lecture 1 block 4 Flashcards

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lecture 1 - principles of killing microbes: recognition of extracellular bacteria in solution

block 4 - extracellular bacteria + complement


connection btw innate/adaptive system

- innate response - inflammation, complement activation, phagocytosis, destruction of pathogen

-adaptive - effector cells + antibodies eliminate pathogen

-build B/T cells so infection gone quickly in future

***innate gives time for the adaptive system to develop (take days/weeks)

  • only innate by self may get rid of it or dampen growth of pathogen, giving time for adaptive to develop + eliminate pathogen if innate cannot do it itself
    • T cells kill infected cells + antibodies eliminate infection by ADCC

diff pathways of innate immune response


-intracellular bacteria

-extracellular bacteria (this section)

this sections = extracellular bacteria + C' (compliment)

- in ALL cases listed - clearance of pathogen require killing of pathogenic microbes


Immune system protect vs 4 types pathogens

  • response to virus - mostly T cells
    • response to vaccines = B and T helper CD4 cells -> make antibodies that lower viral dose + allow more time for killer T cells (CD8) to develop

extracellular vs intracellular pathogens

  • extracellular bacteria
    • all 4 classes of pathogens can be present in extracellular spaces of infected tissue (bacteria, viruses, fungi, parasites)
  • intracellular
    • some bacteria/viruses have to be inside cell for replication

Q: Innate immune system:

A) in 1st to act (vs adaptive)

B) Either eliminates the pathogen or slows its growth until adaptive system can develop

C) May involve NK mediated killing of infected cell

D) All of above




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Opsonization - bacteria coated (ex: w/ antibody or complement) = making it more readily ingested by phagocytes

  • coat pathogen w/ any molecule that make it easier to phagocytose
    • phagocytic cells have receptors for antibody/complement depending what it is(?)

complement - collection of plasma proteins that act in a cascade of rxns to attack extracellular forms of pathogens

Left: bacterial toxins bind w/ antibodies = neutralize toxic activity by preventing toxin from interacting w/ receptor on human cells

  • complex bind w/ macrophage receptors + ingest

right: bacteria in extracellular space: opsonized w/ IgG -> constant region points out + binds w/ receptors on macrophages -> ingest entire thing


innate immune system response to extracellular bacteria - complement

see: complement attach to bacteria -> phagocytosed -> go in cell in phagolysosome - ingested

neutrophil net - neutrophils die + form nets trapping microbes

  • killing by toxic anti-microbial molecules by neutrophils + macrophages = neutrophils die - form nets

Q: which = innate immune response to extracellular bacteria

A) opsonization by complement

B) by antibodies

C) T cell killing

D) all correct



Neutrophil info cont from last card: reserves of neutrophils stored in bonemarrow

  • released when needed to fight infection
  • -> travel to enter infected tissue + engulf + kill bacteria
  • -> neutrophils die in tissue + are engulfed + degraded by macrophages
  • = pus leftover = dead neutrophils

How neutrophils get to infection (bacteria)

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  • directed there by interaction w/ adhesion molecules
  • cytokines induce expression of selectin (+adhesion molecules) on vascular endothelium
    • = enable it to bind to leukocytes + rolling adhesion (can now walk along bc bind to selectin)
  • 4 stages extravasation
    • LFA1 (an integrin on leukocyte) + ICAM1 (adhesion molecule on endothelium)
    • neutrophil squeeze btw endothelium cells -> penetrate connective tissue (diapedesis) + migrate to infection along CXCL8 chemokine gradient (attracted to it so follow it)

Q: neutrophil direction to tissue sites of infection is NOT mediated by:

A) selectin on vascular endothelium

B) Rolling adhesion, integrins on leukocyte and adhesion

C) Chemokine CXCL8 made by macrophages at infection site

D) neutrophil squeezing btw endo cells + penetrating connective tissue (diapedesis)

E) T-B binding to neutrophil + directing it to sites of infection



binding of bacteria to neutrophil receptors induces phagocytosis + microbial killing

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  • recognize diff things on bacteria
  • receptors for extracellular bacteria:
    • N-formyl-Met receptor - important
    • CR4 - specific for bacterial lipopolysaccharide (LPS)
    • Complement

bacteria bind to any of these receptors = stimulate its own phagocytosis + degradation


complement proteins - function (the actual complement particles)

complement proteins: serum + tissue proteins continually made by liver


  • opsonization - coat surface of microbe = efficient phagocytosis
  • make pores - similar to perforin
    • by MAC - membrane attack complex
      • "MACPF" - for perforin system
      • "MAC" - for complement system
  • inflammation - recruitment of more immune cells to infection site

complement mechanism

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complement - major innate path evolved to kill extracellular bacteria in blood/instersititial fluids (plasma in btw cells)

  • activation - self assembly into complexes -> kill bacteria
  • alternative pathway - 1st to act, happen on pathogen surface (NO PAMPS)
  • lectin path - 2nd, mannose binding lectin (MBL) bind to pathogen surface (PAMPS = carbohydrate like mannose)
  • classical - last, antibody bind to specific antigen on pathogen surface (PAMP = antibody)
    • OR CRP can also start pathway w/o antibodies
  • ALL PATHS = complement activation + have their C3 convertase
    • alternative c3convertase = C3bBb
    • lectin/classical use (i forgot what its called)
  • ALL PATHS CONVERGE - cleave C3 -> C3b + C3a
    • C3b - bind to surface of bacteria + generate inflammation
  • rest = same for all
    • recruit inflammatory cells
    • opsonize pathogens = facilitate uptake/killing by phagocytes
    • perforation of pathogen membrane (by C9 -> MAC)
  • = death of pathogen

pore forming proteins

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MACPF domain proteins - highly conserved DNA/protein sequence

C9 forms the pore - poly C9 - complement membrane attack complex

pore = 100 amstrongs diameter

extracellular bacteria - killed by C9 (forms pore)

virus infected cells killed by P1 + intra bacteria killed by P2

assembly of/presursors of MAC

  • C5b bind w/ C6 = C5b-6 complex + bind C7 = C5b-6-7 complex + bind C8 = C5b-6-7-8 complex
    • binds to C9 + act as catalyst in polymerization of C9
    • MAC ITSELF = C9

Q: bactericidal pore of MAC is formed by polymerization of:

A) C9

thats the answer (other ones were c2,3, or 1)


innate system can detect unique molecular bacterial patterns not present in eukaryotes

  • bacterial structures not found in eukaryotes (ex: peptidoglycan, lipids, etc.)
    • GRAM + retain purple stain - thick peptidoglycan
    • GRAM - do not keep stain - counterstain (red/pink) - thin layer


  • = molecular structures in microorganisms NOT present in higher organisms
  • recognized by PRRs
    • recognition induce innate system
  • each PAMP requires its specific receptor
  • bacteria dont usually contact cell surfaces - theyre protected by mucus/fatty layer + keratin
  • trauma/damage = acess for bacteria to cells/body fluid
  • if bacteria make contact w/ cell surfaces - cellular recognition molecules
  • if bacteria get in blood/body fluids - recognition by soluble proteins

Q: PAMPs are:

A) ions left behind by pathogenic bacteria

B) molecules in microorganisms (not in higher organisms)

C) disease patterns in infected patients

D) recognized by alternative path of complement



Q: Bacterial PAMPS are:

A) Lipid molecules

B) carb molecules

C) proteoglycans

D) nucleotide sequences

E) all of above



see how pamps highly conversed (in plants even)



complement system (HOW IT WORKS) + protection vs extracellular bacteria

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  1. bacterial cell surface induce cleavage + activation of complement
  2. complement fragment covalently bond to bacterium + other fragment attract effector cell
  3. complement receptor of effector cell binds to the complement fragment on the bacterium
  4. effector cell engulfs the bacterium, kills it, and breaks it down

myeloid cells in adaptive immunity

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lymphoid tissues in the body

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bone marrow - precursor white blood cells

  • if go to thymus -> become T cells
  • if not -> B cell/ other cells/ differentiate

macrophages express receptors for many microbial constituents

-already know mannose, glucan, scavenger receptors bind cell wall carbohydrates of bacteria, yeast, etc. + TLRs recognize diff bacterial components from gram+/- bacteria


complement = important way phages takeup + kill extracellular bacteria (dont need antibodies to recognize + dont need adaptive system to be activated)


fixation of complement

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C3 - central / most important complement of system

  • cleaved = C3a + C3b
    • C3b - bound covalently to pathogen surfac + act as opsinogen (facilitate phagocytosis)
    • C3a - anaphylatoxin (induce inflammation) - recruit fluid + inflammatory cells to sites of antigen deposition

Q: classical, alternative, lectin path of complement all share

A) antibody activation of C1

B) carb binding to receptors on macrophage

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

D) spontaneous hydrolysis of C3

E) recognition of PAMPs