macrophage interactions

Question 1

bacteria can be divided in two groups based on if they live in or out of the cell

Answer 1

extracellular bacteria: live outside of host cels and cause disease (Staphylococcus, streptococcus, pseudomonas, etc)

intracellular: there are cytoplasmic and phagosomal and cause disease from within

Question 2

Stratagies used by extracellular pathogens to resist getting killed by phagocytes

Answer 2

3 ways:
1. Avoid recognition by phagocyte (colonize regions where ther arent phagocytes like skin, minimize inflammatory response by modifying LPS, inhibit phaocyte chemotaxis, hide Ag surface with a capsule, evade opsonization thru proteins

2. Inhibit phagocyte engulfment (Produce a capsule or anti phagocytic determinents on surface)
3. Kill or damage phagocytes (Secrete or deliver enzymes or toxins that inhibit or damage host cell)

Question 3

Stratagies used by intracellular pathogens to resist getting killed by phagocytes

Answer 3

3 ways:

1. inhibit phagosome-lysosome fusion (secreting protens that block phagosome maturation)
2. Survive in the phagolysosome (produce enzymes that block acid ROI and RNI)
3. Escape from phagosome( secrete enzyme that degrade phagosomal membrane

Question 4

Pros and cons of being intracellular pathogen

Answer 4

Pros: environment nutrient rich, live in a protected space from immune Sys. and bacterial competitors

Cons: must overcome host barriers, resist inate and acuired immune, survive in a hostile environment (pH, antimicrobial peptites, etc)

Question 5

What is a macrophage

Answer 5

first line of defense-innate immunity, derived from peripheral blood monocytes, leave vasculature and differentiate into tissue macrophages, activated upon ingestion of bacteria or byproducts, and cytokines and chemokines

Macrophage internalize inert and biological particles using various mechanism thru recognition , uptake, maturation and killing (with Ag presentation)

Question 6

Bacterial recognition

Answer 6

Phagocytes recognize: bacterial cell wall or membranes and immune system components following opsonization.

bacteria can be recognized by multiple host receptors and specific interaction can define events of phagocytosis

LPS, papilli, flagella, proteins can be recognized
capsules mask the foreign shit

Question 7

Macrophages express a variety of receptors

Answer 7

PRRs recognize bacterial structures including LPS (gram-) and LTA (gram +)

Receptors that recognize plasma derived molecules (collectins, petraxins, complement)

Receptors that recognize specific bacterial elements

Receptor engagement elicits different host cell responses

Extracellular pathogens avoid recognition

Question 8

Bacterial uptake

Answer 8

recognition between ligand and receptor initiates activation

Surface structure remodeled by actin and cytoskeletal components

Phagosome has the bacterium

internalization is usually passive (site specific)

Question 9

Entry into non phagocytic cells requires that bacteria actively induce their own uptake

Answer 9

trigger mechanism (salmonella)- membrane blebbing

zipper mechanism (listeria)- just slide into the cell

Question 10

Maturation of bacteria containing phagosomes

Answer 10

maturation of phagosome proceeds by fusuion of endocytic vesicles. Depending on the vesicle surface they can be early or late endosomes and end up fusing with a lysosome and make a phagolysosome (very late endosome) Microtubules have create the cytoskeleton

further maturation= lower pH

Question 11

How do bacteria alter phagosome traficking

Answer 11

Survive and replicate in phagosome
Escape and replicate in Cytosol
Modulate Endocytic pathway
Alternate trafficking pathway