Transcript Lecture 21

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
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.
WBCs are formed by
differentiation of
stem cells produced
in the bone marrow.
Figure 23.12
Figure 23.11
monocyte
PMN
lymphocyte
Figure 23.13
Figure 23.14
Lymphoid Organs
• Primary lymphoid organs
•
- Where lymphocytes
mature
•
- e.g.: Thymus
• Secondary lymphoid organs
•
- Where lymphocytes
encounter antigens
•
- e.g.: Spleen and lymph
nodes
Figure 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
Figure 23.22
Figure 23.23
Figure 23.24
The Acute Inflammatory Response
• Animation: The basic inflammatory response
Click box to launch animation
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
Phagocytosis
• Animation: Phagocytosis
Click box to launch animation
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
Figure 23.28
When an NK cell encounters a cell lacking these
markers, it secretes perforins protein into the
target cell.
- Creates membrane pores to lyse cell
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
Toll-Like Receptors
LBP
LAM
LPS
Bacteria
LBP
Viral
dSRNA
LTA
LPS
Yeast
Bacteria
PGN
BLP
MycoBacterial
19KDa Protein
MD2
T T
L L
R R
4 4
CD14
TRAM
SIGIRR
T
L
R
1
ST2
Uropathogenic
Bacteria
T
L
R
2
T
L
R
2
CD14
TRIF
k
NF- B
Pathway
k
T
L
R
6
T
L
R
5
TIRAP
Rac
PI3K
TIRAP
PI3K Rac
RIP2
TIRAP
BTK
DNA
CpG
MALP2
IRF8
NF- B
IRAKM
IRAK4
TRAF6
UEV1A
Triad3
IKKs
MKK6
MKK3
TAB2
TAB1
TAK1
MKK7
MEKK3
IKKs
I B
k
IRF7
TRIF
NF- B
RIP3
TBK1
TRAF6
BTK
e
k
IFN-
IRF3
2009
ProteinLounge.com
aIRF7
IFN-b
TANK
IKK
p38
I B
IRAK
TRAF6
RIP
C
IRAK2
ECSIT
ENDOSOME
k
IRAK1
TRAF6
k
NF- B
k
NF- B
JNK
CREB
SLAM,CD80,
CD83
IRF8
TNF,COX2,
IL-18
C-Jun
IFN-Responsive
Genes
ATF2
iNOS Signaling
2009
ProteinLounge.com
C
LPS
LBP
Ribonucleotide
Reductase
SOD
GSH
ONOO-
O2NF-kB
IkBs
Degradation
NADPH
Oxidase
P
NO
P
Viral
Protease
IRF1
P
P
NF-kB
IRF1
HMGI/g
Hu
R
Calm
AP-1
Virus(Herpesvirus,
Picornaviruses,
Flaviviruses
and Coronaviruses)
Calm
iNOS
iNOS
Viral
Polyprotein
iNOS mRNA
L-Arginine+O2
Destabilization
iNOS
Viral RNA