Innate Immune System

Question 1

Functions of Innate IS:

Answer 1

1. Complement Activation
2. Inflammation
3. Cell Activation
   
   • -cytokine & chemokine production
   • -phagocytosis
4. Priming of adaptive immune response

Question 2

Defensins and Cathelicidins functions/MOA

Answer 2

Antimicrobial peptides. (short) Associated with physical barriers. Expressed in epithelial cells

MOA: membrane destruction by integrating into microbial membrane, aggregating, and poking holes in membrane

• chemokine role to bring in other IS cells to infection site.
• slows down pathogen

Question 3

Defensins

2 classes:
Alpha–
Beta–

Answer 3

Beta stand peptides connected by disulfide bonds

Alpha: in granules of PMNs and Paneth cells
Beta: secreted by mucosal surface epithelia

Question 4

Cathelicidins

Answer 4

Alpha helical peptides

Question 5

Defensins: Alpha

• -Human neutrophil peptide (HNP):
• -Human Definsins (HD):

Answer 5

–Human neutrophil peptide (HNP) 1-4 :
PMNs, monocytes, and lymphocytes

–Human Definsins (HD) 5-6: paneth cells of s. intestines

Question 6

Defensins: Beta

–Human beta defensing (HBD):

Answer 6

epithelial tissues mostly

sometimes: monocytes, macrophages, and dendritic cells.

Question 7

HSC–> Myeloid progenitor cells

Answer 7

GM-CSF

IL-3

Question 8

Myeloid Pro–> basophil, eosinophil pro, granulocyte-macropahge pro?

Answer 8

GM-CSF

IL-3

Question 9

Basophil pro –> basophil

Answer 9

GM-CSF
IL-3
IL-4

Question 10

Eosinophil pro–> eosinophil

Answer 10

GM-CSF
IL-3
IL-5

Question 11

granulocyte-macropahge pro –> Neutrophil

Answer 11

GM-CSF
IL-3
G-CSF

Question 12

granulocyte-macropahge pro –> monocyte

Answer 12

GM-CSF
IL-3
M-CSF

Question 13

Monocyte–> Dendritic cell

Answer 13

GM-CSF

IL-4

Question 14

Monocyte –> Macrophage

Answer 14

GM-CSF

M-CSF

Question 15

Monocyte –> Neutrophil

Answer 15

IL-8

Question 16

Congenital neutropenia

Answer 16

• Lack of GM-CSF–so you can’t produce any cells downstream of myeloid precursor
• Frequent bacterial infections

Question 17

Name the cells that form the bridge between innate and adaptive immunity.

Answer 17

APCs!

Question 18

TLR1+

TLR2

Answer 18

PAMPS Recognized:

• –Triacylated lipoproteins (PAM3CSK4)
• –Peptidoglycans
• –Lipopolysaccharides

Production: AP-1 & NF-kB Inflammatory Cytokines (IC)

Question 19

TLR2+

TLR6

Answer 19

PAMPS Recognized: Diacylated lipoproteins (FSL-1)

Production: AP-1 & NF-kB –>IC

Question 20

TLR3

Answer 20

PAMPS Recognized:

• dsRNA (poly I:C)
• tRNA
• siRNA

Production: IC & IFN-beta

Question 21

TLR4

Answer 21

PAMPS Recognized:

• -Lipopolysaccharides (LPS)
• -Paclitaxel

Production: IC & IFN-Beta

Question 22

TLR5

Answer 22

PAMPS Recognized: Flagellin

Production: IC

Question 23

TLR7

Answer 23

PAMPS Recognized:

• -ssRNA
• -Imidazoquinolines (R8
• -Guanosine analogs

Production: IC & IFN-alpha

Question 24

TLR8

Answer 24

PAMPS Recognized:

• -ssRNA
• -Imidazoquinolines

Production: IC & IFN-alpha

Question 25

TLR9

Answer 25

PAMPS Recognized: - -CpG DNA - -CPG ODNs Production: IC & IFN-alpha

Question 26

TLR10

Answer 26

PAMPS Recognized: Profilin-like proteins Production: IC

Question 27

TRLs that produce both IC and Type1 IFN?

Answer 27

3, 4, 7-9 Beta: 3-4 Alpha: 7-9

Question 28

"Mother of all immune system transcription factors"?

Answer 28

NF-kappaB

Question 29

Stimulation of TLRs initiates cascades that lead to activation of...

Answer 29

AP-1 NF-kappaB Interferon regulatory factors --IRFs 3 and 7

Question 30

Proinflammatory cytokines?

Answer 30

TNF-alpha IL-6 IL-12

Question 31

Pro-inflammatory cytokines?

Answer 31

TNF-alpha IL-6 IL-12

Question 32

Activation of NF-kappaB:

Answer 32

1. Expression of pro-inflammatory genes (TNF alpha) 2. Increased phagocytosis 3. Increased efficiency of antigen presentation

Question 33

C5b

Answer 33

byproduct of complement activation and opsonization | -acts as focal point for deposition of membrane attack complex

Question 34

Hallmarks of inflammation

Answer 34

1. Influx of fluid (edema) 2. Increased temp (hyperthermia) 3. Decreased oxygenation 4. Influx of WBCs

Question 35

Triggers of inflammation:

Answer 35

- Complements C5a stimulation of basophils and mast cell degranulation - Macrophages - NK cells

Question 36

Changes in acute inflammation:

Answer 36

1. increased blood supply to affected area 2. Increase capillary permeability 3. Increase in leukocyte migration into affected tissue.

Question 37

Pro-inflammatory cytokines?

Answer 37

TNF-alpha: produced by macs IL-1 IFN-gamma

Question 38

Cells of acute vs chronic inflammation

Answer 38

Acute: Neutrophils and activated helper T cells Chronic: macrophages, cytotoxic T cells, and B cells.

Question 39

granulocyte-macropahge pro --> Neutrophil

Answer 39

GM-CSF IL-3 G-CSF

Question 40

PMNs

Answer 40

- Granules - First responders (phagocytic) - Have FcR to bind antibodies GM-CSF IL-3 G-CSF

Question 41

Eosinophils

Answer 41

-bilobed nucleus -phagocytic -Granules contain Major Basic Protein MBP is toxic to HELMINTHS GM-CSF, IL3, IL5

Question 42

Basophils

Answer 42

- Multilobed nucleus - Express FcR1 receptors for IgE so IgE is always on their surface - release histamine-->allergic response - activated by complement C5a and C3a GM-CSF, IL3, IL4

Question 43

Monocytes:

Answer 43

Form macrophages Horseshoe shaped nucleus long lived

Question 44

Macrophages

Answer 44

Major producer of cytokines Highly activated by IFNs APC

Question 45

Dendritic Cells | Classical vs Follicular

Answer 45

Classical: process and present foreign protein antigens to T cells Follicular: form immune complexes to B cells in LYMPHOID FOLLICLES

Question 46

Dendritic Cells | Classical vs Follicular

Answer 46

Classical: process and present foreign protein antigens to T cells Follicular: form immune complexes to B cells in LYMPHOID FOLLICLES *Take naive T cells and activate them

Question 47

DC1 Location? Produces?

Answer 47

From myeloid precursor Location? Diffuse Produces: IL-8

Question 48

DC2 Location? Produces?

Answer 48

Lymphoid precursor Location? restricted to T cell areas of secondary lymphoid organs and tissues Produces? mainly type I interferons

Question 49

NK Cells

Answer 49

Innate immunity - IFNs ramp up granule production in NKs - Look for missing MHC I molecules on cell surfaces Lymphoid progenitor cell --> NK IL-3 SCF and IL-2

Question 50

Chronic Granulomatous Disease

Answer 50

- Inability to produce hydrogen peroxide and hypochlorous acid - Inability to kill phagocytosed bacteria

Question 51

Leukocyte Adhesion Deficiency (LAD)

Answer 51

- Lack of INTEGRIN subunit, the common beta chain - Inability to RECRUIT innate immune cells to site of inflammation - Increased susceptibility to bacterial, fungal, and viral infections

Question 52

Complement Defects

Answer 52

Increased susceptibility to bacterial infections -Reduced ability to remove immunocomplexes

Question 53

Chediak-Higashi Syndrome

Answer 53

Defect in gene LYST (CHS1), a lysosomal trafficking gene that affects lysosomes and meanosomes -Increased susceptibility for bacterial infections.