Immune recognition of viruses
The body's defense system reacts to viral invasion in two stages:
- Activation of innate immunity. Based on the recognition of viral nucleic acids (e.g., double-stranded RNA). This task is performed by pattern recognition receptors (PRRs) located in cytoplasmic granules. The main role is played by Toll-like receptors: TLR-3, TLR-7, TLR-8, and TLR-9.
- Activation of adaptive immunity. Viral envelope proteins are recognized by B-lymphocytes. The antibodies they produce target surface antigens.
The presence of pathogen molecules recognized by receptors drives the mobilization of innate immunity and the triggering of specific adaptive responses.
Mechanisms of antigenic structure alteration
To survive, pathogens continuously change the structure of molecules targeted by the immune system. Several types of such variability are distinguished:
- Antigenic drift. The result of a series of point mutations in genes. The structure of protective antigens changes smoothly and gradually. Previously formed immunity works, but only partially, and does not protect against the final variants of variation.
- Antigenic shift. An abrupt, sharp change in antigens due to the exchange of genetic material between different microbial lineages (often occurring in an intermediate host). In this case, prior immunity does not protect against the new variants at all.
- Switching of variant-specific antigens. Sequential expression of products from different genes within a single host. The pathogen constantly escapes immune control, which determines the remittent (relapsing) course of the infection.
Variability of surface antigens (using influenza as an example)
There is a direct correlation: the more important an antigen is for generating protective immunity, the higher its variability. Changes in the antigenic spectrum of the influenza virus from epidemic to epidemic are due to the varying stability of its proteins:
- Hemagglutinin (H): exhibits extremely high variability, changing with every new epidemic.
- Neuraminidase (N): exhibits significantly lower variability, changing every 2–3 epidemics.
- Matrix protein (M): part of the nucleocapsid envelope, stable, with no variability.
Due to drift and shift, antigenic properties can change even within a single epidemic, leading to reinfection in individuals who have already recovered.
Superantigens and polyclonal response
Some molecules (e.g., bacterial exotoxins) act as superantigens. They interact with the $\beta$-chains of the T-cell receptor (TCR) and the lateral surface of the MHC molecule.
This interaction induces a polyclonal response, which is not an adaptive reaction because it is non-specific and not directed against a specific pathogen. Severe pathological consequences ensue:
- Polyclonal proliferation of a massive pool of T-cells.
- Massive, inadequate cytokine release.
- Massive apoptosis of activated T-cells at the final stage.
The consequence of this massive apoptosis is the depletion of the lymphocyte pool, leading to pronounced temporary immunosuppression.
Briefly: answers to topical questions
Which specific bacterial exotoxins are classified as superantigens?
Bacterial exotoxins with superantigen properties include heat-stable enterotoxins, especially staphylococcal ones, and streptococcal exotoxins.
- Heat-stable enterotoxins can enter the systemic circulation, where they exhibit superantigen properties; this property is most pronounced in staphylococcal heat-stable enterotoxins.
- Streptococcal exotoxins A, B, and C, as well as exotoxins F, SSA, X, G, H, and Z, possess superantigen properties.
Which viruses are characterized by antigenic shift?
Antigenic shift is a specific feature exclusively of influenza A virus. This process is an abrupt change in the specificity of protective surface antigens (hemagglutinin and neuraminidase). It occurs as a result of reassortment—the exchange of entire RNA segments during simultaneous infection of a single cell by different virus subtypes. Previously established immunity offers absolutely no protection against the new altered variants, which is the main cause of pandemics.
What mechanisms ensure antigenic variation in gonococci?
Antigenic variation in gonococci (Neisseria gonorrhoeae) is driven by phase variation mechanisms and unstable expression of surface structures.
- Pili — exhibit phase variation, capable of switching between piliated and non-piliated states depending on gene expression.
- Protein II (Opa) — promotes attachment to cells, but is not always expressed (in its absence, gonococci form serum-resistant colonies).
Due to high antigenic variability, post-infection immunity to the pathogen does not develop.
What role do intermediate hosts play in the antigenic shift of the influenza virus?
Intermediate hosts can serve as a reservoir for influenza virus antigens and an environment where the exchange of entire RNA segments occurs during simultaneous infection of a single cell by different virus variants. This leads to reassortment and the emergence of new virus strains. For instance, the genome of the pandemic pN1H1 strain is a combination of genetic material from swine, avian, and human influenza viruses.
Drift is like a drifting ice floe: changes occur slowly due to point mutations. Shift is like shifting tectonic plates: a sudden, abrupt change in antigens due to the exchange of genetic material, which completely shatters prior immunity.
Class and exam questions
Why is a wave-like course of fever observed in sleeping sickness?
The causative agent (Trypanosoma brucei) has about a thousand genes encoding surface glycoprotein. As soon as the immune system produces antibodies against one variant, the parasite expresses the next gene, causing a new wave of the disease (remittent course).
What is the danger of the response to superantigens?
The response is non-specific and unproductive. Instead of targeted defense, there is an inadequate release of cytokines followed by massive apoptosis of T-lymphocytes, leading to the loss of immune cells and temporary immunosuppression.
Can antigenic properties change within a single epidemic?
Yes, through antigenic drift and shift mechanisms, microbial antigens can change so rapidly that recovered individuals can be reinfected during the same season.
What else to study on this topic
- Structure of the viral nucleocapsid and functions of internal protein enzymes
- Mechanisms of pattern recognition receptors (PRRs) and TLRs in granules
- Mutation process within bacterial species and serotype formation
- The role of PAMP molecules in innate immunity
- Pathogen immunomodulators: how macromolecules block effector immunity
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