Lecture 13 - Autoimmune Diseases, HIV, AIDS PDF

Adaptive Immunity Autoimmune diseases, HIV, AIDS  Adaptive Immune System ▪ Adaptive immunity is the body’s ability to react specifically to a microbial infection. ▪ The body’s response to the first contact with a particular antigen is called the primary response. Specifi...

Adaptive Immunity Autoimmune diseases, HIV, AIDS  Adaptive Immune System ▪ Adaptive immunity is the body’s ability to react specifically to a microbial infection. ▪ The body’s response to the first contact with a particular antigen is called the primary response. Specific cells are activated to destroy the antigen. ▪ Memory cells respond to subsequent contact with the same antigen.  Types of Specific Immunity Humoral immunity – also called antibody- mediated immunity – based on antibody activity Cellular immunity – also called cell-mediated immunity – based on action of specific kinds of T lymphocytes T cell and B cell development  Antigens ▪ An antigen (or immunogen) is a chemical substance that causes the body to produce specific antibodies. ▪ As a rule, antigens are proteins or large polysaccharides. Antibodies are formed against specific regions on antigens called epitopes, or antigenic determinants.  Antigens ▪ A hapten is a low-molecular-mass substance that cannot cause the formation of antibodies unless combined with a carrier molecule; haptens react with their antibodies independently of the carrier molecule. ▪ e.g., penicillin  Antibodies ▪ An antibody, or immunoglobulin, is a protein produced by B cells in response to an antigen and is capable of combining specifically with that antigen.  Immunoglobulin Classes ▪ IgG antibodies are the most prevalent in serum; they provide naturally acquired passive immunity, neutralize bacterial toxins, participate in complement fixation, and enhance phagocytosis. ▪ IgM antibodies consist of five monomers held by a joining chain; they are involved in agglutination and complement fixation. ▪ IgA antibodies are monomers; secretory IgA antibodies are dimers that protect mucosal surfaces from invasion by pathogens. ▪ IgD antibodies are on B cells; they may assist the immune response. ▪ IgE antibodies bind to mast cells and basophils and are involved in allergic reactions.  Immunological Memory ▪ The relative amount of antibody in serum is called the antibody titer. ▪ The peak IgG titer in the primary response occurs 10–17 days after exposure to an antigen. ▪ The peak titer in the secondary response occurs 2–7 days after exposure.  Types of Adaptive Immunity ▪ Immunity resulting from infection is called naturally acquired active immunity; this type of immunity may be long-lasting. ▪ Antibodies transferred from a mother to a fetus (transplacental transfer) or to a newborn in colostrum results in naturally acquired passive immunity in the newborn; this type of immunity can last up to a few months. ▪ Immunity resulting from vaccination is called artificially acquired active immunity and can be long-lasting. ▪ Artificially acquired passive immunity refers to humoral antibodies acquired by injection; this type of immunity can last for a few weeks. ▪ Serum containing antibodies is often called antiserum or gamma globulin.  Autoimmune Diseases Autoimmune disease - the immune system acts in response to self-antigens and causes damage to one’s own organs. Risk factors - hormone differences, genetic susceptibility, previous infections, vitamin D deficiency. Autoimmune reactions, and the diseases they cause, can be cytotoxic, immune complex, or cell-mediated in nature.  Cytotoxic Autoimmune Reactions Multiple sclerosis - neurological disease in which autoantibodies, T cells, and macrophages attack the myelin sheath of nerves. Symptoms include fatigue, weakness, in some cases, eventual severe paralysis. The Epstein-Barr virus is considered as a prime suspect. No cure Treatment with interferons, monoclonal antibodies, and several drugs.  Immune Complex Autoimmune Reactions Graves’ disease - condition when the thyroid gland is stimulated to produce increased amounts of thyroid hormones. Myasthenia gravis - disease in which muscles become progressively weaker. Muscles controlling the diaphragm and the rib cage may fail to receive the necessary nerve signals, and respiratory arrest and death result. Systemic lupus erythematosus - systemic autoimmune disease involving immune complex reactions result from deposits of immune complexes in the kidney glomeruli. Rheumatoid arthritis is a disease in which immune complexes of IgM, IgG, and complement are deposited in the joints.  Cell-Mediated Autoimmune Reactions Insulin-dependent diabetes mellitus - common condition caused by immunological destruction of insulin-secreting cells of the pancreas. Psoriasis is an autoimmune disorder. Symptoms - itchy, red patches of thickened skin. Treatment - with immunosuppressants that target T cells Autoimmune disorders  Stem Cells Stem cells are capable of renewing themselves and can be differentiated into other organ-specific specialized cells. Embryonic stem cells (ESCs) can be harvested from a blastocyst. Stem cells attracts great interest in medicine.  Bone Marrow Stem Cells Recipients lack the capacity to produce B cells and T cells vital for immunity or who are suffering from leukemia. The aim of bone marrow transplants is to enable the recipient to produce healthy red blood cells. Such transplants can result in graft-versushost (GVH) disease.  Grafts Graft - transfer of a tissue from one part of the body to another, or from one person to another, without the transfer of the blood supply of the grafted tissue. - Autograft - Isograft - Allografts Xenotransplantation products - tissues or organs that have been transplanted from animals.  Immune System and Cancer Cancer cells are normal cells that have undergone transformation, divide uncontrollably, and possess tumor-associated antigens. The response of the immune system to cancer is called immunological surveillance. Cytotoxic T lymphocytes recognize and lyse cancerous cells.  Immunotherapy for Cancer Prophylactic vaccines against liver and cervical cancer are available. HPV and HBV vaccines protect against some cancers. Herceptin consists of monoclonal antibodies against a breast cancer growth factor. Immunotoxins are chemical poisons linked to a monoclonal antibody; the antibody selectively locates the cancer cell for release of the poison.  Immunodeficiencies Immunodeficiencies can be congenital or acquired. Congenital immunodeficiencies are due to defective or absent genes. A variety of drugs, cancers, and infectious diseases can cause acquired immunodeficiencies.  Acquired Immunodeficiency Syndrome (AIDS) HIV Infection The Structure of HIV Retrovirus, genus Lentivirus RNA virus Glycoprotein spikes termed gp120 gp41 The Infectiveness and Pathogenicity of HIV Latent and active HIV infection in CD41 T cells Latent and active HIV infection in macrophages  Subtypes of HIV HIV-1 - 99% of cases worldwide Almost half of people diagnosed with HIV-1 have subtype C. HIV-2 is endemic in West Africa  The Stages of HIV Infection HIV infection is categorized by clinical phases: phase 1 (asymptomatic), phase 2 (indicator opportunistic infections), and phase 3 (CD4+ cells < 200 cells/μl). The progression from HIV infection to AIDS takes about 10 years. The life of an AIDS patient can be prolonged by the proper treatment of opportunistic infections. Long-term survivors and elite controllers may hold the key to HIV treatment.  Diagnostic Methods Serological Blood tests to detect HIV antibodies. Rapid tests using urine, fingerstick or blood Seroconversion – time between infection and the appearance of detectable antibodies. PCR  HIV Transmission Transfer or direct contact with, infected body fluids such as blood and semen. Kissing is not known to transmit HIV Transmission include sexual contact, breast milk, transplacental infection of a fetus, blood-contaminated needles, organ transplants, artificial insemination, and blood transfusion. AIDS Worldwide  Preventing and Treating AIDS Preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) for HIV are used to prevent infection after a recent exposure. Antiretroviral Therapy (ART) Fusion and Entry Inhibitors Reverse Transcriptase Inhibitors Integrase Inhibitors Protease Inhibitors Vaccine development is difficult because there are different antigenic clades and the virus remains inside host cells. References Gerard J. Tortora, Berdell R. Funke, Christine L. Case - Microbiology_ an introduction-Pearson (2018), Chapter 19