Spleen and Lymphoid Tissues

• Primary lymphoid organs (bone marrow and thymus) are essential for lymphocyte development.
• Secondary lymphoid tissues serve as filters and provide an environment for leukocytes to enter, encounter antigens, and proliferate before re-entering circulation.
• The spleen and lymph nodes are organized secondary lymphoid organs.

Spleen

• A large secondary lymphoid organ that filters blood, responding to systemic infections.
• The spleen has two major compartments: red pulp and white pulp, separated by a marginal zone.
• The red pulp consists of sinusoids populated by macrophages and erythrocytes, where old and damaged cells are removed.
• The white pulp surrounds branches of the splenic artery, forming a periarterial lymphoid sheath (PALS).
• Dendritic cells present antigens in the T cell zone of the PALS.
• Activated T cells activate B cells that migrate to primary follicles in the marginal zone.
• Upon antigen stimulation, primary follicles develop into secondary follicles containing germinal centers, where B cells differentiate into plasma cells.

Germinal Centers

• Specialized structures within secondary lymphoid organs where activated B cells proliferate, differentiate, and undergo somatic hypermutation and class-switch recombination.
• Germinal centers are found in secondary follicles of lymph nodes (cortex) and spleen (white pulp).
• The dark zone contains rapidly proliferating B cells (centroblasts) undergoing somatic hypermutation.
• The light zone contains B cells (centrocytes) interacting with follicular dendritic cells (FDCs) and T follicular helper cells (Tfh).
• Germinal centers facilitate B cell maturation into plasma cells or memory B cells.
• Antibody optimization occurs through mutation and selection processes in germinal centers.
• Germinal centers contribute to long-term immunity by generating memory cells.
• Antigen presentation by follicular dendritic cells and Tfh cell help are associated processes.

Lymph Node

• Organized; provides an ideal microenvironment for lymphocytes to encounter and respond to antigens from tissues and blood.
• Morphologically divided into the outer cortex, inner paracortex, and central medulla.

Cortex

• The outer cortex contains B cells, macrophages, and dendritic cells arranged in primary follicles.

Paracortex

• Contains primarily T cells and is a thymus-dependent area.
• The paracortex is positioned between the outer cortex and the medulla in secondary lymphoid organs.
• It is rich in T cells and dendritic cells, and acts as a site where initial interactions between T cells and antigen-presenting cells (APCs) occur.

Medulla

• Primarily contains plasma cells that secrete antibodies.
• Initial interaction between antigen and lymphocyte takes place in the paracortex, followed by migration to primary follicles of the cortex.
• T cells activate B cells and develop secondary follicles with central germinal centers.
• High endothelial venules (HEVs) in the paracortex allow circulating lymphocytes to enter the lymph nodes.
• Upon antigen entry, dendritic cells migrate to the paracortex to present antigens to T cells, activating them.

Lymphatic System

• Picks up foreign antigens and carries them to organized lymphoid tissues.
• Secondary lymphoid tissues sample body fluids for foreign antigens.
• Splenectomy or lymphatic dysfunction can lead to increased incidence of bacterial sepsis.

Lymphoid Organs

• Remove foreign material from the lymph and act as lookout points for immune defenses.
• Diffuse lymphoid tissue is a loose arrangement of lymphoid cells typically in the lining of the gastrointestinal and respiratory tracts.
• Lymph nodes are tightly packed clusters of lymphoid cells and protein.
• Unfiltered lymph fluid drains into lymph nodes where foreign material is detected by dendritic cells.
• Dendritic cells sample the lymph and present antigens to B cells.
• If a foreign antigen is presented, the B cell turns into a plasma cell; antibodies flow into the lymph.

Spleen Function

• The spleen receives blood.
• Red pulp destroys old and defective blood cells, recycling their components.
• The spleen keeps red blood cells and platelets available.

MALT (Mucosal Associated Lymphoid Tissues)

• Includes tonsils, Peyer's patches, and gut/bronchial-associated lymphoid tissues.
• Provides defense against microbial invaders at mucosal surfaces.
• MALT, GALT, and BALT are connected to the lymphatic system.

MALT Types

GALT (Gut-Associated Lymphoid Tissue)

• Found in the gastrointestinal tract
• Includes Peyer's patches in the small intestine.

BALT (Bronchus-Associated Lymphoid Tissue)

• Found in the lungs and airways
• Defends against respiratory pathogens.

NALT (Nasal-Associated Lymphoid Tissue)

• Found in the nasal passages
• Includes tonsils, to defend airborne pathogens.

Tonsils

• Palatine: located at the sides of the back of the mouth.
• Lingual: located at the base of the tongue.
• Pharyngeal: located on the roof of the nasal pharynx.
• All contain lymphocytes, macrophages, granulocytes, and mast cells.

Peyer's Patches

• Nodules in the submucosa of the intestine.
• M cells deliver samples of foreign antigen to the submucosa.
• Activated lymphocytes can migrate to primary follicles and develop into secondary follicles with germinal centers.

Mucosal Membranes

• Digestive, respiratory, and urogenital systems are major sites of entry for potential pathogens.
• MALT, GALT, and BALT defend vulnerable membrane surfaces.
• Mucosal-associated tissues range from cell clusters in the lamina propria to organized structures like tonsils and Peyer's patches.
• Intestinal villi contain a lymphatic draining system that samples the intestinal environment.

Peyer's Patches in Depth

• Dome-like structures enriched in lymphoid tissue for immune responses.
• Villi contain blood vessels to transport nutrients.
• Lymphatics from Peyer's patches and villi drain into the mesenteric lymph node.
• The lamina propria is a network of loose connective tissue within the villi.
• Crypts at the base of the villi host stem cells.
• The epithelium and its overlying mucus form a barrier against microbial invasion.
• M cells transport material across the epithelial barrier via transcytosis.
• Dendritic cells extend dendrites between epithelial cells to sample antigens.
• Antigen sampling results in tolerogenic activation.

Regulatory T Cells

• Dendritic cells convert T cells into regulatory T cells (Tregs).
• Tregs migrate to the lamina propria of the villi and secrete IL-10.
• IL-10 suppresses immune cells and maintains immune presence, preventing unnecessary inflammation.

IgA in MALT

• Predominant immunoglobulin isotype secreted in MALT.
• IgA prevents pathogens from adhering to and invading epithelial cells (immune exclusion).
• Secreted as a dimeric form linked by a J chain and a secretory component.
• Plasma cells in the lamina propria produce IgA, which is transported across epithelial cells.
• IgA neutralizes pathogens and toxins without triggering strong inflammatory responses.
• Deficiency in IgA can lead to increased susceptibility to infections at mucosal surfaces.

Overview of primary and secondary lymphoid organs. The spleen filters blood and removes damaged cells. Its white pulp contains the periarterial lymphoid sheath (PALS) where dendritic cells present antigens and activate T and B cells.