Immunity: definition and organization
Immunity is a system of organs and cells that ensures the maintenance of the body's antigenic homeostasis through the recognition, engulfment, and destruction of foreign molecules, as well as the formation of immunological memory. Structurally, the immune system is divided into central (primary) organs — the thymus and red bone marrow — and peripheral (secondary) organs — the spleen, lymph nodes, and MALT (mucosa-associated lymphoid tissue).
The thymus is the site of T-lymphocyte differentiation and selection: positive and negative selection of thymocytes involving nurse cells and dendritic cells. The red bone marrow contains hematopoietic stem cells that give rise to erythrocytes, platelets, granulocytes, monocytes, and B-lymphocytes. The spleen, lymph nodes, and MALT provide the site for naive lymphocytes to encounter antigens and develop a specific response.
Innate and adaptive immunity
Innate immunity is non-specific, acts immediately, and is mediated through anatomical and physiological barriers, phagocytosis, and vascular responses. Key cells include neutrophils and macrophages, which recognize PAMPs (pathogen-associated molecular patterns) via Toll-like receptors. Humoral factors include the complement system (classical, lectin, and alternative activation pathways), C-reactive protein, mannose-binding lectin, lysozyme, defensins, interferons, and cytokines.
Adaptive immunity develops more slowly, but exhibits high specificity due to the diversity of TCR and BCR receptors (around 10¹⁸ variants). It is mediated by T-killers (CD8⁺), T-helpers Th1, Th2, Th17, T-regulatory cells, and B-cells. Antigen recognition occurs via MHC I (on all nucleated cells) and MHC II (on antigen-presenting cells).
Immune response: cellular and humoral
The immune response begins with the capture of an antigen by a dendritic cell, its processing, and presentation in a complex with MHC. A naive helper T cell interacts with MHC II via its TCR; the direction of the response is chosen depending on the type of pathogen.
- Cellular response (against bacteria and tumors): Th1 secretes IL-2, the dendritic cell secretes IL-12; cytotoxic T lymphocytes are activated, destroying the target with perforins and granzymes with the induction of apoptosis.
- Humoral response (against viruses and extracellular bacteria): Th2 releases IL-4, activates B cells which transform into plasma cells, synthesizing IgM first and then switching to IgG during isotype switching.
Antibody isotypes: IgM — primary response, low affinity, potent complement activation; IgG — highly specific, appears after 2 weeks; IgA — secretory, located in mucous membranes; IgE — reagins in sensitization; IgD — B-cell receptor. The termination of the response is mediated by regulatory T cells and suppressor T cells via IL-10, and memory cells are formed.
Immunopathology and classification of immunodeficiencies
Immunopathology studies the patterns of immune response disorders. Main forms: immunodeficiencies (primary and secondary), type 1–4 hypersensitivity, autoimmune processes, and lymphoproliferative diseases. An immunodeficiency state is impaired functioning of one or more components of innate or adaptive immunity, manifesting as increased susceptibility to infections and tumors.
Primary immunodeficiencies (PIDs) are hereditary disorders caused by defects in genes encoding immune system proteins: receptors, enzymes, cytokines, and differentiation factors.
Innate immunity defects
- Humoral defects: deficiency of complement components, lysozyme, acute-phase proteins, cytokines, interferons. This leads to recurrent bacterial infections and impaired opsonization.
- Cellular defects: impaired chemotaxis, motility, and phagocytic activity of neutrophils and macrophages; neutropenias of various origins.
- Leukocyte adhesion deficiency (LAD): a defect in P- and E-selectins or integrins prevents the attachment of leukocytes to venule endothelium and their diapedesis into the inflammation site.
- Toll-like receptor defects impair PAMP recognition. The formation of NETs (neutrophil extracellular traps) by neutrophils involving the mitochondrial antiviral signaling protein has been described as a mechanism of antiviral defense.
Adaptive immunity defects
These affect the T-cell lineage, B-cell lineage, or both simultaneously. In severe combined immunodeficiency (SCID), the differentiation of both lineages is impaired — for example, due to adenosine deaminase deficiency or DNA repair defects. Wiskott-Aldrich syndrome is associated with a defect in the WASP membrane receptor protein and manifests with thrombocytopenia, eczema, and infections.
- DiGeorge syndrome: aplasia or hypoplasia of the thymus resulting from abnormal development of the third and fourth pharyngeal pouches; precursor T cells fail to differentiate into mature T lymphocytes, impairing cellular immunity.
- B-cell defects: X-linked agammaglobulinemia (Bruton agammaglobulinemia) due to a mutation in the Btk tyrosine kinase, impaired isotype switching (hyper-IgM syndrome), and selective IgA deficiency. Antibody production decreases, and recurrent pyogenic infections develop.
- Cytotoxic function defects: the inability to synthesize perforins and granzymes makes the elimination of infected and tumor cells impossible.
It is fundamentally important to understand: a deficiency at any link — from antigen recognition to the effector phase — impairs pathogen elimination, which clinically manifests as chronic, opportunistic infections and a predisposition to cancer.
Key points
- Immunity is divided into innate (fast, non-specific) and adaptive (slow, specific, with memory).
- Antigen presentation via MHC I activates CD8⁺ cytotoxic T cells, while presentation via MHC II activates CD4⁺ helper T cells.
- Th1/IL-2 directs the cellular response, whereas Th2/IL-4 directs the humoral response with antibody production by plasma cells.
- Primary immunodeficiencies are hereditary genetic defects of immune system proteins.
- Innate immunity defects: complement, phagocytosis, leukocyte adhesion, TLRs.
- Adaptive immunity defects: SCID, DiGeorge syndrome, Wiskott-Aldrich syndrome, Bruton agammaglobulinemia.
- Clinically, PIDs manifest as recurrent infections, opportunistic pathogens, and tumors.
- Understanding the normal immune response is the key to understanding the pathogenesis of any immunodeficiency.