mucosal immunology Flashcards
general features of immunity at epithelial barriers
- outer epithelial layer to prevent microbial invasion
- underlying connective tissue containing immune cells that mediate innate immune response and effector arm of adaptive response (lymphocytes, dendritic cells, macrophages, and mast cells)
- in mucosal tissues: MALT is secondary lymphoid tissue
- draining lymph nodes where adaptive immune responses are initiated/amplified
regional immune systems
- mucosal immune systems = GI, bronchopulmonary, and GU mucosal barriers
- cutaneous (skin) immune system
challenges to and special structures/cells of the GI immune system
Challenges
- tolerance of food antigens
- tolerance of commensal microbiota
- large SA
Special structures and cells
- structures: tonsils, peyer’s patches, lamina propria, follicles
- intestinal epithelial cells secrete mucus
- M cells sample antigens in lumen
- Paneth cells make defensins
- IgA and IgM neutralize bugs
- dendritic cells sample lumen/lamina propria for antigen, induce T cell tolerance and B cell IgA class switching, activate effector T cells, imprint gut homing phenotype of B and T cells
challenges to and special structures/cells of the respiratory immune system
Challenges
- exposure to airborne pathogenic and innocuous microbes
Structures and cells
- structures = tonsils, adenoids
- ciliated respiratory epithelial cells make mucus and defensin and move mucus
- IgA, IgM, and IgG neutralize microbes
challenges to and special structures/cells or the cutaneous immune system
Challenges
- large SA
Structures/cells
- structures: keratinizing stratified squamous epithelial barrier
- keratinocytes make keratin, cytokines, and defensins
- langerhans cells sample epidermis for antigens
- dendritic cells sample dermis for antigen, induce T cell tolerance, activate effector T cells, and imprint skin homing T cell phenotype
organization and function of the GI immune system
intestinal barrier to microbes:
- adjacent epithelial cells connected by tight junctions protect lamina propria
- extensively glycosylated mucin proteins form viscous physical barrier overlying cells of the GI tract
- mucins can combine with glycolipids to form a protective glycocalyx
innate immune protection
- defensins produced by intestinal epithelial cells
- TLR’s and cytoplasmic NLR’s differentiate between pathogenic and commensal
- dendritic cells and macrophages in the lamina propria inhibit inflammation
- IL-17 and IL-22 contribute to immune defense; TGF-B, IL-10, and IL-2 maintain homeostasis
adaptive immune protection
- GALT = subepithelial lymphoid tissues including tonsils and peyer’s patches
- M cells sample luminal antigens and transport to GALT APC’s
- humoral immunity = IgA secretion
- T cell subsets:
- Th17 secrete IL-17 and IL-22, enhancing epithelial barrier function
- Th2 involved in parasite defense
- Tregs suppress inappropriate responses
organization and function of the respiratory immune system
Innate immunity
- physical barrier = pseudostratified columnar epithelium
- chemical barrier = mucus, defensins, cathelicidins
- alveolar surfactants (collectins) and alveolar macrophages
Humoral immunity
- IgA in the upper airway
- IgE
Cellular immunity
- T cell response: dendritic cells present antigens to T cells in peribroncial and mediastinal lymph nodes => Th2 cell differentiation
organization and function of the GU immune system
Innate
- epithelial lining = langerhans, dendritic cells, macrophages
Humoral
- mainly IgG, even though it is mucosal
Cell mediated
- B and T cells in genital mucosa
organization and function of cutaneous mucosa
Innate
- physical barrier = keratinized squamous epithelial layer
- chemical barrier = defensins and cytokines secreted by keratinocytes
- dendritic cells
Cell mediated
- langerhans cells activated via TLR engagement => express CCR7 chemokine receptor => migrate to T cell zones through the lymphatic vessels
- CD4+ and CD8+ effector/memory cells; Th1, Th2, and Th17 cells
- Th17 cytokines (IL-17 and IL-22) => cathelicidins and defensins
- Th2 cytokines IL-4 and IL-13 suppress defensins and cathelicidins
celiac disease
regional mucosa = small bowel mucosa
immune mediators = gluten and transglutaminase 2A specific IgA and IgG, CD4+ T cell responses to gliadin
pathophys = chronic inflammation, malabsorption, nutritional deficiencies
food allergies
regional immune system = GI
immune mediators = Th2 dependent IgE response, activation of mast cells
pathophys = inflammation, anaphylaxis, failure of adaptive immune tolerance to food antigens
MALT lymphoma
regional immune system = lymphoid follicles in gastric lamina propria
immune mediators = chronic h. pylori infection
pathophys = malignant transformation of B cells
IBD
regional immune system = GI (ulcerative colitis is colonic mucosa)
immune mediators = defects in innate immunity to commensals (polymorphisms in related genes), abnormal Th1/Th17, defective Tregs
pathophys = pain, vomiting, diarrhea, weight loss from chronic inflammation
C. diff colitis
regional immune system = colon
immune mediators = alteration to normal flora
pathophys = abx alter gut flora => inflammation
chronic rhinosinusitis
regional immune systems = nasal/respiratory airway and mucosa
immune mediators = innate defects (barrier, mucus clearance, antimicrobial peptides), abnormal activation of eosinophils/mast cells/innate lymphoid cells, activated T and B cells
pathophys = chroic inflammation => nasal obstruction, drainage, facial pain/pressure
