Dendritic Cells and Gut Immunity

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Questions and Answers

What role do dendritic cells (DCs) play in antigen uptake in the intestine?

They induce a direct immune response by destroying pathogens.

They only circulate in the blood and do not interact with epithelial cells.

They are recruited to the epithelial border by chemokines released from epithelial cells. (correct)

They store antigens and do not migrate after antigen uptake.

Which cells primarily predominate in the epithelium of a healthy gut?

CD8+ T cells (correct)

Mast cells and DCs

CD4+ T cells and eosinophils

B cells and macrophages

What is the significance of effector CD4+ T cells in the lamina propria?

They only respond to viral infections.

They help maintain a balance between effector and regulatory T cells. (correct)

They primarily reside in lymph nodes and do not interact with tissue.

They are primarily involved in IgA production.

Which Th cell type is associated with secreting IL-17 in the ileum and colon?

Th17 cells Signup and view all the answers

Which statement regarding the healthy gut is true?

It resembles a chronic inflammatory state in the absence of infection. Signup and view all the answers

What is the role of induced regulatory T cells (Treg) in the immune system?

They balance proinflammatory Th1, Th2, and Th17 cells. Signup and view all the answers

What characterizes the state of oral tolerance?

It creates an immunosuppressive state to prevent reactions to harmless antigens. Signup and view all the answers

Which of the following is NOT a mechanism involved in oral tolerance?

Creation of antibodies against food antigens. Signup and view all the answers

Where are commensal organisms typically found in the human body?

In various sites including the mouth, stomach, and vagina. Signup and view all the answers

What is the physiological significance of TGFb and IL-10 expressed by Treg cells?

They contribute to immunosuppressive functions. Signup and view all the answers

What is the primary function of the mucosal immune system?

To protect mucosal surfaces and distinguish harmful from non-harmful antigens Signup and view all the answers

Which type of immune cell is predominantly found in the mucosal immune system such as GALT?

Lymphocytes Signup and view all the answers

What role do M cells play in mucosal immunity?

They take up particles from the gut lumen by endocytosis/phagocytosis Signup and view all the answers

How do physiological barriers contribute to mucosal immunity?

They provide structural support and prevent pathogen entry. Signup and view all the answers

Which of the following tissues is part of the mucosal immune system?

Bronchus-associated lymphoid tissue (BALT) Signup and view all the answers

What is meant by 'sterilizing immunity' in the context of mucosal immunity?

An immune response capable of preventing the establishment of subsequent infections. Signup and view all the answers

Which characteristic helps the mucosal immune system to quickly respond to pathogens?

Rapid turnover of epithelium from epithelial stem cells. Signup and view all the answers

Why is it important for the mucosal immune system to differentiate between harmful and non-harmful antigens?

To prevent unnecessary immune responses to food and commensals. Signup and view all the answers

What is the role of gut commensal bacteria in immune system development?

They are essential for the metabolism of food and the synthesis of co-factors. Signup and view all the answers

How do immature dendritic cells (DCs) affect the generation of Treg cells?

They activate naïve T cells in mesenteric lymph nodes. Signup and view all the answers

What is the primary function of TGFb produced by Treg cells?

To promote IgA secretion in activated B cells. Signup and view all the answers

What mechanism prevents commensals from invading the epithelial layer?

Tight junctions between epithelial cells confine them to the gut lumen. Signup and view all the answers

What consequence might result from commensals entering the bloodstream?

Infection in pathological states. Signup and view all the answers

Which cytokine drives Th17 differentiation in the presence of gut commensals?

IL-23 Signup and view all the answers

What description best characterizes the role of DCs in relation to gut commensals?

DCs can take up antigens by squeezing between epithelial cells. Signup and view all the answers

What is a key factor in limiting intestinal inflammation?

Physiological inflammation mechanisms. Signup and view all the answers

Study Notes

Mucosal Immunology

Mucosal immunity is a crucial component of the body's defense against pathogens.
Pathogens commonly enter the body through mucosal surfaces.
Local immunity, involving IgA and IgG, and cellular immunity are important defense mechanisms at these sites.
Mucosal immunity can sometimes provide sterilizing immunity (like against influenza).
It is vital for dealing with pathogens that circumvent later immune responses.

Learning Objectives

Understand the normal function of the mucosa and associated immune tissue.
Comprehend how mucosal immunity responds to food antigens, commensals, and pathogens in the digestive tract.

What's Special About Mucosal Immunity

Most pathogens enter the body through mucosal surfaces.
Local immune responses (IgA/IgG and cellular immunity) act as a primary defense against pathogens.
Mucosal immunity can induce sterilizing immunity in some cases (influenza).
It's especially important for pathogens that evade subsequent immune responses.

Physiological Barriers

Tight junctions within the mucosa's structure are a significant barrier.
Epithelial cells turnover rapidly, originating from stem cells.
Mucus and glycocalyx coat the surfaces.
Ciliated surfaces facilitate movement of material.
Optimal pH levels are present.
Physiological microflora also contributes to defense.

Mucosal Immune System (MALT)

Protects mucous-coated surfaces (GI, GU, respiratory tracts).
Comprises significant immune tissue (approximately 75% of lymphocytes).
Mucosa is permeable, thus susceptible to infection.
Most pathogens gain entry through mucous membranes.
Contact with non-pathogenic molecules (like food proteins and commensal bacteria) is also common.
Mucosal immunity must differentiate between pathogens and innocuous entities.

Mucosal Immune System (MALT) - Examples

GALT (gut-associated lymphoid tissue)
NALT (nose-associated lymphoid tissue)
BALT (bronchus-associated lymphoid tissue)
Mucosal systems in the eyes, breast, and urogenital areas

Organisation of MALT

Focuses on intestinal mucosa.
Immune cells (lymphocytes, macrophages, DCs) are found throughout in organized tissues (GALT) or dispersed throughout the mucosal epithelium and underlying connective tissues.
Organized tissues (GALT and mesenteric lymph nodes) are important for immune responses.
Scattered cells are also involved in local immune responses.

Gut-associated Lymphoid Tissue (GALT)

Intestinal lymphocytes are located in organized tissues where immune responses develop and in the gut where they carry out effector functions.
Scattered lymphoid cells are present in the epithelium.
Organized lymphoid tissues include intestinal lumen, lamina propria lymphocytes, and intraepithelial lymphocytes, as well as Peyer's patches, subepithelial domes, isolated lymphoid follicles.

Antigen Uptake in the Intestine

M cells absorb particles from the gut lumen through endocytosis and phagocytosis.
Particles are transported through the cells (transcytosis).
Dendritic cells (DCs) are recruited to the epithelium.
M cell basal borders form pockets encompassing DCs and lymphocytes.
DCs migrate to T cell areas when they absorb antigens, and present to T cells.
Then B cell activation occurs and class switching to IgA.

Effector Cells in the Intestine

Large numbers of effector T cells and plasma cells reside within the intestinal tissues.
Unusual for non-lymphoid tissues.
CD8+ T cells are predominant in the epithelium.
CD4+ T cells, plasma cells, DCs, macrophages, mast cells, and eosinophils are located within the lamina propria.
A healthy gut exhibits a similar structure to a chronic inflammatory state, but this is a normal phenomenon.
Effector and regulatory T cells need to balance one another.

CD4+ T Cells in Lamina Propria

Effector CD4+ T cells are scattered in the lamina propria.
Include Th1 (antibacterial responses), Th2 (anti-parasitic responses), and Th17 cells (ileum and colon, recruiting neutrophils)
Induced regulatory T cells (Treg cells) are CD25+ and suppress inflammation, expressing TGFβ and IL-10

CD4+ T cells in Lamina Propria

Induced regulatory T cells (Tregs) are present, expressing TGFβ and IL-10, which are immunosuppressive.
Th1, Th2, and Th17 cells are balanced by these Tregs. This state is termed physiological inflammation.

Induction of Immune Responses

Gut is exposed to pathogens, non-pathogenic bacteria and other innocuous substances.
Mucosal immune system differentiates between harmful (pathogenic) and harmless.
Commensal organisms are present in various locations (mouth, esophagus, stomach to cervix).

Response to Food Antigens

Oral tolerance generates tolerance toward food antigens.
Both mucosal and systemic immune systems are affected (oral tolerance).
Oral tolerance is a state of immunosuppression in the oral mucosa, preventing reactions to harmless antigens.
It prevents unnecessary immune responses to commensal bacteria and food.

Mechanisms of Oral Tolerance

Anergy and deletion of antigen-specific T cells.
Generation of antigen-specific Treg cells via activation of naÃ¯ve T cells in mesenteric lymph nodes by immature DCs.
unclear how this leads to systemic tolerance.

Response to Commensals

Gut commensal bacteria perform essential functions (metabolism, cofactor synthesis).
Commensals are important for immune development.
They don't produce virulence factors, so they don't invades the epithelium.
However, they are cleared rapidly by phagocytes, therefore do not cause infections.
Commensals are recognized by the immune system but don't induce immune tolerance.
Inflammation in the gut is limited.
commensal-specific Th1 and Th17 effector cells are produced but usually do not initiate inflammatory responses. DCs produce IL-23 to drive Th17 differentiation. Th17 cells generate IL-22, which promotes antimicrobial peptides. Commensal bacteria stimulate cytokine and chemokine production by inhibiting NFκB activity. Microorganisms are controlled in the gut via tight junctions, mucin production, IgA and defensins.

Response to Pathogens

Pathogens are recognized by TLRs and NODs on cell surfaces or within intracellular vesicles.
Intracellular pathogens trigger inflammasome formation and destruction in autophagosomes.
Invasive microorganisms penetrate the epithelium to activate dendritic cells.
TLRs, NOD1, NOD2 activate NFκB, stimulating inflammatory cytokines, chemokines, and other mediators.
These molecules recruit and activate neutrophils, macrophages, and dendritic cells.
Pathogens in the cytoplasm form autophagosomes, then are destroyed inside lysosomes.
Activated dendritic cells expressing co-stimulatory ligands promote differentiation of CD4 into Th1, Th17, and Th2 cells.

Effect of Antibiotics on Commensal Bacteria

Antibiotics can kill commensal bacteria.
Clostridium difficile can colonize and produce toxins.
Toxins cause tissue damage, leading to inflammation.

Summary

Mucosal lining acts as a physical barrier to pathogens and damage.
Specialized immune cells detect and respond to threats.
System learns to tolerate harmless food antigens.
Maintains symbiotic relationship with beneficial bacteria, preventing overgrowth.
Pathogen-associated molecules initiate immune responses via pattern recognition receptors (PRRs), activating immune cells, which promotes inflammation and recruits cells to eliminate the pathogen.

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Description

Explore the important roles of dendritic cells and other immune components in gut health and function. This quiz covers topics such as antigen uptake, cellular predominance in the gut epithelium, and the significance of various T cell types in maintaining gut homeostasis.