Classification of T lymphocytes
T cells are divided into two major functional groups: effector and regulatory.
1. Effector T cells directly eliminate the threat or trigger inflammation:
- Cytotoxic T lymphocytes (CTLs): directly destroy (lyse) target cells. They play a major role in tumor destruction and transplant rejection.
- Delayed-type hypersensitivity (DTH) T cells: release cytokines that attract and activate non-specific inflammatory cells (primarily macrophages). This is necessary to combat intracellular infections and participate in autoimmune reactions.
2. Regulatory T cells control the strength and direction of the immune response:
- T helpers (Th): help B lymphocytes produce antibodies in response to most antigens.
- T suppressors (Ts): inhibit immune responses, regulate their severity, and protect the body from autoimmune aggression.
T-helper subpopulations
T helpers bearing the CD4+ marker can differentiate into four main effector lineages. Their maturation occurs in peripheral lymphoid organs under the influence of local cytokines (with the exception of some regulatory cells).
- Th1 and Th2 (type I and type II T helpers).
- Th17: named for their ability to produce interleukin-17 (IL-17). They protect tissues from extracellular infectious agents by actively recruiting macrophages and neutrophils to the focus.
- Treg (T regulatory cells): maintain overall immune homeostasis. They can be natural (maturing in the thymus) or induced (generated in the periphery).
How a T cell recognizes an antigen
To trigger a response, a T lymphocyte must "see" the antigen. This occurs exclusively in the form of a trimolecular complex:
- The major histocompatibility complex (MHC) molecule on the surface of the antigen-presenting cell.
- The antigen itself (or more precisely, its fragment — the epitope).
- The T-cell receptor (TCR).
The bond is additionally stabilized by coreceptors. T helpers use CD4 to bind to MHC class II molecules, while cytotoxic cells use CD8 to bind to MHC class I molecules.
Activation: the two-signal rule
Simple recognition of a foreign agent is not enough for the proliferation (reproduction) and function of T lymphocytes. Two confirmatory signals are required:
- Specific signal: precise interaction of the TCR receptor with the antigen + MHC complex.
- Costimulatory signal: non-specific action of factors, for example, the release of interleukin-1 (IL-1) by antigen-presenting cells after contact with the lymphocyte. Costimulation is also enhanced by the binding of the CD28 receptor on the T cell.
Having received both signals, CD4+ T cells begin to synthesize mediators: IL-4 and IL-2. The latter is a crucial growth factor required for the replication and completion of differentiation of T lymphocytes.
The role of antigen-presenting cells (APCs)
APCs are capable of phagocytosis and processing complex antigens, after which they display them on their membrane together with MHC class II molecules. This is critically important for inducing a primary response. The main APCs include:
- Dendritic cells: interdigitating (in the T zones of lymphoid organs) and macrophage-like cells (in various tissues).
- Langerhans cells: a specialized variety of dendritic cells in the skin epidermis.
- Macrophages and B cells: can also perform the function of antigen presentation for T helpers.
Interconnection with humoral immunity
Although cellular and humoral immunity are different branches of defense, they work together. The humoral response requires the proliferation of B cells, which transform into plasma cells (localized in the spleen, bone marrow, lymph nodes, mucous membranes, and sites of inflammation). These are the ones that produce antibodies.
- Primary response: upon first encounter with an antigen, specific antibodies appear after 7 days (mainly IgM), and their concentration reaches a maximum after 2 weeks (predominantly IgG).
- Secondary response (memory response): upon re-exposure, the reaction takes only 3–4 days with a massive release of IgG, which persists for several weeks.
Each plasma cell is strictly specific: it synthesizes light chains of only one type (κ or λ) in combination with heavy chains of one class of immunoglobulins.
Briefly: answers to topical questions
Which molecules provide the costimulatory (second) signal during the activation of T lymphocytes?
The costimulatory (second) signal during T lymphocyte activation is provided by the interaction of specific receptors on T cells with ligands on antigen-presenting cells (APCs), as well as by the action of cytokines. The main costimulatory molecules are:
- CD28 — binds to CD80 (B7-1) and CD86 (B7-2) molecules on the APC surface.
- ICOS — interacts with the ICOSL ligand.
- CD40L — binds to the CD40 receptor on B cells during T-B cell cooperation.
- IL-1 — a cytokine produced by APCs after contact with T lymphocytes.
What cytokines are secreted by type 1 and type 2 T helpers (Th1 and Th2)?
Type 1 and type 2 T helpers secrete different sets of cytokines that determine the polarization of the immune response.
| Cell type | Secreted cytokines |
|---|---|
| Th1 | IFN-γ, IL-2, TNF-α, GM-CSF |
| Th2 | IL-4, IL-5, IL-13 |
Th1 cytokines ensure cellular immunity, activation of macrophages, and cytotoxic lymphocytes. Th2 cytokines stimulate the humoral response and participate in the development of allergic reactions.
What is the molecular mechanism of the cytotoxic action of CD8+ T lymphocytes?
The molecular mechanism of the cytotoxic action of CD8+ T lymphocytes (CTLs) is based on antigen-specific lysis of target cells via direct intercellular contact. The process includes the following stages:
- Recognition — CD8+ T lymphocyte receptors bind to foreign peptides presented in complex with MHC class I molecules on the surface of the target cell.
- Granule release — the activated cell secretes perforin and granzyme B.
- Pore formation — perforins embed themselves in the membrane of the target cell.
- Induction of apoptosis — granzymes penetrate inside the cell through pores and trigger a cascade of reactions leading to programmed cell death.
What specific markers are characteristic of regulatory T cells (Treg)?
Regulatory T cells (Treg) are characterized by the expression of a specific set of surface and intracellular markers. The main specific Treg markers are:
- CD4 and CD25 — surface receptors (forming the CD4+CD25hi phenotype).
- FOXP3 — a key intracellular transcription factor that makes cells resistant to apoptosis.
- CTLA-4 and PD-1 are membrane molecules involved in mediating suppressive functions.
- GITR is an additional surface marker.
- αβTCR is the T-cell receptor.
This phenotype is characteristic of both natural and induced (adaptive) regulatory T cells.
The rule of eight for coreceptors: CD4 binds to MHC class II (4 × 2 = 8), while CD8 binds to MHC class I (8 × 1 = 8). The product is always eight!
Class and exam questions
How do cytotoxic T lymphocytes kill infected cells?
They destroy target cells through direct cell-to-cell contact. CTLs (CD8+) recognize endogenous peptides in the complex with MHC class I and induce antigen-specific cell lysis.
What is the function of interleukin-2 (IL-2)?
IL-2 acts as a growth factor for T lymphocytes. It is absolutely essential for their active replication and final maturation after successful antigen recognition.
What is the difference between primary and secondary humoral responses?
The primary response develops slowly (about 7–14 days) with the production of IgM, followed by IgG. The secondary (amnestic) response to a familiar antigen is triggered rapidly, within 3–4 days, and is characterized by a high level of specific IgG.
What else to study on this topic
- Mechanisms of antigen processing within antigen-presenting cells.
- Structural features and functions of MHC class I and II molecules.
- The role of delayed-type hypersensitivity (DTH) cells in the development of autoimmune diseases.
- Synthesis of light (κ and λ) and heavy chains of immunoglobulins in plasma cells.
- Cytokine profile and functions of type 1 and type 2 T helper cells (Th1 and Th2).
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