Innate immunity: the first barriers
Defense against viruses begins long before the activation of specific T and B lymphocytes. Innate mechanisms react immediately.
- Physical and biological barriers: The skin and mucous membranes, as well as the normal microflora and cell glycocalyx, prevent the initial penetration of the pathogen.
- Response to breach: If barriers are breached, secretory components are activated, including the complement system and antimicrobial peptides. For example, $\alpha$-defensins inhibit viral replication, while cathelicidins destroy their envelopes.
- Early cellular migration: Neutrophils are the first to rush to the infection site, followed by macrophages, dendritic cells, and natural killer cells (NK cells). In the first days, activated macrophages and NK cells play the primary role in containing the infection.
Interferons: the universal alarm signal
The interferon (IFN) system is a crucial factor in early antiviral defense, blocking pathogen replication.
- Type I interferons (IFN-$\alpha$, IFN-$\beta$): Secreted by infected cells (primarily plasmacytoid dendritic cells). They cause neighboring cells to produce enzymes that nonspecifically suppress the synthesis of any RNA and proteins. This leads to the death of the infected cell, but deprives the virus of the opportunity to replicate. They also enhance the expression of MHC antigens on the cell surface.
- Type II interferon (IFN-$\gamma$): Acts at the junction of innate and adaptive immunity. It activates macrophages (triggering their microbicidal properties), NK cells, and cytotoxic T lymphocytes.
Cellular mechanisms and target destruction
The main task of cellular immunity is to find and destroy infected cells harboring the virus inside.
- Natural killer cells (NK cells): Recognize cells based on the "missing self" principle. If a virus suppresses the expression of MHC class I molecules on the surface of the target cell, an NK cell attacks it.
- Cytotoxic T lymphocytes (CTLs, CD8+): The main effectors of the adaptive response. They recognize foreign viral peptides presented together with MHC class I. Specific CTLs appear on days 3–4 and peak by days 7–10.
Killing mechanism (granule exocytosis): Both NK cells and CTLs use a similar cytotoxic mechanism. They secrete perforins, which punch pores in the membrane of the target cell. Through these pores, granzymes (serine proteases) enter the interior. Granzymes activate intracellular caspases and degrade DNA, triggering programmed cell death—apoptosis.
Humoral response: the role of antibodies
Antibodies are effective primarily against extracellular forms of the virus.
- On mucous membranes, secretory immunoglobulins (sIgA, sIgM) envelop virions, preventing them from attaching to the epithelium.
- In the systemic circulation, IgG and IgM neutralize viruses and facilitate their phagocytosis.
- Antibodies can trigger complement-dependent lysis of infected cells (via the formation of the membrane attack complex).
- Antibody-dependent cellular cytotoxicity (ADCC) plays an important role: antibodies tag the infected cell, after which NK cells bind to them and destroy the target using perforins and granzymes.
How viruses trick the immune system
The development of an infection is always a competition between the immune system and the virus. Viruses have developed numerous evasion strategies (evasion):
- Blockade of antigen presentation: Adenoviruses and herpes simplex virus reduce the number of MHC class I molecules on the surface, becoming invisible to T lymphocytes.
- Antigenic variation: Influenza viruses and rhinoviruses frequently mutate, changing their antigens, which allows them to escape previously generated antibodies.
- Complement suppression: Cowpox and herpes viruses synthesize proteins that block various components of the complement system.
- Immunosuppression and mimicry: Epstein–Barr virus produces the BCRF1 protein, which is very similar to the human anti-inflammatory cytokine IL-10, thereby suppressing the immune response.
- Latency: Hepatitis B and herpesviruses can integrate their genome into the host DNA and remain dormant for years until favorable conditions for activation arise.
Briefly: answers to topical questions
Which pattern recognition receptors (PRRs) are responsible for the intracellular recognition of viral nucleic acids?
Endosomal Toll-like receptors (TLRs 3, 7, 8, and 9) are responsible for the intracellular recognition of viral nucleic acids.
- TLR-3 recognizes double-stranded RNA (dsRNA), typical of most viruses.
- TLR-7 recognizes single-stranded RNA (ssRNA) of viruses (e.g., influenza, HIV).
- TLR-8 is also involved in the recognition of single-stranded viral RNA.
- TLR-9 recognizes DNA regions enriched with unmethylated CpG repeats, characteristic of viruses and bacteria.
What functions do macrophages perform during a viral infection?
During a viral infection, activated macrophages bear the main virucidal burden in the first days after infection. Macrophages can also serve as a reservoir for virus replication and transport throughout the body. Herpesviruses and poxviruses, in particular, are capable of multiplying within macrophages.
Through which pathways is the complement system activated during viral infections?
The complement system is activated via the classical, lectin, and alternative pathways. The classical pathway is triggered by the antigen-antibody complex; the lectin pathway by the binding of mannose-binding lectin to carbohydrate components; the alternative pathway by the spontaneous activation of C3. In antiviral defense, IgG and IgM can participate in complement activation. The ultimate result of activation is the assembly of the membrane attack complex and lysis of the target cell. Viruses can suppress complement: cowpox virus blocks the classical pathway, and herpes simplex virus blocks both the classical and alternative pathways.
Class and exam questions
How do viruses hide from cytotoxic T lymphocytes?
Antibodies fight viruses located in the extracellular space (neutralizing them and preventing them from entering cells). Cytotoxic T lymphocytes (and NK cells) destroy already infected cells of the body.
How do viruses hide from cytotoxic T lymphocytes?
They can suppress the expression of MHC class I molecules on the surface of the infected cell. Without this complex, T lymphocytes simply "cannot see" viral antigens. However, such cells lacking MHC I become targets for natural killer cells.
What role does apoptosis play in antiviral immunity?
Apoptosis induced by granzyme action allows for the careful destruction of the infected cell along with the viral nucleic acids inside it, without causing massive inflammation and without letting the virus escape to infect new cells.
What else to study on this topic
- Mechanisms of action of antimicrobial peptides (defensins and cathelicidins).
- Features of the activation and function of plasmacytoid dendritic cells.
- Detailed process of the perforin-granzyme mechanism of cellular cytotoxicity.
- Molecular mimicry using the Epstein–Barr virus as an example.
- Mechanisms of formation and maintenance of latent viral infection.
Study the full topic in the «Microbiology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Antiviral immunity" and 4,383 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 141 video lectures on the subject
Other topics in the section "Features of immunity in various locations..."
Free video lessons: microbiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.