Chapter 3      Innate Immunity
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Chapter 3 Innate Immunity. Macrophage interacting with Bacteria. Oct 3, 5 & 12, 2006. 你需要學習的問題 : 有哪些分子及細胞參與先天性免疫反應 (innate immunity) ? 它們的特性是什麼? 什麼叫做「模式辨認受體」 (pattern recognition receptor , PRR) ? 什麼叫做「發炎反應」 (inflammatory response) ? 什麼叫做 Toll-like receptors ? 有何功能?

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Chapter 3 Innate Immunity

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Chapter 3 innate immunity

Chapter 3 Innate Immunity

Macrophage interacting with Bacteria

Oct 3, 5 & 12, 2006

Chapter 3 innate immunity

  • 你需要學習的問題:

  • 有哪些分子及細胞參與先天性免疫反應 (innate immunity)? 它們的特性是什麼?

  • 什麼叫做「模式辨認受體」 (pattern recognition receptor,PRR)?

  • 什麼叫做「發炎反應」 (inflammatory response)?

  • 什麼叫做 Toll-like receptors ? 有何功能?

  • 先天性免疫反應在演化上的意義。

Chapter 3 innate immunity

  • Innate immunity is themost ancient

  • defense against microbes.

  • Some forms of innate immunity has

  • been found in all multicellularplants

  • andanimals.

  • Adaptive immunity evolved injawed

  • vertebratesand is a much more recent

  • evolutionary invention than innate

  • immunity.

Chapter 3 innate immunity

Anatomical Barriers

Chapter 3 innate immunity

Skin and Epithelial Barriers to Infection

Chapter 3 innate immunity

  • How does the innate immune response initiate?

  • The host has “sensors” to detect the invader.

  • Soluble or membrane-bound molecules of

  • the host can precisely discriminate between

  • self (host) and nonself (pathogen).

  • These molecular sensors recognize broad

  • structural motifs(主結構) that are present in

  • microbes but are absent from the host.

Chapter 3 innate immunity

  • Pattern Recognition Receptors (PRR)

  • Because the molecular sensors recognize

  • particular patterns, such receptors of the host are

  • called pattern recognition receptors (PRR)

  • The patterns found on pathogens are called

  • pathogen-associated molecular patterns (PAMP)

  • PRRs : soluble: e.g., complement system

  • membrane-bound: Toll-like receptors (TLR)

  • - PAMPs : combinations of sugars, certain proteins,

  • particular lipid-bearing molecules, and

  • some nucleic acid motifs

Chapter 3 innate immunity


Chapter 3 innate immunity

Localized Inflammatory Response

described by the Romans almost 2000 years ago:





Loss of function

(2nd century by a Greek physician,

Galen 蓋倫, 129 -200 A.D.)

Chapter 3 innate immunity

Vasodilation increase in vascular diameter

rise of blood volume in the area

→ heats the tissue and causes it to redden

Edema increase of vascular permeability

leakage of fluid from the blood vessels

→ accumulation of fluid that swells the tissue

Extravasation adherence of leukocytes to endothelium

→ pass through capillaries and into the tissues

Phagocytosis leukocytes phagocytose invading pathogens

release molecular mediators

recruit and activate effector cells

Chapter 3 innate immunity







Chapter 3 innate immunity

Soluble mediators released by inflammatory cells:

1. Cytokines : hormone- or growth-factor-like proteins

that communicate via cell receptors to

induce specific cell activities, e.g.,

interleukin-1 (IL-1), IL-6 & tumor

necrosis factor α(TNF-α)

2. Chemokines : a subgroup of cytokines whose activity is

their capacity to act as chemoattractants

(agents that cause cells to move toward

higher concentrations of the agent)

Chapter 3 innate immunity

A major role of the cells attracted to the inflamed site

is phagocytosis of invading organisms :

Chapter 3 innate immunity

Leukocyte extravasation is essential for inflammation :

rolling → activation → arrest/adhesion → migration

Chapter 3 innate immunity

Interaction between Neutrophils and Endothelium

  • Cellular Adhesion Molecules (CAMs):

  • Mucin-like CAMs

  • Selectins

  • Integrins

  • Ig-superfamily CAMs

Chapter 3 innate immunity

Soluble Molecules

Chapter 3 innate immunity

Antimicrobial peptides are produced at the site of infection or injury and act locally


Chapter 3 innate immunity

Paneth cells provide host defense against microbes in the small intestines. They are functionally similar to neutrophils (also phagocytic and containing lysozymes). When exposed to bacterial antigens, Paneth cells secrete a number of antimicrobial molecules into the lumen of the crypt, thereby contributing to maintenance of the gastrointestinal barrier.


Chapter 3 innate immunity

Crypt 腺窩

Secretion of defensins by paneth cells within intestinal crypts serves as a primary barrier to bacterial infection

Chapter 3 innate immunity

Paneth cells

Chapter 3 innate immunity

Soluble Pattern Recognition Receptors

Acute phase response (APR) proteins:

- Complement

- C-reactive protein (CRP)

- Mannose-binding lectin (MBL)

Lipopolysaccharide-binding protein (LBP)

Nucleotide-binding oligomerization domain (NOD)

Chapter 3 innate immunity

Acute phase response (APR) proteins:

Complement system (Chapt 7)

C-reactive protein (CRP):

A pentameric protein, which binds phosphorylcholine, which is present on the surface of many microbes. CRP bound to a microbe promotes uptake by phagocytes and activates a complement-mediated attack on the microbe.

Mannose-binding lectin (MBL):

Recognizes mannose-containing molecular patterns found on microbes but not on vertebrate cells. MBL directs a complement attack on the microbes to which it binds.

Chapter 3 innate immunity

Lipopolysaccharide-binding protein (LBP) recognizes lipopolysaccharide (LPS), a component of the outer

cell wall of Gram negative (G -) bacteria.

of G (−) bacteria


Chapter 3 innate immunity

Nucleotide-binding oligomerization domain (NOD) proteins are cytosolic proteins which recognize degraded products of peptidoglycans of Gram positive (G +) bacteria.

Relative structure of gram negative (top) and gram positive (bottom) cell walls.

The major differences lie in the thickness of the rigid peptidoglycan layer and in the presence of an outer membrane. In gram negative cells, the peptidoglycan layer is very thin, being only a few molecules thick, whereas in gram positive cells this layer is very thick.

outer membrane


Chapter 3 innate immunity

gram-positive anthrax bacilli

Gram’s stain (with crystal violet)

of cerebrospinal fluid

Chapter 3 innate immunity

Effectors of Innate Immune Responses to Infection

Chapter 3 innate immunity

Membrane-associated Pattern Recognition Receptors

Chapter 3 innate immunity

Structure of a Toll-like Receptor (TLR)


highly conserved among all members of the TIR family


Chapter 3 innate immunity

(Myeloid differentiation

factor 88)

(IL-1R-associated kinase)

(TNFR-associated factor)

(TGF-activated kinase)

Chapter 3 innate immunity

Cell Types of Innate Immunity



Interferon 


Interleukin 1 (IL-1)

Interleukin 6 (IL-6)

Tumor necrosis Factor  (TNF)

Chapter 3 innate immunity


activated by phagocytosis

The O2 consumed by phagocytes to support ROS production by

the phox enzyme is provided by a metabolic process known as

the respiratory burst, during which O2 uptake by the cell increases severalfold.

Chapter 3 innate immunity

Generation of Nitric Oxide (NO)

in Phagocytes

L-arginine + O2 + NADPH → NO + L-citrulline + NADP

inducible nitric oxide synthetase (iNOS)

NO : accounts for much of the antimicrobial activity of

macrophages against bacteria, fungi, parasitic worms

and protozoa.

Chapter 3 innate immunity

Adaptive Immunity Has to be Initiated by Innate Immunity

Chapter 3 innate immunity

Ubiquity of Innate Immunity

Well-developed system of innate immunity in non-vertebrate phyla

Sea squirt : complement-like lectins

(海鞘) Toll-like receptors

Fruit fly : NFκB family pathway

antibacterial peptide diptericin

prophenoloxidase cascades

– deposition of melanin around invading organisms

Chapter 3 innate immunity

Tomato & other plants :

- generation of oxidative bursts

- raising of internal pH

- localized death of infected regions

- induction of chitinase – digest fungal wall

- induction of α-1,3 glucanase – digest bacterial walls

- antimicrobial peptides

- nonpeptide organic molecules, such as phytoalexins,

that have antibiotic activity

- isolate cells in the infected area by strengthening the

walls of surrounding cells

Chapter 3 innate immunity

  • Questions:

  • What are the differences between innate

  • immunity and adaptive immunity?

  • 2. Describe an inflammatory response.

  • 3. Examples of pattern recognition and the receptors for pattern recognition.

  • 4. How does a phagocyte kill pathogens?

  • 5. How does a dendritic cell bridge innate immunity to adaptive immunity?

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