HIV- pathogenesis Flashcards
Describe the stages of infection seen in the patient after contracting HIV in respect to CD4 count, viraemia (virus in blood) and antibody levels (anti-p24 Ab)/ T-cell levels (represents immune response)
During the primary phase illness, there is a peak in replication for the virus and so viraemia is high but then dips to the lowest levels at the end of this stage
Antibody levels see a sharp increase as a response to this
CD4 count is steady
In the asymptomatic phase (can last over 10 years), viraemia stays low whilst the immune system is keeping it that way
CD4 count start to decline near the end
AIDS stage comes last, seeing a decline in antibodies and CD4 count whilst viraemia increases rapidly
HIV was thought to be a true latent virus (one that stays dormant for a long time but can be activated lots of times e.g cold sores). Describe the symptoms of why HIV was thought to be one?
Long clinical asymptomatic phase
Low levels of virus detected in peripheral blood of asymptomatic patients
Viral replication in vitro only detected in activated T-cells
It was then decided that HIV exhibited clinical latency but not cellular latency. Why was this decided?
The cell turnover is very rapid (half life is
What are the mechanisms used by the virus compared to the host?
Virus: CD4 cell destruction by cytopathology (direct killing) and indirect killing by gp120 Loss of CD4 function Lymph node destruction Viral replication
Host: Cytotoxic T-cell response Antibody response CD8 antiviral factors Chemokines
Near the end of the asymptomatic phase, the balance shifts between the virus and immune system. What happens?
More CD4+ cells killed than produced
Lymph node destruction interferes with immune response
Loss of CD4+ Th11 function
Accumulation of viral variants overwhelms the immune system
What sort of symptoms are seen in the primary infection stage and clinical latency stage?
Primary infection:
Mononucleosis-like syndrome
Fever, malaise, rash, diarrhoea, lymphadenopathy
Clinical latency:
Often no symptoms but sometimes fatigue, weight loss, thrush, shingles
Normal levels of CD4 cells are around 2000/mm^3. HIV infection reduces this. What sort of additional infections do you see with levels of 200-500 CD4 cells/mm^3?
Generalised lymphadenopathy Oral lesions espcandidiases Reactivation of herpes zoster (shingles) Reactivation of latent Mycobacterium tuberculosis Basal cell carcinoma of skin Molluscum contagiosum (poxvirus) Condyloma acuminata (papillomavirus)
What sort of additional infections do you see when levels of CD4 cells are less than 200/mm^3?
Protozoal infections (fungus-like infections) such as Pneumocystis carinii, Taxoplasma gondii, cryptosporidia, microsporidia
Bacterial infections such as Treponema pallidum, Mycobacterium avium intracellulare
Fungal infections such as Candida albicans, cyptococcus neoformans
Viral infections such as CMV, HSV, EBV lymphoma, Kaposi’s sarcoma, anogenital carcinoma
Additional infections is an indirect way that HIV causes its pathogenicity. AIDS is the direct way. It kills T-cells in the immune system, but what other effects does it have on the human body?
2/3 patients gets AIDS dementia complex (ADC) which is the infection of brain macrophages and glial cells (form the architecture of brain- not the neurones)
Symptoms are dementia, motor and behavioural abnormalities and seizures. Developmental problems are seen in children with HIV as their brain is developing
Weight loss is due to infection of gut epithelial macrophages and causes diarrhoea, malabsorption due to blunting of the villae
Also get effects in the lung due to replication in the lung macrophages
What is the official definition of HIV given by the World Health Organisation?
A progressive qualitive and quantitative decline in the CD4+ Th1 lymphocyte subset
HIV types 1 and 2 infect CD4+ cells. Which two major cell groups have CD4 on their surface?
T-lymphocytes
Monocyte derived antigen presenting cells (e.g dendritic cells_
What do T and B-lymphocytes do normally?
B-lymphocytes produce antibodies
T-lymphocytes kill any infected/damaged or cancer cells
T-lymphocytes can be divided into more types. Two types that are important are CD8+ (they simply have CD8 cells on their surface hence the name) Cytotoxic T-cells and CD4+ T-helper cells. What do these do?
Cytotoxic T-cells recognise infected or cancer cells and directly kill those
T-helper cells help the cytotoxic T-cells or B-lymphocytes
T-helper cells can further be divided into Th1 cells and Th2 cells. What do these do?
Th1 cells produce a range of cytokines (e.g IL-2 and IL-12) which help stimulate the productivity of Cytotoxic cells
These Th1 cells are the ones that become infected with HIV
Th2 cells produce cytokines (e.g IL-4 and IL-10) which stimulate B cells to produce antibodies
Apart from T and B cells, what other cells are targeted?
Monocytes (mononuclear phagocytes) which are antigen-presenting cells. These can be macrophages which ingest and breakdown foreign bodies circulating and then present peptides to the T-cells to activate the adaptive immune response.
They can also be dendritic cells which obtain antigen tissues (e.g skin and peripheral blood). They then go to the lymph nodes and activate T-cells. Large amounts of extracellular virus found trapped on the surface of follicular dendritic cells
