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

MyD88 UbC13

Bacteria

MALP2

FlagellinYeast

ZymosanBacteriaLBP

CD14

SIGIRR ST2

MyD88s

TRIF

TRAF6

MyD88MyD88

MyD88

TRAF6

TRAF6

TRAF6

MyD88s

Triad3

UEV1AECSIT

IRAKM ToIIIP

IRF8

C-Jun

CREB

TANK

Myco-Bacterial

19KDa Protein UropathogenicBacteria

DNACpG

ENDOSOME

NUCLEUS

SLAM,CD80,CD83

TNF,COX2,IL-18

IFN-ResponsiveGenes

IRF7

IRF7

IRF8

IFN-b

IRF3

MyD88

IFN-a

NF-kBPathway

TLR4

TLR4

TLR1

TLR2

TLR2

TLR6

TLR5

TLR10

TLR11

TLR12

TLR13

TL

R3

TLR7

TLR8

T L R 9

ViraldSRNA

MyD88TRAM

PGNBLP

IkB

ATF2

LBP

CD14

RacRacTIRAP

IkB

LPS

PI3KPI3KRIP2

RIP2

IRAK4

IRAK1 IRAK2

MKK7

MEKK3

TAK1TAB2

MKK6

p38

JNK

IKKsMKK3

BTK

IKKs

IKKeRIP

RIP3TBK1 IRAK

MyD88TIRAPBTK

LTA

LAM

NF-kB

NF-kB

NF-kB

NF-kB

TIRAP

LPS

Toll-Like Receptors

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iNOS Signaling

P

P

P P

TLR

4

CD14

LBP

NF-kB

NF-kB

STAT1aSTAT1a

NO

IRF1AP-1

HMGI/g

IRF1

MyD88

TRAF6

IkBs

IRAKTAB1

p38

CalmCalm

IKK

Hu R

iNOS iNOS

iNOS

SoxR

S

Oxy

R F U R

GSH

SODAHP Catalase

L-Citrulline

NADPH+O2Viral

Protease

ViralPolyprotein

L-Arginine+O2

Destabilization

iNOS mRNA

IFNg

IFNR1

IFNR2

Viral RNA

Virus(Herpesvirus,Picornaviruses,

Flavivirusesand Coronaviruses)

H2 O

2

ONOO-

O2-

Bacterial DNA

RibonucleotideReductase

DSBs

Bacteria (eg: E. coli

Salmonella, Mycobacterium,

Helicobacter, etc)

Macrophag

e

JAKIkBs

DegradationSTAT1aSTAT1a

NADPHOxidase

LPS

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