Host Defense - GI and Nutritional Pathophysiology Flashcards
What causes physiologic inflammation of the GI tract?
Host resistance and tolerance to bacteria, viruses, fungi, parasites and food borne antigens
What are the two types of pathophysiologic inflammation of the GI tract
- Acute: Infection
- Chronic/recurring: Allergic disorders and chronic inflammation
What are the three types of host defense barriers?
- Immediate: existing physical and chemical barriers
- Early: Existing innate immune cells and mediators
- Late: Activation of the appropriate adaptive immune cells and mediators
What makes up the epithelial and physiologic components of the first line of host defense (immediate)?
- Epithelium: Physical barrier, ion transport
- Physiologic: pH, mucus, microbiota, lysozyme, antimicrobial peptides
*The complement system also contributes
What cells make up the second line of defense (early immunity) and what is a main function of each?
- Phagocytes → Inflammation
- Macrophages → Inflammation
- Granulocytes → anti-parasitic
- NK cells → anti-viral
What cells make up the adaptive immunity component of the host defense?
- T cells
- Helper T cells (CD4)
- Cytotoxic T cells (CD8) → anti-viral
- B cells
Name the types of helper T cells involved in host defense, the interleukin they secrete, and their main function
- Th1: IFN → inflammation
- Th2: IL4 → Anti-parasitic
- Th17: IL17 → Inflammation
What four immunoglobulins are used in host defense?
IgA; IgG; IgE; IgM
In the Immediate-Early defense, what secretions help in host defense?
- Cl- transport → diarrhea
- Antimicrobial peptides (defensins)
- Cytokines/Chemokines
How does the microbiota contribute to immediate host defense?
- Compete for resources with more virulent organisms
- Produce their own antimicrobial peptides (AMPs)
- Keep innate immune cells in an “attentive” state
What are the functions of the following barrier defense proteins?
- Lysozyme:
- Lactoferrin:
- Antimicrobial Peptides:
- Lysozyme: A hydrolase that damages bacterial cell walls
- Lactoferrin: Sequesters free iron which is essential for bacteria - also oxidizes bacterial cell walls
- Antimicrobial Peptides: Forms pores in the membrane of multiple microbes
What is epithelial shedding? How does it contribute to host defense?
Enterocytes born in the crypt migrate from the crypt toward the villus apex, dislodge, and are shed into the lumen (5-6 days)
Micro-organisms (bacteria) are trapped inside the discarded or apoptotic epithelia and excreted in the feces
What are secretagogues? Name them
Secretagogues - Bind to receptors on epithelial surface and signal changes to cAMP which activates CFTR - more mucous secretion
- VIP
- Acetylcholine
- Substance P
- Prostaglandins and Leukotrienes
- Histamine
- Serotonin
What are inhibitors to ion transport? (counteract secretagogues)
Norepinephrine
Somatostatin
How does TGF-ß lead to restitution of the epithelial barrier (repair)?
TGF-ß (transforming growth factor)
- Fibrogenic agent
- Inhibits lymphocyte proliferation
- Stimulates division, differentiation and migration of surrounding epithelial cells
How are the immediate and early defense responses linked?
Dendritic cells
What cytoplasmic and cell surface receptors are responsible for recognizing pathogens (PAMPS)?
Nod-like receptors (NLR): found in cytoplasm
Toll-like receptors (TLR): found on basolateral membrane and on dendritic cells
Mannose receptor: membrane receptor on phagocytes
What PAMPs are recognized by each of the three cell associated receptors?
- TLR: Numerous bacterial, fungal and viral structures
- NLR: Bacterial wall components (peptidoglycans)
- Mannose receptor: Bacterial cell wall carbohydrate; fungal wall glycans
What are the soluble pattern recognition receptors and what PAMPs do they recognize?
- C-reactive protein: microbial cell wall components
- Mannose-binding lectin (MBL): bacterial cell wall carbohydrates
- Complement (C3): Microbial cell walls
- IgM: Bacterial cell walls
What is the function of TLR?
Activates genes necessary for defense against the recognized bacterial, viral, or fungal organism (expression of cytokines TNF, IL-1, IL-6)
What bacteria are associated with the different levels of intestinal infection?
- Minimally invasive:
- Invasive:
- Toxigenic:
- Minimally invasive: Campylobacter; Clostridium; Candida; Cryptococcus
- Invasive: **Listeria; Enteroinvasive E. Coli; **Clostridium and Shigella are opportunists
- Toxigenic: **Enterotoxigenic E. Coli; Vibrio cholerae; ****Clostridium and Shigella are opportunists
Which receptors recognize bacteria (cell associated and soluble)?
- TLR2, 4, and 5
- Nod1, 2
- C3b and MBL
- IgM
Which receptors recognize fungi (cell associated and soluble)?
- TLR3, 4, and 5
- C3b: complement
- IgM
What 3 immune cells are involved in the early response to bacterial invasion?
Neutrophils
Dendritic Cell
Activated Macrophage