Immunology: Thymus and Lymphoid Organs

Thymus

• Attracts circulating T cell precursors from bone marrow
• Essential for T cell maturation
• Composed of cortical and medullary epithelial cells, stromal cells, interdigitating cells and macrophages
• Important for T cell precursor differentiation and education (positive and negative selection)

Secondary/Peripheral Lymphoid Organs

• Lymph nodes
• Spleen
• Mucosal Associated Lymphoid Tissue (MALT)

Lymphocyte-Antigen Encounter

• Occurs in peripheral lymphoid organs

Lymph Node

• Lymphatics drain extracellular fluid from peripheral tissues
• Lymph carries antigen taken up by dendritic cells and macrophages to lymph nodes
• Lymph carries recirculating lymphocytes from lymph nodes back into blood

Mucosal Associated Lymphoid Tissue (MALT)

• Nasal associated lymphoid tissue (NALT)
• Bronchus associated lymphoid tissue (BALT)
• Gut associated lymphoid tissue (GALT)

Distinctive Features of the Mucosal Immune System

• Intimate interactions between mucosal epithelia and lymphoid tissues
• Discrete compartments of diffuse lymphoid tissue and more organized structures like Peyer's patches and isolated lymphoid follicles
• Specialized antigen-uptake mechanisms, e.g., M cells in Peyer's patches
• Activated/memory T cells predominate even in the absence of infection
• Secretory IgA antibodies
• Presence of distinctive microbiota
• Active downregulation of immune responses predominates

GALT

• Peyer's patches - only in the small intestine
• Isolated lymphoid follicles - entire intestine
• Appendix
• Tonsil and adenoid - in throat

Peyer's Patches

• Important sites for the initiation of immune responses in the gut
• 100-200 Peyer's patches in the human small intestine
• Visible to the naked eye, dome-like structure projecting into the intestinal lumen
• Contain B cells in B cell follicles, intercalated by T cell zones and dendritic cells
• Follicle-associated epithelium separates the lymphoid tissue from the gut lumen

M Cells

• Have a folded luminal surface instead of microvilli
• Do not secrete digestive enzymes or mucins
• Directly exposed to microorganisms and particles within the gut lumen
• Bind microbes and internalize them by transcytosis
• Provide a conduit for luminal microbes into the GALT and connected lymphatics
• Targeted by pathogens to gain access to the subepithelial space

Mesenteric Lymph Nodes

• Tissues of the small intestine drain to the mesenteric lymph nodes
• Largest lymph nodes in the body, crucial for initiating and shaping immune responses to intestinal antigens
• Mucosal surface and lymphoid aggregates of the large intestine drain to the mesenteric lymph nodes and the caudal lymph node

Mucosal Immune System

• Contains large numbers of effector lymphocytes even in the absence of disease
• Effector cells are found in two main compartments: the epithelium and the lamina propria

Intraepithelial lymphocytes (IEL)

• Lymphoid component of the epithelium consists mainly of lymphocytes, which are predominantly CD8 T cells, also called IEL
• Type a: express α:β T-cell receptors and CD8α:β heterodimer, possess cytolytic functions like antiviral activity and IFN-γ secretion
• Type b: express α:β or γ:δ T-cell receptors and CD8α:α heterodimer, involved in mucosal repair after inflammatory damage and stimulation of antimicrobial peptide release

IgA

• Dominant class of antibody in the mucosal immune system
• Produced locally by plasma cells in the mucosal wall
• Different forms in the blood and mucosal secretions
• IgA in blood is mainly a monomer
• In mucosal tissues, IgA is almost exclusively a polymer, usually a dimer
• Transported across epithelium by the polymeric immunoglobulin receptor (pIgR) via transcytosis to reach its target antigen
• Functions in various ways

Innate Immunity in the Gut

• Physical barrier: thin layer of permeable epithelium protects underlying tissues, tight junction proteins maintain paracellular permeability
• Mucus layer: large glycoproteins (secreted and membrane-bound) called mucins provide viscosity and protective properties
• Epithelial cells have immunological functions: sloughing, mucus production, antimicrobial peptides (AMPs), cytokines and chemokines, T cell-like cytokines

Intestinal Epithelial Cells (IECs)

• Enterocytes: absorption, mucus, digestive enzymes
• Enteroendocrine cells: hormone production, stem cell factors
• Goblet cells: specialized mucus producers
• Paneth cells: specialized cells defending the crypts in the small intestine and colon
• M cells: antigen and microbe passage to GALT

TLRs on IECs

• Epithelial cells express Toll-like Receptors (TLRs) on both apical and basal surfaces
• Sense bacteria in the gut lumen and those that have penetrated the epithelium

NOD Proteins

• NOD1 and NOD2 act as sensors
• NOD1 recognizes a diaminopimelic acid-containing peptide found in Gram-negative bacteria
• NOD2 recognizes muramyl dipeptide found in most bacterial peptidoglycans
• NOD2 dysfunction is associated with Crohn’s disease

Gut Microbiota and Functions

• 10¹⁴ microbes colonize the GI tract
• Immune response against these microbes is proactive, involving a constant adaptive response
• Inflammation is used sparingly

Cytokines

• Polypeptides secreted by leukocytes and other cells that act on hematopoietic cells
• Modulate immune and inflammatory responses

Test your knowledge on the role of the thymus and peripheral lymphoid organs in the immune system. This quiz covers T cell maturation, lymphocyte encounters, and the functions of various lymphoid tissues. Prepare to explore the intricacies of the mucosal immune system and how it interacts with antigens.