Lecture #2 Innate Immunity

Question 1

4 Functions of a Complement

Answer 1

1. Lysis via MAC
2. Opsonization and phagocytosis via C3B
3. Vasodilation
4. Solubilization and clearance of immunocomplexes

Question 2

Anti Viral Innate Immun Repsonse is Mediated by:

Answer 2

Type I Interferons (A/B IFN): block viral replication within host cell
Natural Killer Cells

Question 3

PAMPS

Answer 3

Pathogen Associated Molecular Patterns

Question 4

PRRs

Answer 4

Pattern Recognition Receptors

Question 5

General Properties of PRRs

Answer 5

Germ line encoded
Non local: identical Rcs on all cells of the same lineage
Discriminate between self and non self

Question 6

Extracellular TLRs

Answer 6

TLR -1, -2, -4, -5, -6

Question 7

Intracellular TLRs

Answer 7

TLR -3, 7, 8, 9

Question 8

TLRs that use MyD88

Answer 8

1, 2, 5, 6, 7, 8, 9

4 uses both MyD88 and TRIF

Question 9

TLRs that use TRIF

Answer 9

TLR3 (only uses TRIF) TLR4 (uses MyD88 too)

Question 10

Cells which TLRs are expressed on

Answer 10

Immune Cells, including monocytes, neutrophils, macrophages and DCs

Question 11

TLR dependent signaling activates:

Answer 11

NF-kB and IRF which lead to transcription of pro-inflammatory genes

Question 12

Necrosis leads to:

Answer 12

Lysis of cell and release of DAMPS (Damage associated molecular patterns)

Question 13

Examples of DAMPs

Answer 13

HMGB1, Uric Acid, HSPs (all lead to activation of NF-kB)

Question 14

Receptor for HMGB1

Answer 14

RAGE (receptor of advanced glycation end products)

Question 15

NOD-Like Receptors

Answer 15

NLRs act as scaffolding proteins that assemble signaling platforms that trigger NF-kB and MAPK pathways.

Control activation of caspases

Respond to DAMPS/PAMPS to form inflammasome

Question 16

Inflammasome Function

Answer 16

Activate caspase 1

Question 17

Caspase 1

Answer 17

Cleaves cytokines IL-1B and IL-18 which drive inflammation

Question 18

Three types of Scavenger Receptors:

Answer 18

SR Class A Type I

SR Class A Type II

MARCO (Macrophage Receptor with Collagenous Structure)

Question 19

3 distinct extracellular structural domains of scavenger receptors

Answer 19

1. SR cysteine-rich (SRCR) domain (absent in SR-A II)
   - recognize gram negative
2. Collagen like domain
3. The a-helical coiled coil domain (absent in MARCO)

Question 20

Functions of SRs

Answer 20

Mediate uptake of oxidized lipoproteins

SR A and CD 36 expressed on macrophages

Bind based on negative charges (bacterial LPS, lipoteichoic acid, nucleic acids, B-glucan, proteins)

Question 21

CD36

Answer 21

On Macrophage

Also coreceptor in TLR2/6 Recognition and response to bacterially derived lipoteichoic acid and diacylated lipopeptides

Question 22

Lectin Receptors

Answer 22

Have conserved carb recognition domain for mannose, N-acetylglucosamine, B-glucans

Both soluble and integral membrane proteins on macrophages and DCs

Trigger cytokine secretion

Question 23

Mannose Receptor Recognize:

Answer 23

Terminal D-mannose, L-fucose, and N-acetyl -D-glucosamine sugars

Phagocytosis of microbes

Question 24

Soluble mannose-binding lectin (MBL)

Answer 24

Also called mannan binding protein (MBP)

Involved in complement activation via lectin pathway

Question 25

Defensins

Answer 25

Small cationic peptides Cationic and hydrophobic regions Produced by epithelial cells, neutrophils, NK cells and CTLs Toxicity to microbes via disruption of there membranes Regulate activation of immune cells in the inflammatory response

Question 26

Cathe’licidins

Answer 26

Antimicrobial peptides produce by neutrophils and epithelial cells in skin, GI and respiratory tract Synth stimulated by cytokines/microbes Directly toxicity and act of leuks. Bind and neutralize LPS Anti inflammatory by blocking inflammasome activation

Question 27

-fMet

Answer 27

Present in prok, not euk Phagocytes use to distinguish self from non self.

Question 28

Origin of mDCs vs. classical DCs/pDCs/Langerhan Cells

Answer 28

Monocytes vs. directly form stem cells

Question 29

How do DCs acquire Ags

Answer 29

Receptor mediate endocytosis and pinocytosis

Question 30

Classical DC’s

Answer 30

I.e. Langerhans In skin mucosa, organ parenchyma Upon activation, migrate to LNs, display Ag to T-lymphocytes

Question 31

Plasmacytoid DCs

Answer 31

Respond to viral infection Recognize nucleic acids, produce soluble IFNs aka IFN a/b which have antiviral activities

Question 32

Explain Mast Cell activation

Answer 32

Activated by cross linking IgE Receptor which releases histamine, serotonin, tryptase, chymase, PGD2 and LTB4.

Question 33

Cell that takes part in both Innate and Adaptive immunity

Answer 33

NK Cells, generated from lymphoid progenitor but function as innate immune cells.

Question 34

Activation and Kiling Mechanism of NK Cell

Answer 34

Activating Rc of NKs (KIRs) recognize ligands, activate PTKs Inhibitory Rcs recognize MHC I and activate PTP = inhibits (don’t kill healthy cells) Viruses inhibit the MHC I complex, NKs see reduced signal as unhealthy and destroy

Question 35

How NK Cells Kill Infected Cells

Answer 35

Release perforins (hole in membrane) Release granzymes (enter perforin hole, activate apoptosis) Release IFN-y (Type II IFN), stimulate phagocytosis via macrophages

Question 36

How are RBCs not destroyed by NK cells if they do not express MHC I?

Answer 36

They express cd47 which serves as a ligand for the inhibitory receptor instead.

Question 37

Acute Phase Proteins (APP)

Answer 37

Systemic inflammation Produced by hepatocytes via cytokines (mainly IL-6) but TNF and IL-1 too Bind some PAMPs and activate inflammation

Question 38

APP Protein Examples:

Answer 38

CRP Mannose Binding Protein A1-acid glycoproteins Serum amyloid P component

Question 39

Two Anti Inflammatory Cytokines

Answer 39

IL-10 and TGF-B