Lecture 8 - Immunity of the Epithelium Flashcards
Why is the immunity of epithelium so important?
- The different types of epithelium are barriers, many of which interact with outside world
- The external environment is a source of many pathogens, so the immunity of the epithelium needs to be strong enough to eliminate them or prevent them from entering the body cavity
Which two sights are areas of major immune activity of the body and why is there so much activity there?
• The GI tract
- large, wet surface; a site of nutrients fo bacteria
- lots of normal flora
- 80% of whole immune system is found in GI tract
• The Skin
- direct contact with atmosphere
What are defensins and how do they work?
- Small cysteine rich cationic proteins
- Active against bacteria, fungi and some viruses
- 18 – 45 amino acid
- Function by binding microbial cell membrane forming a pore like defect
Why is it important to regulate the immune system in the GI tract and how is that done?
• Some macrophages in the GI tract express IL-10 (anti-inflammatory) after phagocytosis of microbes (induced by TGF-β, prevents response to commensal microbes)
Describe the adaptive immune response for the GI tract.
• Major form of adaptive immunity is production and secretion of sIgA
• IgA binds and prevents microbes from invading the
epithelium
- Role of sIgA is to neutralise microbes in the gut lumen
- B cells in the GI tract undergo class switching to IgA
- Major T cells are the Th17 (some Th1 and Th2 cells)
- Major control mechanism is through Tregs (limits inflammation, tolerance of commensal microbes and food)
What are Peyer’s patches?
.• Mainly in distal ilium
• Germinal centre containing B cells, follicular T helper cells, follicular dendritic cells, macrophages.
• Germinal centre is surrounded by IgM/IgD naïve B cells
• Not encapsulated
• Area between follicles and epithelium is called the Dome
• Ratio of B cells to T cells is 5X higher than in lymph nodes
• Ag delivered to Peyer’s patches directly (not via lymphatics) – local immune response
What are M (microfold) cells, where are they found and what do they do?
.• Specialised cells in epithelium overlaying Peyer’s patches (shorter than surrounding epithelium, they are short, irregular microvilli)
- Endocytose / phagocytose antigens and transport to underlying DC, macrophages and lymphocytes
- Important link between lumen of intestine and immune system of intestine
- Main Ag delivery system for GI tract
Describe T-dependant IgA isotype switching in the GI tract.
- High affinity
- Dendritic cells in subepithelial dome of Peyer’s patches capture antigen from M cells, migrate to interfollicular zone, and present to naïve CD4 T cells
- These differentiate into T help cell and presents antigen to B cell.
- Class switch to IgA through CD40L binding to CD40 of B cell and TGF -β
Explain how lymphocytes home back to the GI tract after being activated.
- Effector T cells, IgA B cells and IgA plasma cells circulate back to the GI
- Changes to adhesion molecules and chemokine receptors during activation in GALT and lymph nodes
- Main adhesion molecule to get expressed on T and B cells after activation is α4β7 integrin which binds to MadCAM-1 expressed on venular endothelial cells in lamina propria of gut
- Chemokine CCR9 gets expressed on T and B cells, homes in on ligand CCL25 on intestial epithelial cells
Describe the innate immune features of skin.
- Epithelial cells have tight junctions preventing microbes from passing
- Skin epithelium made of layers of stratified squamous cells (keratinocytes), upper layer of cells die to form keratin (waterproof)
- Mucus produced on surface of mucosal epithelium
What are Langerhans cells, where are they found, what is their function?
- Dendritic cells in epidermis of skin
- Involved in tolerance and activation of T cells
- Express CD1a, MHC class II, Langerin (CD207)
What T cells types are found in the skin and what areas of the skin?
.• Most T cells on the skin are memory T cells
- T cells from infections or prior to infections generated in lymph nodes
- Home back to skin and remain for long periods (resident memory T cells)
- Dermis CD4+ (helper) T cells are Th1, Th2, Th17 and Treg
- Epidermis the majority of T cells are CD8+
Describe the features of the innate immune system of the respiratory tract.
.• Ciliated columnar epithelium
- Barrier (tight junctions between epithelial cells)
- Mucus traps microbes/material
- Cilia moves mucus and microbes/material up away from lungs
- Defensins and cathelicidins also produced
Outline the adaptive immune response of the upper respiratory tract.
- Secretory IgA (as for most mucosal surfaces)
- B cell activation and IgA class switching occurs in the tonsils, adenoids and lymph nodes in mediastinum and next to bronchi
- Few lymphoid follicles in the lamina propria in lower RT compared to GI
- Less humoral response lower in respiratory tract
What is the main difference between the adaptive immune response in the genitourinary tract compared with other mucosal surfaces?
- Very little regional specialization
- Lack of MALT
- IgG predominates rather than IgA (unlike other mucosal surfaces)
