Antigen recognition

Target molecules: what the immune system reacts to

In modern immunology, the triggers of defense reactions are divided into three distinct groups:

• Pathogen-associated molecular patterns (PAMPs). Universal invasion signals of a biologically aggressive agent. These are molecules typical of entire classes of pathogens (viruses, fungi, bacteria) but absent in the host organism. They trigger innate immunity reactions.
• Antigens. High-molecular-weight compounds recognized in a purely individual manner. They serve as targets for adaptive immunity.
• Stress molecules and danger-associated molecular patterns (DAMPs). Endogenous analogs of PAMPs. These are the body's own molecules expressed on the cell membrane in response to damaging factors (infectious, radiation, thermal). They occupy an intermediate position between innate and adaptive responses.

It is important to note that foreignness is not an absolute criterion for an immune attack. The boundaries of tolerance can expand: the immune system does not react to food components or the intestinal microflora. On the other hand, there are immunologically privileged sites (CNS, eye cavity) that are normally excluded from the control of the adaptive system. When tissue barriers are disrupted, these sites themselves become the target of a powerful immune aggression.

Innate immunity receptors

The innate immune response is carried out by myeloid lineage cells (primarily phagocytes) widely distributed in barrier tissues.

The main recognition tool here is pattern recognition receptors (PRRs). Upon binding to PAMPs or DAMPs, they transmit a signal into the cell that activates "inflammation genes". Classical representatives of PRRs are membrane and intracellular Toll-like receptors (TLRs), as well as cytosolic NOD receptors.

A separate group consists of receptors that recognize stress molecules. They are localized predominantly on natural killer (NK) cells and certain T lymphocyte subpopulations. Representatives of this group (e.g., NKG2D, NCR) are capable of recognizing MHC molecules regardless of the antigen bound to them, generating both activating and inhibitory signals.

Antigen-recognizing lymphocyte receptors

The adaptive response has a clonal nature and is provided by lymphoid lineage cells. Antigen-specific receptors feature gigantic variability (millions of domain variants) and are distributed clonally — a single cell carries receptors of only one specificity.

The following varieties are distinguished:

1. B cell receptors (BCRs). They have an immunoglobulin nature. They directly recognize an antigen fragment (epitope). Upon differentiation of a B lymphocyte into a plasma cell, BCRs begin to be secreted in a soluble form — as antibodies.
2. T cell receptors (TCRs). Always remain on the membrane and are not secreted. The $\gamma\delta$TCR variant is capable of recognizing an antigen directly. However, the main variant, $\alpha\beta$TCR, cannot see a native antigen — it strictly requires a prepared fragment packaged in a presenter molecule.

Major histocompatibility complex (MHC) molecules

For the $\alpha\beta$TCR to function, the target cell must display an antigen fragment as part of an MHC complex on its surface. The recognition process depends on the molecule class and the participation of specialized coreceptors:

• MHC-I (class I). Present on the membrane of all cells. They present endogenous peptides from the cytosol. If a cell is infected, MHC-I signals an intracellular problem. These complexes are recognized by T lymphocytes bearing the CD8 coreceptor.
• MHC-II (class II). Expressed only on specialized antigen-presenting cells (APCs). They demonstrate exogenous antigens that entered the cell via endocytosis. Recognized by T lymphocytes with the CD4 coreceptor.

There are also non-classical MHC molecules (e.g., CD1) that present lipid epitopes to NKT cell populations.

The organ basis of immunity

While innate immunity does not require complex intercellular contacts, the adaptive response is based on the constant cooperation of lymphocytes. Since the required cells are clonally distributed, the organism needs mechanisms to recruit them to a single point. This is why adaptive immunity can function only within an organ structure — in central and peripheral lymphoid organs.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Organization and functions of the central and peripheral organs of the immune system
• Mechanisms of transmitting inhibitory signals from NK cell receptors
• The process of exogenous antigen presentation by specialized APCs
• Structural differences between membrane Toll-like and cytosolic NOD receptors
• Features of lipid epitope recognition using CD1 molecules

Other topics in the section "Introduction to Immunology"

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