The Cutaneous Immune System

The Cutaneous Immune System

• The skin is the largest organ of the body, with up to 10^6 immune cells/cm^2.
• It provides the first line of defense against microorganisms through epithelial barriers.
• The skin consists of both innate and adaptive immunity cells.

Epithelial Barriers

• Keratin on the skin's surface prevents most microbes from interacting with and infecting the epithelia.
• Epithelial cells produce antimicrobial peptides, including defensins and cathelicidins, which kill bacteria and some viruses.
• Epithelia contain lymphocytes called intraepithelial T lymphocytes that recognize microbial lipids and react against infectious agents.

Innate Immune Components in Skin

• Most microbial infections are acquired through the epithelial barrier of the skin, gastrointestinal, respiratory, and genitourinary systems.
• Epithelial cells provide physical barriers and antimicrobial molecules.
• Lymphoid cells are also present in the skin.

Pattern Recognition Receptors (PRRs)

• Toll-like Receptors (TLRs) are specific for microbial structures.

Review: Complement

• The complement cascade amplifies the reaction, leading to the generation of a rigid protein-lined transmembrane channel, the membrane attack complex (MAC).

Immune Players in the Skin

• Keratinocytes express high levels of IL-1, which promotes inflammation and repair when the skin is damaged.
• Fibroblasts in the dermis respond to TNFα by releasing IL-15, which activates effector T cells.

Langerhans Cells

• Langerhans cells are a type of immature conventional dendritic cells that reside in the skin.
• They are rich in MHC class II molecules and carry processed antigens.
• They are actively phagocytic and contain large granules known as Birbeck granules.
• They migrate to the lymph nodes, carrying antigens from the skin to the T helper cells.

T Cells in the Skin

• T cells are present in normal skin and immune responses are characterized by T cell infiltration.
• T cells constitute the major cell type present in both normal skin and immune reactions.
• They are characterized by a skin-homing marker CLA (cutaneous lymphocyte antigen) and the chemokine receptors.

Inflammation

• Inflammation is the response of tissue to injury, bringing serum molecules and cells of the immune system to the site of damage.
• Three components of the inflammatory response:
  • Increased blood supply to the region.
  • Increased capillary permeability.
  • Emigration of leukocytes from blood vessels into the tissues.

Immune Reaction to Infection

• Langerhans cells ingest microbes and are activated by bacterial LPS through the TLR signaling pathway.
• Bacterial LPS induces two changes in Langerhans cells:
  • Stimulating them to migrate and enter the lymphatic system.
  • Initiating adaptive immunity by activating CD4 T cells.