Unformatted text preview: Immune System Disorders Immune System Disorders
Hypersensitivity (Allergy): An abnormal response to antigens. Four Types of Hypersensitivity Reactions:
s s s s Type I (Anaphylactic) Reactions Type II (Cytotoxic) Reactions Type III (Immune Complex) Reactions Type IV (Cell-Mediated) Reactions Type I (Anaphylactic) Reactions
x Occur within minutes of exposure to antigen x Antigens combine with IgE antibodies x IgE binds to mast cells and basophils, causing them to undergo degranulation and release several mediators:
Histamine: Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi). 3 Prostaglandins: Contraction of smooth muscle of respiratory system and increased mucus secretion. 3 Leukotrienes: Bronchial spasms.
3 x Anaphylactic shock: Massive drop in blood pressure. Can be fatal in minutes. Mast Cells and the Allergic Response Mast Cells and the Allergic Response Type II (Cytotoxic) Reactions
x Involve activation of complement by IgG or IgM binding to an antigenic cell. x Antigenic cell is lysed. x Transfusion reactions:
ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream. 3 Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.
3 Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta. Type III (Immune Complex) Reactions
x Involve reactions against soluble antigens circulating in serum. x Usually involve IgA antibodies. x Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage.
3 Glomerulonephritis: Inflammatory kidney damage. x Occurs with slightly high antigen-antibody ratio is present. Immune Complex Mediated Hypersensitivity Type IV (Cell-Mediated) Reactions
x Involve reactions by TD memory cells. First contact sensitizes person. 3 Subsequent contacts elicit a reaction.
3 x Reactions are delayed by one or more days (delayed type hypersensitivity).
3 Delay is due to migration of macrophages and T cells to site of foreign antigens. x Reactions are frequently displayed on the skin: itching, redness, swelling, pain. Tuberculosis skin test Poison ivy Metals Latex in gloves and condoms (3% of health care workers) x Anaphylactic shock may occur. Allergic Contact Dermatitis Response to Poison Ivy Hapten Autoimmune Diseases
Loss of self-tolerance leads to production of antibodies or T cells that react against one's own antigens. s Immune system response to self antigens causes damage to organs. s Three types of autoimmune disorders:
x Cytotoxic (Type II reactions) x Immune complex (Type III reactions) x Cell-mediated (Type IV reactions) Autoimmune Diseases A. Type II (Cytotoxic) Autoimmune Reactions Involve antibody reactions to cell surface molecules, without cytotoxic destruction of cells.
x Grave's Disease: Antibodies attach to receptors on thyroid gland and stimulate production of thyroid hormone. 3 Symptoms: Goiter (enlarged thyroid) and bulging eyes.
3 x Myasthenia gravis: Progressive muscle weakness. Antibodies block acetylcholine receptors at neuromuscular synapse. 3 Affects 25,000 Americans (mainly women). 3 Today most patients survive when treated with drugs or immunosuppressants.
3 Autoimmune Diseases
B. Type III (Immune Complex) Autoimmune Reactions
x Systemic Lupus Erythematosus: Affects about 200,000 Americans (90% women). 3 Name derived from red skin rash on face. 3 Autoantibodies react against DNA, blood cells, neurons, and other tissues. 3 When cells die, immune complexes form and deposit under skin, joints, in kidneys, blood vessels, and central nervous system. 3 Inflammation interferes with normal function of these sites (arthritis, rash, kidney damage). 3 Most patients die from kidney damage. 3 No cure. Symptoms treated with anti-inflammatory and immunosuppressive drugs.
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B. Type III (Immune Complex) Autoimmune Reactions (Continued)
x Rheumatoid Arthritis: Affects about 2 million Americans (70%+ women). 3 Cause unknown, but microbial mimicry may be involved. 3 IgM autoantibodies (rheumatoid factors) against IgG form complexes in joint, leading to inflammation and cartilage damage. 3 Often causes finger and joint deformities. 3 No cure. Symptoms treated with anti-inflammatory (aspirin) and immunosuppressive drugs. Physical therapy keeps joints movable. Surgical replacement of joints may be necessary.
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C. Type IV (Cell-Mediated) Autoimmune Reactions (Continued)
Mellitus: x Diabetes affects up to 5% of Americans. x In the U.S., 35,000 people die every year from all types of diabetes mellitus and complications (gangrene, kidney and cardiovascular disease, dehydration, and nerve damage).
3 x Insulin-dependent (Type I or Juvenile) Diabetes Insulin Dependent (Type I or Juvenile) Diabetes: Makes up 10% of diabetes cases. Characterized by insufficient insulin production due to immunological destruction of insulin-secreting cells of the pancreas by T cells. Usually develops before the age of 15. Treated with insulin injections. Acquired Immunodeficiency Syndrome (AIDS) History
x 1950s: Blood samples from Africa have HIV antibodies. x 1976: First known AIDS patient died. x 1980: First human retrovirus isolated (HTLV-1). x 1981: First reports of "Acquired Immunodeficiency Syndrome" in Los Angeles. x 1983: Virus first isolated in France (LAV). x 1984: Virus isolated in the U.S. (called HTLV-III and AIDS-Related Virus, ARV). x 1985: Development and implementation of antibody test to screen blood donors. Acquired Immunodeficiency Syndrome (AIDS) History (Continued)
x 1986: Consensus name Human Immunodeficiency Virus (HIV-1). Related virus (HIV-2) identified.
x 1992: AIDS becomes the leading cause of death among adults ages 25-44 in the U.S. x 1997: Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails. x 2001: World Health Organization predicts up to 40 million infected individuals. More than 22 million have already died. AIDS: A Leading Cause of Death Among People Aged 25-44 years in U.S.
40 35 30 25 20 15 10 5 0 1982 1986 1990 1994 AIDS Accidents Cancer Homicide Deaths per 100,000 people aged 25-44 years People Living with HIV/AIDS by End of 2001
Western Europe 560,000 East Europe & Central Asia 1'000,000 East Asia & Pacific 1'000,000 North America 950,000 Caribbean 420,000 North Africa & Middle East 500,000 South/South East Asia 5.6 million Latin America 1.5 million Sub-Saharan Africa 28.5 million Australia & New Zealand 15,000 Total: 40 million people Structure of the Human Immunodeficiency Virus HIV is a Retrovirus Life Cycle of HIV
1. Attachment: Virus binds to surface molecule (CD4) of T helper cells and macrophages.
3 Coreceptors: 3 CXCR4 Required for HIV infection. and CCR5 mutants are resistant to infection. 2. Fusion: Viral envelope fuses with cell membrane, releasing contents into the cell. HIV Life Cycle: Attachment Requires CD4 Receptor plus a Coreceptor Life Cycle of HIV
3. Reverse Transcription: Viral RNA is converted into DNA by unique enzyme reverse transcriptase. RNA ---------------------> DNA Reverse transcriptase is the target of several HIV drugs: AZT, ddI, and ddC.
Reverse transcriptase HIV Life Cycle: Reverse Transcriptase Converts RNA into DNA Life Cycle of HIV
4. Integration: Viral DNA is inserted into host cell chromosome by unique enzyme integrase. Integrated viral DNA may remain latent for years and is called a provirus. 5. Replication: Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated. HIV Life Cycle: Latent versus Active Infection HIV Life Cycle: Latent versus Active Infection in Macrophages AIDS Associated Disease Categories
1. Gastrointestinal: Cause most of illness and death of late AIDS. Symptoms:
x Diarrhea x Wasting (extreme weight loss) x Abdominal pain x Infections of the mouth and esophagus. Pathogens: Candida albicans, cytomegalovirus, Microsporidia, and African AIDS patient with slim disease Source: Tropical Medicine and Parasitiology, 1997 Opportunistic Oral Yeast Infection by Candida albicans in an AIDS Patient Source: Atlas of Clinical Oral Pathology, 1999 AIDS Associated Disease Categories
2. Respiratory: 70% of AIDS patients develop serious respiratory problems. Partial list of respiratory problems associated with AIDS:
3 3 3 3 3 3 Bronchitis Pneumonia Tuberculosis Lung cancer Sinusitis Pneumonitis Chest X-Ray of AIDS Patient with Tuberculosis AIDS Associated Disease Categories
3. Neurological: Opportunistic diseases and tumors of central nervous system. Symptoms many include: Headaches, peripheral nerve problems, and AIDS dementia complex (Memory loss, motor problems, difficulty concentration, and paralysis). AIDS Associated Disease Categories
4. Skin Disorders: 90% of AIDS patients develop skin or mucous membrane disorders.
3 Kaposi's sarcoma 1/3 male AIDS patients develop KS Most common type of cancer in AIDS patients Herpes zoster (shingles) 3 Herpes simplex 3 Thrush 3 Invasive cervical carcinoma
3 5. Eye Infections: 50-75% patients develop eye conditions.
CMV retinitis 3 Conjunctivitis
3 Extensive tumor lesions of Kaposis's sarcoma in AIDS patient. Source: AIDS, 1997 Chronic Herpes Simplex infection with lesions on tongue and lips. Source: Atlas of Clinical Oral Pathology, 1999. Non-Hodgkin's Lymphoma & ascites in AIDS patient Source: Tropical Medicine and Parasitiology, 1997 Drugs Against HIV
x Reverse Transcriptase Inhibitors: Competitive enzyme inhibitors. Example: AZT, ddI, ddC. x Protease Inhibitors: Inhibit the viral proteases. Prevent viral maturation. x Problem with individual drug treatments: Resistance. x Drug Cocktails: A combination of:
One or two reverse transcriptase inhibitors 3 One or two protease inhibitors.
3 x Drug cocktails have been very effective in suppressing HIV replication and prolonging the life of HIV infected individuals, but long term effectiveness is not clear. Stages of HIV Infection Antibody Levels, T Cell Counts, and HIV Concentration After Infection Transmission of AIDS (Worldwide)
1. Sexual contact with infected individual: All forms of sexual intercourse (homosexual and heterosexual). 75% of transmission. 2. Sharing of unsterilized needles by intravenous drug users and unsafe medical practices: 5-10% of transmission. 3. Transfusions and Blood Products: Hemophiliac population was decimated in 1980s. Risk is low today. 3-5% of transmission. 4. Mother to Infant (Perinatal): 25% of children become infected in utero, during delivery, or by breast-feeding (with AZT only 3%). 5-10% of transmission. HIV Transmission in United States and Rest of the World Perinatal Transmission of AIDS Source: Tropical Medicine and Parasitiology, 1997 ...
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- Fall '11
- Autoimmune Diseases, HIV Life Cycle, aids patient, autoimmune reactions