Specialized Lymphocytes

Introduction

Specialized lymphocytes, including the NK Cells, NKT cells, gamma delta T cells Intraepithelial lymphocytes, MAIT cells, B1 cells, and marginal zone cells serve as a bridge between innate and adaptive immunity.

This special class of lymphocytes spans hours to days after introduction to antigen. They possess limited receptor diversity appearing early in development during fetal and perinatal periods.

Specialized lymphocytes are activated by carbs, glycolipids, small non-peptides, self-molecules, and conserved microbial molecules. They are characterized by non-classical self recognition on MHC class I-like and non-classical MHC class I molecules.

This class is unusual in their employment of a combination of both activating and inactivating signals for function where activation or inactivation must compete against each other.

## Location and Function

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### NK Cells

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Blood, bone marrow, spleen, liver, lungs, and lymph nodes.

For activation, NK cells must overcome the existing stimulus of inactivation. The inhibitory receptors block the killing of healthy self cells, recognize and spare MHC Class I bearing cells, and recognize HLA-A, B, C, E, and G.

Activating receptors bind receptors of viral infection and injury. NKG2D binds stress-induced ligands MICA, MICB, and ULBP. Activators include cytokines: IFN-gamma, IFN beta, IL-12 and 15, Tumor Necrosis Factor while other pro-inflammatory cytokines amplify the NK Cell response. Also heat shock proteins, and bacteria-sourced phosphoantigens.

NK Cells also possess about 1-5 KIR receptors. The KIR receptors are one of two major classes of NK Cell receptors including the Ly49 family of NK Cell receptors which function very similarly.

The effector mechanisms of NK Cells include cytotoxicity via lytic granules and the release lf proinflammatory cytokines, most notably, Inteferon gamma.

Unlike the CD8 T cells, NK cells provide protection when MHC class I is down regulated. Lacking in this NK Cell advantage correlates to outbreak of viral infection, especially herpes.

### NKT Cells

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Blood, bone marrow, spleen, liver.

### Gamma-Delta T cells

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Located in the Squamous epithelium.

Phenotypical characteristics: Most are double negatives, reside in the intestine via CD8aa.

Specialized to recognize microbial and damaged induced molecules. CD3 composition differs in lacking delta. This results in a stonger signal, not needing costimulation.

Peripheral locations: Resides in a variety of epithelia including the oral cavity, reproductive tracts, and intestines, as well as lymphoid organs.

Gamma-delta T cells possess the effector functions of proinflammatory cytokine IFN-gamma via the T cell receptor, cytotoxicity via perforin-induced NKG2D, antiinflammatory cytokines, IL-10, and tissue growth factors

Antigen expression makes gamma delta T cells very specific. Humans possess dominance in Vgamma9 and Vdelta2

Additional receptors for activation: NKG2D/DAP10 pathways recognize stress, injury, inflammation, non-classical MHC character.

### Intraepithelial lymphocytes

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Intestine.

* Mucosa-Associated Invariant T Cells: Intestinal, subepithelial.
* B1 Cells: Serosal cavities.
* Marginal Zone Cells: Spleen.