The Adaptive Immune Response: T lymphocytes and Their Functional Types

Core Concepts

T cell development: education in the thymus

Precursor cells migrate from the bone marrow to the thymus, where they proliferate and rearrange their TCR genes so that each developing cell expresses a unique receptor. The thymus then runs two screening exams. Positive selection keeps T cells whose TCRs can bind the body's own MHC molecules (class I or class II) — cells that cannot are useless and die. Negative selection eliminates T cells whose TCRs bind too strongly to self-peptides presented on MHC, removing dangerous self-reactive cells. The survivors exit as mature, self-tolerant T cells that recognize foreign peptides only in the context of self MHC. This "MHC restriction" is a defining feature of T cell recognition and a frequent exam theme.

Antigen presentation: MHC class I and class II

T cells cannot see free antigen; it must be chopped into peptides and displayed on MHC molecules. MHC class I molecules are expressed on virtually all nucleated cells and display peptides from inside the cell — endogenous proteins, including viral proteins made by an infected cell. MHC class II molecules are expressed mainly on professional antigen-presenting cells (APCs) — dendritic cells, macrophages, and B cells — and display peptides from material the cell has engulfed (exogenous antigens). The T cell's co-receptor enforces the match: CD8 binds MHC class I (so CD8 T cells watch the "inside" of cells), while CD4 binds MHC class II (so CD4 T cells respond to antigen captured by APCs). Activation requires more than TCR binding, however: a co-stimulatory signal (classically B7 on the APC engaging CD28 on the T cell) is needed. TCR engagement without co-stimulation leaves the T cell unresponsive (anergic) — a safeguard that helps prevent reactions against healthy tissues.

Helper T cells (CD4): the orchestrators

Helper T cells do not kill; they secrete cytokines that direct other cells. After activation, they differentiate into subsets, a commonly taught framework of which includes: Th1 cells, which activate macrophages and support cell-mediated immunity (important for intracellular pathogens); Th2 cells, which help B cells switch antibody classes and support responses against parasites and allergens; Th17 cells, which recruit neutrophils and defend mucosal surfaces; and regulatory T cells (Tregs), which suppress immune responses and restrain autoimmunity. The cytokine environment during activation determines which subset develops. Helper T cells also deliver direct help to B cells (Topic 4) and secrete IL-2, the growth factor that drives T cell proliferation after activation.

Cytotoxic T cells (CD8): the killers

Cytotoxic T lymphocytes (CTLs) patrol for cells displaying foreign peptides on MHC class I — for example, a virus-infected cell presenting viral peptides, or a tumor cell presenting mutated proteins. When a CTL's TCR recognizes its specific peptide–MHC I complex (with co-stimulation where needed), the CTL forms a close contact and releases granules containing perforin, which punches pores in the target membrane, and granzymes, which enter through the pores and activate the target's own apoptosis machinery. CTLs can also trigger apoptosis through Fas–Fas ligand interactions. The infected cell dies before the virus can finish replicating, and the CTL survives to kill again. This makes CTLs the main defense against viruses, intracellular bacteria, and tumors.

Memory T cells and the power of the second response

Some activated T cells become long-lived memory T cells. On re-exposure to the same antigen, memory cells respond faster and in greater numbers than naive cells did the first time — the basis of immunological memory and of vaccine protection. The first (primary) encounter takes days to build an effective response; the second (secondary) encounter is quicker, stronger, and often prevents disease altogether.

Common Confusions