Exam 1: Dr. Kaplan Inflammation: Mechanisms 2

Question 1

What are the 3 ways on innate immune cell killing?

Answer 1

Phagocytosis
Release of antimicrobial products
Targeted destruction of infected host cells

Question 2

What do the innate immune cell killings defend against?

Answer 2

A variety of pathogens without eliciting help from the adaptive system

Question 3

How quickly can the innate immune cell killing mechanisms be deployed?

Answer 3

Immediately without previous exposure, but can continue to work after adaptive immune response has been mounted

Question 4

What are 3 types of phagocytes?

Answer 4

Macrophages
Neutrophils
Dendritic cells

Question 5

What are the 3 stages of phagocytosis?

Answer 5

Recognition and adhesion of particles on plasma membrane of phagocyte
Membrane and cytoskeletal reorganiztion to mediate particle engulfment and creation of a phagosome
Maturation of phagosome to microbicidal and degradative phagolysosome

Question 6

What are examples of some PRRs?

Answer 6

MR/CD206
Dectin-1
Scavenger receptor A1
Phosphatidyl serine receptor

Question 7

What does MR/CD206 recognize?

Answer 7

Mannose and fucose on bacteria, fungi, and viruses

Question 8

What does dectin-1 recognize?

Answer 8

β-glucan residues on fungi

Question 9

What does scavenger receptor A1 recognize?

Answer 9

Polyanionic ligands on various microbes

Question 10

What does phosphatidyl serine receptor recognize?

Answer 10

Phosphatidyl serine on apoptotic cells

Question 11

What is recognition mediated by?

Answer 11

PRRs and opsonic receptors

Question 12

What is opsonization?

Answer 12

Process whereby particles are coated with a protein-binding enhancer to enhance phagocytosis

Question 13

What are the 2 major opsonins that mammals have?

Answer 13

Complement (C3b)

Antibody (IgG)

Question 14

What can also act as an opsonin when bound to microbes?

Answer 14

CRP

Question 15

What are 2 examples of opsonic receptors?

Answer 15

CR3

FCγ1R/CD64

Question 16

What does CR3 recognize?

Answer 16

C3b on an surface bound by C3b

Question 17

What does FCγ1R/CD64 recognize?

Answer 17

The Fc portion of the IgG antibody on any surface bound by IgG

Question 18

What does the phagocytosis of irregularly shaped microbes or several microbes require?

Answer 18

Alteration in morphology

Question 19

What does recognition of particle by phagocytic receptors result in?

Answer 19

Tight adhesion of microbe to phagocyte and clusters the receptors together

Question 20

How long does the phagosome last?

Answer 20

Only a few seconds, but quickly evolves to an acidic, oxidative, degradative, antimicrobial chamber

Question 21

What does the evolution of the phagolysosome evolution involve?

Answer 21

Fusion of the phagosome with endosomes and lysosomes in the cell

Question 22

What does the phagosome do?

Answer 22

Recruits protein complexes that actively pump protons into it, reducing pH

Question 23

What can the lower pH reduced by the protein complexes recruited by phagosomes do?

Answer 23

Kill microbes and activate antimicrobial enzymes that have been delivered to the phagosome

Question 24

What does a phagosome do in neutrophils?

Answer 24

It also fuses with a modified lysosome containing high concentrations of antimicrobial proteins

Question 25

What is an oxidative or respiratory burst?

Answer 25

Assembly of NADPH oxidase on phagosomal membrane

Question 26

What does NADPH oxidase do?

Answer 26

Transfers unpaired electrons from NADPH to molecular oxygen generating superoxide

Question 27

What is superoxide?

Answer 27

Extremely reactive and damaging | Reacts with hydrogen ions to form hydrogen peroxide

Question 28

What is hydrogen peroxide?

Answer 28

A powerful oxidant that can be converted to hydroxyl radicals in presence of ferrous ions, which is damaging to all macromolecules

Question 29

What can neutrophils make?

Answer 29

The antimicrobial enzyme myeloperoxidase

Question 30

What does myeloperoxidase do?

Answer 30

Combines hydrogen peroxide with chloride ion to make hypochlorite ion (bleach)

Question 31

What are the antimicrobial enzymes, proteases, improtant for?

Answer 31

Bridging innate with adaptive immunity

Question 32

What can the amino acid arginine be converted to?

Answer 32

Nitric oxide

Question 33

Why is nitric oxide important?

Answer 33

It is a signaling molecule

Question 34

How is nitric oxide antimicrobial?

Answer 34

By reacting with DNA and microbial enzymes

Question 35

What can nitric oxide combine with?

Answer 35

Superoxide to form peroxynitrite

Question 36

What is peroxynitrite extremely reactive with?

Answer 36

Lipid, DNA, and proteins

Question 37

What does bleach do?

Answer 37

Kills bacterium

Question 38

What can nitric oxide cause?

Answer 38

Vasodilation

Question 39

What are the 3 reactive oxidative burst products that cause damage to proteins and DNA in the bacterium?

Answer 39

Superoxide anion Hydrogen peroxide Hydroxyl radical

Question 40

What oxidative compounds do macrophages and neutrophils generate in the phagosome?

Answer 40

``` Reactive oxygen species Reactive nitrogen intermediates Reactive hypochlorite (Neutrophils only) ```

Question 41

What cells do degranulation?

Answer 41

Neutrophils and eosinophils

Question 42

What is released in mast cell degranulation?

Answer 42

Vasoactive substance

Question 43

What is released in neutrophil and eosinophil degranulation?

Answer 43

Cytotoxic and degradative proteins and peptides

Question 44

What does degranulation result in?

Answer 44

Injury to surrounding tissue

Question 45

What are eosinophils specialists at?

Answer 45

Antiparasite leukocytes

Question 46

Why are eosinophils the early responders to parasites?

Answer 46

They are often too big to phagocytose

Question 47

What do eosinophil granules contain?

Answer 47

Major basic protein (an anti-helminthic cytotoxin) Eosinophil cationic protein Eosinophil-derived neurotoxin Eosinophil peroxidase

Question 48

What is the eosinophil cationic protein?

Answer 48

A pore forming protein that punches holes in cell membranes and/or can digest RNA

Question 49

What can punch holes in the cell membranes?

Answer 49

Eosinophils and complement

Question 50

What is the eosinophil-derived neurotoxin?

Answer 50

A ribonuclease with antiviral properties

Question 51

What does eosinophil peroxidase do?

Answer 51

Facilitates oxidative damage by generating hydrogen peroxide

Question 52

What are neutrophil extracellular traps?

Answer 52

Sticky, meshlike substance neutrophils can extrude into extracellular space to which bacteria and yeast stick and are killed

Question 53

What do NETs allow?

Answer 53

Immobilization of microbes and protects from surrounding tissue from destruction

Question 54

What are fibers of the NET?

Answer 54

Neutrohils own DNA, which results in the death of the neutrophil

Question 55

What do NK cells identify?

Answer 55

Potentially infected host cells since some microbes are intracellular and cannot be engulfed, ensnared in a NET, or killed by extracellular release of cytotoxins

Question 56

What are NK cells classified as?

Answer 56

Lymphocytes, but do not possess antigen specific receptors

Question 57

What do NK cells express?

Answer 57

Several receptors that recognize sick and stressed host cells Receptors to recognize cells that are not displaying their self markers because they have not been altered by the pathogen

Question 58

What do NK cells kill?

Answer 58

Infected or transformed cells

Question 59

What do NK cells serve as?

Answer 59

The bridge to adaptive immunity

Question 60

What do NK cell recognize?

Answer 60

Receptors on host cells

Question 61

What happens if the receptors on host cells are not expressed?

Answer 61

The NK cell will destroy that cell

Question 62

What receptors do NK cells use?

Answer 62

Killer lectin-like receptors | Killer cell immunoglobulin-like receptors

Question 63

What do receptor sense?

Answer 63

Ligands that indicate abnormality

Question 64

What do NK cell-activating receptors do?

Answer 64

Directly detect conserved viral proteins on surface of infected cells May also detect modified ligands

Question 65

What do all nucleated cells express on the surface?

Answer 65

MHC I

Question 66

What do NK cells do with MHC I?

Answer 66

Recognize it as an indication of normal function

Question 67

What do inhibitory signals to NK cells do?

Answer 67

Override the activating signal from identifying an altered protein

Question 68

What happens once an NK cell encounters a host cell that triggers it activating receptor without triggering its inhibitory receptor?

Answer 68

The NK cell will kell the infected/altered cell

Question 69

What is the killing mechanism of NK cells similar to?

Answer 69

The killing mechanism of Tc cells

Question 70

What do NK cells release?

Answer 70

Lytic granules

Question 71

What is different about the release from NK cells when compared to the release from neutrophils or eosinophils?

Answer 71

It is directed

Question 72

What do NK cells form with the target cell?

Answer 72

A tight are of adhesion with the target cell (NK immunological synapse)

Question 73

What is the NK immunological synapse?

Answer 73

Collection of adhesion molecules carefully arranged by NK cytoskeleton

Question 74

What does the NK immunological synapse act to do?

Answer 74

Dock the NK cell with target cell

Question 75

What does the NK immunological synapse form?

Answer 75

Tight seal so that granule contents are only released to the target cell

Question 76

What are the cytotoxic molecules associated with the NK immunological synapse?

Answer 76

Perforin | Granzyme

Question 77

What does perforin do?

Answer 77

Inserts itself into plasma membrane of target cell forming pores

Question 78

What is granzyme?

Answer 78

A family of serine proteases that enter via pores made by perforin

Question 79

Why does an NK cell not die as a result of killing a target cell from the release of perforin and granzyme?

Answer 79

It is resistant to its own perforin and granzyme

Question 80

What is antibody-dependent cell-mediated cytotoxicity by NK cells?

Answer 80

Similar to how antibodies enhance phagocytosis, antibodies can also augment NK cell-mediated cytotoxicity

Question 81

After an adaptive humoral response generates circulating antibodies to the microbe, what can the antibodies do?

Answer 81

Attach to a viral or neoplasm-associated antigens on the surface of cells

Question 82

What can NK cells recognize antibody-coated cells with?

Answer 82

Their Fc receptors