6 - Innate 4: Effector

Question 1

What is an example of a small extracellular threat?

Answer 1

Bacteria

Question 2

What is an example of a large extracellular threat?

Answer 2

Multicellular parasites

Question 3

What are some intracellular infections?

Answer 3

Virus, some bacteria, some parasites

Question 4

What are 3 effector functions?

Answer 4

1. Phagocytosis and killing of microbes within phagosome
2. Release of antimicrobial products to kill extracellular microbes and parasites
3. Targeted destruction of infected/transformed host cells by NK-mediated cytotoxicity

Question 5

Which immune cells are “professional” phagocytes?

Answer 5

Neutrophils (granulocyte) and Macrophages (monocytic-phagocytic lineage)

Question 6

What are 3 specialized lineages of phagocytic leukocytes?

Answer 6

1. Kupffer cells (liver)
2. Langerhans cells (epithelium)
3. Microglia (CNS)

Question 7

What are the 3 basic steps of phagocytosis?

Answer 7

1. Recognition and adhesion plasma membrane
2. Membrane/cytoskeleton reorganization; engulfment; phagosome
3. Maturation to microbicidal and degradative phagolysosome

Question 8

Is there collateral damage with phagocytosis?

Answer 8

No

Question 9

What are PRRs?

Answer 9

Phagocytic-pattern Recognition Receptors

Question 10

What do PRRs do?

Answer 10

They recognize PAMPs on pathogens and recognize apoptotic host cells

Question 11

Why is it important for macrophages to recognize apoptotic host cells?

Answer 11

Because they “clean up” after inflammation, which assists in the healing process

Question 12

What do C-type lectin receptors recognize?

Answer 12

Terminal mannose/fucose residues

Question 13

What do scavenger receptors recognize?

Answer 13

Mostly lipoproteins on bacteria

Question 14

What occurs inside the cell during phagocytic engulfment?

Answer 14

The cytoskeleton is remodelled to allow involution of the plasma membrane and the creation of a new intracellular vacuole (phagosome)

Question 15

What are the 2 opsonin receptors macrophages have?

Answer 15

1. Complement receptors
2. Immunoglobulin Fc receptors

Question 16

What is the ligand that gets deposited on the surface of a pathogen that can be recognized by a complement receptor?

Answer 16

C3b (or its cleavage products)

Question 17

What is the ligand that gets deposited on the surface of a pathogen that can be recognized by an immunoglobulin Fc receptor?

Answer 17

Antibody

Question 18

What is the purpose of having opsonin ligands/receptors?

Answer 18

They tag fast-moving blood-borne pathogens and make them easier to recognize by other immune cells for more effective immunity

Question 19

What events follow phagocytosis?

Answer 19

1. Proton pumps insert into phagosomal membrane to acidify interior
2. Endosomal/lysosomal compartments (containing hydrolytic and antimicrobial enzymes) fuse with the phagosome
3. The phagosome now becomes an acidic, digestive, antimicrobial phagolysosome

Question 20

What is the main way pathogens avoid destruction once in a phagosome?

Answer 20

They prevent the fusion of the endosome/lysosome so that the phagosome does not become an ouchy phagolysosome

Question 21

What is the intraphagosomal environment like?

Answer 21

-Acidic
-Has antimicrobial peptides
-Has hydrolases
-Low availability of essential nutrients
-Oxidative radicals (ROS)

Question 22

What is formed from the reaction of ROS (reactive oxygen species) and RNI (reactive nitrogen intermediates)?

Answer 22

Unstable free radicals

Question 23

Why must the ROS stay within the phagolysosome?

Answer 23

Because they can cause damage to any cells, including the host cells

Question 24

What are 4 ROS (from weakest to strongest if u can)?

Answer 24

Free radical superoxide (O2-)
Hydroxyl radical (OH)
Hydrogen peroxide (H2O2)
Hypochlorous acid (HClO)

Question 25

Which enzyme do only neutrophils have that allow them to produce hypochlorous acid?

Answer 25

Myeloperoxidase (MPO)

Question 26

Which ROS does NADPH Oxidase produce?

Answer 26

Free radical superoxide Hydroxyl radical Hydrogen peroxide

Question 27

What is ClO- similar to?

Answer 27

Bleach!

Question 28

Where is myeloperoxidase stored in a neutrophil?

Answer 28

In azurophilic granules

Question 29

What reaction does myeloperoxidase catalyze?

Answer 29

Hydrogen peroxide + Cl- ----> hypochlorous acid

Question 30

When is hypochlorous acid synthesized?

Answer 30

During neutrophil's respiratory burst

Question 31

What cofactor does MPO require?

Answer 31

Heme peroxidase (iron)

Question 32

If pus has a green tinge to it, what does that mean?

Answer 32

Lots of neutrophils are present with lots of MPO

Question 33

What allows for more efficient bacterial recognition by phagocytic cells?

Answer 33

The addition of complement and immunoglobulin-based opsonins

Question 34

What are 4 proteins that stimulate eosinophil degranulation?

Answer 34

-Major basic protein -Eosinophil cationic protein -Eosinophil peroxidase -Eosinophil-derived neurotoxin

Question 35

What is a major side effect of eosinophil degranulation?

Answer 35

Hypersensitivity triggered by IgE

Question 36

What does major basic protein stimulate?

Answer 36

-Cytotoxin and helmithotoxin -Mast cell degranulation

Question 37

What does Eosinophil cationic protein stimulate?

Answer 37

Cationic ribonuclease and pore forming

Question 38

What does Eosinophil peroxidase stimulate?

Answer 38

Oxidizes a variety of substrates in the presence of hydrogen peroxide

Question 39

What does Eosinophil-derived neurotoxin stimulate?

Answer 39

Ribonuclease (anti-viral activity)

Question 40

What is degranulation by neutrophils?

Answer 40

The release of hydrolases that cause a respiratory burst into the extracellular space

Question 41

Which hydrolases are released during neutrophil degranulation?

Answer 41

-Proteases -MPO -NADPH oxidase

Question 42

What is the issue with neutrophil degranulation?

Answer 42

Collateral damage to host

Question 43

What does NETs stand for?

Answer 43

Neutrophil Extracellular Traps

Question 44

What are NETs?

Answer 44

Large extracellular fibers that contain strands of chromatin and globular proteins with antimicrobial proteins

Question 45

What is the release of NETs stimulated by?

Answer 45

PAMPs and cytokines

Question 46

What is the function of NETs?

Answer 46

Bind, neutralize and kill pathogens at sites of inflammation and in blood vessels

Question 47

What happens to the neutrophils after it releases a NET?

Answer 47

It DIES

Question 48

What are NK cells?

Answer 48

Lymphocytes with granules that do not require activation and lack immunologic specificity and memory

Question 49

Are NK cells innate or adaptive?

Answer 49

Innate!

Question 50

Which surface markers do NK cells usually express?

Answer 50

Ones for immunoglobulins like CD16 and Fc

Question 51

How do NK cells recognize target cells?

Answer 51

They look for MHC1 complex on host cells. No MHC1 = death

Question 52

What are activated NK cell functions?

Answer 52

- Kill altered self cells (tumours, virally infected) - Directly killing pathogens - Produce cytokines that induce adaptive responses against the altered self cell

Question 53

How are cytotoxic functions regulated?

Answer 53

A balance between signals from activating and inhibitory receptors

Question 54

What do inhibitory receptors recognize?

Answer 54

MHC 1 complex on nucleated host cells

Question 55

What must the target cell display to induce apoptosis by an NK cell?

Answer 55

Altered MHC1 expression and activating ligand

Question 56

What do activating receptors recognize?

Answer 56

Ligands (viral products) on target cells or IgG (ADCC)

Question 57

What does ADCC stand for?

Answer 57

Antibody-dependent cell cytotoxicity

Question 58

What occurs once a NK cell decides another cell must die?

Answer 58

The NK forms an immune synapse and degranulates. The granules contain perforins and granzymes which induce apoptosis

Question 59

What are perforins?

Answer 59

C9 related proteins that form pores in the membrane of target cells

Question 60

What are granzymes?

Answer 60

Proteases that enter target cells through perforin pores and initiate apoptosis

Question 61

What is good about NK-mediated cytotoxicity?

Answer 61

Theres not collateral damage; its very precise and effective

Question 62

What is the purpose of having ADCC?

Answer 62

Enhancement of an innate effector mechanism following adaptive immune response

Question 63

How is NK's cytotoxic function initiated with IgG?

Answer 63

NK cells recognize surface-bound IgG through Fc receptors, which stimulate the cytotoxic function

Question 64

What is the best way for NK cells to kill target cells? *EXAM QUESTION*

Answer 64

Antibody-dependent cellular cytotoxicity (ADCC) The antibodies binding to the pathogens antigens make killing it much more effective!

Question 65

How can R. equi survive in a foal with rattles?

Answer 65

The bacteria block acidifcation and fusion with late endosomes and lysosomes