Immunodeficiency Disorders

Immunodeficiency disorders Dr. Mehzabin Ahmed

Immuno deficiency Diseases: Classification 1) Primary immuno deficiency 2) Acquired immuno deficiency

Primary immuno deficiency diseases

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May affect one or multiple components of the immune system including B cells, macrophages, NK cells and complement

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they are characterized by 

increased susceptibility to infection,

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↑ incidence of autoimmunity and malignancy.

E.g.: B cells - X- linked agamma globulinemia common variable deficiency. T cells - Di George's syndrome B&T cells - Severe combined immuno deficiency Complement - Defects in specific complement components.

Acquired immuno deficiency

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A variety of agents including drugs, irradiation, and ultraviolet light can produce acquired immuno deficiency.

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However, chronic infection with HIV, which causes acquired immuno deficiency is very important. 

HIV binds to the surface glycoprotein GP 120 on the T helper cells. The expression of CD4 allows this binding

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entry of virus is facilitated by chemokine receptors such as CCR5 - CCR2

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persistent infection follows and the continuous deletion of CD4+ T cells and accompanying destruction of cytotoxic T lymphocyte and B lymphocytes results in host becoming more susceptible to opportunistic infections.

HIV infection 

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Mode of spread is by sexual contact, Parental inoculation (infected syringes & needles) and from mother to child (vertical transmission) HIV binds to CD4 receptors on helper T cells. It gets internalized and after reverse transcription gets integrated into host genome and  may remain latent for months to years or  may form complete viral particles that may bud off the cell membrane.  Extensive budding leads to cell death. Along with this method of T cells loss, apoptosis of normal or uninfected CD4+ T cells occurs. Thus there is a rapid T cell depletion. In addition to T cells, monocytes and macrophages, which also carry the CD4 molecules, are infected.  They serve as reservoirs of the virus and to transport the virus to the nervous system.  In the late stages, when T cells numbers decline rapidly, these macrophages are the sites of continued viral replication.

Stages of HIV infection: 3 stages 1)      Acute, viraemic stage:  Viraemia, and infection of Lymphnodes,  lasts for 6-12 weeks.  Virus specific immune response by cytotoxic CD8+ T cells occurs which results in seroconversion. 2)      Chronic, latent phase:  Virus replication continues along with a gradual decline of CD4+ counts  may last from 7-10 years. 3)      Final, crisis phase:  Rapid decline of CD4+ T cells weight loss, diarrhoea, opportunistic infections, and secondary neoplasms.  patients with CD4+ T cells counts less than 200 /ml. are having AIDS even if clinical features are not seen.  Acquired Immuno - deficiency syndrome caused by HIV - I.  It is characterized by  profound suppression of T cell - mediated immunity,  opportunistic infections,  secondary neoplasms and  neurologic disease.

AIDS Opportunistic infections:  Candida, cytomegalovirus, Mycobacteria, cryptococcus, Toxoplasma, herpes, histoplasma, and pyogenic bacteria can cause severe infections in an immunocompromised patient. Neoplasms:  Kaposi’s sarcoma and B- Cell, Non-Hodgkin's lymphoma are found to occur with an increased frequency in these patients. CNS:  Acute aseptic meningitis, Myelopathy, Peripheral neuropathy, Encephalopathy - AIDS dementia complex affected the CNS function in AIDS patients.  Year mortality rate in AIDS = 85%  Longer period - 100%.

Treatment 

Anti-HIV (also called antiretroviral) medications are used to control the reproduction of the virus and to slow or halt the progression of HIVrelated disease

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Four classes of these anti HIV drugs: 1. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), bind to and block the action of reverse transcriptase, a protein that HIV needs to reproduce. 2. Nucleoside Reverse Transcriptase Inhibitors (NRTIs), are faulty versions of building blocks that HIV needs to make more copies of itself. When HIV uses an NRTI instead of a normal building block, reproduction of the virus is stalled. 3. Protease Inhibitors (PIs), disable protease, a protein that HIV needs reproduce itself. 4. Fusion Inhibitors, are newer treatments that work by blocking HIV entry into cells.