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  1. 1. Unit 3 Disturbances of the Immune System 1 UNIT 3 Disturbances of the Immune System James A. Rankin RN, PhD Associate Professor Faculty of Nursing University of Calgary
  2. 2. Unit 3 Disturbances of the Immune System 2 Unit 3 Table of Contents Overview................................................................................................................4 Aim.....................................................................................................................4 Objectives...........................................................................................................4 Orientation to the Unit........................................................................................4 Resources............................................................................................................5 Web Links...........................................................................................................5 Section 1: The Normal Immune Response.........................................................6 Immune Responses.............................................................................................7 For Your Interest...............................................................................................10 Section 2: Aquired Immune Deficiency Syndrome (AIDS)............................15 Etiology.............................................................................................................15 Prevalence.........................................................................................................16 Populations at Risk...........................................................................................17 Pathogenesis......................................................................................................18 Modes of Transmission.....................................................................................19 Clinical Manifestations.....................................................................................20 Surveillance.......................................................................................................20 Prognosis and Trajectory..................................................................................22 Learning Activity #1.........................................................................................23 Study Questions................................................................................................24 Section 3: Immunodeficiency.............................................................................25 Phagocytosis.....................................................................................................25 Complement......................................................................................................25 Hypersensitivity................................................................................................26 Autoimmune Linked Disease............................................................................27 Glossary...............................................................................................................30 Acronym List.......................................................................................................30 Checklist of Requirements.................................................................................30 Answers to Learning Activities..........................................................................30 Learning Activity #1.........................................................................................30
  3. 3. UNIT 3 Disturbances of the Immune System Advances in technology and molecular biology in the late eighties, have led to a dramatic increase in knowledge with respect to the immune system (Gallo & Montagnier, 1988). The research effort that is directed towards understanding the Human Immunodeficiency Viruses (HIV) has succeeded in advancing this knowledge base. While it is perhaps true that the Acquired Immune Deficiency Syndrome (AIDS) epidemic has brought the science of immunology to the fore, not only to health professionals but also to the public at large, it is important to note that AIDS represents one example of many conditions in which the immune system is involved. You will quickly realize as you proceed through the pathophysiology units that there are in fact very few diseases about which we know the etiology. For example the immune system is implicated to a greater or lesser extent with certain cancers, ulcerative colitis, Crohn’s disease, multiple sclerosis and rheumatoid arthritis to name a few. In recent years researchers have identified strong links between the immune system and the nervous system. It would appear that one system can be affected by the other. In addition it has been suggested that the individual is capable of influencing the immune system at a conscious level (Solomon, 1987; Petrie et al., 1999). That is, we can suppress or enhance the response of the system consciously! Researchers have also found that the endocrine system is involved too. The name given to the science that has emerged is psychoneuroimmunoendocrinology (usually shortened to psychoneuroimmunology!). For further reading on this fascinating area you might wish to look at Blalock (1984); Plant & Friedman (1981); Ader (1981); Solomon & Moos (1964). Please note that these additional readings are for interest only, the material contained within them will NOT be tested.
  4. 4. 4 Unit 3 Disturbances of the Immune System Overview Aim The aim of this unit is to increase your knowledge of the immune system and the normal immune response. You will then be expected to use this knowledge to facilitate your understanding of various disorders resulting from immune system dysfunction Objectives On completion of this unit you will be able to: 1. Describe the mechanisms involved in the normal immune response. 2. Describe the B and T cell lines. 3. Discuss the etiology and pathophysiology of Acquired Immune Deficiency Syndrome (AIDS). 4. Briefly describe the mechanisms involved in auto-immune linked diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis). 5. Relate your knowledge of the immune response to certain immunodeficiency and hypersensitivity states. Orientation to the Unit This is a fairly heavy unit; you may want to divide it into sections and take your time with each section. For example, the readings could constitute one section, then the normal immune system, AIDS, and finally immunodeficiency states. I would strongly recommend that you do not attempt this unit in one “sitting”. I would also recommend that you work through this unit with the course textbook (Porth, 2005. Chapter 19 ) right beside you as I refer to it as you work through the unit. In order to complete this unit it is recommended that you do the required readings listed below. In addition you may wish to brush up on your knowledge of the immune system by reading an appropriate anatomy and physiology text. In the previous unit on wound healing, you already studied some of the principles and processes involved in the non-specific immune response (i.e. inflammation). In this unit you will build on and expand that knowledge. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  5. 5. Resources Requirements Porth, C. M. (2005). Pathophysiology – Concepts in Altered Health States (7th ed). Philadelphia: Lippincott. Web Links All web links in this unit can be accessed through the Web CT system.
  6. 6. 6 Unit 3 Disturbances of the Immune System Section 1: The Normal Immune Response As previously discussed in the Wound Healing unit, the inflammatory response is mounted within seconds of being stimulated either by injury or invasion by an antigen. One of the features of the inflammatory response is that it is nonspecific. What does “nonspecific” mean? This is perhaps best answered with respect to the immune response which is specific. Before looking at this it is important to understand what an antigen is. Essentially an antigen is any substance capable of stimulating an antibody response. There are a number of characteristics of the immune response including: •Specificity—This refers to the ability of certain cells of the immune system to produce an antibody that is specific to a particular antigen. When a host is invaded by an antigen, for example the streptococcus bacterium, not just any antibodies are produced. The antibodies are specific to the streptococcus and are capable of dealing with it in a number of ways. •Memory—This is an interesting property of the immune system and provides the basis for vaccine therapy. When a host is exposed to an antigen, an antibody response is mounted (the primary response). On subsequent exposure at a different time to the same antigen, a rapid and large antibody response (the secondary or anamnestic response) is seen. This secondary response is due to cells known as memory cells. Can you see how this property relates to vaccine therapy? •Self and Non-self—A healthy immune system has the ability to recognize those cells that belong to the host as “self” and any other cells as “non-self”. Any time that the host is invaded by an antigen the immune system recognizes this as “foreign” (or non-self) and therefore mounts a response to this. This is of course a protective defense mechanism. This property works against us in the case of organ transplantation. The immune system does not “know” that a transplanted organ has been put there for beneficial purposes and so it recognizes it as foreign and attacks. Hence, people with organ transplants require immunosuppressive drugs to prevent the immune system from doing its job! When the immune system (for some reason) breaks down it can start to attack its own host cells. This is what appears to happen in auto-immune linked diseases, (Greek, auto = self). This is dealt with later in the unit. •Hypersensitivity—This will be dealt with later in the unit too. Suffice to say at this point, that this is an extremely abnormal Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  7. 7. immune response which rather than contributing to recovery can actually produce tissue damage. Immune Responses Four types of immune responses have been identified. 1. The Humoral Response or humoral antibody response, as the latter name implies, involves the production of antibodies. Another name for antibodies is “immunoglobulins,” this is commonly abbreviated to Ig. There are five classes of immunoglobulins: IgA; IgD; IgE; IgG and IgM. The Ig’s enter the bloodstream (and other areas) and combine with antigens to form an antigen-antibody complex (or immune complex) which is capable of destroying the antigen by various means. 2. Cell Mediated Immunity (CMI)—Cell mediated immunity is carried out by the T lymphocytes. The T lymphocytes are capable of “recognizing” antigens and directly attacking and neutralizing them. The immunity is carried out by cells of the immune system rather than antibodies, hence the immunity is cell mediated. 3. Phagocytosis 4. Complement Response, each of these will be dealt with later in the unit. The immune system consists of many different types of cells which interact with one another in establishing an immune response. It is not necessary to memorize all the types of cells involved, it is better to try and gain an understanding of the system in general.
  8. 8. 8 Unit 3 Disturbances of the Immune System Overview of the Immune System The generic name for cells of the immune system is “white blood cells”, or LEUCOCYTES (leuco/leuko = white; cyte = cell). There are five cell types: 1. neutrophils These are collectively 2. eosinophils known as 3. basophils granulocytes 4. monocytes 5. lymphocytes There are two lymphocyte cell lines: Humoral Response Cell Mediated Immunity B cells T cells w w “BURSA” THYMUS w w PLASMA CELL MATURE T CELL w w IgM IgA IgG T cells differentiate into: IgD IgE killers, memory, helpers, w suppressors, lymphokine producers Memory cells w Humoral response—against bacterial CMI response—against viruses, infection (e.g., staphylococci, intracellular bacteria, fungi, graft pneumococci) rejection immunological surveillance (e.g., destroys neoplastic cells) The B cells are so called because early research in birds demonstrated the existence of an organ in the gastrointestinal tract called a “bursa,” the removal of which meant that the bird’s humoral response was eliminated. A bursa has not been demonstrated in humans, however it is believed that the bone marrow is the site of maturation of B cells, hence it is known as the “bursa equivalent.” The T cells on the other hand derive their name from the fact that they go through a maturation process in the thymus gland. The thymus (please note it is thymus and not thyroid) gland occupies a space in the mediastinum. The thymus is active until puberty and then it atrophies. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  9. 9. Note: the textbook states that the cells that leave the thymus are “immature.” This should be interpreted as “inactive.” In summary then, the B cells are lymphocytes that are responsible for humoral antibody response. They differentiate into plasma cells and the plasma cells synthesize large amounts of antibodies (immunoglobulins). The Ig’s are specific to the invading antigen. Memory B cells are responsible for mounting the secondary (anamnestic) response when the host is invaded by the same antigen at a different point in time. The humoral response defends the host against extracellular bacterial infection. The T cells are lymphocytes that are responsible for cell mediated immunity (CMI). T cells mature in the thymus gland and can differentiate into different cell types. The CMI defends the host against viruses, intracellular bacteria, fungi and, is responsible for graft rejection and immunological surveillance. ALL of the cells of the immune system take part in the overall immune response. Stop for a break! This next section is not necessary for exam purposes.
  10. 10. 10 Unit 3 Disturbances of the Immune System For Your Interest Before looking at AIDS you might be interested in knowing how your immune system recognizes itself? If you are not interested in this, then skip to the next part of the unit that deals with AIDS. The following content is NOT on the exam so it is quite safe to skip it if you wish. (Honest! — Trust me, I’m a nurse). How does your immune system recognize you? Well the answer to that is all in your genes! 1. First of all, a major group of genes have been identified. The genes have been found on four loci (Latin, loci = places) on the short arm of chromosome number 6 (See Figure 3.1 for an overview). Figure 3.1 Overview of major histocompatibility complex on chromosome 6 2. These genes code for proteins (as most genes do) and the proteins that they code end up on the cell surface of most cells of your body. To get a handle on this you have to try and think at a microscopic level. We (in our MACROscopic world) tend to think of cells as flat round things we see in biology textbooks. However, the advent of the electron microscope and the photographs we can get from it (known as electron Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  11. 11. micrographs) has helped us to try and visualize cells as three dimensional . So we have to think of the cell as a three dimensional object with a cell surface that is not nice and smooth but rather full of lumps, bumps, flagpoles and holes! 3. Back to the proteins on the cell surface (the flagpoles)—The proteins are known as: •histocompatibility antigens OR These names all •HLA antigens OR refer to the same •HLA determinants things By now you may have some questions you want to ask. Let me see if I can anticipate some them: a. Why are the proteins called histocompatibility antigens? b. Why are the proteins called HLA antigens? c. Why are the proteins called antigens? d. Why are the proteins called HLA determinants? Answers: e. The proteins are called histocompatibility antigens because the area on the chromosome where the genes that code for the proteins are found, is known as the major histocompatibility complex (or MHC). (See Figure 3.2 on the next page) f. The proteins are known as HLA antigens because a scientist called Dausset found the proteins on Human Leucocyte (system) A, in 1954.
  12. 12. 12 Unit 3 Disturbances of the Immune System Figure 3.2 The major histocompatibility complex on chromosome 6 g. The proteins are called antigens because they would act as antigens (i.e. stimulate the immune response) if they were found in someone else’s body. In other words, if you had to get one of my kidneys (I can’t think why you would want it!), then the proteins (or antigens) on the surface of my kidney cells would signal (remember the flagpoles) your immune system. Your immune system would spring into action and “know” immediately that this was not your kidney! h. They are called HLA determinants because the cell surface proteins help determine the different types of cells. 4. Remember I said that the area on the chromosome where the genes are found is known as the major histocompatibility complex? Well the area is also known as the HLA complex. Can you see why from the above information? If not, read over part 3 again. Remember the 4 loci (places) on the chromosome? These represent four areas on the MHC where the genes are located and they are designated A, B, C and D/DR. The proteins (or antigens) that are coded by the genes are divided into two classes. The proteins from loci A, B, and C are known as class I antigens. Most cells have these, except for red blood cells, they have their own (about 80 or so). The proteins from locus (note: loci, plural; locus, singular) D/DR are known as class II antigens and they are mostly found on B lymphocytes. (See Figure 3.3) Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  13. 13. Figure 3.3 The four gene loci (A, B, C and D/DR) on the major histocompatibility complex In summary your immune system recognizes you because: •There are genes located on the short arm of Chromosome 6 •On the short arm there is an area called the Major Histocompatibility Complex (MHC) •There are four places (loci) on the MHC designated A, B, C and D/ DR •At these loci genes are found that code for proteins (also known as antigens -- HLA antigens) •The genes at loci A, B, and C code for Class I antigens -- most cells have these except red blood cells •The genes at locus D/DR code for Class II antigens --found mostly on lymphocytes •The antigens act as cell surface markers (flagpoles). This allows for self and non-self distinction by the immune system.
  14. 14. 14 Unit 3 Disturbances of the Immune System Figure 3.4 Cell surface markers and self and non-self distinction by the immune system In Figure 3.4, above the cell surface, markers (the flagpoles) allow the immune system (in this case a macrophage) to recognize that the cell is not foreign. 5. Quite apart from the kidney transplant story above, the HLA antigens (= histocompatibility antigens = HLA determinants = proteins = cell surface flagpoles) are also involved in tissue to tissue distinction within the same individual. 6. The quality and quantity of the immune response is in part controlled by genes in the HLA (MHC) complex. They are known as immune response or Ir genes. If you are interested in reading more about the immune system I would recommend the book by Michael Taussig listed in the references. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  15. 15. Section 2: Aquired Immune Deficiency Syndrome (AIDS) Before we begin—a word of advice: Acquired immune deficiency syndrome is thought of as a fairly "new" infectious disease. It is one that has received huge amounts of media attention and sensationalism as well as widespread interest among health care workers and researchers. Due to the vast amount of research that is being done it seems as though new knowledge about the disease is being discovered almost daily. Thus any document concerning AIDS can quickly become outdated and this particular unit is no exception. It is your professional responsibility to keep your knowledge current especially in an area where there is rapid turnover of research findings. While newspaper reports may be entertaining, very few are informative to the level required for professional practice. It behooves us as health care professionals to obtain our knowledge from respectable scientific journals and textbooks and we have to be extremely cautious in the way that we interpret reports from the mass media. Etiology Between October 1980 and May 1981, five cases of Pneumocystis carinii pneumonia were reported in young and otherwise healthy homosexual males in Los Angeles (Centers for Disease Control, 1981). This was unusual as this type of pneumonia had only occurred before in older patients who were immunosuppressed. In addition, in early 1981 a larger than usual number of cases of Kaposi’s sarcoma was seen in young homosexual males (Centers for Disease Control, 1981). This was of note because this type of cancer was almost always seen in elderly people (both males and females). The Centers for Disease Control initiated a surveillance program as it was believed that what was being seen was the emergence of a new disease. •1983 Montagnier and his co-workers at the Pasteur Institute in Paris isolate a new virus from the swollen lymph glands of a patient. It is named Lymphadenopathy Associated Virus (LAV). •1984 Gallo and his co-workers in the US perform a detailed study of a new virus. It is named Human T cell Lymphotropic Virus type III (HTLV type III).
  16. 16. 16 Unit 3 Disturbances of the Immune System It was later discovered that both LAV and HTLV III viruses were the same. By international agreement the virus is now known as the Human Immunodeficiency Virus (HIV). To date two viruses have been identified, HIV I and HIV II. It would appear that HIV II is more prevalent in certain parts of Africa, in particular West Africa, whereas HIV I is more common in North America. It is important to note that both HIV I and HIV II can cause AIDS. It is also important to note that an HIV infected individual may or may not have AIDS. Infection by the HIV virus may cause a progressive dysfunction of the immune system; the disease known as AIDS is a late (or end stage) manifestation of this process (Redfield & Burke, 1988). Other important points: •Being HIV positive means that the infected individual has raised sufficient antibody levels in the blood that can be detected on screening. It is more correct to say that an individual is HIV antibody positive. •An individual may be infected with the virus and not be HIV antibody positive on testing. This is because it may take anywhere from a few weeks to a few months for that individual to raise a sufficient antibody titre i.e. seroconvert. •Initially it was thought that those individuals who were HIV antibody positive went on to develop AIDS within 2 years of being infected. This incubation period was extended to 5 years, currently it is thought that it may be 30 years or more. This has obvious implications for the spread of the disease. Anyone who is HIV antibody positive is capable of transmitting the virus, and of course, infecting others. Prevalence Strictly speaking, the prevalence of a disease indicates the number of individuals in a population who have a disease at a particular point in time. The incidence, quantifies the number of new cases that develop in a population in a given time period. This time period is usually one year, however in the case of AIDS it is not uncommon to see monthly or six monthly statistics. As of November 30, 1988 a total of 139,886 cases of AIDS had been reported to the World Health Organization (WHO), (AIDS Information, 1989). However, there have been difficulties with recognition, diagnosis and reporting, especially in the developing countries. It is estimated by WHO that there may be more than 200,000 cases of AIDS worldwide and that between 5-10 million people are infected with HIV (Mann, Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  17. 17. Chin, Piot & Quinn, 1988). More recently, projections from WHO (WHO web site, 2000) suggest that 3.4 million adults and children are living with HIV/AIDS worldwide. The largest number infected live in sub- Saharan Africa (24.5 million). Other points: •In North America high HIV infection rates are found among: o homosexual and bisexual males o people with haemophilia o intravenous drug abusers o children born to infected mothers o heterosexual partners of infected persons •Males have higher prevalence than females •Higher prevalence rates have been recorded in persons between 20 to 45 years of age In Africa the prevalence picture is quite different: •Females are equally infected as males •Transmission of the virus by homosexual activity or intravenous drug abuse is low or absent •Perinatal transmission is common •HIV II is more prevalent than HIV I It is important to note that HIV infection and therefore AIDS does not only occur in those men or women who engage in homosexual practices. Anyone can be infected and therefore anyone can get AIDS. Populations at Risk The HIV is transmitted by three main routes: by contaminated blood, sexual contact with infected semen, and intrauterine/peripartum/postpartum exposure to infected body fluids (blood, breast milk) (Friendland & Klein, 1988). Populations at risk are therefore those who: 1. Are exposed to contaminated blood by virtue of their lifestyles (intravenous drug users), by specific disorders (hemophiliacs), and by situational incidents (transfusion recipients).
  18. 18. 18 Unit 3 Disturbances of the Immune System 2. Are exposed to contaminated semen (homosexual/bisexual men, sexual partners of intravenous drug users, and anyone engaging in unprotected sexual activity with a partner/partners whose antibody status is unknown). 3. Are children of infected mothers. Children can become infected in utero (transplacental transmission), during birth (blood to blood transmission) or after birth (breast milk). However, unless clinical manifestations of AIDS present in these children, it is impossible to decide their antibody status until approximately 18 months after birth since HIV antibodies are transmitted from mother to child regardless of whether the child is infected or not (Giaguinto, DeRossi & Laverda, 1988). HIV has been isolated from blood, semen, vaginal secretions, saliva, tears, breast milk, urine, serum, cerebrospinal fluid, and alveolar fluid. Only blood, semen, breast milk and vaginal fluids have been directly implicated in transmission. Pathogenesis Main points: •HIV is a lentevirus which belongs to the family of retroviruses. •Retroviruses carry their genetic information in ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA). •The main target in HIV infection is T4 helper cells. (You will recall that helpers are a subset of the T lymphocyte line). •Briefly the process is as follows: o HIV gains access to the blood of the host. o HIV binds to T4 helpers. o The virus binds to the T4 cells with the help of a receptor molecule known as CD4. CD4 is a cell surface protein (or antigen) found on T4 helper cells (we discussed flagpoles in the section on immune recognition) o HIV contains an enzyme, reverse transcriptase, which allows the RNA to be transcribed into DNA. o Some of the DNA is incorporated into the T4 cell’s own DNA. o Replication of the viral DNA may now take place. In other words the viral DNA can instruct the T4 cell to make more viruses! o The viral DNA may lie dormant in the T4 cell. The stimulus to turn on the DNA is not known. Hence an individual may be infected with the virus but for some reason his T4 cells have not been instructed to make more viruses. When the Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  19. 19. instruction is given and vast amounts of virus is produced the individual goes on to develop AIDS. o The virus is replicated, lyses the T4 cell and goes on to infect other T4 cells and other cells of the immune system e.g. monocytes. Monocytes can cross the blood-brain barrier. It is thought that the virus gains access to the CSF and the brain tissue by being transported across the blood-brain barrier in the monocytes. You will recall that the humoral response is mounted by the B cells (antibody production) and the T lymphocytes (especially the killers) are responsible for cell mediated immunity. Both of these responses are coordinated and organized by the T4 helper cells. In other words the very cells that are designed to orchestrate the humoral and CMI responses are the prime targets for the virus! Thus the virus is not just responsible for infecting the T4 helpers but also for indirectly “knocking out” the individual’s capability of mounting an immune response. This leaves the host susceptible to: •All forms of infection (viral, bacterial, fungal, protozoan) •No immunological surveillance—hence neoplasms develop •No immunological “memory”—hence infections which would otherwise be controlled can become established (opportunistic infections) Modes of Transmission From the preceding discussion and from your readings you probably are aware of the modes of transmission of the virus: •Sexual intercourse—especially receptive anal intercourse •Parenteral o IV drug abuse o Blood and blood products (e.g. whole blood, plasma, cellular components and clotting factors) •Transplacental •The virus has also been isolated in a number of body fluids (e.g., tears, saliva and breast milk)
  20. 20. 20 Unit 3 Disturbances of the Immune System Clinical Manifestations Evaluation and Treatment In the absence of a cure for AIDS, patient management is focused on treating the various disorders resulting from the immune system dysfunction. A variety of therapies for the infections and malignancies commonly encountered in AIDS patients already exist while development of new ones is rapidly underway. However, due to the current impossibility of eliminating the virus or halting viral replication, the disease course is characterized by recurrent overwhelming infections and cancers which ultimately result in the patient’s death. Nursing management of AIDS patients includes interdependent and independent nursing functions. Interdependent functions include administration of medications, oxygen and intravenous fluids. Diligent observation and assessment of the patient’s responses to the prescribed therapeutic regimen are important nursing functions. Independent nursing interventions include maintaining nutritional status, comfort measures, patient education, skin and mouth care and psychosocial support. AIDS is a fatal disease which has a profound effect on all aspects of an individual’s life. The primary objective of nursing care is to assist the patient in meeting all of his biopsychosocial needs and strive to increase quality of life by providing holistic, compassionate nursing care. text for treatment, prevention and evaluation information. Surveillance The Centers for Disease Control expanded the case definition for AIDS in 1995 to include: •All human HIV infected adults and teens (who are 13 yrs or older) who have either: o < 200 CD4 + T lymphocytes/ul o < 14% CD4 + T cells relative to total lymphocyte count Or •Any of the following 3 clinical conditions (including HIV infection) o pulmonary TB o recurrent pneumonia, or o invasive cervical cancer Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  21. 21. The expanded case definition still contains the 23 other clinical conditions in the 1987 AIDS surveillance definition (Centers for Disease Control, 1992). Comprehensive, ongoing assessment of patients’ responses to treatment and overall status includes monitoring of T4 cell count in peripheral blood. T4 count below 400 cells/mm3 indicates profound immune system dysfunction and imminent danger of infections which very quickly can become life threatening. Arterial blood gases, hemoglobin levels, and granulocyte counts provide important information about oxygenation of blood, phagocytic potential in the presence of bacterial infections and the competency level of the bone marrow. Parameters such as blood albumin and blood urea nitrogen (BUN) provide the nurse with important information about the patient’s nutritional status. Frequent assessment of the neuropsychiatric status can lead to early detection of debilitating, life-threatening CNS infections.
  22. 22. 22 Unit 3 Disturbances of the Immune System Prognosis and Trajectory Following infection by the HIV, some individuals develop flu-like symptoms (low-grade fever, muscle weakness, fatigue). It is currently unknown whether all HIV seropositive individuals go on to develop AIDS but the time period between infection and onset of AIDS has been reported to be a long as 8-9 years and may be as long as 20 years or more. Development of symptoms such as lymphadenopathy, fatigue, fever, weight loss, night sweats and diarrhea marks the beginning of what is now know as HIV disease (formerly AIDS-related complex or ARC). When infections and cancers listed in the CDC (1987) case definition of AIDS develop, the individual has reached the last phase in the spectrum of HIV infection. The fatality rate of AIDS is 100% (Mann, Chin, Piot & Quinn, 1988). In the US between 80-90% of people with AIDS diagnosed before 1986 have already died (Heyward & Curran, 1988). More information can be obtained from: •Centers for Disease Control (1994). Revised classification system for human immunodeficiency varus infection in children less than 13 years of age. Morbidity & Mortality Weekly Report. (No. RR-12). •Also the following websites: Centers for Disease Control and Prevention http://www.cdc.gov/epo/mmwr/other/case_def/aids97.html University of California San Francisco HIV Insight http://hivinsite.ucsf.edu/akb/1997/o1class/index.html Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  23. 23. Learning Activity #1 Here is a quick quiz on AIDS (answers at the end of the section). Based on your reading, complete the following questions: 1. The cause of AIDS is: a. pneumocystic carinii b. human immunodeficiency virus c. human herpes virus 6 d. unknown 2. AIDS is characterized by a breakdown in: a. the humoral immune response b. the inflammation process c. the cell-mediated immune response d. macrophage activity 3. The cell type most profoundly depleted in AIDS is: a. B-cells b. macrophages c. T4 cells d. T8 cells 4. The opportunistic infection most commonly encountered in people with AIDS is: a. Pneumocystis carinii pneumonia b. Cryptosporidium c. Toxoplasmosis d. Salmonella 5. The cancer most commonly encountered in people with AIDS is: a. Testicular cancer b. Lymphoma c. Kaposi’s sarcoma d. colorectal cancer 6. AIDS has never been diagnosed in individuals belonging to which of the following groups: a. school children b. homosexual men c. intravenous drug users d. women of childbearing age e. none of the above
  24. 24. 24 Unit 3 Disturbances of the Immune System 7. Infection by the etiologic agents in AIDS can be transmitted by: a. semen only b. semen, blood, breast milk c. semen, blood, tears d. casual contact Study Questions The following questions are provided to help you synthesize the information you have obtained from your readings. It is highly recommended that you work on these in small groups. 1. A young woman has recently been diagnosed with AIDS. She has some questions about the cause and disease trajectory. How would you go about giving her the information? 2. A group of adolescents approach you with questions about AIDS. They specifically want to know how it is transmitted and how they can avoid the infection. What would you tell them? 3. An AIDS patient suffering from recurrent episodes of pneumocystic carinii pneumonia asks you for the reason behind this particular condition. What is your answer? Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  25. 25. Section 3: Immunodeficiency Immunodeficiency may be viewed as a diminished capability of the immune system to mount an immune response. The immune system may be diminished either in quantity or quality. You will recall the four types of immune response mentioned earlier: 1. Humoral antibody response 2. Cell mediated immunity (CMI) 3. Phagocytosis 4. Complement The first two listed above have been described. Let’s take a look at the other two. Phagocytosis Phagocytosis is a function of the neutrophils and macrophages. These cells are attracted to a site of inflammation and essentially ingest and destroy the invading organism. Complement The biochemical and immunological complexity of the complement system is beyond the scope of this unit, therefore only a brief overview will be given here. Complement is a plasma protein system consisting of a sequence of 9 proteins (C1 to C9The proteins are normally present in an inactive form, and their actions are closely involved with the inflammatory and the immune response. Complement may be activated by plasmin and thrombin. Both of these substances are present in acute inflammation. Enzymes that are released from dead neutrophils (i.e. after phagocytosis) may also activate complement. The complement system enhances the inflammatory response by: •opsonization of bacteria—this makes it easier for neutrophils and macrophages to phagocytose •attracting neutrophils to the site of inflammation by the use of chemical mediators—this process is known as chemotaxis •increasing vasodilation and permeability at the site of inflammation In immunodeficiency states one or more of these immune mechanisms may be involved. Immunodeficiency states may be classified as: •primary immunodeficiency (hereditary or congenital)
  26. 26. 26 Unit 3 Disturbances of the Immune System •secondary immunodeficiency (acquired after birth) Some Examples: 1. Secondary humoral (antibody) immunodeficiency • Multiple myeloma. This involves multiple malignant masses of plasma cells scattered throughout the skeletal system. (See pp. 910-912 of the course text) 2. Secondary cell mediated immunodeficiency • There may be transient suppression of CMI with temporary viral infections • Acquired immune deficiency syndrome is an example of a more permanent type of CMI immunodeficiency 3. Secondary phagocytic immunodeficiency •This type of immunodeficiency can be drug induced. Large amounts of steroids and/or other chemotherapeutic agents can severely suppress the number of phagocytic cells. 4. Primary complement immunodeficiency •A hereditary disease known as angio-edema is an example of an immunodeficiency state affecting the complement system. The disease causes local and painful edema in the skin, lungs and gastrointestinal tract. The C2 kinin pathway is involved causing uncontrolled increase in the permeability of the vessels at the affected sites. Hypersensitivity A hypersensitivity reaction occurs when an immune response contributes to tissue damage rather than recovery. The term is synonymous with allergic reaction. There are four types of reaction; only type 1 will be dealt with here. Type I Immediate or Anaphylactic This type of reaction is mediated by IgE. IgE and an antigen form an antigen-antibody complex on the surface of a mast cell with the release of large amounts of the vasoactive substance histamine. Histamine causes smooth muscle constriction (except for smooth muscle in blood vessels) an increase in permeability of blood vessels. This reaction is immediate and progressive. A generalized reaction is life threatening. Not only is histamine released from mast cells in the respiratory and gastrointestinal tracts but it is also released into the bloodstream from basophils. Basophils are white blood cells which act as circulating mast cells. Anaphylactic shock will be dealt with in a later unit Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  27. 27. Autoimmune Linked Disease 1. Systemic lupus erythematosus, 2. Hashimoto’s thyroiditis, 3. Rheumatoid arthritis
  28. 28. 28 Unit 3 Disturbances of the Immune System 4. References Ader, R. (Ed.). (1981). Psychoneuroimmunology. New York: Academic Press. AIDS Information. (1989). Oncology information services, 5(3). Leeds University Press: Author. Blalock, J. E. (1984). The immune system as a sensory organ. Journal of Immunology, 132(3), 1067-1070. Centers for Disease Control. (1981). Kaposi’s sarcoma and pneumocystis pneumonia among homosexual men: New York City and California. Morbidity and Mortality Weekly Review, 30, 305-307. Centers for Disease Control (1993). Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morbidity and Mortality Weekly Review.41(No.RR-17). Friendland, G. H., & Klein, R. S. (1988). Transmission of the human immunodeficiency virus: An updated review. International Nursing Review, 35(2), 44-54. Gallo, R. C., & Montagnier, L. (1988). AIDS in 1988. Scientific American, 259(4), 41-48. Giaguinto, W. L., De Rossi, A., & Laverda, A. (1988). Natural history of pediatric HIV infection (Abstract #7227). Fourth International Conference on AIDS. Stockholm, Sweden. Grady, C. (1988). HIV: Epidemiology, immunopathogenesis and clinical consequences. Nursing Clinics of North America, 23(4), 683-696. Heyward, W. L., & Curran, J. W. (1988). The epidemiology of AIDS in the U.S. Scientific American, 259(4), 72-81. Mann, J.M., Chin, J., Piot, P., & Quinn, T. (1988). The international epidemiology of AIDS. Scientific American, 259(4), 82-89. Petrie, K.J., Booth, R.J., Elder, H., & Cameron, L.D. (1999). Psychological influences on the perception of immune function. Psychological Medicine, 29, 391-397. Plant, S. M., & Friedman, S. B. (1981). Psychosocial factors in infectious disease. In R. Ader (Ed.), Psychoneuroimmunology, pp. 11-30. Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health States (7th ed). Philadelphia: Lippincott Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
  29. 29. Reckling, J., & Neuberger, G. (1987). Understanding immune system dysfunction. Nursing 87, 17(9), 34-41. Redfield, R. R., & Burke, D. S. (1988). HIV infection: The clinical picture. Scientific American, 259(4), 90-99. Royal Society of Canada. (1988). AIDS: A perspective for Canadians. Ottawa: Author. Solomon, G. F. (1987). Psychoneuroimmunology: Interactions between central nervous system and immune system. Journal of Neuroscience Research, 18, 1-9. Solomon, G. F., & Moos, R. H. (1964). Emotions, immunity and disease: A speculative theoretical integration. Archives of General Psychiatry, 11, 657-674. Soloman, P. (1990). Projections of the Australian AIDS epidemic. Royal Society of Medicine: The AIDS Letter, 21, 1-3. Taussig, M. (1984). Processes in pathology (2nd ed.). Scarborough: Blackwell Mosby Book Distributors. Van De Graaff, K. M., & Fox, S. I. (1992). Concepts of human anatomy and physiology (3rd ed.). Dubuque, IA: Wm. C. Brown Publishers. World Health Organization Web site (2000). http://www.unaids.org/epidemic_update/report/index. Report on global HIV/AIDS epidemic – June 2000.
  30. 30. 30 Unit 3 Disturbances of the Immune System Glossary Acronym List Checklist of Requirements u Read Print Companion: Disturbances of the Immune System u Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health States (7th ed). Philadelphia: Lippincott. Chapter 19 Answers to Learning Activities Learning Activity #1 1. b 2. c 3. c 4. a 5. c 6. e 7. b Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary

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