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THE IMMUNE SYSTEM AND HIV VIRUS Definition: An immune system is a system of biological structures and processes within

an organism that protects it against diseases by identifying and killing pathogens and tumor cells. Immunology Immunology is a science that examines the structure and function of the immune system. It covers the study of all aspects of the immune system, having significant relevance to health and diseases. Further investigation in this field is expected to play a significant role in promotion of health and treatment of diseases. Complications of detection The body detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. However, detection is further complicated as pathogens can evolve rapidly, and adapt to avoid the immune system and allow the pathogens to successfully infect their hosts. To counter this challenge Organisms have evolved multiple mechanisms that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. In eukaryotes such as plants and insects, these mechanisms include: Antimicrobial peptides called defensins, Phagocytosis Complement system. Jawed vertebrates, including humans, have even more sophisticated defense mechanisms. Vertebrate immune system The typical vertebrate immune system consists of many types of proteins, cells, organs, and tissues that interact in an elaborate and dynamic network. The human immune system adapts over time to recognize specific pathogens more efficiently. This adaptation process is referred to as "adaptive immunity" or "acquired immunity" and creates immunological memory. Immunological memory, created from a primary response to a specific pathogen, provides an enhanced response to secondary encounters with that same, specific pathogen.

The secondary response

Primary response can take 2 days and up to 2 weeks to develop. After the body gains immunity towards a certain pathogen, when infection by that pathogen occurs again, the immune response that is triggered is called the secondary response. Surface barriers to pathogens Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. Chemical barriers protect against infection. Vaginal secretions serve as a chemical barrier following menarche (beginning of menstrual function) when they become slightly acidic. Semen contains defensins and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens. Cellular barriers to pathogens Leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system. The innate leukocytes include the phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils and natural killer cells. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. Innate cells are also important mediators in the activation of the adaptive immune system. Innate or Genetic Immunity: Immunity an organism is born with. Genetically determined. May be due to lack of receptors or other molecules required for infection. Innate human immunity to canine distemper. Immunity of mice to poliovirus. Acquired Immunity: Immunity that an organism develops during lifetime. Not genetically determined. May be acquired naturally or artificially. Development of immunity to measles in response to infection or vaccination.

The layered defences The immune system protects organisms from infection with layered defenses of increasing specificity. In simple terms, physical barriers prevent pathogens such as bacteria and viruses from entering the organism. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response.

If pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system, which is activated by the innate response. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered

Antigens Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. In immunology, self molecules are those components of an organism's body that can be distinguished from foreign substances by the immune system. Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response. Lymphocytes and adaptive response The adaptive immune response is antigen-specific and requires the recognition of specific non-self antigens during a process called antigen presentation. The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response (that which involves antibodies), whereas T cells are involved in cellmediated immune response. There are two major subtypes of T cells: the killer T cell and the helper T cell. Killer T cell are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. Helper T cells regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will mount in response to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks. Passive memory Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother.

During pregnancy, a particular type of antibody, called IgG, is transported from mother to baby directly across the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother. Breast milk, especially colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies

Active memory and immunization Long-term active memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through vaccination. The principle behind vaccination (also called immunization) is to introduce an antigen from a pathogen in order to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism Inducing Immunogenicity Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based on acellular components of micro-organisms, including harmless toxin components. Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells of the innate immune system and maximize immunogenicity. Disorders of human immunity The immune system is a remarkably effective structure that incorporates specificity, inducibility and adaptation. Failures of host defense do occur, however, and fall into three broad categories: immunodeficiencies, autoimmunity, and hypersensitivities (Includes Inflammatory diseases)

Immunodeficiencies Immunodeficiencies occur when one or more of the components of the immune system are inactive resulting in recurring and life-threatening infections. The ability of the immune system to respond to pathogens is diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence.

Causes of immune dysfunction In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function. However, malnutrition is the most common cause of immunodeficiency in developing countries.

Causes of reduced immune responses Diets: - Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentrations, and cytokine production. - Deficiency of single nutrients such as iron; copper; zinc; selenium; vitamins A, C, E, and B6; and folic acid (vitamin B9) also reduces immune responses. Specific foods may also affect the immune system; for example, fresh fruits, vegetables, and foods rich in certain fatty acids may foster a healthy immune system. Likewise, fetal undernourishment can cause a lifelong impairment of the immune system.

Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection. Immunodeficiencies can also be inherited or 'acquired'. - Genetic disease: Chronic granulomatous disease, where phagocytes have a reduced ability to destroy pathogens, is an example of an inherited, or congenital, immunodeficiency. - AIDS and some types of cancer cause acquired immunodeficiency. Pharmaceuticals The Immune system and HIV Viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. A virus is a very small organism, called a micro-organism or sometimes a germ. It can only be seen using a very specialized microscope called an electron microscope. 16,000 HIV viruses can fit on the head of a pin. Viruses multiply by getting inside the cells of the body and use these cells as a factory in which to reproduce themselves. Examples of other viruses that make people sick are the common cold virus, the polio virus, the measles virus, the hepatitis virus and more recently, the Severe Acute Respiratory Syndrome (SARS) virus. There are currently no drugs that can eliminate virus in human body. HIV stands for Human Immunodeficiency Virus while AIDS stands for Acquired Immune Deficiency Syndrome. AIDS is caused by the HIV virus. A very important component of the immune system is a group of cells called CD4 cells, sometimes also called the T helper cells. These are specialized white blood cells, controlling the functioning of the immune system. We

can think of these CD4 cells as immune system army commanders. When a foreign organism enters the body, the CD4 cells give the command for the immune system to attack the invader.

When the HIV virus gets into the human body, it attacks the immune system. Although there are many different viruses that can cause illnesses in humans, HIV differs from these in that it is the only virus we know of that specifically attacks the CD4 cells. The HIV virus gets inside the CD4 cells and multiplies there. Up to 10 million viruses are produced daily. HIV gradually disables or destroys more and more of the CD4 cells. Without the commanders, the defense force is not able to defend its territory properly. The immune system also produces antibodies (weapons) to combat the HIV virus, but they are not able to overcome the virus. These antibodies are usually what we measure when we do HIV tests. Over time, the immune system gradually becomes increasingly weakened as a result of the HIV virus. We say the immune system becomes deficient or compromised, or the person is immunodeficient. This is the reason for the terms human IMMUNODEFICIENCY virus and acquired IMMUNE DEFICIENCY syndrome. In very rare cases, people are born with immune deficiencies, and certain kinds of cancer treatments also weaken the immune system; but HIV is by far the most common cause of immune deficiency in the world today. When the immune system is weakened, the body gradually loses its ability to fight off diseases caused by other microorganisms, and so the person becomes vulnerable to many infections. People with HIV can contract the same infections as other people, for example, pneumonia or diarrhea or STIs, but they get these common infections more often and more severely. As a result of the weak immune system, people with HIV are also vulnerable to certain infections that do not usually cause illness in people without HIV. Although these infections can get into the body of a healthy person, a healthy immune system destroys the infection easily and the person does not become sick. In a person whose immune system is weak, the infections have an opportunity to multiply inside the person and make them sick. These infections are called opportunistic infections, because they make use of the opportunity provided by a weak immune system. Examples of opportunistic infections include candida (infection of the mouth and throat), Pneumocystis carinii pneumonia and cryptococcal meningitis. The weakened immune system also makes the body vulnerable to certain kinds of cancers, e.g., Kaposis sarcoma, cancer of the cervix.

Because of the variety of infections and cancers that can affect a person with HIV, they can show a variety of different symptoms and signs. The word SYNDROME refers to a group of symptoms and signs that can all be part of the same underlying medical condition, in this case HIV/AIDS.

Summary of functioning of the immune system

Antigen
Macrophage

Cellular immunity

Helper T - Cell

Antibody Immunity

Active Cytotoxic T-Cell Kills Infected Cells


Memory T- Cell

Active B - Cell
Plasma Cell
Memory B-Cell

Antibodies
Deactivates Antigens