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Immunology, the HIV
life cycle and stages of
infection
Anele Waters
HIV Research Nurse
North Middlesex Hospital, London
Objectives
– To explain how the immune system works
– To describe the role of the CD4 cells within the
immune system
– To discuss the life cycle of the HIV virus
– To describe the stages of HIV infection
The healthy body
• Under attack everyday
• Viruses, bacteria, funghi, protozoa
• The body is protected by structures and
processes that fight infection
The immune system
Non-specific Immunity (Innate) Specific Immunity (Adaptive)
Antigen-Independent response Antigen-Dependent response
Immediate maximal response
Lag time between exposure
and maximal response
Not antigen-specific
Antigen-specific
No immunologic memory
Immunologic memory
Lymphocytes
Lymphocytes
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Type of Leukocyte (white blood cell)
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Contain B cells and T cells in
addition to Natural Killer cells
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Part of the Adaptive immune system
B cells
•
Humoral immune response
•
Principal function to make antibodies for
specific antigens
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Identify and neutralize foreign invaders
•
Become memory B cells after activation by
antigen interaction
T cells
Cell mediated immune response
Types of T cells
• T helper (AKA CD4 cells)
• Cytotoxic
• Memory
• Regulatory
• Natural Killer T cells
Function of T helper
(CD4 cells)
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Directs immune system
• Signals maturation of B cells
• Activates cytotoxic T cells
and macrophages
The Human Immunodeficiency
Virus (HIV)
The virus
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Lentivirus type of Retrovirus
Isolated in 1983
Called HIV in 1985
Related simian
immunodeficieny virus (SIV)
• HIV-1 and HIV-2
• Bushmeat or Hunter theory
Early history of HIV
•Two samples from Kinshasa, Congo, 1959 and 1960
•16-year-old boy from Missouri USA who died in 1969
•Norwegian sailor who had been to Cameroon in 60’s died in
1976
•A Danish surgeon who travelled to Zaire in 1972, died in 1977
•Children involved in research in Uganda 1973
Stages of HIV infection
• Primary HIV infection
• Asymptomatic HIV infection
• Symptomatic HIV infection
• AIDS diagnosis
Primary HIV infection
• Seroconversion illness
• Fever, rash, sore throat, similar to glandular
fever
• Symptoms soon after exposure and usually
lasts 2weeks
• 50-90% have some degree of symptoms
Primary HIV infection
• Inflammatory response
• HIV-specific CD4 cells are infected
• Antibody tests are negative
• Antigen positive
• HIV viral load elevated
Primary HIV infection
• HIV antibodies (within 6 wks but <3 mths)
• Window period
• High levels of HIV in blood, sexual fluids
and/or breast milk.
• Highly infectious!
Asymptomatic HIV infection
•This stage lasts for an average of 7 to 10 years
•Free from major symptoms
(lymphadenopathy)
•Viral load drops from seroconversion but
remains infectious
•HIV antibody positive
•Not dormant, very active in the lymph nodes
Symptomatic HIV infection
•Over time immune system becomes severely
damaged
•The lymph nodes and tissues become damaged
•HIV mutates and becomes more pathogenic
•CD4 cells become depleted
•Symptoms start mild and increase in severity
•Emergence of opportunistic infections
Symptomatic HIV infection
Unexplained weight loss
Recurrent respiratory tract infections
Herpes zoster
Recurrent oral ulceration
Rashes
Fungal nail
Unexplained chronic diarrhoea
Unexplained persistent fever
Persistent oral candidiasis
Oral hairy leukoplakia
Severe bacterial infections
Gingivitis or periodontitis
Unexplained anaemia
Progression to AIDS
1993 European AIDS case definition (used by
Europe, Canada, Australia and Japan)
HIV positive
One of the specified 28 Opportunistic illnesses
(OIs)
Does not include CD4 <200 without an OI
Opportunistic infections
Called “opportunistic” because they take
advantage of the weakened immune system.
With healthy immune systems exposure to
certain viruses, bacteria, or parasites cause no
problems.
These same bacteria and viruses cause great
damage to a weakened immune system.
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AIDS defining
Pneumocystis jirovecii pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection
Candidiasis: Esophageal, bronchi, trachea or lungs
Extra pulmonary, pulmonary, disseminated tuberculosis
Kaposi’s sarcoma
Cytomegalovirus, disease and retinitis
Encephalopathy, HIV related
Herpes simplex, bronchitis, pneumonitis, esophagitis, chronic>1mth
Disseminated mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
Mycobacterium (avium complex, TB, kansasii, other)
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis
Chronic isosporiasis
Lymphoma (cerebral, Burkitt’s, immunoblastic,non-Hodgkin)
Salmonella (sepsis, recurrent)
Toxoplasmosis (brain)
Wasting syndrome
Pneumonia (recurrent)
Cervical cancer (invasive)