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Bacteriology > Macrophages > Flashcards

Macrophages Flashcards

1
Q

Bacteria can be divided into two groups based on where they live

A
  • intracellular

- extracellular

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2
Q

extracellular bacteria

A

-these bacteria live outside the cell an cause disease

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3
Q

intracellular bacteria

A

-these bacteria live inside the host cell and cause disease

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4
Q

how do extracellular bateria resist killing by phagocytes

A
  • avoid recognition by phagocytes
  • inhibit phagocyte engulfment
  • kill or damage phagocyte
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5
Q

How do extracellular pathogens avoid recognition by phagocytes

A

1.Colonizeregionsnotaccessibletophagocytes– unbrokenskin
2.Minimizeinflammatoryresponse‐ modifiedLPS
3.Inhibitphagocytechemotaxis– Streptococcalstreptolysin
4.Hideantigenicsurface– GroupAStrephyaluronicacidcapsul
e
5.Evadeopsonization – Staph.aureusProteinA

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6
Q

How do extracellular pathogens inhibit phagocyte engulfment

A

6.Producecapsuleorotheranti‐phagocyticdeterminantsonsurface–
HyaluronicacidcapsuleinGroupAStrep

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7
Q

How do extracellular pathogens kill or damage phagocytes

A

Secreteordeliverenzymesortoxinsthatinhibitordamagehostcell
– Pneumolysin inStreptococcuspneumoniae

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8
Q

How do intracellular pathogens resist killing by phagocytes

A
  • Inhibitphagosome‐lysosomefusion:
  • Surviveinsidephagolysosome:
  • Escapefromphagosome:
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9
Q

How do intracellular pathogens inhibit phagocome-lysosome fusion

A

1.Secreteproteinsthatblockphagosomematuration– typeIII
secretionsysteminSalmonellatyphimurium

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10
Q

How do intracellular pathogens survive inside the pagolysosome

A

2.ResistdegradationbyacidicpH,produceenzymesableto
counteractROIandRNIradicals,etc – productionofKatG (catalase)
orSodA (superoxidedismutase)

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11
Q

How do intracellular pathogens escape from the phagosome

A

Secreteenzyme(s)thatdegradephagosomal membrane– LLLO

(Listeriolysin O)productioninListeriamonocytogenes

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12
Q

Benefits of being intracellular

A

Environmentusuallynutrientrich
Livewithinaprotectedniche

-shelteredfromimmunecomponents
‐ shelteredfrombacterialcompetitors

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13
Q

Limitations of being intracellular

A 
Mustovercomehostbarriers
Resistinnateandacquiredimmunecomponents
Survivewithinhostileenvironment
‐pH,antimicrobialpeptides,reactive
oxygen/nitrogenspecies,other
bacteriocidal enzymes
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14
Q

Obligate intracellular pathogens

A

-live only within cell
Chlamydia
Rickettsiaspp.
Coxiella burnetii

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15
Q

Facultative intracellular pathogens

A

can live in or outside of the cells

Mycobacteriumtuberculosis
Salmonellaspp.
Brucella spp.
Legionellapneumophila
Shigella spp.
Francisella tularensis
Listeriamonocytogenes
Escherichiacoli
Yersiniaspp.
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16
Q

Brief review of macrophages

A 
-• Firstlineofdefense‐innate
immunity
- Derivedfromperipheralblood
monocytes
-Leavevasculatureand
differentiateintotissue
macrophages
-Activateduponingestionof
bacteriaorbacterialproducts,
alsoactivatedbycytokinesor
chemokines
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17
Q

What do phagocytes including macrophages do

A

internalizeinertand
biologicalparticlesusingvariousmechanisms

-regardless of the mechanism used to take it up, it results in taking in the particle and putting in a membrane capsules called the phagosome

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18
Q

What are the five functional steps of phagocytosis

A
  1. Recognition
  2. Uptake
  3. Maturation
  4. Killing
  5. Antigen
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19
Q

Describe step 1 of phagocytosis

A

Bacterial recognition
Phagocytes recognize:
-components of the bacterial cell wall or membrane
-components of the immune system following opsonization
-bacteria can be recognized by multiple host receptors, and the specific interaction can define subsequent events in steps of phagocytosis

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20
Q

What are some things that phagocytes recognize

A
  • peptidoglycan layer
  • surface proteins
  • flagellum
  • pili
  • capsules are how they attemtp to avoid this recogniztion
21
Q

Capsules

A

mask the epitopes so that the bacteria isn’t recognized by the phagocyte

22
Q

Macrophages express a variety of receptors

A
  • PRRs recognize conserved bacterial structures including LPS (Gram -) and LTA (gram +)
  • receptors that recognize plasma-derived molecules deposited on bacterial surface (collectins, pentraxins, comlemetn
  • receptors (C-type lectins, leucine-rich proteins) that recognize other signature elements on bacteria
  • receptor engagement generates different host cell responses depending on receptor. Multiple surface receptors may be engaged by single bacterium
23
Q

how do extracellular pathogens avoid recognition

A

capsules

24
Q

Describe step 2 in the steps of phagocytosis

A
  • recognition between ligand and receptor initiates transmembrane activation cascade-signal transduction
  • surface structure remodeled by polymerizing and depolymerizing actin and other cytoskeletal components
  • bacteria is internalized within a membrane bound compartment termed a phagosome
  • internalization process into a phagocytic cells is usually passive; however some bacteria influence their own internalization
  • some bacteria employ specialized entry mechanisms to avoid normal phagosome maturation steps
25
Q

Describe the process of remodeling of macrophage membrane

A
  • in macrophages this is a passive process. Does not require that bacteria induce their own uptake
  • plasma membrane remodeling occurs only at site of recognition
  • plasma membrane extensiosn-due to loacal actin polymerization
26
Q

However some bacteria undergo specialized phagocytosis

A
  • looping phagocytosis: Francisella tularensis causes phagocyte arm to wrap around
  • coiling phagocytosis: Legionella penumophila causes the phagocyte to spiral around it
27
Q

What does entry into non-phagocytic cells require

A

bacteria to induce their own uptake

28
Q

Describe the trigger mechanism and which organism does it

A

Salmonella typhimurium

  • Major membrane perturbation
  • major cytoskeletal remodeling
  • promoted by bacterial effector proteins injected into the host cell
29
Q

Describe the zipper mechanism and which organism does it

A

Listeria monocytogenes

  • minimal cytoskeletal remodeling
  • bacteria “slide” into cell. Also involves bacterial proteins (causes massive membrane blebbing)
30
Q

Step 3 of Phagocytosis

A

Maturation of bacteria containing phagosomes

  • maturation proceeds by fusion with endocytic vesicles
  • depending on the proteins present on the surface of the phagosome they are termed “early” or “late”endosomes
  • Early endosomes display: Rab 5, Tfr, and FPM
  • Late endosome display: Rab7, EEA1, M6PR, LAMP-1, and 2, and H ATPase and other FPM.
  • phagolysosomes display Cathepsin D, LAP and H ATPase
31
Q

What is the cytoskeletal component that allows maturation of the phagosome from the periphery to the rperinuclear region

A

Microtubules

32
Q

Describe the differences between phagosomal vesicles

A

The phagolysosome has way more proteins etc on its surface. for example it has way more H ATPases bc it is needs to make its internal environment super acidic to KILL bacteria

33
Q

Phagogosome Maturation

A

Dynamic series of fusion events leading to phagosome acidification and fusion of phagosome with the lysosome

34
Q

bacteria and the phagosome maturation process

A

intracellular bacteria can block or alter steps in the maturation process

35
Q

How does macrophage activation influence the baility of bacteria to alter phagosome maturation

A

-bacteria want to stop phogosome maturation, but macrophage activation reduces the ability of bacteria to alter maturation

36
Q

How do bacteria alter phagosome trafficking

A
  1. They survive and replicate in the phagolysosome
  2. Escape and replicate in the cytosol
  3. Modulate the endocytic pathway
  4. Alternative trafficking pathway
37
Q

Which bacteria alter phagosome trafficking by surviving and replicating in the phagolysosome

A

-Coxiella spp.

It is able to replicate in the phagolysosome! It isn’t killed in there

38
Q

What bacteria escape and replicate in the cytosol

A
  • Rickettsia
  • Shigella
  • Escherichia coli
  • Listeria
  • Francisella

they create a protein that destroys the phagosomal membrane so they can be FREE in the cytosol to replicate

39
Q

Which baterica modulate the endocytic pathway

A
  • Mycobacterium
  • Salmonella

-they prevent he phagosome from fusing with the lysozome `

40
Q

Which bacteria make an alternative trafficking pathway

A
  • Legionella
  • Brucella
  • Chlamydia
41
Q

How do lysosomes kill bacteria

A
  • oxygen dependent killing:
  • iNOS generated nitric oxide
  • NADPH oxidase generates superoxide

-Oxygen independent

42
Q

Describe step 5 of phagocytosis

A

processing of bacterial antigens

  • antigen degraded to oligopeptides (13-18 amino acids)
  • Binding to Class I or Class II MHC and antigen presentation on surface
  • Stimulation of T-cell responses
  • Degraded material is exocytosed and can be presented by nearby APC
43
Q

How does bacterial internalization activate Macrophages

A
  • induce cytokine production which is beneficial when released in moderation for short duration
  • mediate lymphocyte recruitment and macrophage activation
  • mediate cross activation of other immune cells
  • increase vascular permeability
44
Q

What are some not so good consequences of bacteria ingestion by macrophages

A
  • tissue injury and disease upon continuous stimulation
  • ROI, RNI and hydrolytic enzymes lead to tissue damage
  • TNFa and IL1 lead to fever, wasting and septic shock
  • persistant infections lead to chronic inflammation
  • phagocytes contribute to autoimmune diseases
  • can act as trojan horse to disseminate pathogens
45
Q

what are the two categories of intracellular pathogens

A
  • obligate or faculatative

- a number of disease causing bacteria are intracellular pathogens of macrophages

46
Q

Uptake of bacteria by macrophages is a multi step process that involves:

A
  • recognition
  • internalization
  • maturation
  • killing
  • antigen presentation
47
Q

Intracellular pathogens have evolved strategies that enhance their survival within phagocytic cell. these include

A
  • the ability to resist acidic pH and lysosome degradation enzymes
  • escape from the phagosome
  • prevention of phagosome maturation
  • alterations in the trafficking pathway
48
Q

What is a bad thing that can happen from macrophage activation

A

macrophage activation can lead to detrimental host response that includes overstimulation of immune system

Bacteriology (15 decks)

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