Skin immune system

Key differences from mucosal immunity

Cutaneous lymphoid tissue is significantly less developed than mucosal tissue. It lacks conventional lymphoid follicles — all defense relies exclusively on diffuse lymphoid elements.

Unlike mucous membranes, a minimal amount of foreign agents penetrates through the intact skin barrier. Furthermore, M cells are completely absent in the epidermis. This means the skin lacks the mechanism for forced antigen capture and transport that is so actively used in the gut or respiratory tract.

Afferent link: antigen uptake

The afferent (sensory) part of the system is represented by dendritic cells. Their main task is to engulf foreign material, migrate to regional lymph nodes, and present it to T lymphocytes.

Two pools of such cells operate in the skin:

1. Classical myeloid dendritic cells — functionally and morphologically analogous to those present in mucous membranes.
2. Langerhans cells — a specialized cutaneous variant of macrophages. Their main distinguishing features are the presence of specific intracellular Birbeck granules and the expression of the lectin receptor langerin (CD208) on their membrane.

Efferent link: who provides defense in situ?

The effector part of the system is distributed among the skin layers, with the cellular landscape of the epidermis and subepithelial layer differing significantly.

Epidermal cells T lymphocytes dominate here (vast majority being effector and memory cells that have previously encountered antigen). The ratio of CD4+ and CD8+ subpopulations here completely matches that in the systemic circulation, which distinguishes the skin from mucous membranes.

A key feature of cutaneous CD4+ T cells is the presence of the CLA molecule (an addressin which is a fucosylated P-selectin receptor). This marker ensures specific homing — strictly directed migration of memory lymphocytes bearing it from the bloodstream back into skin tissues.

γδ T cells are also present in the epidermis. Their numbers are higher than in peripheral blood, but lower than mucosal values. A significant portion of them are direct descendants of cells that emigrated from the thymus back in the embryonic period.

Keratinocytes play a special role. Under the action of bacterial products and pro-inflammatory cytokines, these ordinary epithelial cells transform: they acquire the properties of typical macrophages, begin to phagocytose pathogens, and even present antigens to memory T cells.

Dermal cells A broader spectrum of immune system cells is localized in the subepithelial layer: B lymphocytes, NK cells, and various representatives of innate immunity are found here.

Lymphocyte recirculation

Immune defense is impossible without constant tissue patrolling. Lymphocyte recirculation is the continuous cycle of cells in which they move through the stromal framework, leave lymphoid organs, and then return to them.

The classical recirculation pathway looks like this:

1. Exit from the lymphoid organ along with the flow of efferent lymph (cells from the spleen enter the blood directly).
2. Passage through the thoracic lymphatic duct.
3. Dumping into the systemic bloodstream.
4. Penetration through the walls of postcapillary venules back into the lymphoid tissue (into the same or another organ).
5. Directed movement to specific localization sites within the organ.
6. Repetition of the cycle.

Class and exam questions

What else to study on this topic

• Structure and functions of the CLA molecule (addressin)
• Ultrastructure and role of Birbeck granules in Langerhans cells
• Origin and tasks of γδ T cells in the epidermis
• Mechanism of lymphocyte diapedesis through postcapillary venules
• Pro-inflammatory cytokines activating keratinocytes

Other topics in the "Adaptive Immunity" section

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