Lecture 23!

Lecture Overview

  • Date: 11/19/25

    • Instructor: Beth M. Stadtmueller, PhD

    • Position: Assistant Professor of Biochemistry, Biomedical and Translational Sciences

    • Lecture Title: Immune System Interactions with Infectious Disease: Commensal and Pathogenic Bacteria and Other Non-Viral Pathogens

Key Terms

  • Peyer’s patches

  • Isolated lymphoid follicles (ILFs)

  • Lamina propria

  • Cryptopatches

  • Paneth cells

  • Tuft cells

  • Intraepithelial lymphocytes

  • Goblet cells

  • M cells

  • CD103+ dendritic cells

  • IgA

  • Pathobionts

  • Vegus nerve

  • TH1-type response

  • Dysbiosis

  • Inflammatory Bowel Disease (IBD)

  • Celiac Disease

  • TH2-type response

  • Trypanosome

  • Induction phase

  • Effector phase

Learning Objectives

  1. Describe cell types associated with immune system activity in the gut mucosa.

  2. Describe mechanisms of tolerance to commensal microbes.

  3. Understand how commensal microbes influence immune responses.

  4. Understand how the host induces inflammatory responses in the same regions where tolerance needs to be maintained.

  5. Understand basic mechanisms associated with host responses to pathogenic bacteria, parasites, and fungi, and the differences associated with intracellular and extracellular infections.

Immune System in the Gut

  • Gastrointestinal tract (GIT) is a vast surface area exposed to both commensal and pathogenic organisms.

  • Must achieve a balance between immune tolerance (to ensure non-responsiveness to commensal bacteria) and inflammation (for pathogen defense).

Gut-Associated Lymphoid Tissue (GALT)

  • Organizes immune responses in the gut via various structures:

    • Peyer’s patches: Organized lymphoid tissue with distinct B cell and T cell zones.

    • Isolated lymphoid follicles (ILFs): Source of IgA-producing B cells.

    • Cryptopatches: A region in the lamina propria between intestinal villi, containing unique epithelial cells.

    • M cells: Transport antigens from the gut lumen to the lamina propria, helping in antigen presentation.

  • Gut immune cells such as CD103+ dendritic cells interact with naïve B and T cells and have significant roles in immune education.

Mechanisms of Tolerance

  • Tolerance Mechanisms:

    • Tolerance is prioritized in the gut immune system due to the presence of commensal bacteria.

    • Factors like BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) are crucial for IgA synthesis.

    • IL-10 and TGF-β serve as anti-inflammatory cytokines to prevent excessive immune reactions.

    • Various immune cells (TREG, TFH, TH17, ILC3s) maintain this tolerance by secreting appropriate cytokines.

  • Induction of IgA:

    • The synthesis of IgA can occur via T-cell dependent and independent mechanisms, largely under the influence of TGF-β.

Impact of Commensal Bacteria

  • Commensal bacteria influence host immune responses positively after establishing tolerance.

    • They provide competition against potential pathogens and modulate inflammatory processes within the gut.

    • An interesting observation is that the small intestine hosts fewer microorganisms compared to the large intestine, which harbor a more complex microbiome.

    • Germ-free mice studies reveal differences in immune responses attributed to the absence of commensal bacteria.

    • Certain bacteria (e.g., SFB) promote TH17 and IgA production, illustrating the co-evolution of humans and commensals.

Dysbiosis and Disease Associations

  • Dysbiosis: Refers to an imbalance in the gut microbiome, often linked with conditions such as Inflammatory Bowel Disease (IBD) and Celiac Disease.

    • IBD: Comprises two main diseases:

    • Crohn’s Disease: Characterized by an inappropriate TH1 immune response.

    • Ulcerative Colitis: Related to an inappropriate TH2 immune response.

    • Celiac Disease:

    • An autoimmune disorder triggered by gluten, marked by IL-15 production leading to intestinal epithelial cell death and excessive immune activation.