Lecture 2 block 4 Flashcards

Set Details Share
created 6 days ago by cocordrgz
updated 6 days ago by cocordrgz
show moreless
Page to share:
Embed this setcancel
code changes based on your size selection

opsonization stuff

  • neutrophils have receptors for many bacterial/fungal constituents
    • bind to bacteria, engulf, destroy
    • done bc of receptors (CD14, CR4, etc.)
    • = bacteria bind + initiate own phagocytosis

importance of FMet

formylated N-terminal (fMet)

  • in bacteria - why havent they evolved to stop using this if phagocytic cells use it to find them?
    • function in bacteria: control of protein quality - bad/misfolded proteins are degraded by peptide deformylase (PDF)
      • if dont have PDF, cant degrade bad proteins
      • recently found: can target bacteria by making thing that recognizes this
      • found PDF catalysed removal of formyl groups from new proteins = new antibacterial drug target
  • formylated N-terminal (fMet) can act as a degradation signal at level of translation (cotranslational)

Q: neutrophils go after specific molecules released from bacteria, which is necessary for which bacterial process?

A) DNA polymerase, DNA replication

B) RNA polymerase, transcription

C) N- formyl-Met, degradation of bacteria misfolded proteins

D) complement, phagocytosis



neutrophils lacking PI3k are defective in migration directionality

  • study:
    • wild type neutrophils
    • PI3k -/- neutrophils

chambers w/ fMLP (N-formyl-met) gradients ->

  • ***neutrophils move towards it (they go to the nformyl met (direction))
  • WT neutrophil have overlay of f-actin/ATK (protein kinase)
  • PI3k -/- (mutation in kinase) = imperfect overlap = doesnt move in right direction

***PI3k 1/2 kinase is required for regulation of f-actin + establishment of pseudopod toward chemotactic gradients

= neutrophils need PI3k kinase + f-actin to move towards bacteria


Q: neutrophils lacking ___________ which regulates ___________ in them, are not able to migrate properly to chemotactic gradients of bacteria

A) PI3 kinase, f-actin

B)GFP, red fluorescent protein
C)F-Met, degraded proteins

D) receptor for Ig, bacterial recognition

E) receptor for TNF-a, inflammation



SUMMARY: what do you need for neutrophils to follow / engulf bacteria?

  • bacteria need to have / emit formyl - methionine (fmet) residues/peptides to attract neutrophils
  • neutrophils need to have receptor for fmet + be able to move their membrane (via actin + PI3k) to direct pseudopods toward chemoattractanty gradient + bacteria
  • WHY DO BACTERIA NOT EVOLVE TO NOT USE fmet??? -> for degranulation of bacterial misfolded proteins - need it

fmet = main reason neutrophils can find bacteria


Q: exoskeleton formed by

C) peptidoglycan layer

correct answer (didnt write others)


Q: which of 3 pathways become activated soonest after infection?
C) alternative

correct answer (didnt write others)


2nd part of lecture - molecular effector systems

  1. activation of complement + killing of extracellular bacteria
  2. classical and alternative pathways
  3. MAC poly C9

3 pathways of complement - recognition of pathogen in intersititial space by soluble proteins

  • alternative path
    • complement is an opsonin
  • lectin path
    • recognize carbs on bacterial surface, (most important one = mannose)
  • classical path
    • depend on antibodies, involve adaptive system

classical pathway

card image

C3a, C4a, C5a = anaphylatoxins - cause smooth muscle contraction, histamine release from mast cells, enhance vascular permeability

  • + mediate chemotaxis, inflammation, + generate oxygen radicals
  • signal adaptive system to stimulate it

antigen/antibody complex


Q: classical, alternative, lectin paths of complement activation all have

A) antibody activation of C1

B) carb binding to specific receptors on macrophages

C) generation of C3 convertase to convert C3 -> C3b/C3a

D) spontaneous hydrolysis of C3

E) recognition of PAMPs



reminder - overview

card image
  • EACH PATHWAY USE THEIR COMPLEMENT RECEPTORS to start, then each have C3 convertase
  • deposition of Cb3 on bacteria = central event of complement activation
    • result = opsonization of bacteria and = more susceptible to phagocytosis

C3 deficiency (genetic) causes:

  1. recurrent pus causing infection (can be lethal)
    • kids w/o C3 = chronic infection (esp on mucus membranes) = lead to sepsis
  2. no/little opsonization
  3. chronic infection in mucosal sites/gums

***need opsonization for removal of bacteria


alternative path of complement activation

card image
  • does NOT require PAMPs to initiate
  • constituitively (always) active
  • does not distinguish btw bacterial / host cells (other molecules like DAF keep host cells from being opsonized)
    • we protect our own cells from it
  • negative regulation (shut down) by host = critical to not kill own cells
  • bacteria cannot shut down the pathway (only our own molecules can)


card image

continuously active - changes rates depending on recognition of self/nonself


fixation of complement

card image

activated C3b bind to bacterial cell wall covalently to bind w/ anything w/ a hydroxyl group or amino group

***cleavage by 1 of the 3 pathways


how ALTERNATIVE pathway starts

card image
  • water activate
  • C3 + water -> iC3 (by hydrolysis + now have changed conformation allowing binding of B by D)
  • -> bind to B
  • D cleave B -> Bb
  • Bb + iC3 complex = iC3Bb = soluble C3 convertase (not the end C3 convertase)
  • -> iC3Bb cleave C3 = C3a + C3b
  • -> C3b deposited on pathogen surface (nothing was on pathogen surface until now)
  • constant C3 trickle = drizzle of C3b all the time on surface = trickle down hypothesis


card image

now pathogen surface have C3b

  • not inhibited, so bind B -> cleave by D = Bb (again)
    • = surface bound C3 convertase = C3bBb
      • RAPIDLY TURNOVER C3 molecules + coats bacteria w/ C3 = positive feedlack amiplification loop -> opsonize pathogen to be phagocytosed

***Alternative path C3 convertase = C3bBb


Hoe host determined by complement tissue

card image
  • P (properdin) - turn more C3 -> C3b for opsonization = stabilize C3bBb
    • prevents degradation of C3bBb
  • Factor H - counteract this w/ factor I (protease) = iC3b cant bind factor B
    • help block complement activation
    • want it bc wanna have enough C3 in system,/blood/serum incase subsequent infection
    • dont deplete it all so have for later
  • host cell surfaces - C3b unable to stably bind to B or Bb bc not host membrane
    • DAF - decay accelerating faster (DSS)
    • MCP - membrane cofactor protein (CD46)
    • = block/disrupt convertase = out cells cannot be destroyed by complement = protected

Q: C3 convertase, C3bBb

A) cleaves + activates protease factor I

B) cleaves proteoglycan of bacterial cell wall

C) forms MAC

D) covalently bound to bacterial cell wall



Q: host cells may be protected by complement lysis by

A) CD4 cells

B) CD8 cells


D) NK cytokines

E) IgG3