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Immunology > 6 - Innate 4: Effector > Flashcards

6 - Innate 4: Effector Flashcards

1
Q

What is an example of a small extracellular threat?

A

Bacteria

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2
Q

What is an example of a large extracellular threat?

A

Multicellular parasites

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3
Q

What are some intracellular infections?

A

Virus, some bacteria, some parasites

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4
Q

What are 3 effector functions?

A
  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
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5
Q

Which immune cells are “professional” phagocytes?

A

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

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6
Q

What are 3 specialized lineages of phagocytic leukocytes?

A
  1. Kupffer cells (liver)
  2. Langerhans cells (epithelium)
  3. Microglia (CNS)
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7
Q

What are the 3 basic steps of phagocytosis?

A
  1. Recognition and adhesion plasma membrane
  2. Membrane/cytoskeleton reorganization; engulfment; phagosome
  3. Maturation to microbicidal and degradative phagolysosome
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8
Q

Is there collateral damage with phagocytosis?

A

No

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9
Q

What are PRRs?

A

Phagocytic-pattern Recognition Receptors

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10
Q

What do PRRs do?

A

They recognize PAMPs on pathogens and recognize apoptotic host cells

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11
Q

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

A

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

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12
Q

What do C-type lectin receptors recognize?

A

Terminal mannose/fucose residues

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13
Q

What do scavenger receptors recognize?

A

Mostly lipoproteins on bacteria

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14
Q

What occurs inside the cell during phagocytic engulfment?

A

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

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15
Q

What are the 2 opsonin receptors macrophages have?

A
  1. Complement receptors
  2. Immunoglobulin Fc receptors
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16
Q

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

A

C3b (or its cleavage products)

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17
Q

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

A

Antibody

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18
Q

What is the purpose of having opsonin ligands/receptors?

A

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

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19
Q

What events follow phagocytosis?

A
  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
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20
Q

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

A

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

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21
Q

What is the intraphagosomal environment like?

A

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

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22
Q

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

A

Unstable free radicals

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23
Q

Why must the ROS stay within the phagolysosome?

A

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

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24
Q

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

A

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

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25
Q

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

A

Myeloperoxidase (MPO)

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26
Q

Which ROS does NADPH Oxidase produce?

A

Free radical superoxide
Hydroxyl radical
Hydrogen peroxide

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27
Q

What is ClO- similar to?

A

Bleach!

28
Q

Where is myeloperoxidase stored in a neutrophil?

A

In azurophilic granules

29
Q

What reaction does myeloperoxidase catalyze?

A

Hydrogen peroxide + Cl- —-> hypochlorous acid

30
Q

When is hypochlorous acid synthesized?

A

During neutrophil’s respiratory burst

31
Q

What cofactor does MPO require?

A

Heme peroxidase (iron)

32
Q

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

A

Lots of neutrophils are present with lots of MPO

33
Q

What allows for more efficient bacterial recognition by phagocytic cells?

A

The addition of complement and immunoglobulin-based opsonins

34
Q

What are 4 proteins that stimulate eosinophil degranulation?

A

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

35
Q

What is a major side effect of eosinophil degranulation?

A

Hypersensitivity triggered by IgE

36
Q

What does major basic protein stimulate?

A

-Cytotoxin and helmithotoxin
-Mast cell degranulation

37
Q

What does Eosinophil cationic protein stimulate?

A

Cationic ribonuclease and pore forming

38
Q

What does Eosinophil peroxidase stimulate?

A

Oxidizes a variety of substrates in the presence of hydrogen peroxide

39
Q

What does Eosinophil-derived neurotoxin stimulate?

A

Ribonuclease (anti-viral activity)

40
Q

What is degranulation by neutrophils?

A

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

41
Q

Which hydrolases are released during neutrophil degranulation?

A

-Proteases
-MPO
-NADPH oxidase

42
Q

What is the issue with neutrophil degranulation?

A

Collateral damage to host

43
Q

What does NETs stand for?

A

Neutrophil Extracellular Traps

44
Q

What are NETs?

A

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

45
Q

What is the release of NETs stimulated by?

A

PAMPs and cytokines

46
Q

What is the function of NETs?

A

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

47
Q

What happens to the neutrophils after it releases a NET?

A

It DIES

48
Q

What are NK cells?

A

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

49
Q

Are NK cells innate or adaptive?

A

Innate!

50
Q

Which surface markers do NK cells usually express?

A

Ones for immunoglobulins like CD16 and Fc

51
Q

How do NK cells recognize target cells?

A

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

52
Q

What are activated NK cell functions?

A
  • Kill altered self cells (tumours, virally infected)
  • Directly killing pathogens
  • Produce cytokines that induce adaptive responses against the altered self cell
53
Q

How are cytotoxic functions regulated?

A

A balance between signals from activating and inhibitory receptors

54
Q

What do inhibitory receptors recognize?

A

MHC 1 complex on nucleated host cells

55
Q

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

A

Altered MHC1 expression and activating ligand

56
Q

What do activating receptors recognize?

A

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

57
Q

What does ADCC stand for?

A

Antibody-dependent cell cytotoxicity

58
Q

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

A

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

59
Q

What are perforins?

A

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

60
Q

What are granzymes?

A

Proteases that enter target cells through perforin pores and initiate apoptosis

61
Q

What is good about NK-mediated cytotoxicity?

A

Theres not collateral damage; its very precise and effective

62
Q

What is the purpose of having ADCC?

A

Enhancement of an innate effector mechanism following adaptive immune response

63
Q

How is NK’s cytotoxic function initiated with IgG?

A

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

64
Q

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

A

Antibody-dependent cellular cytotoxicity (ADCC)

The antibodies binding to the pathogens antigens make killing it much more effective!

65
Q

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

A

The bacteria block acidifcation and fusion with late endosomes and lysosomes

Immunology (18 decks)

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