Innate Immunity 1

Question 1

what 2 types of surfaces does a pathogen enter through?

Answer 1

1. mucosal
2. epithelial

Question 2

what allows a pathogen to cause infection?

Answer 2

pathogen must breach one of the barriers thru various routes of entry

Question 3

why is human skin resistant to E. coli colonization despite exposure?

Answer 3

• nutrients, pH
• can’t breach
• skin can make antimicrobial protein against gram-neg

Question 4

what are 4 examples of epithelial surfaces that are barriers?

Answer 4

1. skin
2. gut epithelium
3. respiratory epithelium
4. mucosal membranes

Question 5

how do saliva, hair, mucous, and tears provide innate immunity?

Answer 5

contain molecules that are antimicrobial

Question 6

what are 2 types of protective substances produced by the epithelial layers?

Answer 6

1. acidic pH
2. antimicrobial peptides

Question 7

what are 4 cell types involved in innate immunity?

Answer 7

1. neutrophils + other granulocytes
2. monocytes/macrophages
3. dendritic cells
4. NK cells + other innate lymphoid cells (ILCs)

Question 8

describe the different types of monocytes/macrophages

Answer 8

all have same function but different types based on tissue

Question 9

what are the 2 types of mature dendritic cells?

Answer 9

1. conventional DCs
2. plasmacytoid DCs

Question 10

what are 3 types of molecules involved in innate immunity?

Answer 10

1. enzymes
2. anti-microbial peptides
3. complement

Question 11

what is an example of an enzyme involved in innate immunity and its function?

Answer 11

lysozyme –> digests peptidoglycan of gram-pos bacteria

Question 12

what is an example of an anti-microbial peptide involved in innate immunity and its function?

Answer 12

defensins –> disrupt the cell membrane

Question 12

what is the definition of phagocytosis?

Answer 12

engulfument and internalization of pathogens/pathogen components upon binding to receptors on surface of phagocytes

Question 13

what are the 3 types of phagocytes?

Answer 13

1. macrophages
2. granulocytes (neutrophils)
3. immature DC

Question 14

phagocytosis can lead to: (3)

Answer 14

1. removal and killing of pathogen
2. cleaning debris from killing pathogens
3. production of antigenic peptides to present to T cells

Question 15

what are the 2 types of phagocytes that produce antigenic peptides to present to T cells?

Answer 15

1. DCs
2. macrophages

Question 16

how do phagocytes recognize pathogens?

Answer 16

by receptors, usually PRRs

Question 17

do all PRRs induce phagocytosis? are all receptors involved in phagocytosis PRRs?

Answer 17

no

no

Question 18

how does indirect phagocytosis occur?

Answer 18

phagocyte recognize opsonins on pathogen surface

Question 19

what are opsonins?

Answer 19

soluble proteins that are bound to microbial surfaces

Question 20

what is another name for opsonins?

Answer 20

soluble pattern-recognition patterns

Question 21

what is the role of opsonins?

Answer 21

enhance phagocytosis

Question 22

what is the enhancement of phagocytosis called?

Answer 22

opsonization

Question 23

what is an example of an opsonin?

Answer 23

antibody

Question 24

what are the 5 steps of phagocytosis?

Answer 24

1. phagocytosis initiated by receptors interacting with microbes (PAMP) 2. pseudopodia extend from the phagocytic cell 3. pathogen is internalized in a phagosome 4. phagosome fuses with 1+ lysosomes to make a phagolysosome and lysosomal contents are released 5. phagolysosome acidifies and acquires antimicrobial peptides + enzymes to kill microbe

Question 25

what is a phagosome?

Answer 25

large membrane-enclosed endocytic vesicle that internalizes pathogens

Question 26

what allows for the acidification and production of antimicrobial peptides/enzymes?

Answer 26

the fusion of phagosome and lysosome

Question 27

what is unique about neutrophil phagocytosis?

Answer 27

they contain primary and secondary granules in cytoplasm (INSTEAD OF LYSOSOMES) which fuse with phagosomes and produce antimicrobial peptides

Question 28

what does the phagolysosome do to kill microbes? (4)

Answer 28

1. produce antimicrobial proteins + peptides 2. low pH 3. hydrolytic enzymes 4. oxidative attack

Question 29

what are the 2 types of hydrolytic enzymes produced during phagocytosis?

Answer 29

1. lysozyme 2. proteases

Question 30

what does oxidative attack do?

Answer 30

creates ROS to damage microbial membranes and intracellular components

Question 31

why can phagocytes produce ROS?

Answer 31

phagocytes have a unique NADPH oxidase enzyme complex (phagosome NADPH oxidase)

Question 32

what happens when ROS is produced by NADPH oxidase?

Answer 32

increased oxygen consumption --> respiratory burst

Question 33

does the phagolysosome affect innate or adaptive immunity?

Answer 33

both!

Question 34

what are the 3 roles of the phagolysosome in innate immunity?

Answer 34

1. pathogen killing 2. pathogen processing 3. pathogen presentation to sensory cytosolic receptors

Question 35

what are the 3 roles of the phagolysosome in adaptive immunity?

Answer 35

1. antigen degeneration 2. antigen processing 3. antigen presentation

Question 36

what happens to cells that have undergone apoptosis?

Answer 36

they are cleared by phagocytes

Question 37

how are cells cleared once they die?

Answer 37

the dead/dying cells express DAMPs which signal for them to be eaten

Question 38

what does DAMP stand for?

Answer 38

Damage-Associated Molecular Patterns

Question 39

what is CD47?

Answer 39

expressed by healthy cells (most cell types) that signal for them NOT to be eaten

Question 40

how does CD47 work?

Answer 40

CD47 binds SIRPalpha (signal regulatory protein alpha) on macrophages to INHIBIT PHAGOCYTOSIS

Question 41

What type of cells express elevated levels of CD47?

Answer 41

tumour cells

Question 42

where are macrophages located?

Answer 42

they are located at tissue

Question 43

where are neutrophils located?

Answer 43

they are recruited to the site of infection

Question 44

what is pus?

Answer 44

dead and dying neutrophils

Question 45

what do neutrophils produce?

Answer 45

Neutrophil Extracellular Traps (NETs)

Question 46

what percent of neutrophils produce NETs?

Answer 46

20-60%

Question 47

what is the role of NETs? (2)

Answer 47

1. traps microorganisms to prevent spread 2. produce antimicrobial peptides/enzymes

Question 48

what can granule enzymes in neutrophils do to microbes?

Answer 48

they enter the nucleus to modify histones so CHROMATIN DECONDENSES

Question 49

what allows for the production of NETs?

Answer 49

once chromatin is decondensed, PM ruptures and cytoplasm/nucleoplasm are released to form NETs

Question 50

what is the "macrophage of the brain"

Answer 50

microglia

Question 51

what is the role of microglia?

Answer 51

establishing proper neuronal connections for brain development, memory, learning

Question 52

what is multiple sclerosis?

Answer 52

inflammatory disease w myelin/neuron breakdown, causing toxic debris

Question 53

how is toxic debris in MS removed?

Answer 53

by microglia and other macrophages (but this does not fix the missing neurons!)

Question 54

in general, what are microglia required for?

Answer 54

CNS repair

Question 55

what happens when the microglia receptor is KO?

Answer 55

cells cannot migrate to site of damage --> no phagocytosis