Dynamics of the immune response and serological markers
The logic of the immune response upon infection is based on a clear timeline from the moment of initial contact with the pathogen to the stage of full-blown AIDS.
Immediately after infection, the «seronegative window» period begins. During this time, specific antibodies to the virus are completely absent in the blood. On average, this stage takes about 3 months, although depending on individual host reactivity, it can vary from 2 weeks to 6–10 months.
The main marker for early diagnosis during this period is the viral p24 antigen. Using enzyme-linked immunosorbent assay (ELISA), it can be detected as early as 1–2 weeks post-infection. This protein circulates in the bloodstream until approximately the 8th week, after which its concentration drops sharply. Notably, a second massive release of p24 levels occurs only at the terminal stage of the disease.
Then the phenomenon of seroconversion occurs: the p24 antigen disappears, and specific immunoglobulins begin to be produced.
- Antibodies to surface glycoproteins (gp120 and gp41) persist in the body for life.
- In contrast, antibodies to the core protein (p24) become depleted over time.
A drop in the p24 antibody titer has important prognostic significance — it directly correlates with the progression of the infection to the AIDS stage.
It is important to note that protective (sterilizing) immunity against the pathogen is not formed. Although antibodies are produced, their neutralizing activity remains extremely low. This is due to the high mutagenicity of the virus: it continuously changes its structure, forming new variants («quasispecies»), and successfully evades immune surveillance.
Clinical classification (according to V.I. Pokrovsky)
In domestic clinical practice, the classification of the infectious process stages developed by Academician V.I. Pokrovsky is traditionally used. It reflects the gradual increase in immunodeficiency:
- Incubation period. Calculated from the moment of virus penetration to the appearance of the first clinical symptoms of acute infection or the onset of antibody production. It takes from 3 weeks to 3 months.
- Stage of primary manifestations. At this stage, symptoms of acute viral infection appear and seroconversion occurs. This phase lasts for approximately 1 year.
- Subclinical stage. Characterized by a slow, latent progression of immunodeficiency. Distinct clinical manifestations are absent. This is the longest stage, lasting about 6–7 years.
- Stage of secondary diseases. Immunodeficiency reaches clinically significant levels, against which severe concomitant pathologies join the process. This phase usually ends 10–12 years after the onset of the disease.
- Terminal stage (AIDS). Characterized by a severe, absolutely irreversible course of secondary diseases, which ultimately lead to the patient's death.
AIDS-defining and opportunistic diseases
The main clinical feature of the disease is that the symptoms themselves are not triggered by the immunodeficiency virus. The entire severe presentation is a consequence of the development of opportunistic infections under conditions of critically suppressed immunity.
Typical pathogens affecting patients in late stages include:
- Pneumocystis jirovecii — causes severe Pneumocystis pneumonia;
- Toxoplasma — leads to destructive lesions of the central nervous system;
- Cryptosporidia — provoke persistent, debilitating intestinal infections;
- Fungi (genus Candida, causative agents of histoplasmosis) — cause generalized mycoses.
At the stage of full-blown AIDS, so-called AIDS-defining diseases develop, the presence of which directly indicates terminal immunodeficiency. Among infectious lesions, viral (severe herpesvirus infection, viral hepatitis B and C), bacterial (active tuberculosis, salmonellosis, various atypical mycobacterioses), and protozoal lesions (cerebral toxoplasmosis) are distinguished. A special place is occupied by oncological diseases. Kaposi's sarcoma and various malignant lymphomas are highly specific for the AIDS stage. Severe nervous system lesions, manifesting as various neurological disorders, are also characteristic.
Briefly: answers to topical questions
Which pathogens cause severe opportunistic infections in late stages of HIV?
In late stages of HIV infection, severe opportunistic diseases are caused by protozoa, viruses, bacteria, and fungi. Typical pathogens include:
- Pneumocystis (Pneumocystis jirovecii) — causes Pneumocystis pneumonia.
- Toxoplasma — leads to CNS damage (toxoplasmosis).
- Cryptosporidia — cause intestinal infections (cryptosporidiosis).
- Cytomegalovirus — causes a generalized infection with multi-organ lesions (retinitis, pneumonia, encephalitis).
- Fungi — cause candidiasis and histoplasmosis.
Herpes viruses, hepatitis B and C viruses, mycobacteria (tuberculosis, mycobacteriosis), and salmonellae also play a significant role.
Which immune system cells are the main targets for the human immunodeficiency virus?
The main targets for the human immunodeficiency virus are cells bearing the CD4 receptor on their surface. These include:
- T-helper cells — activated CD4+ T-lymphocytes (primarily Th1 and Th2 subpopulations), which die upon interaction with the virus.
- Macrophages — tissue macrophages and monocytes, which are not destroyed and serve as a reservoir of infection.
- Myeloid dendritic cells and Langerhans cells — act as carriers and reservoirs of the virus.
- Microglial cells — neuroglial cells that also undergo the cytopathic effect of the virus.
Which enzymes are part of the HIV virion core and ensure its replication?
The core (nucleocapsid) of the HIV virion contains a complex of enzymes encoded by the pol gene that ensure viral replication. These include:
- Reverse transcriptase — revertase (RNA-dependent DNA polymerase), which synthesizes a complementary DNA strand on a viral RNA template.
- Integrase — ensures the integration of the resulting viral DNA into the host cell chromosome.
- Protease — is part of the capsid enzyme complex and participates in replication processes.
Which transmission routes of the pathogen are characteristic of HIV infection?
HIV infection is characterized by three main transmission routes:
- Sexual route — infection occurs during unprotected heterosexual and homosexual contacts.
- Hematogenous route — injection and parenteral route, which is realized through intravenous drug use, transfusion of blood and its products, organ and tissue transplantation, as well as the use of non-sterile medical instruments.
- Vertical route — transmission of the virus from an infected mother to the child during pregnancy (transplacentally), directly during childbirth, or through breastfeeding.
For quick memorization of Pokrovsky's stages, use the acronym ISSTT: Incubation, Primary manifestations, Subclinical, Secondary diseases, Terminal.
Class and exam questions
Why don't antibodies protect against disease progression in HIV infection?
The virus constantly mutates in the body, creating new structural variants called «quasispecies». Because of this, the antibodies produced have low neutralizing activity and are unable to provide protective immunity.
How does the p24 marker behave at different stages of infection?
The p24 antigen appears in the first 1–2 weeks after infection and drops sharply by the 8th week. A second high spike of this protein is observed only in the terminal stage (AIDS).
What is the direct cause of symptoms in the AIDS stage?
The virus itself does not produce a specific, prominent clinical picture in the late stages. All severe manifestations are caused by opportunistic infections (pneumocystosis, toxoplasmosis) and oncological processes (Kaposi's sarcoma, lymphomas) against the background of a destroyed immune system.
What else to study on this topic
- Mechanisms of viral immune evasion
- Structure and functions of gp120 and gp41 glycoproteins
- Pathogenesis of Pneumocystis pneumonia in immunodeficiencies
- Kaposi's sarcoma: etiology and clinical features
- Modern methods of laboratory diagnostics for HIV (ELISA, immunoblotting, PCR)
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