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GI/Nutrition > Host Defense - GI and Nutritional Pathophysiology > Flashcards

Host Defense - GI and Nutritional Pathophysiology Flashcards

1
Q

What causes physiologic inflammation of the GI tract?

A

Host resistance and tolerance to bacteria, viruses, fungi, parasites and food borne antigens

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2
Q

What are the two types of pathophysiologic inflammation of the GI tract

A
  • Acute: Infection
  • Chronic/recurring: Allergic disorders and chronic inflammation
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3
Q

What are the three types of host defense barriers?

A
  • Immediate: existing physical and chemical barriers
  • Early: Existing innate immune cells and mediators
  • Late: Activation of the appropriate adaptive immune cells and mediators
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4
Q

What makes up the epithelial and physiologic components of the first line of host defense (immediate)?

A
  • Epithelium: Physical barrier, ion transport
  • Physiologic: pH, mucus, microbiota, lysozyme, antimicrobial peptides

*The complement system also contributes

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5
Q

What cells make up the second line of defense (early immunity) and what is a main function of each?

A
  • Phagocytes → Inflammation
  • Macrophages → Inflammation
  • Granulocytes → anti-parasitic
  • NK cells → anti-viral
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6
Q

What cells make up the adaptive immunity component of the host defense?

A
  • T cells
    • Helper T cells (CD4)
    • Cytotoxic T cells (CD8) → anti-viral
  • B cells
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7
Q

Name the types of helper T cells involved in host defense, the interleukin they secrete, and their main function

A
  • Th1: IFN → inflammation
  • Th2: IL4 → Anti-parasitic
  • Th17: IL17 → Inflammation
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8
Q

What four immunoglobulins are used in host defense?

A

IgA; IgG; IgE; IgM

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9
Q

In the Immediate-Early defense, what secretions help in host defense?

A
  • Cl- transport → diarrhea
  • Antimicrobial peptides (defensins)
  • Cytokines/Chemokines
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10
Q

How does the microbiota contribute to immediate host defense?

A
  1. Compete for resources with more virulent organisms
  2. Produce their own antimicrobial peptides (AMPs)
  3. Keep innate immune cells in an “attentive” state
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11
Q

What are the functions of the following barrier defense proteins?

  • Lysozyme:
  • Lactoferrin:
  • Antimicrobial Peptides:
A
  • 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
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12
Q

What is epithelial shedding? How does it contribute to host defense?

A

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

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13
Q

What are secretagogues? Name them

A

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
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14
Q

What are inhibitors to ion transport? (counteract secretagogues)

A

Norepinephrine

Somatostatin

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15
Q

How does TGF-ß lead to restitution of the epithelial barrier (repair)?

A

TGF-ß (transforming growth factor)

  • Fibrogenic agent
  • Inhibits lymphocyte proliferation
  • Stimulates division, differentiation and migration of surrounding epithelial cells
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16
Q

How are the immediate and early defense responses linked?

A

Dendritic cells

17
Q

What cytoplasmic and cell surface receptors are responsible for recognizing pathogens (PAMPS)?

A

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

18
Q

What PAMPs are recognized by each of the three cell associated receptors?

A
  • TLR: Numerous bacterial, fungal and viral structures
  • NLR: Bacterial wall components (peptidoglycans)
  • Mannose receptor: Bacterial cell wall carbohydrate; fungal wall glycans
19
Q

What are the soluble pattern recognition receptors and what PAMPs do they recognize?

A
  • C-reactive protein: microbial cell wall components
  • Mannose-binding lectin (MBL): bacterial cell wall carbohydrates
  • Complement (C3): Microbial cell walls
  • IgM: Bacterial cell walls
20
Q

What is the function of TLR?

A

Activates genes necessary for defense against the recognized bacterial, viral, or fungal organism (expression of cytokines TNF, IL-1, IL-6)

21
Q

What bacteria are associated with the different levels of intestinal infection?

  • Minimally invasive:
  • Invasive:
  • Toxigenic:
A
  • 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
22
Q

Which receptors recognize bacteria (cell associated and soluble)?

A
  • TLR2, 4, and 5
  • Nod1, 2
  • C3b and MBL
  • IgM
23
Q

Which receptors recognize fungi (cell associated and soluble)?

A
  • TLR3, 4, and 5
  • C3b: complement
  • IgM
24
Q

What 3 immune cells are involved in the early response to bacterial invasion?

A

Neutrophils

Dendritic Cell

Activated Macrophage

25
Q

What soluble mediators are involved in the early immune response to bacterial infection?

A
  • IL-6: proinflammatory cytokine
  • TGF-ß: proinflammatory cytokine
  • IL-12: Released by immature dendritic cell → activates macrophages
  • TNF and IL-1: released from PMNs and mature dendritic cells → activates endothelial cells
26
Q

Describe how dendritic cells recruit T-cells in bacterial infection

A
  1. Dendritic cells migrate into Peyer’s patch and present a peptide antigen with an MHC II molecule
  2. Presents to Naive T Cell (CD4+)
  3. IL-12 produced by dendritic cells → T cell differentiates into Th1 which produces IFN-γ
  4. IFN-γ stimulates production of IgG
27
Q

What is required for T cell differentiation into Th17 cells?

A

Environment rich in IL-6, IL-23, and TGF-ß

28
Q

What happens during the resolution phase of intestinal **bacterial **infection? (Role of Th17 cells, Th1 cells and antibodies)

A
  1. T cells migrate back to lamina of gut to fight infection
  2. Th1 cells produce IFN-γ which increases ion transport and increases ROS killing by macrophages
  3. Th17 cells interact with activated macrophages, and upon seeing pathogen again, release IL-22 and IL-17 which increase the epithelial defense barrier
  4. IgG and IgA plasma cells - opsonization
29
Q

What causes increased immune cell trafficking to the inflamed gut?

A

Chemokines, C5a

30
Q

What are the three complement pathways?

A

Alternative pathway: C3 complement binds to microbe

Classical pathway: IgM binds to microbe

Lectin pathway: Mannose binding lectin

31
Q

What are three common viral pathogens and what receptors recognize them?

A
  • Viruses: Rotavirus, Norwalk, Enteroviruses
  • PRRs: TLR3, 7, 9, RIG1 (NLR), IgM
32
Q

What types of T-cells are involved in the anti-viral immune response?

A

CD8 positive T cells interact with MHC I and viral antigen

33
Q

In anti-viral immune response, how does the natural killer cell assist in T cell differentiation?

A

NK cells produce IL-12 which causes naive T cells to become Th1 cells

NK cells also release IFN-γ

34
Q

What are three types of intestinal parasites discussed in class? Which is most dangerous and which is most symbiotic?

A
  • Worst → best
    • Trematodes > Nematodes > Cestodes (most symbiotic)
35
Q

What are the granulocytes and why are they important?

A

Granulocytes are important for defense against helminth parasites

  • Eosinophils
  • Basophils
  • Mast Cells
36
Q
  • How do granulocytes defend the host?
  • How are they activated?
  • What does their activation depend on?
A
  • How do granulocytes defend the host?
    • By releasing their granule contents into the extracellular space (degranulation)
  • How are they activated?
    • By Ag-bound IgE binding cell surface FcεRI
  • What does their activation depend on?
    • Depends on previous exposure to an Ag
37
Q

What does granulocyte excretion include?

A
  • Vasoactive amines → SM contraction
  • Proteases → disrupts parasite tegument
  • Cytoknes/Leukotrienes/Prostaglandins → Stimulate macrophages, activate endothelial cells, increase leukocyte migration
38
Q

What T-cell is important in the defense against parasites?

A

Th2 cells secrete IL-4, IL-5 and IL-13 which induce mast cells and eosinophils against helminthic parasites

GI/Nutrition (36 decks)

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