BIOL 435 Ch. 4 Part Two (Innate Immunity)

Question 1

C-type lectin receptors (CLRs)

Answer 1

• activate innate and inflammatory responses

- generally recognize CHO componenents of fungi, viruses, mycobacteria, parasites and allergens

Question 2

CLRs trigger pathways

Answer 2

-leading to TFs that induce expression of proinflammatory cytokines
>INF alpha/beta
>IL-1beta
>TNF
>IL-23

Question 3

NOD-like receptors

Answer 3

• nucleotide oligomerization domains-receptors
• cytosolic PRRs activated by intracellular PAMPs and DAMPs
• induce expression of genes encoding antimicrobial proteins and peptides
• initate autophagy

Question 4

initiate autophagy (NOD-receptors)

Answer 4

-by forming autophagosomes that fuse with lysosomes to then kill bacteria

Question 5

NOD1 and NOD2

Answer 5

• bind PAMPs of intracellular microbial components

ex. bacterial cell wall fragments

Question 6

RIG-1-like receptors (RLRs)

Answer 6

• recognize viral dsRNAs
• function as cytosolic PRRs
• trigger signalling pathways that activate IRFs and NF-kappa beta TFs

Question 7

IRFs

Answer 7

• interferon regulatory factors
• lead to increased expression of interferons (IFN-alpha and IFN-beta)
• potent antiviral cytokines

Question 8

dsRNA

Answer 8

-only with viruses

Question 9

PRR signalling pathways

Answer 9

-activate expression of a large variety of genes
>antimicrobial peptides
>type 1 interferons
>cytokines
>chemokines
>enzymes (iNOS an COX2)

Question 10

COX2

Answer 10

1. Arachidonate to prostaglandins: pain sensations

2. Promote inflammation

Question 11

Type 1 interferons

Answer 11

• IFN-alpha and IFN-beta
• potent antiviral effects
• inhibit viral replication, transcription and translation
• activate NK cells
• regulate macrophages and T-cells

Question 12

signalling through TNF receptors

Answer 12

• binding of TNF activates cytoplasmic death domain (DD)
• response depends on cell and its environment
  1. Cell survival and immune response
  2. Apoptosis: cut in a clean way (doesn’t lead to inflammation)

Question 13

innate immune response steps

Answer 13

1. Leukocytes in blood respond to chemical attractants released by pathogens and signals from nearby injuried cells
2. Leukocytes squeeze between cells of the capillary wall
3. Within damaged tissue, neutrophils release chemicals to break apart pathogens
   >monocytes differentiate into macrophages
   >phagocytosis
   >take some bacteria to a lymph cell to start an adaptive response

Question 14

phagocytosis

Answer 14

-engulfment and internalization of materials for their clearance and destruction
-microbes are recognized by receptors on phagocytes
>may recognize soluble opsonin protein bound to microbes

Question 15

phagocytes

Answer 15

• macrophages, neutrophils, dendritic cells
• may recognize PAMPs directly through PRR binding
• may be induced indirectly through opsonization

Question 16

opsonins

Answer 16

• soluble pattern recognition proteins
• mannose binding lectin (MBL)
• complement proteins
• C-reactive protein
• Antibodies

Question 17

opsonization

Answer 17

• ‘to make tasty’

- the process of chemical modification that enhance binding to a phagocytoic cell=enhances phagocytosis

Question 18

phagosomes

Answer 18

-fuse with lysosomes or granules

Question 19

destruction occurs through

Answer 19

• enzyme degradation
• antimicrobial proteins
• toxic effects of ROS and RNS

Question 20

respiratory burst

Answer 20

-intracellular killing
-bleach fireball
-ROS lead to cell death
>neutrophils sometimes commit suicide for the greater good

Question 21

cell death induced by receptor activated signal pathways

Answer 21

• apoptosis
• NETs
• pyroptosis

Question 22

apoptosis

Answer 22

• cell death induced by TNF binding to TNFR, NK cells and T cytotoxic cells
• clean, tidy, controlled

Question 23

NETs

Answer 23

• neutrophil extracellular traps

- activation requires NADPH oxidase and generation of ROS

Question 24

pyroptosis

Answer 24

• induced by inflammasome activation eliminates infected macrophages allowing release of IL-1beta and IL-18
• messy

Question 25

IL-1beta and IL-18

Answer 25

- made in cytosol, not in a vesicle - need to be cleaved to be activated - then cells commit suicide to release them

Question 26

apoptosis steps

Answer 26

1. Cell shrinks, chromatin condenses 2. Membrane starts blebbing, organelles disintegrate 3. Nucleus and organelles collapse, membrane continues to bleb 4. Apoptotic bodies form 5. Macrophages phagocytose apoptotic bodies * no inflammation

Question 27

NETs steps

Answer 27

1. Signals from PRR activate neutrophils 2. Phagosome NADPH oxidase (PHOX) is induced and intracellular membrane begin to break down 3. Granule enzymes neutrophils elastase (NE) and myeloperoxidase (MPPO) enter the nucleus and modify histones >chromatin decondenses 4. PM ruptures and cytoplasm and nucleoplasm are expelled forming NETs 5. Cells die form NEToses

Question 28

inflammasome formation

Answer 28

- may be due to signalling of TLR, NOD-like receptor and others - allows cleavage of procaspase 1 to caspase-1

Question 29

caspase-1

Answer 29

-cleaves pro-IL-1beta and pro-IL-18 into IL-1beta and IIL-18 | >may lead to cell death to release them (pyropotosis)

Question 30

IL-1beta

Answer 30

-potent inflammatory cytokine (and IL-18)

Question 31

proinflammatory cytokines and chemokines triggered by

Answer 31

-innate responses to infection, damage or harmful substances

Question 32

early components of inflammation include

Answer 32

- increase vascular permeability | - recuritment of neutrophils and other leukocytes from the blood to the side of damage/infection

Question 33

5 inflammatory signs

Answer 33

1. Heat: vasodilation, increased blood flow 2. Redness: increased blood flow 3. Swelling: plasma through gaps 4. Pain: pressure on nocireceptors 5. Loss of function

Question 34

inflammatory response steps

Answer 34

1. Tissue damage - release chemoattracts and vasoactive factors - these trigger a local increase in blood flow and capillary permeability 2. Influx of fluid and cells 3. Neutrophils and other phagocytes migrate to site of inflammation 4. Phagocytes and antibacterial substances destroy bacteria

Question 35

later stages of inflammation

Answer 35

- acute phase responses (APRs) - induced by acute inflammaoty triad - incrased synthesis/secretion of antimicrobial proteins by liver

Question 36

antimicrobial liver proteins examples

Answer 36

- MBL: mannose binding lectin - CRP: C-reactive protein - complement components * activate other processes that help eliminate pathogens

Question 37

acute inflammatory triad

Answer 37

1. IL-1 2. TNF-alpha 3. IL-6

Question 38

innate lymphoid cells (ILC)

Answer 38

- derived from common lymphoid progenitor cells | - include NK cells and 6 other ILC populations

Question 39

NK cells found in

Answer 39

-lymphoid tissue and recirculate

Question 40

other ILC found

Answer 40

-in epithelium

Question 41

ILC group based on

Answer 41

-cytokines produced

Question 42

ILCs lack PRRs

Answer 42

-are not activated directly by pathogens

Question 43

NK cells

Answer 43

- lymphocytes with innate immune functions - express a limited set of receptors for self-proteins - activated and perform 1 of 2 functions

Question 44

NK receptors induced by

Answer 44

- infections - malignant transformations (ex. cancer) - other stresses

Question 45

activated NK cell functions

Answer 45

1. Kill altered self-cell by releaseing perforin and gronzymes inducing apoptosis 2. Produce cytokines that induce adaptive responses against the altered self-cell