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Figure 23.1. Figure 23.3. Human Microbiota – Respiratory Tract. The lungs and trachea are usually sterile. The ciliated mucous lining of the trachea, bronchi, and bronchioles makes up the mucociliary escalator . - Sweeps foreign particles up and out of the lung. Figure 23.5. - PowerPoint PPT Presentation
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Human Microbiota – Respiratory Tract• The lungs and trachea are usually sterile.• The ciliated mucous lining of the trachea, bronchi,
and bronchioles makes up the mucociliary escalator.• - Sweeps foreign particles up and out of the
lung
Figure 23.5
Human Microbiota – Stomach• Stomach has very high acidity.• - Few microbes survive.• - Helicobacter pylori• - Survives at pH 1• - Burrows into protective
mucus• - Causes gastric ulcers Figure 23.6
Decreased stomach acidity = Hypochlorydia
- Caused by malnourishment
- Vibrio cholerae survives stomach passage.
- Establishes infection in less acidic intestine
Overview of the Immune System• Nonadaptive (innate) immunity• - Barriers to infection• - Nonspecific responses to destroy invading cells• - Present at birth
• Adaptive immunity• - Reaction to specific antigens• - Parts of foreign proteins, sugars, chemicals• - Body reacts to antigens when exposed.• - Retains “memory” of those antigens• - Faster response if exposed a second time
Cells of the Immune System• Blood is composed of red
blood cells, white blood cells, and platelets.
Figure 23.11WBCs are formed by
differentiation of stem cells produced in the bone marrow.
Figure 23.12
Lymphoid Organs• Primary lymphoid organs• - Where lymphocytes
mature• - e.g.: Thymus
• Secondary lymphoid organs• - Where lymphocytes
encounter antigens• - e.g.: Spleen and
lymph nodesFigure 23.16
• The gastrointestinal system possesses an innate system called gut-associated lymphoid tissue (GALT).
• - Includes tonsils and Peyer’s patches
• - Specialized M cells take up microbes from the intestine and release on the other side for macrophages.
Figure 23.17
• Animation: The basic inflammatory response
Click box to launch animation
The Acute Inflammatory Response
Phagocytosis• Phagocytes must avoid attacking host cells.• - Host cell glycoprotein CD47 prevents attack.• Phagocytes is enhanced by opsonization.• - Microbial cells are coated with antibodies.
Figure 23.27
Natural Killer Cells• Destroy infected and
cancerous host cells• Healthy cells make surface
MHC class I antigens.• - Cancerous and
infected cells stop making MHC I
When an NK cell encounters a cell lacking these markers, it secretes perforins protein into the target cell.
- Creates membrane pores to lyse cell
Figure 23.28
Toll-Like Receptors• Microbes possess unique structures that immediately
tag them as foreign.• - These pathogen-associated molecular
patterns (PAMPs) are recognized by Toll-like receptors present on various host cell types.
• Once bound to their ligands, the TLRs trigger an intracellular regulatory cascade.
• - Cause host cell to release proteins called cytokines
• - Bind to various immune cells, and direct them to engage the invader
TAB1
MD2
TRIFMyD88
MyD
88 UbC13
Bacteria
MALP2
Flagellin
YeastZymosanBacteria
LBPLBP
CD14
SIGIRR ST2ST2
MyD88s
TRIF
TRAF6
MyD88MyD88
MyD88
TRAF6
TRAF6
TRAF6
MyD88sMyD88s
Triad3
UEV1A
ECSITECSIT
IRAKM ToIIIP
IRF8
C-Jun
CREB
TANK
Myco-Bacterial
19KDa ProteinUropathogenic
Bacteria
DNACpG
ENDOSOMEENDOSOME
NUCLEUS
NUCLEUS
SLAM,CD80,CD83
SLAM,CD80,CD83
TNF,COX2,IL-18
TNF,COX2,IL-18
IFN-ResponsiveGenes
IFN-ResponsiveGenes
IRF7
IRF7
IRF8
IFN-bIFN-b
IRF3
MyD88
IFN-aIFN-a
NF-kBPathwayNF-kBPathway
TLR4
TLR4
TLR4
TLR4
TLR1
TLR1
TLR2
TLR2
TLR2
TLR2
TLR6
TLR6
TLR5
TLR5
TLR10
TLR10
TLR11
TLR11
TLR12
TLR12
TLR13
TLR13
TL
R3
TL
R3
TLR7
TLR7
TLR8
TLR8
T L R 9T L R 9
ViraldSRNA
MyD88
TRAM
PGNPGNBLPBLP
IkB
ATF2ATF2
LBPLBP
CD14CD14
RacRacTIRAPTIRAP
IkB
LPS
PI3KPI3KRIP2
RIP2
IRAK4
IRAK1 IRAK2
MKK7
MEKK3
TAK1TAB2
MKK6
p38
JNKJNK
IKKsIKKsMKK3
BTK
IKKs
IKKeRIP
RIP3TBK1
IRAK
MyD88TIRAPTIRAPBTK
LTALTA
LAMLAM
NF-kB
NF-kB
NF-kB
NF-kB
TIRAPTIRAP
LPS
Toll-Like Receptors
2009ProteinLounge.com 2009ProteinLounge.com
C
iNOS Signaling
P
P
P P
TLR
4
CD
14
LBP
NF-kB
NF-kB
STAT1aSTAT1a
NO
IRF1AP-1
HMGI/g
IRF1
MyD88
TRAF6
IkBs
IRAKTAB1
p38
CalmCalm
IKK
Hu R
iNOS iNOS
iNOS
So
xRS
Oxy
R F U R
GSH
SODAHP Catalase
L-Citrulline
L-Citrulline
NADPH+O2
NADPH+O2Viral
ProteaseViral
Protease
ViralPolyprotein
ViralPolyprotein
L-Arginine+O2L-Arginine+O2
DestabilizationDestabilization
iNOS mRNAiNOS mRNA
IFNg
IFNR1
IFNR2
IFNR1
IFNR2
Viral RNAViral RNA
Virus(Herpesvirus,Picornaviruses,
Flavivirusesand Coronaviruses)
Virus(Herpesvirus,Picornaviruses,
Flavivirusesand Coronaviruses)
H2 O
2
H2 O
2
ONOO-ONOO-
O2-O2-
Bacterial DNA
Bacterial DNA
RibonucleotideReductase
RibonucleotideReductase
DS
Bs
DS
Bs
Bacteria (eg: E. coli
Salmonella, Mycobacterium,
Helicobacter, etc)
Bacteria (eg: E. coli
Salmonella, Mycobacterium,
Helicobacter, etc)
Macrophag
eM
acrophag
e
JAKIkBs
DegradationIkBs
Degradation
STAT1a
STAT1a
NADPHOxidase
LPS
2009ProteinLounge.com 2009ProteinLounge.com
C