Quiz 3

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Questions and Answers

Why is the differentiation between Gram-positive and Gram-negative bacteria therapeutically important?

  • Gram-positive bacteria produce LPS, which can cause complications during treatment.
  • The structural differences affect antibiotic permeability and susceptibility. (correct)
  • Gram-positive bacteria are only susceptible to a single class of antibiotics.
  • Gram-negative bacteria lack peptidoglycan, making them unaffected by penicillin-based drugs

A scientist isolates a bacterial species from a patient sample. Initial tests reveal it is a bacillus, does not ferment lactose, and is oxidase-positive. Which of the following is the MOST likely identity of this bacteria?

  • Streptococcus pyogenes
  • Pseudomonas aeruginosa (correct)
  • Staphylococcus aureus
  • Escherichia coli

What is the primary function of Toll-like receptors (TLRs) in the immune system?

  • To recognize specific microbial components and activate signaling pathways (correct)
  • To produce antibodies that neutralize pathogens in the bloodstream
  • To directly kill infected cells through the release of cytotoxic granules
  • To regulate body temperature in response to infection

Why is the activation of NFκB considered a crucial step in the immune response?

<p>It regulates the expression of genes involved in inflammation, immunity, and cell survival (D)</p> Signup and view all the answers

Which cellular process would NOT be directly influenced by NFκB activation?

<p>Protein synthesis (A)</p> Signup and view all the answers

How do steroids alleviate symptoms in patients with Crohn's disease and ulcerative colitis?

<p>By inhibiting the activation of NFκB, reducing inflammation in the gut (C)</p> Signup and view all the answers

Lipopolysaccharide (LPS) is MOST associated with which type of bacteria and what potential health consequence is associated if enters the circulatory system?

<p>Gram-negative; endotoxic shock (A)</p> Signup and view all the answers

Which of the following BEST describes the primary function of cytokines?

<p>Signaling molecules that mediate cell-to-cell communication (A)</p> Signup and view all the answers

Which cytokine primarily functions to stimulate the differentiation of naïve T cells into Th1 cells and enhance NK cell activity?

<p>Interleukin-12 (IL-12) (B)</p> Signup and view all the answers

Which of the following best describes the function of Tumor Necrosis Factor-alpha (TNF-α)?

<p>Promoting endothelial activation and facilitating immune cell recruitment. (C)</p> Signup and view all the answers

A researcher is studying cytokine signaling pathways. If they observe activation of the JAK-STAT pathway, which type of cytokine receptor is most likely involved?

<p>Type I Cytokine Receptors (Hematopoietin Receptors) (A)</p> Signup and view all the answers

Following exposure to a pathogen, a macrophage releases cytokines that act on nearby cells to induce an inflammatory response. This type of signaling is best described as:

<p>Paracrine (C)</p> Signup and view all the answers

Which of the following characterizes interferons' mechanism of action against viral infections?

<p>Interfering with multiple stages of the viral replication cycle. (A)</p> Signup and view all the answers

Which family of cytokines is primarily responsible for stimulating leukocyte movement and is categorized based on the arrangement of cysteine residues?

<p>Chemokines (B)</p> Signup and view all the answers

A patient presents with symptoms of cachexia, including muscle atrophy and significant weight loss. Dysregulation of which cytokine is most likely contributing to this condition?

<p>Tumor Necrosis Factor-alpha (TNF-α) (B)</p> Signup and view all the answers

Which signaling pathway is activated by TNF receptors and leads to the transcription of pro-inflammatory genes?

<p>NFκB Activation Pathway (C)</p> Signup and view all the answers

Which type of cytokine receptor is known to activate G-protein coupled receptor (GPCR) signaling, leading to actin cytoskeleton rearrangement and chemotaxis?

<p>Chemokine Receptors (A)</p> Signup and view all the answers

If a researcher is investigating the effects of a cytokine that primarily acts by stimulating proliferation and differentiation of hematopoietic precursors, which type of cytokine are they most likely studying?

<p>Colony Stimulating Factor (D)</p> Signup and view all the answers

Which of the following interleukins is categorized as anti-inflammatory?

<p>IL-4 (D)</p> Signup and view all the answers

A drug that inhibits the activity of Janus Kinases (JAKs) would directly interfere with signaling from which type of cytokine receptor?

<p>Type I Cytokine Receptors (D)</p> Signup and view all the answers

Which signaling molecules are expressed early on in the host defense mechanism against multiple viruses?

<p>Interferons (B)</p> Signup and view all the answers

A researcher discovers a new cytokine that inhibits tumorigenesis and viral replication. Based on the information, which known cytokine does this new cytokine most closely resemble in function?

<p>Tumor Necrosis Factor (TNF) (C)</p> Signup and view all the answers

A pharmaceutical company aims to develop a drug that can specifically block the recruitment of neutrophils to sites of infection. Which of the following cytokines should this drug target to achieve the desired effect?

<p>Interleukin-8 (IL-8) (C)</p> Signup and view all the answers

Flashcards

Gram-negative bacteria

Bacteria with less peptidoglycan, no (lipo)teichoic acid, and an outer membrane of lipopolysaccharide.

Gram-positive bacteria

Bacteria with thick peptidoglycan and (lipo)teichoic acid, retaining dye during staining.

Escherichia coli

A common gram-negative bacilli, lactose fermenter, and oxidase negative.

Pseudomonas

A gram-negative bacilli, known for being a non-lactose fermenter and oxidase positive.

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Toll-like receptors (TLRs)

Receptors that sense microbial products inside and outside of human cells.

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NFκB importance

Regulates cytokines, factors for cell survival, and inflammation response in immunity.

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Lipopolysaccharide (LPS)

A complex in the outer membrane of gram-negative bacteria, linked to endotoxin effects.

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Cytokines

Low molecular weight proteins that act as cell-signaling molecules, regulating immune responses.

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Pro-inflammatory cytokines

Cytokines that promote inflammation; examples include TNFa, IL1, IL6.

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Anti-inflammatory cytokines

Cytokines that reduce inflammation; examples include IL-10 and IL-4.

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Interleukins

A diverse group of cytokines that communicate between leukocytes.

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Chemokines

Cytokines that stimulate the movement of leukocytes; divided into four families.

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Tumor necrosis factors (TNF)

Cytokines that regulate immune cells and induce inflammation; chiefly produced by macrophages.

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Colony stimulating factors

Cytokines that stimulate the proliferation and differentiation of blood cell precursors.

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Interferons

Cytokines that inhibit viral replication; includes types I, II, and III.

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Autocrine signaling

Cell signaling where the signal acts on the same cell that secreted it.

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Paracrine signaling

Cell signaling where the signal acts on nearby cells.

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Endocrine signaling

Cell signaling where signals act on distant cells via the bloodstream.

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TNF-α

A pro-inflammatory cytokine that induces fever and activates endothelial cells.

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IL-1

A cytokine that promotes inflammation and induces fever.

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JAK-STAT signaling

A pathway activated by Type I and II cytokine receptors for cell differentiation.

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NFκB pathway

A signaling pathway used by TNF receptors that promotes inflammation.

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IL-8

A chemokine that recruits neutrophils to sites of infection.

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Study Notes

Gram-Positive vs. Gram-Negative Bacteria

  • Gram-positive bacteria: Possess peptidoglycan and (lipo)teichoic acid in their cell walls. Alcohol does not create pores, dye is retained.
  • Gram-negative bacteria: Have less peptidoglycan and no (lipo)teichoic acid. Possess an outer membrane of lipopolysaccharide (LPS). Alcohol dissolves lipids, creating pores and causing dye loss.
  • Examples of Gram-negative: Escherichia coli, Pseudomonas, Haemophilus influenzae
    • E. coli: Bacillus shape, lactose fermenting, oxidase-negative.
    • Pseudomonas: Bacillus shape, non-lactose fermenting, oxidase-positive.
    • Haemophilus influenzae: Bacilli (rod-shaped) or gram-negative coccobacilli (short rods).
  • Examples of Gram-positive: Staphylococci, Streptococci
    • Staphylococci: Cocci (spherical) arranged in clusters.
    • Streptococci: Cocci arranged in chains.

Toll-like Receptors (TLRs) and NF-κB Activation

  • TLRs: Detect microbial products inside and outside human cells, initiating immune responses. Different TLRs detect different microbial products.
  • NF-κB activation: A crucial signaling pathway for immunity.
  • NF-κB function: Regulates the expression of various genes involved in:
    • Cytokines: Regulates pro-inflammatory and anti-inflammatory cytokines.
    • Immune response genes: Crucial for immune cell function (e.g., B7, IL-2, AgR, MHC).
    • Inflammation: Genes for inflammation (e.g., complement, defensins, COX-2).
    • Apoptosis and cell survival: Genes (e.g., Bcl2, Bcl-xL, SOD, cFLIP, IAPs) important for cell death and survival.
    • Cell cycle: Regulates cell cycle proteins like Cyclin D1.
    • Growth factors: Regulates growth factor expression.
    • Inflammation & adhesion: Regulates the expression of factors involved in inflammation and adhesion pathways (e.g., VCAM, ICAM, selectins).
  • Diseases associated with dysregulation: Inflammatory conditions like Crohn's disease, ulcerative colitis.

Lipopolysaccharide (LPS)

  • LPS: A complex component of the outer membrane of Gram-negative bacteria.
  • Toxicity: A gram-negative bacterial endotoxin. If LPS enters the bloodstream, it can trigger a severe toxic response, including fever, rapid breathing, low blood pressure, and potentially fatal endotoxic shock.

Cytokines

  • Cytokines: Low-molecular-weight proteins that act as cell messengers, stimulating, inhibiting, or affecting cell behavior.
    • Local action: Mostly act locally (paracrine or autocrine).
    • Types: Pro-inflammatory (e.g., TNF-α, IL-1, IL-6, IL-8) and anti-inflammatory (e.g., IL-1ra, IL-10, IL-4, IL-11).
  • Class details:
    • Interleukins (ILs): Primarily for communication between leukocytes (immune cells).
    • Chemokines: Stimulate leukocyte movement. Four families based on cysteine structure.
    • Tumor Necrosis Factors (TNFs): Produced mainly by macrophages, key in immune responses; can induce inflammation, fever, apoptosis, sepsis, cachexia, inhibit tumorigenesis.
    • Colony-Stimulating Factors (CSFs): Stimulate hematopoietic progenitor cell development.
    • Interferons (IFNs): Broad-spectrum antiviral agents that inhibit viral replication. Three classes exist, differing in their functions.

Cytokine Actions and Macrophage Release

  • Macrophages Exposed to pathogens: Release cytokines (TNF-α, IL-1, IL-6, IL-8, IL-12, IFN-γ).
  • Functions of these cytokines:
    • TNF-α: Inflammation, endothelial activation, immune cell recruitment.
    • IL-1: Inflammation, fever, lymphocyte activation.
    • IL-6: Fever, acute-phase protein production, B cell differentiation.
    • IL-8: Chemotaxis of neutrophils.
    • IL-12: Th1 cell differentiation, NK cell activation.
    • IFN-γ: Enhances macrophage activity, antigen presentation, Th1 support.

Cytokine Receptors and Signaling

  • Cytokine receptors: Classified based on structure and signaling pathways.
    • Type I (e.g., IL-2, IL-6): JAK-STAT signaling.
    • Type II (e.g., IFNs): JAK-STAT signaling.
    • TNF receptors: NF-κB activation.
    • Chemokine receptors (GPCRs): G-protein coupled receptor signaling (chemotaxis).
  • JAK-STAT signaling: Important in cell differentiation.
  • NF-κB activation: Critical for inflammation.

Autocrine, Paracrine, Endocrine Actions

  • Autocrine: Acts on the same cell (e.g., IL-2 and T-cell proliferation).
  • Paracrine: Acts on nearby cells (e.g., cytokines and growth factors).
  • Endocrine: Acts on distant cells via the bloodstream (e.g., insulin and adrenaline).

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