Acquired Immunodeficiency Syndrome (AIDS) Caused by HIV

Mary E. Miller

• Verlag: Momentum Press
• Jahr: 2017
• ISBN:
  9781944749941
• Thema: Ciencias biológicas
• Thema: Genética y genómica

Acquired immunodeficiency syndrome, or AIDS, is a disease of the im¬mune system that is caused by the human immunodeficiency virus (HIV). AIDS has caused significant loss of life with considerable social and eco¬nomic consequences worldwide. HIV must infect a host cell in order to replicate, and once infected, the host cell is unable to function properly. Since HIV infects specific cells of the host immune system, HIV infec¬tion impairs the ability of the patient to fight infections and kill cancer cells, therefore most deaths associated with HIV infection occur due to cancer or opportunistic infections. There is no cure for HIV, but advance¬ments in treatments mean that an HIV positive person could experience a normal lifespan with sustained daily care and medication designed to prevent HIV replication and spread. These medications primarily target viral proteins that allow HIV to infect host cells, replicate, and spread in the body. Work continues to find a way to eliminate HIV from patients and develop new pharmaceutical targets to address concerns of drug re¬sistant strains of HIV. Worldwide awareness of how the virus infects, is treated, and spreads within populations is a critical component to control the current AIDS pandemic.

CHAPTER 1

Symptoms and Diagnosis of Acquired Immune Deficiency Syndrome (AIDS)

AIDS is a progressive disease of the immune system. In AIDS, HIV infection causes damage to specific cells of the immune system, leading to symptoms associated with decreased immune function. The symptoms of AIDS are related primarily to the ability of the HIV virus to infect only a few types of cells in the human body—particularly those cells that express the receptor cluster of differentiation 4 (CD4). CD4 is expressed only in a small percentage of cells in the immune system (CD4+, pronounced CD4 positive). To fully understand the symptoms of AIDS and the pathogenic effect of HIV infection, it is important to understand how our immune system normally works, the cells that are involved, and the role that CD4+ cells play in immunity. The human immune system is complex, where the impairment of one component can have a dramatic effect on the function of many aspects of immunity. In the case of HIV, immune system complexity is particularly problematic since the normal progress of HIV infection destroys the very immune cells needed to fight infections.

CD4 is expressed on the surface of specific immune cells, mostly T cells, though there are other types of CD4+ immune cells. T cells are a type of lymphocyte, which is a type of white blood cell. White blood cells play a critical role in immune response, and unlike red blood cells, lymphocytes do not transport oxygen through the body. Both red and white blood cells are originally formed from hematopoietic stem cells located in the bone marrow, the soft internal region of the bone that supports cellular growth and replenishment. Hematopoietic stem cells reproduce and differentiate into several different cell types, including lymphocytes. Stem cells differentiate into B cells or T cells, and T cells are able to migrate to the thymus as part of their maturation. B and T cells are each capable of interacting with foreign molecules in the body, and stimulating a response that will help remove them. Molecules that trigger a response from a B or T cell are called antigens, and antigens are often proteins encoded by non-human genomes. When a human protein receptor on a lymphocyte binds to an antigen, the immune cell triggers an immune response. In this way, antigens encoded by viruses or bacteria can be identified, targeted, and destroyed by our immune system.

Collectively, a person’s population of B and T cells can interact with a vast variety of antigens. However, any given B cell or T cell produces many copies of only one type of specific antigen receptor, each of which can bind to only one specific type of antigen. When an individual B cell physically binds to its antigen, the B cell rapidly produces more receptor-like molecules that are secreted from the B cell into the fluids of the body. These secreted versions of the receptors are called antibodies (Ab) or immunoglobulins (Ig), which can bind to the same antigen type. B cells allow the immune system to recognize antigens in the fluids of the body because B cells produce antibodies that circulate in our blood and lymph where they can bind to antigens and target them for removal by an efficient immune response. Frequently, scientists isolate antibodies as treatment for disease because these proteins bind tightly to specific proteins of a pathogen and target that pathogen for destruction. Antibodies can also be used as diagnostic tools, since the presence of a pathogen in a patient can be detected when the patient’s antibodies bind very tightly to it. Some forms of tests for HIV infection make use of a patient’s antibodies in this way.

T cells do not secrete their antigen receptor, nor do they make antibodies. T cells receptors are activated by antigens that are displayed on the surface of particular types of cells that use a set of proteins called the major histocompatibility complex (MHC), also in humans referred to as human leukocyte antigen (HLA). Most cells in our body, with the exception of red blood cells, display MHC class I (MHC I) on their surfaces. Specialized lymphocytes produce MHC class II (MHC II) proteins on their surfaces. These MHC protein complexes function as an antigen-presenting system for T cells and their receptors. Generally, MHC I molecules display small segments of proteins (called peptides) that are translated in the same cell that displays the peptide. MHC II molecules display peptides that were originally produced outside the cell displaying it. For example, a host cell such as a macrophage might engulf an invading pathogenic bacterium in order to kill the invading cell. Protein components of the bacteria are bound by MHC II, and moved to the surface of the macrophage so that the captured bacterial protein antigen is “presented” on the outside of the macrophage. When the bacterial antigen peptide is displayed on the surface of a cell by an MHC II molecule, a T cell receptor on the surface of the T cell might be able to recognize and bind to the antigen/MHC complex on the surface of an antigen-presenting cell. The CD4 protein displayed on the surface of T cells helps the T cell receptor bind to antigen presented with MHC II. CD4 also binds directly to antigen presented by MHC II molecules. If the population of CD4+ T cells drops in the body, the immune system is crippled in its ability to recognize antigen-presenting cells, and therefore is crippled in its ability to mount a vigorous immune response triggered by pathogenic antigens.

To summarize, when a T cell receptor interacts with an MHC plus peptide, the T cell receptor activates its T cell and initiates an immune response. The type of response depends on the type of T cell (and cognate MHC type) involved. CD4+ cells capable of being infected by HIV include helper T cells, monocytes, macrophages, and dendritic cells. Helper T cells recognize MHC II plus antigen, whereas cytotoxic T cells (also called CD8+ cells) recognize MHC class I plus antigen. Helper T cells produce cytokines, molecules that are secreted from the cell to stimulate other immune cells, such as B cells. In this way, appropriate B cell function requires a healthy population of CD4+ T cells. When HIV infects and impairs the function of CD4+ cells, it broadly limits the immune system. People with reduced numbers of CD4+ cells have weakened response to infections which can lead to opportunistic infections and cancers that normally are eliminated by a healthy and vigorous immune system.

As HIV infects cells of the immune system, symptoms of infection are described in three stages. These stages are defined by the amount of virus present in the patient, or viral load, and the loss of CD4+ T cells of the host immune system. Stage 1 is considered an acute infection and occurs between two to four weeks after infection by the virus. Stage 1 symptoms include flu-like symptoms such as fever, chills, rash, night sweats, sore throat, muscle aches, swollen lymph nodes, and mouth ulcers. Some individuals do not feel sick during stage 1, and do not feel any symptoms. Stage 2 is clinical latency, also referred to as asymptomatic HIV, or a chronic HIV infection. During stage 2, an individual has very low levels of HIV replication with very mild or no discernable symptoms. A stage 2 individual can spread the virus, and remains in stage 2 for a variable amount of time, from weeks to decades. If viral replication is triggered and the viral load increases, the infection progresses to stage 3 which is when most patients are diagnosed with AIDS. Stage 3 is when a patient’s CD4+ T cell count drops below 200 cells/mm³ (cells per cubic millimeter) of blood, whereas a healthy person has 500–1600 cells/mm³ CD4+ cells. Symptoms during stage 3 may include fever, chills, sweating, swollen lymph glands, weight loss, and fatigue. When the immune system is compromised in an AIDS patient, the likelihood of opportunistic infections increases. If an individual in stage 2 is diagnosed with any one of the following opportunistic infections, their diagnosis is moved to stage 3 even if their CD4+ count is greater than 200 cells/mm³.

• Candidiasis of the trachea, bronchi, esophagus, or lungs is caused by the fungus Candida

• Invasive cervical cancer

• Coccidioidomycosis pneumonia caused by the fungus Coccidioides immitis

• Cryptococcosis pneumonia caused by the fungus Cryptococcus neoformans

• Cryptospporidiosis diarrheal disease for more than one month caused by the protozoan Cryptosporidium

• Cytomegalovirus diseases, particularly of the retina but also including pneumonia, gastroenteritis, and brain infection

• HIV related encephalopathy of the brain

• Herpes simplex virus associated ulcers for more than one month, bronchitis, pneumonia, or esophagitis.

• Histoplasmosis pneumonia caused by the fungus Histoplasma capsulatum

• Isosporiasis intestinal disease for more than one month caused by the protozoan Isospora belli

• Kaposi’s sarcoma cancer caused by Kaposi’s sarcoma herpesvirus or human herpesvirus 8

• Many types of lymphoma (cancer of the lymph system)

• Tuberculosis of the lungs caused by the bacterium Mycobacterium tuberculosis

• Mycobacterium avium complex

• Pneumonia caused by the parasite Pneumocystis carinii

• Pneumonia that recurs in one or both lungs

• Progressive multifocal leukoencephalopathy of the brain and spinal cord caused by the John Cunningham (JC) virus.

• Salmonella septi...