GI Host Defense Flashcards
What are some first lines of defense in the GI system? (Immediate)
Epithelium: physical barrier, ion transport (diarrhea)
Physiologic: pH, mucus, microbiota, lysozyme, antimicrobial peptides
Complement
What are some second lines of defense in the GI system? (early)
Phagocytes –> inflammation
Macrophages –> inflammation
Granulocytes –> anti-parasitic
NK cells –> antiviral
What are some components of the adaptive immunity of the GI system?
T cells: helper T cells (CD4)
Cytotoxic T cells (CD8)
B cells: IgA, IgG, IgE, IgM
What are the different T cell types involved in the adaptive immunity of the GI system?
Th1: IFN –> inflammation
Th2: IL4 –> anti-parasitic
Th17: IL17 –> inflammation
What are some roles of commensals in the GI system?
- Compete for resources with more virulent organisms
- Produce their own antimicrobial peptides (AMPs)
- Keep innate immune cells in an attentive state
What do defensins do?
Penetrate the lipid bilayer of bacteria and form pores
What are some examples of secretagogues?
VIP Acetylcholine Substance P Prostaglandins & leukotrienes Histamine Serotonin
What are some examples of inhibitors?
Norepinephrine
Somatostatin
How can CF lead to intestinal obstruction?
Mutations in the gene for cAMP-responsive apical anion channel –> near absence of electrolyte secretion
How does TGF-beta lead to restitutive epithelium?
It is fibrogenic agent – inhibits lymphocytes proliferation and also stimulates division, differentiation and migration of surrounding epithelial cells
What links the early innate responses with late adaptive immune response?
Dendritic cells
What cell types express TLRs?
Plasma membrane of epithelial cells, dendritic cells, macrophages, and PMNs
What PAMP do TLRs recognize?
Numerous bacterial, fungal and viral structures
What cell types express NLRs?
Cytoplasm of epithelial cells, macrophages, PMNs
What PAMPs do NLRs recognize?
Bacterial wall components (peptidoglycans)
What cells types express mannose receptors?
It is a membrane receptor on phagocytes that recognizes bacterial cell wall, carbohydrate and fungal wall glycans
What are some examples of soluble recognition receptors?
C-reactive protein - recognizes microbial cell wall components
Mannose-binding lectin - recognizes bacterial cell wall carbohydrates
Complement-C3 - recognizes microbial cell walls
IgM - recognizes bacterial cell walls
What is the function of TLRs?
Activate genes necessary for defense against the recognized bacterial, viral or fungal organism.
Which intestinal bacterial infections are minimally invasive?
Campylobacter
Clostridium
Candida
Cryptococcus
Which intestinal bacterial infections are invasive?
Listeria
Enteroinvasive E. coli
Opportunist: Clostridium, Shigella
Which intestinal bacterial infections are toxigenic??
Enterotoxigenic E. coli
Vibrio cholerae
(Clostridium)
(Shigella)
Alternative complement pathway
Cleave C3 protein binds bacterial surface
Classical complement pathway
Ab (IgM, IgG) binds to bacterial surface
Lectin complement pathway
Mannose binding lectin binds surface of bacteria
What are some GI viruses that can lead to disease?
Rotavirus
Norwalk
Enteroviruses
What are some intestinal parasites? How does our immune system respond to them?
Trematodes
Nematodes
Cestodes
*Too big to be phagocytes
What type of cell is important in defense against helminth parasites?
Granulocytes: eosinophils, basophils, mast cells
*Non-phagocytic –> they defend the host by releasing their granule contents into the extracellular space
How are granulocytes activated?
Ag-bound IgE binding cell surface FceRI
**So it depends on previous exposure to an Ag (sensitization)
What are some things that granulocytes release?
Vasoactive amines Prostaglandins Leukotrienes Proteases Cytokines
