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.

Figure 23.11WBCs are formed by

differentiation of stem cells produced in the bone marrow.

Figure 23.12

PMN

monocyte

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 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

Figure 23.22

Figure 23.23

Figure 23.24

• 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

• Animation: Phagocytosis

Click box to launch animation

Phagocytosis

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

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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

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C