Cellular immunity

Initiation and antigen processing

The initiation of a specific response is always preceded by cell death and nonspecific inflammation (at the portal of entry of the infection, the zone of tumor necrosis, or tissue transplantation). The vascular endothelium reacts to decay products, allowing granulocytes and monocytes into the tissues, where they transform into macrophages.

Macrophages and other antigen-presenting cells (APCs) phagocytose foreign agents. Inside the APC, the antigen enters the endosome, where enzymes cleave it into short peptides (15–20 amino acids). Simultaneously, class II major histocompatibility complex (MHC-II) molecules are synthesized in the rough endoplasmic reticulum of the APC.

To prevent MHC-II from prematurely binding to the cell's own proteins during transport, its active site is covered by a blocking peptide chain (the "chastity belt"). The complex moves through the Golgi apparatus and fuses with the endosome. There, the protective chain is removed, MHC-II captures peptides (both own and foreign), and is transported to the cell membrane. Statistically, only about 0.1% of these complexes contain the required foreign antigenic determinant.

Meeting in lymphoid tissue and activation

The APC with the processed antigen migrates from the focus of inflammation to the T zones of peripheral lymphoid organs (for example, the paracortical zone of lymph nodes). There, the selection of lymphocyte clones takes place.

To ensure precise targeted assistance, a triple cell complex is formed: the APC simultaneously binds to an inactive T helper and a T killer.

• Having recognized the antigen, the T helper secretes interleukin-2, which stimulates its own division (autocrine regulation).
• Having matured, the T helper activates a neighboring T killer.
• The activated T killer transforms into an immunoblast and begins to actively divide (clonal expansion), forming a pool of memory T cells and mature effector cells.

It is important to note that only preparation takes place in the lymph nodes: the attack on targets itself will be carried out in the periphery.

Effector phase: destruction mechanisms

Mature T killers leave the lymphoid tissue, locate target cells via antigenic determinants, and carry out their cytotoxic function. There are two main mechanisms of target death:

1. Osmotic shock. The T killer releases the protein perforin. Perforin molecules embed themselves into the membrane of the attacked cell, forming hydrophilic pores. This disrupts the osmotic balance and leads to death.
2. Apoptosis. Enzymes called granzymes penetrate inside the target cell through the formed perforin pores. Additionally, the Fas receptor ("death receptor") is activated on the target's surface, which triggers a cascade of programmed cell death.

Alternative response scenarios

Depending on the type of threat, the immune system may deviate from the classical interaction scheme:

• Viral infections: the response can proceed without T helpers. T killers are activated directly by dendritic cells or independently recognize the altered target cell.
• Intracellular parasites (e.g., rickettsiae): macrophages take on the role of primary killers. T helpers merely issue a stimulating signal to them.
• Transplant rejection: T killers are capable of attacking foreign tissues. It is hypothesized that this becomes possible due to somatic mutagenesis of T-cell receptor genes in dividing lymphocytes, resulting in the selection of clones with high affinity for foreign MHC-I molecules.

Class and exam questions

What else to study on this topic

• Mechanisms of cross-presentation of antigens
• Structure and functions of the major histocompatibility complex (MHC-I and MHC-II)
• Somatic mutagenesis of T and B lymphocyte receptors
• The role of interleukins in autocrine and paracrine stimulation
• Molecular pathways of apoptosis: Fas receptor and granzymes

Other topics in the section "Hematopoietic and lymphoid organs"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.