Non-sterile immunity

Essence of the phenomenon and cellular basis

The main feature of infectious (non-sterile) immunity lies in the macroorganism's inability to completely eliminate the invading antigen. Defense mechanisms do not lead to complete elimination of the microbe, but effectively restrain its generalization.

The key link is delayed-type hypersensitivity (DTH, type IV hypersensitivity). The effector response proceeds via two interrelated pathways:

• Classic delayed-type hypersensitivity, which is regulated by a subpopulation of CD4+ lymphocytes (T-helper cells).
• Direct cellular cytotoxicity, initiated and executed by CD8+ lymphocytes (cytotoxic T lymphocytes).

Upon contact of T lymphocytes with macrophages, two outcomes are possible: immune cytolysis with elimination of the target, or granulomatous inflammation aimed at isolating the undigested agent.

Granuloma as a morphological substrate

In a number of infections, the phagocytic process remains incomplete: macrophages engulf microbial bodies, yet lysis does not occur. The pathogen continues to live inside epithelioid cells. The body responds by forming a granuloma — a specific cellular wall.

The morphological barrier plays a dual biological role:

1. Protective function — mechanical and immunological localization of the focus, preventing the infection from disseminating through organs and tissues.
2. Damaging function — destruction of macrophages, formation of foci of tissue necrosis, and subsequent fibrosis leading to an irreversible decline in the functional activity of the affected organ.

This balance ensures the maintenance of protective immune tension precisely due to the constant presence of antigenic determinants inside the granulomatous focus.

Clinical examples: tuberculosis and toxoplasmosis

A classic model is tuberculosis, where incomplete phagocytosis keeps mycobacteria inside epithelioid cells, preventing bacterial dissemination at the cost of local fibrosis and necrosis.

Another striking example is toxoplasmosis. Upon invasion by Toxoplasma gondii, a complex non-sterile immune response is formed:

• both cellular links (DTH) and humoral factors are involved;
• in the early acute stage, IgM class antibodies are synthesized, whereas the concentration of specific IgG antibodies reaches a maximum by weeks 4–8;
• allergic sensitization of the organism is registered from the 4th week of the disease (intradermal test with toxoplasmin) and persists for years against the background of antigen presence;
• in newborns, a high titer of specific antibodies in both mother and child simultaneously serves as a marker of congenital infection.

For comparison, in other infectious pathologies (such as scarlet fever), immunity is not non-sterile, but rather persistent and lifelong, directed against the erythrogenic toxin, although premature suppression of the infection with antibiotics may prevent its full maturation.

Class and exam questions

What else to study on this topic

• Serological verification of toxoplasmosis: dynamics of IgM and IgG antibodies, Sabin-Feldman reaction
• Molecular genetic (PCR) diagnostics of toxoplasmosis in HIV infection and congenital forms
• Specifics of antibacterial therapy for toxoplasmosis: pyrimethamine regimen and use of spiramycin in pregnant women
• Mechanisms of early and late phases of immediate-type hypersensitivity (types I, II, and III reactions)
• Toxic, purulent-necrotic, and allergic syndromes in the pathogenesis of streptococcal infection

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