Immune Deficiency in Cancer

Chapter 8 This chapter outlines the different types of immune system alterations, specifically hypersensitivity reactions and deficiencies in immunity. Hypersensitivity reactions can be categorized by the immunologic mechanism causing the disease and the source of the antigen being attacked by the immune system. There are four main types of hypersensitivity reactions: type I (IgE-mediated reactions), type II (tissue-specific reactions), type III (immune complex-mediated reactions), and type IV (cell-mediated reactions). Immune deficiency in cancer Cancer cells can inhibit the immune response and release immunosuppressive chemicals Late-stage malignancies often result in a generalized deficiency of the immune response, making individuals more susceptible to infections Mechanisms include bone marrow replacement, decreased function of NK and T lymphocytes, and release of immunosuppressive chemicals Immunosuppressive treatments A wide range of medications can affect the immune response, including anesthetics, analgesics, antithyroid medications, and antimicrobial agents, among others Treatments intentionally used to suppress the immune system, such as corticosteroids, can control hypersensitivity diseases and prevent rejection of transplanted tissues Chemotherapy and irradiation treatments for cancer can also deplete the immune system Acquired immunodeficiency syndrome (AIDS) HIV infection leads to AIDS, a secondary immune deficiency HIV suppresses CD4-positive Th cells, which are crucial for the development of both humoral and cellular immunity AIDS is the most advanced stage of HIV infection and creates a generalized immune deficiency HIV/AIDS statistics As of 2017, there were 36.9 million people living with HIV/AIDS worldwide, with the majority in Sub-Saharan Africa Approximately 1.8 million people became infected with HIV in 2016 About 75% of people with HIV know their status, and 21.7 million were accessing antiretroviral therapy by the end of 2017 Transmission of HIV HIV infection is a bloodborne infection Typical routes of transmission include blood or blood products, intravenous drug abuse, sexual activity, and maternal-child transmission The most common route worldwide and in the United States is through heterosexual activity Children can contract HIV from their mothers across the placenta, during delivery, or through breastfeeding Pathogenesis of AIDS HIV is a retrovirus that carries genetic information in the form of single-stranded RNA HIV structure includes enzymes (reverse transcriptase, integrase, protease) and glycoproteins on its surface The first step of the HIV life cycle is attachment to the target cell through binding to CD4 molecules and chemokine coreceptors Fusion of the virus to the cellular membrane allows the release of the viral capsid into the target cell Antiretroviral medications can block viral attachment and fusion Once inside the target cell, HIV reverse transcriptase converts RNA into DNA, which is then inserted into the cell's genetic material by HIV integrase If the cell is activated, viral information is transcribed and translated, leading to the production of viral components The viral enzyme HIV protease processes the viral components and assembles the virion core Antiretroviral medication A group of antiretroviral medications can block different steps in viral attachment, fusion, and replication HIV Life Cycle and Drug Intervention: HIV infection begins with attachment and fusion of the virus to host cells Reverse transcription converts viral RNA into DNA The provirus is integrated into the host cell genome HIV proteins are synthesized and virion assembly occurs Budding and release of new virions complete the life cycle Drug interventions can target different stages of the life cycle Clinical Manifestations of AIDS: AIDS is primarily characterized by the depletion of Th cells This leads to a weakened immune response to infections and cancers At the time of diagnosis, individuals may present with various conditions AIDS-Defining Opportunistic Infections and Neoplasms: Various infections, including protozoal, helminthic, fungal, and bacterial infections, may occur in individuals with HIV infection These infections can affect different organs and systems in the body Salmonella infections (septicemia, recurrent) Salmonella infections can lead to septicemia and may recur Viral Infections Cytomegalovirus can affect the pulmonary, intestinal, retinal, or CNS Herpes simplex virus can cause localized or disseminated infections Progressive multifocal leukoencephalopathy is a viral infection Varicella-zoster virus can cause localized or disseminated infections Neoplasms Invasive cancer of the uterine cervix Kaposi sarcoma Non-Hodgkin lymphomas such as Burkitt and immunoblastic Primary lymphoma of the brain Stages of HIV Infection Acute HIV syndrome Wide dissemination of the virus Seeding of lymphoid organs Opportunistic diseases can occur Clinical latency with no symptoms Constitutional symptoms may appear Severe CD4+ T cell suppression leading to AIDS Diagnostic and Screening CDC recommends routine screening for HIV infection HIV is diagnosed by measuring HIV antibodies, HIV p24 antigen, and confirmed by HIV DNA tests Symptoms and Progression Early-stage HIV disease presents with mild symptoms resembling influenza More serious symptoms and signs appear as the disease progresses AIDS Diagnosis AIDS is diagnosed when HIV infection is associated with various clinical conditions These conditions include opportunistic infections, cancers, and chronic diseases A CD4+ T cell count of <200/mm³ is indicative of AIDs