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Cellular Immunity

Immunitas cellularis

For medical students3 min readUpdated 2026-10-10

Cellular immunity is a type of specific immune response mediated by T-lymphocytes. It is responsible for destroying intracellular pathogens, tumor cells, and transplant rejections, as well as regulating other arms of the immune system and stimulating nonspecific inflammation.

Main targetIntracellular pathogens, viruses, and tumor cells

Key cellsT-lymphocytes (helpers, cytotoxic cells, suppressors)

Dual signalA mandatory requirement for full activation and proliferation of T-cells

Antiviral defenseDestruction of infected cells before mature viral particles are released

Classification of T-Lymphocytes

T-cells are divided into two major functional groups: effector and regulatory.

1. Effector T-cells directly eliminate threats or trigger inflammation:

Cytotoxic T-lymphocytes (CTLs): directly destroy (lyse) target cells. They play a primary role in tumor destruction and graft rejection.
Delayed-type hypersensitivity (DTH) T-cells: secrete cytokines that recruit and activate cells of nonspecific inflammation (primarily macrophages). This is essential for fighting intracellular infections and participating in autoimmune reactions.

2. Regulatory T-cells control the strength and direction of the immune response:

T-helper cells (Th): help B-lymphocytes produce antibodies in response to most antigens.
T-suppressor cells (Ts): inhibit immune responses, regulate their intensity, and protect the body from autoimmune aggression.

T-Helper Subpopulations

T-helper cells expressing the CD4+ marker can differentiate into four major 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 initiate a response, a T-lymphocyte must "see" the antigen. This occurs exclusively in the form of a trimolecular complex:

A major histocompatibility complex (MHC) molecule on the surface of an antigen-presenting cell.
The antigen itself (more specifically, its fragment — the epitope).
The T-cell receptor (TCR).

The bond is further stabilized by coreceptors. T-helpers use CD4 to bind MHC class II molecules, while cytotoxic cells use CD8 to bind MHC class I molecules.

Activation: The Two-Signal Rule

Simple recognition of a foreign agent is insufficient for the proliferation and function of T-lymphocytes. Two confirming signals are required:

Specific signal: precise interaction of the TCR receptor with the "antigen + MHC" complex.
Costimulatory signal: nonspecific action of factors, such as 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.

Upon receiving both signals, CD4+ T-cells begin synthesizing mediators: IL-4 and IL-2. The latter is a crucial growth factor required for the replication and terminal differentiation of T-lymphocytes.

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. Major APCs include:

Dendritic cells: interdigitating (in the T-zones of lymphoid organs) and macrophage-derived cells (in various tissues).
Langerhans cells: a specialized subset of dendritic cells in the skin epidermis.
Macrophages and B-cells: can also perform antigen presentation for T-helpers.

Relationship with Humoral Immunity

Although cellular and humoral immunity are separate branches of defense, they work in concert. The humoral response requires B-cell proliferation into plasma cells (localized in the spleen, bone marrow, lymph nodes, mucous membranes, and sites of inflammation). These cells are responsible for antibody production.

Primary response: upon first encounter with an antigen, specific antibodies appear after 7 days (mainly IgM), and their concentration peaks after 2 weeks (predominantly IgG).
Secondary response (memory response): upon re-exposure, the reaction takes only 3–4 days with a massive surge of IgG, which persists for several weeks.

Each plasma cell is strictly specific: it synthesizes light chains of only one type (κ or λ) combined with heavy chains of a single immunoglobulin class.

Mnemonic

The rule of eights for coreceptors: CD4 binds to MHC class II (4 × 2 = 8), and CD8 binds to MHC class I (8 × 1 = 8). The product is always eight!

Frequently asked questions

Which molecules provide the costimulatory (second) signal during T-lymphocyte activation?

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 cytokine action. Major costimulatory molecules:

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.

Which cytokines are secreted by Type 1 and Type 2 T-helper cells (Th1 and Th2)?

Type 1 and Type 2 T-helpers secrete distinct 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 promote cellular immunity, macrophage activation, and cytotoxic lymphocyte function. Th2 cytokines stimulate the humoral response and participate in allergic reactions.

What is the molecular mechanism of the cytotoxic action of CD8+ T-lymphocytes?

The molecular mechanism of CD8+ T-lymphocyte (CTL) cytotoxicity is based on antigen-specific lysis of target cells via direct cell-to-cell contact. The process includes the following stages:

Recognition — receptors of CD8+ T-lymphocytes bind to foreign peptides presented in complex with MHC class I molecules on the target cell surface.
Granule exocytosis — the activated cell secretes perforin and granzyme B.
Pore formation — perforins insert into the target cell membrane.
Induction of apoptosis — granzymes enter the cell through the pores and trigger a cascade 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. Major specific Treg markers:

CD4 and CD25 — surface receptors (forming the CD4+CD25hi phenotype).
FOXP3 — a key intracellular transcription factor rendering cells resistant to apoptosis.
CTLA-4 and PD-1 — membrane molecules involved in executing suppressive functions.
GITR — an additional surface marker.
αβTCR — T-cell receptor.

This phenotype is typical for both natural and induced (adaptive) regulatory T-cells.

How do cytotoxic T-lymphocytes kill infected cells?

They destroy target cells through direct cell-to-cell contact. CTLs (CD8+) recognize endogenous peptides complexed with MHC class I molecules 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 following 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 yield of specific IgG.

Go deeper

Mechanisms of antigen processing inside antigen-presenting cells.
Structural features and functions of MHC class I and II molecules.
The role of delayed-type hypersensitivity (DTH) cells in the pathogenesis 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).