BIOL 315: Introduction

to Immunology
F2019 Lecture Slides
10/17/2019

Gerald L. Buldak, Ph.D.

Loyola University Chicago
©2019, Gerald L. Buldak, Ph.D.
NETs: Neutrophil Extracellular Traps 2
 What Happens Post-Phagocytosis?
Type of Response Specific Products

Free O2 radicals – “Oxidative Burst” Superoxide (O2-), H2O2, hydroxyl radical

(·OH), hypochlorous ion (OCl-)

Acidification pH ≈ 3.5 – 4.0

Toxic nitrogen NO (nitric oxide)

Antimicrobial peptides Defensins etc.

Enzymes Lysozyme, acid hydrolases

Competitors Lactoferrin (sequesters Fe) and vitamin B12-

binding protein
©2019, Gerald L. Buldak, Ph.D. 3
SIGNALING
“Help!”

©2019, Gerald L. Buldak, Ph.D. 4

This Photo by Unknown Author is licensed under CC BY-ND

SQUIRREL!!!

This Photo by
Unknown Author
is licensed under
CC BY-NC-ND
©2019, Gerald L. Buldak, Ph.D. 5
 ENDOSOMES

CYTOPLASM

©2019, Gerald L. Buldak, Ph.D. 6

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“Das ist ja toll!”
“That’s amazing/weird!”
-Christiane Nüsslein-Volhard (1985)

Drosophila melanogaster fly (Toll-/-) that succumbed to Neurospora crassa

infection.

Leulier & Lemaitre (2008) Toll-like receptors: taking an evolutionary approach.

Nature Reviews Genetics 9: 165-178.
©2019, Gerald L. Buldak, Ph.D. 8
 EC

N
EXTRACELLULAR
PLASMA
MEMBRANE
CYTOPLASM

TM

CYTOPLASM
Cp ENDOSOME

INTERIOR
C

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TLR1:TLR2 recognizes triacyl lipopeptides
TLR2:TLR6 recognizes diacyl lipopeptides
TLR11: Murine only; recognizes ©2019,
intactGerald
peptides
L. Buldak, Ph.D. 10
Pioneers

Ruslan Medzhitov, Ph.D. Charles Janeway, MD

Yale University, HHMI Yale University, HHMI

©2019, Gerald L. Buldak, Ph.D. 11

 EC
N Ag-binding

LRR
TM

C TIR Toll-Interleukin-1 Receptor

“Accessory proteins”

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 triacyl
lipopeptides

diacyl
lipopeptides
flagellin
TLR1
TLR2 Nucleus

CpG DNA
TLR6 LPS

ssRNA
dsRNA
TLR4
TLR5

TLR3
TLR7
TLR9
Endosome

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 TRAF: TNF receptor-associated
factor
MyD88: Myeloid differentiation
primary response gene 88
IRAK: IL-1R-Associated Kinase
TAK: TGF-β-Associated Kinase
NEMO: NF-κB Essential Modifier
IKK: IκB Kinase

IκB
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 • Heterodimeric TF
• p50/p52 (NF-κB1/2)
• Rel (c-Rel, Rel-A, Rel-B)
• Maintained in inactive state by the
Inhibitor of NF-κB (IκB)
• IκB inactivated via phosphorylation by
one or more forms of IκB kinase (IKK)
• IκB-P
P
• Releases NF-κB to cytoplasm
• NF-κB translocates to nucleus
• IκB-P polyubiquitinated and degraded

©2019, Gerald L. Buldak, Ph.D. 17

 TRIF: Toll receptor-associated
activator of Interferon
TRAM: Toll receptor-associated
molecule
TRAF: TNF receptor-associated
factor
IRAK: IL-1R-Associated Kinase

TRAF3

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 TRAF: TNF receptor-associated
factor
MyD88: Myeloid differentiation
primary response gene 88
IRAK: IL-1R-Associated Kinase
IRF: Interferon Response Factor

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 Joost Oppenheim, MD
NIH Center for Cancer Research

https://ccr.cancer.gov/Cancer-and-Inflammation-Program/joost-j-oppenheim
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TNF-α
IL-6
IL-1β
IL-12

CXCL8

BACTERIUM

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Do something! Go somewhere!

Neutrophils

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 AUTOCRINE
IFN-α/IFN-β (“Type I IFNs”)

PARACRINE

“Anti-viral”
Activate Mφ ↑MHC-I AND MHC-II ΔTF expression (STAT-1 & STAT-2)
Activate DCs ↑B7.1/B7.2 (CD80/CD86)
↑CD40
↑MHC-I expression
Activate NK cells (→IFN-γ)
Recruit LCs via chemokines
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 Endothelium
Epithelium

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