Secondary Immunodeficiency PDF

Secondary Immunodeficiency Prepared by: Dr. Ghada Ali 1 Objectives 1. Discuss the important properties and transmission of HIV 2. Discuss the immunological virological basis of HIV/AIDS 3. Define AIDS, and differentiate a disease from a syndrome 4. Discuss opportunistic infections rel...

Secondary Immunodeficiency Prepared by: Dr. Ghada Ali 1 Objectives 1. Discuss the important properties and transmission of HIV 2. Discuss the immunological virological basis of HIV/AIDS 3. Define AIDS, and differentiate a disease from a syndrome 4. Discuss opportunistic infections related to AIDS 5. Explain the impact of HIV on tuberculosis patients 2 Acquired immunodeficiency syndrome (AIDS)  Acquired immunodeficiency syndrome (AIDS).  From the time of its discovery in 1981 among homosexual males in the United States to its emergence as a worldwide pandemic, no affliction has affected modern life as much.  Belong to the lentivirus subfamily of the retroviridae.  A person infected with HIV is considered to be infected for life. 3 Acquired immunodeficiency syndrome (AIDS)  This is due to greatly reduced helper T cell numbers caused by infection with the retrovirus human immunodeficiency virus (HIV)  NOTE: HIV infection with HIV is not AIDS; HIV infection typically leads to AIDS in untreated patients.  AIDS: 1. The presence of several opportunistic or rare infections along with infection by human immunodeficiency virus (HIV). 2. Severe decrease in the number of lymphocytes called helper T cells (less than 200 cells /μL of blood) and a positive test showing the presence of HIV. 4 Important Properties of HIV  HIV are medically important members of the retrovirus family.  Enveloped virus.  Icosahedral capsid  With reverse transcriptase type called retroviruses, because it uses reverse transcriptase to make a DNA copy of its genome in the virion  Two copies of a single-stranded, positive-polarity RNA (+ssRNA) genome. 5  HIV  Two antigenic glycoproteins characterize its envelope:  The larger glycoprotein, named gp120, is the primary attachment molecule of HIV.  The smaller glycoprotein, gp41, promotes fusion of the viral envelope to a target cell. 6 7 Causative organism (HIV)  The effects of these structural characteristics—antigenic variability and the ability to fuse with host cells—interfere with clearance of HIV from a patient.  Its antigenicity changes during the course of prolonged infection, making an effective antibody response against it difficult.  The gene that encodes gp120 mutates rapidly, resulting in many antigenic variants.  Antibodies against p24 do not neutralize HIV infectivity but serve as important serologic markers of infection. 8 Transmission  Sexual contact (including vaginal, anal, and oral sex, either homosexual or heterosexual).  Intravenous drug abuse.  Blood transfusions.  Organ transplants.  Tattooing.  Accidental medical needle sticks rarely.  Across the placenta and breast milk. 9 Pathogenesis 1. HIV uses gp120 and gp41 to attach to and enter target cells through CD4 on a target cell’s. 2. Endocytosis: The CD4-gp120 complex binds to another membrane receptor, called Fusin (also known as CXCR4), which triggers the cell’s membrane to move out and surround the virus forming an endosome. 3. GP 41 on the viral envelope evidently then facilitates fusion of the envelope with the endosome membrane letting the viral capsid to be introduced intact into the cell’s cytosol. 4. The viral capsid uncoats, releasing viral RNA and proteins. 10 Pathogenesis 11 Clinical course 1. In the acute stage:  Which usually begins 2 to 4 weeks after infection.  A mononucleosis like picture of fever, lethargy, sore throat, and generalized lymphadenopathy occurs.  A maculopapular rash on the trunk, arms, and legs (but sparing the palms and soles).  leukopenia occurs, but the number of CD4 cells is usually normal.  A high-level viremia typically occurs, and the infection is readily transmissible during this acute stage. 12 Clinical course  The lower limit of CD4 count considered as normal is 500 cells/µL. People with this level or higher are usually asymptomatic.  The frequency and severity of opportunistic infections significantly increase when the CD4 counts fall below 200 cell/µL.  A CD4 count of 200/µL or below is an AIDS-defining condition. 13 Clinical course 2. Middle stage of HIV infection (latent period) long measured in (7- 11) years.  The patient is asymptomatic during this period.  A syndrome called AIDS-related complex (ARC) can occur during the latent period.  The most frequent manifestations are persistent fevers, fatigue, weight loss, and lymphadenopathy 14 Clinical course  No specific symptoms accompany this stage, and the patient is often unaware of the infection.  Integrated viruses continue to replicate and virions are released into the blood to such an extent that the body cannot make enough helper T cells.  Over the course of 5–10 years, the number of helper T cells declines to a level that severely impairs the immune response.  The rate of antibody formation falls precipitously as helper T cell function is lost. 15 Clinical course 3. The late stage: of HIV infection is AIDS, manifested by a decline in the number of CD4 cells to below 200/µL and an increase in the frequency and severity of opportunistic infections. 16  Clinical course 17 Immunological virological basis of HIV/AIDS  Physicians diagnose AIDS based on unexplained weight loss, fatigue, fever, and fewer than 200 CD4 lymphocytes per microliter (μl)10 of blood combined with other signs and symptoms, which vary according to the diseases involved  Demonstration of antibodies against HIV. Recall that by definition AIDS is the presence of one or more rare diseases and anti-HIV antibodies 18 Opportunistic Infections (example) Protozoal Pneumocystis carinii (now thought to be a fungi), toxoplasmosis, crytosporidosis Fungal Candidiasis, Crytococcosis meningitis Coccidiodomycosis, and disseminated histoplasmosis; Bacterial Mycobacterium avium complex, MTB atypical mycobacterial disease Salmonella septicaemia multiple or recurrent pyogenic bacterial infection 19 Opportunistic Tumours  The most frequent opportunistic tumour, Kaposi's sarcoma, is observed in 20% of patients with AIDS.  KS is observed mostly in homosexuals and its relative incidence is declining. It is now associated with a human herpes virus 8 (HHV-8).  Malignant lymphomas are also frequently seen in AIDS patients.  The two most characteristic manifestations of AIDS are Pneumocystis pneumonia and Kaposi’s sarcoma. 20 Kaposi’s Sarcoma 21 Laboratory Diagnosis  Serology is the usual method for diagnosing HIV infection.  Screening assays - ELISA  Confirmatory assays - Western blot 22 Laboratory Diagnosis  The presumptive diagnosis of HIV infection is made by the detection of antibodies in the patient’s serum to the p24 protein of HIV using the (ELISA) test.  Because there are some false-positive results with ELISA test, the definitive diagnosis is made by Western blot (also known as Immunoblot) analysis.  OraQuick is a rapid screening immunoassay for HIV antibody that uses an oral swab sample that can be done at home. Results are available in 20 minutes. 23 Laboratory Diagnosis  The inability to detect antibodies prior to that time can result in “false-negative” serologic tests (i.e., the person is infected, but antibodies are not detectable at the time of the test). BUT can be transmit the disease to others during this period.  If the antibody test is negative but HIV infection is still suspected, then a polymerase chain reaction (PCR)–based assay for the amount of viral RNA in the plasma (i.e., the viral load).  The amount of virus produced (i.e., the viral load) is important in the prognosis of infection and guide treatment decisions. 24 Laboratory Diagnosis  The number of CD4-positive T cells is another important measure that guides the management of infected patients.  It is used to determine whether a patient needs chemoprophylaxis against opportunistic organisms, to determine whether a patient needs anti-HIV therapy, and to determine the response to this therapy.  The lower limit of CD4 count considered as normal is 500 cells/µL. People with this level or higher are usually asymptomatic.  The frequency and severity of opportunistic infections significantly increase when the CD4 counts fall below 200/µL.  A CD4 count of 200/µL or below is an AIDS-defining condition 25 Prognostic tests  It is important to monitor the patient regularly for signs of disease progression and response to antiviral chemotherapy.  HIV viral load - HIV viral load in serum may be measured by assays which detect HIV-RNA e.g. RT-PCR.  HIV Antigen tests - CD4 counts IS MORE effective. 26  HIV has three main mechanisms by which it evades the immune system: 1. Integration of viral DNA into host cell DNA, resulting in a persistent infection. 2. High rate of mutation of the env gene 3. The production of proteins that down regulate class I MHC proteins required for cytotoxic T cells to recognize and kill HIV-infected cells. The ability of HIV to infect and kill CD4- positive helper T cells further enhances its capacity to avoid destruction by the immune system. 27  HIV and Tuberculosis  Patients deficient in cellular immunity, such as patients with AIDS, are at much higher risk for disseminated, life-threatening tuberculosis.  It can disseminate via the bloodstream to many internal organs. Dissemination can occur at an early stage if cell-mediated immunity fails to contain the initial infection or at a late stage if a person becomes immunocompromised. 28  HIV and Tuberculosis  In immunocompromised patients such as those with AIDS who have CD4 cell counts of less than 200/mL.  M. avium-intracellulare complex is the most common bacterial cause of disease in AIDS patients. The organisms are widespread in the environment, including water and soil.  They are highly resistant to antituberculosis drugs.  Clarithromycin is currently recommended for preventing disease in AIDS patients. 29 Reference  Bauman, Robert W., Elizabeth Machunis-Masuoka, and Cecily D. Cosby. Microbiology: With diseases by body system. 4th ed. Benjamin Cummings, 2012  Levinson, Warren. Review of medical microbiology and immunology. 13rd ed. The McGraw-Hill Companies, 2014. page 717-721 30 31