Disorders Associated With The Immune System |
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26. Define immune deficiency. |
May be congenital or acquired
Congenial deficiencies are due to defective or absent genes.
Congenital immune deficiencies include:
Athymic Nude Mouse
Lack of cell-mediated immunity makes a good model for studying leprosy.
Drugs, cancers, and infectious diseases can cause acquired immune deficiencies.
Acquired immune deficiencies include:
Thought to have originated from a mutant monkey virus in Central Africa during the1930’s.
The virus was probably contained in villages until the end of colonialism brought about urbanization and highway systems (travel and urban blight).
The earliest documented case is from a patient who died in 1959 in what was then Leopoldville, Belgian Congo. Preserved samples of this patient's blood have anti-HIV antibodies.
The first confirmed case of AIDS in the Western world was that of a Norwegian sailor who died in 1976 and is thought to have become infected in 1961 or 1962.
AIDS is the final stage of HIV infections.
HIV is a retrovirus with ss RNA, reverse transcriptase, and a phospholipid envelope with gp 120 spikes.
Spikes attach to CD4 receptors and coreceptors on host cells (helper T cells, macrophages, and dendritic cells).
HIV Structure and Attachment to Receptors on Target T-cell
Viral RNA is reverse transcribed to DNA, integrates into host chromosome and directs synthesis of new viruses or remains latent as a provirus.
HIV evades the immune system by latency, hiding in vacuoles, using cell-cell fusion, and by antigenic change (reverse transcription is subject to a lot of errors).
Latent and Active HIV Infection in CD4 T-cells
Latent and Active HIV Infection in Macrophages
Genetically distinct groups of HIV are classified into clades (HIV-1 has 11, most common major type, HIV-2 rare in U.S., found in western Africa).
HIV infection is categorized by symptoms:
Also categorized by CD4 T cell numbers: below 200/mm3 is reported as AIDS (true for Category A and B also).
Progression from HIV infection to AIDS takes about 10 years.
The Progression of HIV Infection
The Lives of AIDS patients can be prolonged by the proper treatement of opportunisitic infections.
HIV antibodies detected by ELISA, antigens detected by Western blotting.
Plasma viral load tests detect viral nucleic acid and are used to quantify HIV in blood.
HIV Transmission
Transmission is by sexual contact, breast milk, contaminated needles, transplacental infection, artificial insemination, and blood transfusion.
Blood transfusions are not a likely source of infection in developed countries.
Modes of HIV Transmission in the United States
U.S., Canada, western Europe, Australia, northern Africa, and parts of South America transmission has been by injecting drug use (IDU) and male-to-male sexual contact. Heterosexual transmission is increasing.
Sub-Saharan Africa transmission is primarily heterosexual contact.
Eastern Europe and Asia – transmission is by IDU and heterosexual contact.
The use of condoms and sterile needles prevents the transmission of HIV.
Vaccine development is difficult because the virus remains inside host cells and undergoes antigenic shifts rapidly.
Current chemotherapeutic agents target the viral enzymes reverse transcriptase and protease.
Studies on people with resistance may provide some insight into vaccine development.
Exposed but not infected:
About 1% of the population have mutations in the CCR5 molecule that don't provide most strains of HIV with the required co-receptor to gain entry into cells. These people are mostly European and the mutation is rarely seen in Africans and Asians. There is, however, a group of African prostitutes resistant to infection that seem to have a population of agressive CTLs that prevent infection.
Long-term nonprogressors:
There is another group of people who, although infected, have not progressed to AIDS and are expected to exceed 25 years post infection survival. The mechanism of nonprogression is unknown.