BIOL 453 Lecture 2.3 | 06/11/2026: Secondary Lymphoid Organs: Detailed Analysis of Spleen, MALT, and Mucosal Immunity

The Anatomical Structure and Cellular Organization of the Spleen

• The Splenic Capsule and Blood Flow: The spleen is encased in a capsule, which serves as its outermost protective layer. Blood enters the organ through splenic arteries which branch into smaller vessels within the tissue.

• Splenic Arteries and Primary Follicles: As splenic arteries establish themselves within the organ, they form the sites for primary follicles.

  • Cellular Density: These follicles contain an immense number of cells, estimated at hundreds of thousands ($100,000$s) of B cells.

  • Primary State: These are termed primary follicles because no immune response has yet been initiated. If no immune response occurs, they remain in this primary state.

• The Periarteriolar Lymphoid Sheath (PALS): T cells enter the spleen and take up residence in a specific region surrounding the splenic arteries known as the PALS.

  • T Cell Population: There are thousands of T cells present within the PALS.

  • Residence: While they surround the primary follicles, they can also reside within them during activation processes.

• Activation and Secondary Follicles: An immune response is initiated when there is cross-linking of B cell receptors ($BCR$s) with an immunizing agent or pathogen.

  • T Cell Facilitation: A dendritic cell facilitates the activation of a $CD4+$ helper T cell through antigen processing and presentation.

  • $CD40$ Interaction: The activated T cell induces the expression of the $CD40$ ligand ($CD40L$). When the T cell enters the follicle, the $CD40L$ interacts with the $CD40$ receptor on the surface of the B cell to provide the necessary activation signal.

  • Transition: Once activation occurs, the follicle is transitioned into a secondary follicle.

• Effector Exit: Following activation, the helper T cells and the differentiated B cells (now plasma cells secreting antibodies) exit this region of the spleen to enter the circulatory system.

Histological Partitioning: White Pulp and Red Pulp

• The White Pulp: In histological biopsies (staining), the region encompassing the periarteriolar lymphoid sheath and the entry points of the splenic arteries appears light or white.

  • Function: This is the site where antigens and immune receptor cells enter the spleen to occupy the tissue.

• The Red Pulp: The regions of the spleen where blood returns to the circulatory system via the splenic veins appear red when stained.

  • Function: After activation in the white pulp, effector cells ($CD4+$ helper cells and plasma cells) and their products (cytokines and antibodies) exit the white pulp and enter the red pulp to rejoin the general circulation.

The Marginal Zone (MZ) and T-Independent B Cells

• Definition of the Marginal Zone: The marginal zone ($MZ$) is a specific region in the spleen where specialized cell types reside.

• Absence of T Cells: Notably, the marginal zone lacks T cells.

• T-Independent B Cells: Because T cells are absent, this region contains a subpopulation of B cells that recognize T-independent antigens.

  • Signal Requirements: These B cells do not require the $CD40L$ to $CD40$ binding interaction for activation. They require a "second signal" but can be activated by free pathogens flowing through the blood in the spleen.

  • Antigen Presentation: B cells are specialized antigen-presenting cells ($APC$s) capable of antigen processing and presentation.

Mucosa-Associated Lymphoid Tissue (MALT) and Epithelial Barriers

• Definition: $MALT$ comprises the lymphoid tissue associated with various mucous membranes throughout the body.

• Structural Composition:

  • Epithelial Monolayer: The barrier consists of a single layer of epithelial cells.

  • Goblet Cells: Interspersed within the epithelial cells are "bunny-shaped" goblet cells.

  • M Cells (Microfold Cells): Another specialized "bunny-shaped" cell is the M cell, which acts as an inductive site for the investigation of immunological challenges.

• Connective Tissue: Beneath the monolayer of epithelial, goblet, and M cells lies a layer of connective tissue where the $MALT$ structure is established.

• Comparison to Other Organs: $MALT$ exhibits less striking organization compared to the lymph nodes and the spleen. The structure is less rigid, with B cells and $CD4+$ helper T cells scattered throughout the connective tissue rather than held in fixed locations.

The M Cell Inductive Site and Transcytosis

• Pathogen Internalization: Pathogens that colonize the mucous membranes are brought into the $MALT$ via the M cell.

• Process of Transcytosis:

  • Definition: Transcytosis is the process where a substance enters on the apical membrane (the side facing the lumen/mucus) and exits from the basolateral membrane (the side facing the internal tissue), or vice versa.

  • Mechanism: The M cell undergoes endocytosis to internalize the pathogen, moves it through the cell in a transport vesicle, and deposits it into the underlying $MALT$.

B Cell Activation and IgA Secretion in the MALT

• Activation Pathway:

  1. Pathogens are deposited in the $MALT$ via M cell transcytosis.

  2. B cells bind antigens via their receptors, facilitating cross-linking.

  3. T cell receptors ($TCR$s) recognize peptide fragments and produce $CD40L$.

  4. Interaction between $CD40L$ and $CD40$ activates the B cell.

  5. $TH_2$ (T-helper 2) cells produce a specific array of cytokines.

• Class Switching to IgA: In most cases, these cytokines induce a class switch to the antibody isotype $IgA$, which is the most abundant isotype in mucous membranes.

• Structure of IgA:

  • Dimeric Form: All $IgA$ in these regions is dimeric in nature, consisting of two antibodies bound together by a joining protein ($J-chain$).

• Export via Poly-Ig Receptor:

  • To reach the mucus layer where the pathogen resides, the dimeric $IgA$ binds to a poly-Ig receptor on the basolateral membrane of the epithelial cells.

  • The complex undergoes transcytosis in the opposite direction (basolateral to apical).

• The Secretory Component: During transcytosis, the poly-Ig receptor is processed and cleaved. A fragment of the receptor remains attached to the antibody complex. This fragment is known as the secretory component.

  • Function: The secretory component confers resistance to certain proteases produced by pathogens in the mucus layer.

• Pathogen Removal:

  • Agglutination: $IgA$ causes pathogens to clump together.

  • Neutralization: This prevents pathogens from attaching to epithelial cells.

  • Mucociliary Elevator: In the lungs, microvilli and cilia create an upward flow of mucus. Agglutinated pathogens are moved up the "mucociliary elevator" to the esophagus, where they are swallowed into the inhospitable, acidic environment of the stomach and intestinal tract.

Categorization of MALT by Location

• BALT (Bronchus-Associated Lymphoid Tissue): Localized in the large tubes (bronchi) leading into the lungs.

• NALT (Nasal-Associated Lymphoid Tissue): Localized in the nasopharyngeal tract.

• GALT (Gut-Associated Lymphoid Tissue): Localized throughout the gastrointestinal tract, including the stomach, small intestine, and large intestine.

Memory Cells and G0 Arrest

• Effector vs. Memory Cells: While effector cells are the most abundant during an immune response, a minor subcategory of cells enters a state of $G_0$ arrest.

• Function: These cells remain inactive and do not participate in the immediate immune response. They serve as memory cells that will only be activated if the primary effector cells fail to resolve a future challenge.

Questions & Discussion

• Question from Student: [Inaudible regarding splenic processing or antigen presentation]

• Instructor Response: "Yeah. Sounds good. Yeah. Absolutely. Yeah. Alright. Any other questions? Okay. So now, we're doing the spleen. We're getting to the final site…"