, if a barrier is broken (for example, if the skin is broken by a wound), the risk of infection increases.
In addition, the physical barriers are defended by "good" bacteria that live in the area and by secretions containing enzymes that can destroy harmful bacteria. Examples are tears in the eyes, secretions in the digestive tract, and normal "gut flora" (bacteria) that live in the digestive tract.
Nonspecific (innate) immunity is present at birth. It is so named because its components treat all foreign substances in much the same way. Acute inflammation is the most important process involved in nonspecific immunity. During inflammation, white blood cells (such as neutrophils and macrophages) rapidly travel from the blood into the tissues to kill invading organisms and remove injured cells. Other white blood cells involved in nonspecific immunity are monocytes (which develop into macrophages), eosinophils, basophils, and natural killer cells. These nonspecific types of white blood cells usually act on their own to destroy invaders. The complement system and cytokines are molecules produced by the immune system that also participate in nonspecific immunity.
Specific (adaptive) immunity is acquired and improves with time. As the immune system encounters different antigens, it learns the best way to attack each type, and it begins to develop a memory for that antigen. Specific immunity is so named because it tailors its attack to a specific antigen previously encountered. It takes time to develop specific immunity after initial exposure to a new antigen; however, when the antigen is encountered in the future, the response is more rapid and more effective than that generated by nonspecific immunity. Specific immunity involves the action of lymphocytes (B cells and T cells), antibodies, antigen-presenting cells, and cytokines.
Most vaccines work by stimulating the development of specific immunity. Vaccines have been developed for many diseases in horses and are an effective way to enhance the immune response.
To destroy invaders, the immune system must first recognize them. It can make this distinction because all cells have unique markers on their surface that identify them. A cell with markers on its surface that are not identical to those on the body’s own cells is identified as being foreign. The immune system then attacks that cell.
Some white blood cells (B cells) recognize invaders, or antigens, directly. When a B cell recognizes and attaches to the antigen, it produces antibodies, which coat the surface of the virus or bacteria to stop it from multiplying or infecting other cells. This process is called neutralization. Antibodies also label the foreign invaders so that other immune defenses can find and attack them. To prevent inappropriate immune responses, B cells usually require "permission" from helper T cells to produce antibodies.
T-cells are white blood cells that also need help from cells that first ingest the invader and break it into fragments. The fragments are then presented to the T cells so that they can recognize and destroy them. These helper cells are called antigen-presenting cells.
After an infectious organism has been eliminated, most of the immune cells and antibodies that fought the infection disappear. However, a small group of “memory” immune cells remain in the body. If the memory cells are later exposed to an antigen they remember, they help the body respond much faster and more strongly. This is why vaccines successfully prevent many diseases. Vaccines prime the immune system to respond quickly by exposing the T and B cells to the antigens on the infectious organism.
The immune system does not always function properly. Immune system disorders, called immune-mediated disorders, occur when the immune system is overactive or underactive. Disorders resulting from an underactive immune system, called immunodeficiencies, put animals at an increased risk for infections. Alternatively, an overactive immune system can attack parts of its own body that it misidentifies as foreign, causing what is known as an autoimmune disorder. At other times, the immune system overreacts to foreign invaders by producing too many antibodies (called gammopathies) or other chemicals (known as hypersensitivity or allergic reactions). There can be excessive responses of nonspecific (innate) or specific (adaptive) immunity.
Systemic inflammatory response syndrome is a form of shock that occurs in response to severe infections or injuries. When a severe infection causes this syndrome, it is referred to as septic shock. In response to infection or injury, a number of signalling proteins (called cytokines) are released to direct inflammation. However, severe infections or injuries can release a large amount of these proteins, which can cause fever, low blood pressure, abnormal blood clotting, multiple organ failure, and death.
There are four general classifications or types of excessive responses of specific (adaptive) immunity.
Type I reactions are excessive immune responses triggered by antibodies, mast cells, and eosinophils. They include allergic reactions, the most serious of which is anaphylaxis. Anaphylaxis is a rare, life-threatening, immediate allergic reaction to something that has entered the body (for example, eaten or injected). In a normal immune system, the binding of an antigen to an antibody activates various cells, which produce chemicals, such as histamines. In anaphylaxis, the body activates an excessive number of cells, resulting in the production of very large numbers of histamines and other chemicals. These chemicals can profoundly affect various organs, such as the blood vessels. The severity of the reaction depends on the type and amount of antigen, the amount of antibodies produced, and the route of exposure. Agents that can cause anaphylactic and allergic reactions include biting insects, vaccines, drugs, food, and blood products.
Type II reactions occur when an antibody binds to an antigen present at the surface of the body's own cells. This activates a cell-killing series of proteins called complement, resulting in cell death and tissue damage. An infection can trigger this reaction, or "cross-reactive" antibodies can target normal cells. Some animals appear to be born with a higher risk of this disorder. Signs of Type II hypersensitivity vary, and they depend on the organ in which the reaction is occurring. Immune-mediated destruction of red blood cells and platelets are the most common Type II reactions. The skin and muscles are other potential targets. The method of diagnosis also varies depending on the affected organ. Supportive treatment consists of elimination of the infectious agent (if determined) and anti-inflammatory or immunosuppressive drug treatment.
Type III reactions occur when a large number of antigen–antibody complexes lodge in small blood vessels, causing inflammation and tissue damage. There are many possible reasons for the continuous presence of antigens, including persistent infections, cancer, and longterm exposure to inhaled antigens. Some animals can react and produce antibodies against their own tissue. However, in many cases, the cause of the disease is unidentifiable. The most commonly affected sites include the joints, skin, kidneys, lungs, and brain. Signs vary and may include fever, skin lesions, lameness that shifts from leg to leg, painful or swollen joints, behavioral changes, diarrhea, and abdominal pain. An immune complex disease is usually diagnosed with blood tests, biopsies, and by ruling out other causes of disease. Treatment generally includes supportive treatment for the affected organ, removal of the causative agent, or treatment of the infection (such as appropriate antibiotic treatment for bacterial infection). Drugs that suppress the immune system may be needed to stop the continued formation of immune complexes and to decrease the inflammation associated with these reactions.
Type IV reactions or delayed hypersensitivity occurs more than 24 hours after the body was exposed to an antigen. Unlike the other types of reactions that involve antibodies, Type IV reactions involve immune cells, such as T cells and macrophages. The antigens responsible for the development of Type IV reactions can come from bacteria, parasites, viruses, chemicals, and certain cells. This type of reaction can occur in any organ. For this reason, the signs will vary. The reaction is diagnosed based on excluding other causes for organ-specific diseases and by laboratory tests on the tissue. The goals of treatment are to provide supportive treatment based on the organ-specific disease process, to identify (if possible) and eliminate the source of the antigen causing the reaction, and to control inflammation and immune suppression.
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