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Chapter 18 AIDS and Other Immune Disorders 9/1/12 MDufilho 1 Autoimmune Diseases • Occur more often in the elderly • Are more common in women than in men • May result when an individual begins to make autoantibodies or cytotoxic T cells against normal body components 9/1/12 MDufilho 2 Autoimmune Diseases • Causes of Autoimmune Diseases – Estrogen may stimulate destruction of tissue by cytotoxic T cells – Some maternal cells may cross the placenta and trigger autoimmune disease later in life – Environmental factors include viral infections – Genetic factors include certain MHC genes – T cells may encounter self-antigens that are normally “hidden” – Microorganisms may trigger autoimmunity because of molecular mimicry – Failure of the normal control mechanisms of the 9/1/12 MDufilho 3 immune system Autoimmune Diseases • Examples of Autoimmune Diseases – Two major categories – Systemic autoimmune diseases – Single-organ autoimmune diseases 9/1/12 MDufilho 4 Autoimmune Diseases • Type III (Immune Complex–Mediated) Hypersensitivity – Systemic lupus erythematosus – Autoantibodies against DNA result in immune complex formation – Many other autoantibodies can also occur – Against red blood cells, platelets, lymphocytes, muscle cells 9/1/12 . – Trigger unknown – Immunosuppressive drugs reduce autoantibody formation MDufilho inflammation – Glucocorticoids reduce 5 Figure 18.10 The characteristic facial rash of systemic lupus erythematosus 9/1/12 MDufilho 6 Autoimmune Diseases • Examples of Autoimmune Diseases – Single-organ autoimmune diseases – Autoimmunity affecting blood cells – Autoimmune hemolytic anemia – Autoimmunity affecting endocrine organs – Type I diabetes mellitus – Graves’ disease 9/1/12 MDufilho 7 Autoimmune Diseases • Examples of Autoimmune Diseases – Single-organ autoimmune diseases – Autoimmunity affecting nervous tissue – Multiple sclerosis – Autoimmunity affecting connective tissue – Rheumatoid arthritis 9/1/12 MDufilho 8 Immunodeficiency Diseases • Conditions resulting from defective immune mechanisms • Two general types – Primary – Result from some genetic or developmental defect – Develop in infants and young children – Acquired – Develop as direct consequence of some other recognized cause – Develop in later life 9/1/12 MDufilho 9 Immunodeficiency Diseases • Primary Immunodeficiency Diseases – Many inherited defects in all the body’s lines of defenses – Chronic granulomatous disease – Severe combined immunodeficiency disease (SCID) – DiGeorge syndrome – Bruton-type agammaglobulinemia 9/1/12 © 2012 Pearson Education Inc. MDufilho 10 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – Result from a number of causes – Severe stress – Excess production of corticosteroids suppresses cell-mediated immunity – Malnutrition and environmental factors – Inhibit production of B cells and T cells – Acquired immunodeficiency syndrome (AIDS) – Opportunistic infections, low CD4 cells, presence of HIV 11 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – AIDS pathogenesis and its virulence factors – Human immunodeficiency virus (HIV) – Retrovirus – Two major types – HIV-1 is prevalent in the United States and Europe – HIV-2 is prevalent in West Africa 12 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – AIDS pathogenesis and its virulence factors – Origin of HIV – Likely arose from mutation of the simian immunodeficiency virus (SIV) – Estimated to have emerged in the human population around 1930 13 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – Epidemiology of AIDS – HIV is transmitted primarily via sexual contact and intravenous drug use – HIV is also transmitted across the placenta and in breast milk – Certain behaviors increase the risk of infection – Anal intercourse – Sexual promiscuity – Intravenous drug use – Sexual intercourse with anyone engaging in the previous three behaviors 14 Table 18.6 Opportunistic Infections Associated with AIDS 15 Organisms causing infections Figure 18.19 The course of AIDS CD4 T cells/mm3 blood Death HIV RNA copies/ml plasma Primary infection Opportunistic diseases Clinical latency Weeks Years HIV in blood CD4 (helper) T cell count Antibody against HIV 17 18 Figure 18.15 Artist’s conception of HIV ssRNA genome gp120 gp41 tRNA Protease Envelope Integrase Reverse transcriptase Capsid 20 Figure 18.16 The replication cycle of HIV-overview 21 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – Epidemiology of AIDS – First recognized in young male homosexuals in the U.S. – Now found worldwide – HIV in blood, semen, saliva, vaginal secretions, and breast milk concentrated enough to cause infection – Must be injected into the body or contact a tear or lesion in the skin or mucous membranes 22 Figure 18.20 The global distribution of HIV/AIDS North America Western and Central Europe 1.4 million 850,000 Caribbean 240,000 Latin America 2 million Eastern Europe & Central Asia 1.5 million East Asia & Pacific North Africa & Middle East 310,000 South & Southeast Asia 850,000 3.8 million Sub-Saharan Africa 24.4 milion Australia & New Zealand 59,000 23 Figure 18.21 Modes of HIV transmission in males over 12 years of age in the U.S. during 2007 Adult Males Male homosexual contact plus use of injected drugs Use of injected drugs 3% 12% 32% Heterosexual contact 53% Other 0.5% Male homosexual contact 24 9/1/12 MDufilho 25 MDufilho Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – Diagnosis, treatment, and prevention – Diagnosis involves detecting antibodies against HIV – Can indicate infection with HIV but not presence of AIDS – Small percentage of infected individuals are long-term nonprogressors – Appear not to develop AIDS – Possibly because of defective virions, mutated coreceptors for the virus, or well-developed immune systems 27 Immunodeficiency Diseases • Acquired Immunodeficiency Diseases – Diagnosis, treatment, and prevention – Antiretroviral therapy (ART) – A “cocktail” of several antiviral drugs – Reduces viral replication, but infection remains – Vaccine development has been problematic – Diseases associated with AIDS are treated individually – Individuals can slow the AIDS epidemic with numerous personal decisions 28