Week 29 Mucosal Immunology

Course Overview

Course Code: BIOS6220

Title: Advanced Immunology

Week 19 Focus: Mucosal Immunology, Lecture 1

Instructor: Dr. Jerome Korzelius

Institution: University of Kent

Key Topics in Mucosal Immunology

Mucosal Immune System Structure

• Examination of the nature and architecture of the mucosal immune system, particularly focusing on the gut and mechanisms that lead to oral tolerance regarding food antigens.

• The mucosal immune system is composed of diffuse lymphoid tissues that serve as a defense against pathogenic invasions through mucosal surfaces.

Immune Responses

• Discusses specialized B- and T-cell responses present in the mucosal immune system in relation to gut health.

• The responses are tailored to handle specific conditions within the gut, maintaining a balance between responsiveness to pathogens and tolerance to non-threatening antigens.

Microbiome's Role

• Understanding the microbiome and its role in maintaining homeostasis within the gut.

• Highlighting interactions between gut microbiota and the immune cells, which influences the development of immune responses and overall health.

Reference Texts

• Janeway’s Immunobiology (9th Ed) - Chapter 12

• Kuby Immunology (8th Ed) - Chapter 13

Structure of the Mucosal Immune System

• Components: The mucosal immune system consists of a complex array of tissues found throughout the body, focusing on:

  • Gastrointestinal Tract: Includes structures such as Peyer's patches and lymphoid follicles, essential for antigen recognition.

  • Respiratory Tract: Contains immune components capable of combating airborne pathogens.

  • Urogenital Tract: Protects against infections while maintaining tolerogenic responses.

  • Mammary Glands: Provide immune support through the secretion of antibodies in breast milk.

  • Salivary Glands: Produce secretory IgA to guard against pathogens entering through the oral cavity.

  • Others (e.g., conjunctiva, middle ear): These mucosal sites also house immune cells and contribute to the first line of defense against infections.

Significance of GALT

• The gut-associated lymphoid tissue (GALT) is the oldest part of the adaptive immune system, critical for responding to antigens and developing tolerance, especially within the gut.

• Comprises the majority of the body's lymphocytes and is essential for producing immunoglobulins like IgA, which plays a key role in mucosal immunity.

• The significant surface area of the intestines (~400m²) reinforces its role in immunological defense, allowing for extensive interaction with antigens.

Anatomical Features and Immune Response Mechanisms

Distinct Features

• The mucosal immune system is marked by:

  • Extensive interactions between mucosal epithelia and lymphoid tissues, enabling robust immune surveillance.

  • Presence of specialized structures such as Peyer’s patches that are integral to lymphocyte maturation and response.

  • Antigen-uptake mechanisms (e.g., M-cells) that capture and facilitate the processing of antigens, playing a pivotal role in initiating immune responses.

Immune Regulation

• Characteristically, healthy mucosal epithelia exhibit features akin to a chronic inflammatory response, containing a significant number of effector lymphocytes and leukocytes poised for rapid action.

Challenges to Mucosal Integrity

Infectious Agents

• A vast majority of infections enter through mucosal pathways, particularly the gastrointestinal tract, leading to substantial morbidity and mortality globally.

Tolerance Mechanisms

• The mucosal immune system constantly encounters numerous non-pathogenic antigens, such as food proteins and commensal microorganisms, necessitating tolerance.

• This is central to avoiding inappropriate immune responses which could lead to autoimmune conditions (e.g., Celiac Disease, Crohn’s Disease).

Mechanisms of Antigen Capture and Presentation

Capture Mechanisms

• M-cells facilitate the transport of antigens from the gut lumen to dendritic cells and lymphocytes, thus activating immune responses efficiently and effectively.

• Pathogen exploitation of this entry route highlights vulnerabilities within the mucosal defense strategies, necessitating constant adaptation.

T Cell Activation and Homing

• Gut-homing T- and B-cells express specific integrins (e.g., α4β7), allowing them to bind to mucosal vascular addressin (MAdCAM-1) on endothelial cells.

• This specificity is crucial for regulating immune cells destined for mucosal linings, ensuring a tailored response for both the small and large intestines.

The Role of Dendritic Cells in Immune Tolerance

Dendritic Cell Functions

• CD103+ dendritic cells represent the first line of defense, facilitating the generation of regulatory T cells (iTregs), which are vital for maintaining tolerance and homeostasis in the gut environment.

• The interplay between dendritic cells and T cells ensures the fine-tuning of immune responses against harmless antigens.

Macrophage Role

• Lamina propria macrophages contribute to tolerance by secreting IL-10, which promotes survival and expansion of iTregs, further inhibiting inflammatory responses.

Summary of Mucosal Immune Functionality

Immune System Complexity

• The mucosal immune system must differentiate between pathogens and non-harmful antigens, utilizing various specialized cells and structures to modulate the immune response without triggering inflammatory damage.

Microbiome Relationship

• The gut microbiome plays an essential role in mediating the balance between host defenses and tolerance, affecting physiological health, immune responses, and susceptibility to diseases.