Immune System Overview

Skin and Mucosal Surfaces

• Skin and mucosal surfaces act as physical barriers against infection.
• They prevent pathogens from entering the body.

### Lymphoid Tissues

• Lymphoid tissues are either primary or secondary.
• Primary lymphoid tissues, also known as generative organs, allow lymphocytes to express antigen receptors and mature.
• Secondary lymphoid tissues, also known as peripheral organs, initiate and develop immune responses to foreign antigens.

The Gastrointestinal Immune System

• The gastrointestinal (GI) tract is a continuous epithelial cell layer sitting on a basement membrane.
• The GI tract contains the MALT (mucosa-associated lymphoid tissue), a layer of loose connective tissue called the lamina propria.
• The MALT contains blood vessels, lymphatic vessels, and lymphocytes.

M cells in the Small Intestine

• M cells are located in the gut epithelium in regions called follicle-associated epithelium which overlie Peyer's patches and other GALT structures.
• M cells deliver antigen from the lumen to the GALT.
• M cells are distinguishable from absorptive epithelial cells because of their thin glycocalyx, short and irregular microvilli, and large fenestrations which enhance antigen uptake.

Homing Properties of Intestinal Lymphocytes

• The gut-homing properties of effector lymphocytes are imprinted in lymphoid tissues.
• Dendritic cells in GALT are induced by cytokines.
• When activated by antigen in the GALT, naive B and T cells are exposed to retinoic acid produced by dendritic cells, inducing the expression of CCR9 and α4β7.
• Effector lymphocytes enter the circulation and home back to the gut lamina propria.

IgA Class Switching in the Gut

• IgA class switching in the gut occurs by both T-dependent and T-independent mechanisms.
• In T-dependent IgA class switching, dendritic cells in the subepithelial dome of Peyer's patches capture antigens delivered by M cells and migrate to the interfollicular zone, where they present antigen to naive CD4+ T cells.
• Activated T cells differentiate into helper T cells with a T follicular helper phenotype, engaging in cognate interactions with antigen-presenting IgM+ B cells.

Transport of IgA Across Epithelial Cells

• IgA is produced by plasma cells in the lamina propria of mucosal tissue and binds to the poly-Ig receptor at the base of an epithelial cell.
• The complex is transported across the epithelial cell and released into the lumen by proteolytic cleavage.
• This process of transport across the cell, from the basolateral to the luminal surface, is called transcytosis.

### Antigen Sampling by Intestinal Dendritic Cells

• Dendritic cells (DCs) and macrophages are abundant in the GI immune system.
• They stimulate protective effector T cell responses or induce regulatory T cell responses.
• DCs in the lamina propria take up and process protein antigens from microbes that are in the lumen or have breached the epithelial barrier.
• They transport these antigens via lymphatics to mesenteric lymph nodes.

Effector and Regulatory T Cells in the Intestinal Mucosa

• In the GI tract, different subsets of effector CD4+ T cells are induced by and protect against different microbial species.
• Th17 effector T cells and regulatory T cells are abundant in the intestinal mucosa.
• Bacterial antigen-specific Th17 cells differentiate from naive CD4+ T cells in GALT, and require cytokines, including interleukin-6 (IL-6) and IL-23, from dendritic cells (DCs).
• Regulatory T cells require antigen presentation by DCs; the nature of these antigens is unknown.

### The Cutaneous Immune System

• The epidermis provides a physical barrier to microbial invasion.
• The epidermis is made up of keratinocytes which actively respond to pathogens and injury by producing antimicrobial peptides and cytokines.

### The Cutaneous Immune System (Continued)

• The skin-homing properties of effector lymphocytes are imprinted in skin-draining lymph nodes.
• Ultraviolet rays in sunlight (UVB) stimulate production of vitamin D, which induces expression of CCR10.
• Interleukin-12 (IL-12) induces expression of the E-selectin ligand CLA and other signals induce CCR4, CCR8, and CCR10 expression.
• These homing molecules direct migration of the effector T cells into the skin.

Immune-Privileged Tissues

• Certain parts of the body, including the brain, eye, testes, placenta, and fetus are called immune-privileged sites because immune responses and inflammation in these areas can cause lethal organ dysfunction or reproductive failure.

Immune-Privileged Tissues (Continued) - Testis

• Immune privilege in the testes limits inflammation that may impair male fertility.
• Many self antigens in the adult testes are first expressed at puberty after the development of a competent immune system.
• This suggests that lymphocytes specific for these antigens are not deleted during development and that immune privilege in the testes may prevent autoimmunity.

Immune-Privileged Tissues (Continued) - Fetus

• The fetus expresses paternally inherited genes that are considered foreign to the mother.
• Maternal antibodies against paternal MHC molecules are easily detectable, which suggests that the mother is exposed to fetal antigens during pregnancy.
• Different molecular and barrier features of the placenta, and local immunosuppression, may also contribute to the fetus not being rejected by the mother.

Explore the fundamental components of the immune system, focusing on skin and mucosal surfaces as barriers against infection. Learn about the roles of lymphoid tissues and the gastrointestinal immune system, including the importance of M cells in the small intestine.