Introduction

to

Immunology王青青Department

ofImmunologyUniversity

School

of

MedicineMedical

ImmunologyWhat

is

Medical

Immunology?Immunologyis

the

study

of

the

ways

inwhich

the

body

defends

itselffrom

infectious

agents

andother

foreign

substances

in

itsenvironment.Immune

system骨髓脾臟淋胸腺Immunology-

The

Basis

of

Medicinethe

physiological

functioning

of

the

immunesystem

in

states

of

both

health

anddisease;malfunctions

of

the

immune

system

inimmunological

disorders;the

physical,

chemical

and

physiologicalcharacteristics

of

the

components

of

theimmune

system.ImmunologyMoleclules:

Ag,

Ig,

MHC…Immune

cells:T,B,

APC,

NK…Immuneresponse:InnateAdaptive

(Cellular,

Humoral)Hypersensitivity

(Allergy)Immune

toleranceImmunodeficiencyTumor

immunity

…BasicImmunologyClinical

Immunology學科特點1、理論深奧、抽象；2、名詞概念的英文縮略語多；3、分子及

水平的內容多；4、前后知識聯系特別緊密；5、是

生命科學最重要的前沿學科之一。醫學免疫學，金伯泉主編，人民衛生Abbas

A

K,

et

al.

Basic

Immunoloy.

3rd

ed.Elsevier

Saunders

2008，第5版Abbas

A

K,

et

al.

Cellular

and

Molecular

Immunology.7th

ed.Elsevier

Saunders

2012Janeway

C

A,

et

al.

Immunobiology.

7th

ed.Garland

Science

Publishing

2007Referencesselfnonselfimmune

responseimmune

toleranceIntroductionContents:Concept

of

ImmunityBrief

HistoryofImmunologyImmunological

FunctionsImmune

ResponseImmune

CellsTissues

and

Organs

of

the

ImmuneSystemImmunopathologyImmunityImmunity:

refers

to

all

mechanisms

used

by

thebody

as

protection

against

environmental

substancesthat

are

foreign

to

the

body.(to

recognize

and

eliminate

foreign

substances)Substances:

microorganisms

( es,

bacteria

etc)and

their

products,

foods,

chemicals,

pollen,

tumorcells,

etc.Immune

system:

immune

tissues

and

organs,immune

cells,

immune

moleculesIntroductionImmune

response:

is

the

responsemade

by

the

host

to

defend

itself

againstthe

introduction

of

foreign

substances.benefits;

damaging

effectsImmunology:

study

the

structure

ofimmune

system

and

its

functions.BriefHistory

ofImmunologyEmpirical

ImmunologyScientific

ImmunologyModern

Immunology1）T etic

principle

of

diversity

and

specificity

of

antibodies2）Gene

cloning

of

T

cell

receptor3）Immunogenetics

and

MHC

restriction4）Cytokines

and

receptors5）Signal

transductionWhat

disease

does

this

man

have?Progression

of

SmallpoxDay

7Day

3Day

5天花

(Pox

)祖國醫學：扶正祛邪、陰陽理論人痘苗(南宋時期)中國古代有關痘苗文獻Edward

Jenner

(1749-1823)Vaccination

(1796)最后一例天花患者阿里毛世界衛生組織宣布消滅天花《備急千金藥方》（孫思邈，唐朝581-682）；《肘后備急

方》（葛洪，東晉283-363）Cao

X.

Immunology

in

China:

the

past,

present

and

future.

Nat

Immunol.

2008;9(4):339-42Louis

PasteurFowl

choleraPasteurella

multocida……vaccine1879ElieMetchnikoff

(Russia),1845-1916,

1908

nobel

prizeEmilvon

Behring

(Germany)

,1854-1917,

1901

nobel

prizeRobert

Koch

(Germany),1843-1910,1905

nobelprizePaul

Ehrlich(Germany)，1854-1915,1908

nobelprizephagocytosis/cellulartheoryfor

theinvestigations

concerningtuberculosis.for

the

workon

serumtherapyespecially

itsapplicationagainstdiphtheria.humoraltheory*

Burnet（1957）Clonal

selection

theoryTop

Immunologist1960

Nobel

prizewinnerModern

Immunology1）T etic

principle of

diversity

and

specificityof

antibodies2）Gene

cloning

of

T

cell

receptor3）Immunogenetics

and

MHC

restriction4）Cytokines

and

receptors5）Signal

transduction……天然免疫識別受體（Toll樣受體，TLR）

樹突狀細胞（DC）：Bruce

A.

Beutler Ralph

M.

SteinmanJules

A.

HoffmanImmunological

FunctionsImmunological

defenseImmunological

surveillanceImmunological

homeostasisimmune

toleranceimmunoregulation免疫系統三大功能的生理和病理表現功能免疫防御免疫穩定免疫監視生理性反應(有利)抵御、清除病原體清除體內衰老、損傷、變性的細胞識別、清除體內突變的細胞病理性反應(有害)超敏反應(過度)免疫缺陷(不足)自身免疫病(過度)發生腫瘤(不足)Xuetao

Cao.Immunology

in

China:

thepast,present

andfuture.Nat

Immunol.

2008,

9:339-342Immune

ResponseIntroductionInnate

immune

responsenatural

immune

responsenon-specific

immune

responseAdaptive

immune

responseacquired

immune

responsespecific

immune

responseInnate

immune

responsePhysiological

barriersskinmucousmembranesPhagocytosispolymorphonuclear

leukocytes

(PMN)monocytes/macrophagesNatural

killer

(NK)

cellComplement

and

acute

phase

proteinsIntroductionInnate

immune

responseIntroductionMacrophage

Attacking

E.coliThe

Nobel

Prize

in

Physiologyor

Medicine

2011朱爾斯·霍夫曼（JulesA.Hoffmann）于1941年生于盧森堡Echternach。他在法國斯特拉斯堡大學學習，于1969年獲得博士

。在德國馬爾堡大學從事博士后工作之后，他回到斯特拉斯堡，從1974年到2009

擔任一個研究斯特拉斯堡分子細胞生物學

的

，并在2007-2008的擔任法國。他還院長。In

1996,

hi

reportedthat

theToll

gene,

wasimportant

for

battlinginfections.B.

Lemaitre

et

al.Cell86,

973–983;

1996布魯斯·巴 （Bruce

A.

Beutler）1957年出生于

芝加哥。1981年在芝加哥大學獲得醫學博士

（MD），之后在紐約的洛克菲勒大學和達拉斯的德克薩斯大學從事科學工作，并發現了LPS（細菌脂多糖）受體。從2000年開始，他成為

LaJolla市斯科利普斯 （The

Scripps

Research

Institute）的遺傳與免疫學教授。The

Nobel

Prize

in

Physiologyor

Medicine

2011Hi eventually

foundLPS-sensing

gene,

and

itlooked

remarkably

likeHoffmann's

Toll.識別細菌脂多糖（LPS）的受體Toll-like

receptor

4A.

Poltorak

et.

al.

Science282,

2085–2088;

1998Adaptive

immuneresponseThe

T

cells

and

B

cells

in

the

bodyrecognize

the

antigen

and,

in

turn,e

activated.

The

activatedlymphocytes

then

proliferate

and

carryout

their

specific

effector

functions.Adaptive immuneresponseIntroductionBCR

(mIg)TCRαβIntroductionAdaptive immuneresponseThe

activation

of

lymphocytesantigen

interacts

with

specific

receptors:B

cell---

BCR

(B

cell

receptor):

membrane

IgTcell---

TCR

(Tcellreceptor)Proliferation

and

differentiation

of

lymphocytesB

cell----cytokines

(IL-4,etc.)T

cell----Antigen-TCR;

co-stimulatory

signal;cytokines(IL-2,IL-7,IL-15)Effector

cells

and

their

functionsB

cell----Antibody; T

cell----CTL,

ThMemorycellsThe

innateanIntroductionptive

immune

responseCharacteristicsCellsMoleculesInnate

immunityResponds

rapidlyNo

memoryNo

or

lowspecificityPhysical

barriersPhagocytes

(PMNsand

macrophages)Natural

killer

cellsHumoral

factorsComplementAcute

phaseProteinsCytokinesAdaptiveimmunityResponds

SlowlyMemoryHighly

specificT

cellsB

cellsDendritic

cellsAntibodiesCytokinesGranzymesDownloaded

from:

StudentConsult

(on

31

May

2006

05:26

PM)?2005ElsevierLinks

between

innate

anptive

immunityIntroductionImmune

Cellshematopoietic

stemcell(HSC)Myeloid

progenitor Lymphoid

progenitorGranulocytes

(eosinophils,neutrophils,

basophils)Monocytes,

macrophagesDendriticcellErythrocyteMegakaryocyteTlymphocyteBlymphocyteNKcellDendriticcell主要的免疫細胞Phagocytic

cellsMonocytes

(blood)/Macrophages

(tissues)functions:

1.

remove

particulate2.

take

up,

process

andpresentantigenic

peptidestoTcellsdistribution:

Kupffer

cells

in

the

livermicroglial

cells

in

the

brainIntroductionIntroductionPhagocytic

cellsmonocyteneutrophilPhagocytic

cellsPolymorphonuclear

granulocytesneutrophils;

basophils;

eosinophils2.neutrophils

are

short-lived

phagocytic

cellsmultilobed

nucleus;

10-20

m3.neutrophils

have

a

large

arsenal

ofantibioticproteinsgranules:

lysosomes;

lactoferrinIntroductionIntroductionPhagocytic

cellseosinophilneutrophilLymphocytes

(except

NK

cells)

are

whollyresponsible

for

the

specific

immunerecognition

of

pathogens,

so

they

initiateadaptive

immune

responses.Lymphocytes

are

derived

from

bone-marrowstemcells.B

lymphocytes

develop

in

the

bonemarrow.T

lymphocytes

develop

in

the

thymus.IntroductionLymphocytesLymphocytes(20-40

percent

of

allblood

leukocytes)B

Lymphocytes⑴

BCR:a

surface

receptor

(mIg)

specific

fora

particular

antigen⑵

B

cells plasma

cellsantibody

(the

same

specificity

as

the

BCR)⑶

humoral

immunityIntroductionAgsecreteTCR:

T-cell

antigen

receptorTCR+

>95%TCR+

1–5%Cytotoxic

T

cells

(CTL)helper

T

cells:

Th1,

Th2,

Th3Regulatory

T

cells

(Treg)

andsuppressor

T

cells

(Ts)IntroductionT

LymphocytesIntroductionTLymphocytesTlymphocyteIntroductionTLymphocytesHuman

T-lymphocyte

Attacking

Fibroblast

Tumor

CellsAntigen

presenting

cells

(APC)Macrophage: powerful

in

antigenprocessingand

destruction,

butlow

in

antigenpresentation.Dendritic

cells

(DC):such

as

Langerhans

Cell(LC),

powerful

in

antigen

processing

andpresentation.IntroductionThe

Nobel

Prize

in

Physiologyor

Medicine

2011發現樹突狀細胞Dendritic

cells,

DC是啟動適應性免疫應答的關鍵細胞R.

M.

Steinman

and

Z.

A.Cohn.J.

Exp.Med.137,

1142–1162;

1973拉爾夫·斯坦曼（Ralph

M.

Steinman）【已故】1943年出生于

蒙特利爾，在麥吉爾大學學習生物學和化學。之后在

哈佛醫學院學習醫學，1968年獲得醫學博士（MD）。于1970年被紐約洛克菲勒大學接納，從1988年起成為免疫學教授。擔任該校免疫學與免疫性疾病中心

。IntroductionNatural

killer

cells

(NK)10-15%

of

blood

lymphocytes,

LGLexpress

neither

T-cell

nor

B-cellantigen

receptorsIntroductionTissues

and

organs

of

theimmune

systemPrimary

(or

central)

lymphoid

organsthe

bone

marrowthe

thymusSecondary

(or

peripheral)

lymphoid

organsthe

spleenlymph

nodesMucosal-associated

lymphoid

tissue

(MALT)IntroductionDownloaded

from:

StudentConsult

(on

31

May

2006

05:26

PM)?2005Elsevierthe

place

in

which

proliferation

of

HSCtakes

placethe

place

in

which

development

andmaturation

of

B

cells

occurThe

lymphoid

progenitor

cells

aretransported

by

circulating

blood

to

thethymus

and

differentiate

into

functionalT

lymphocytesIntroductionBone

marrowThe

thymusCells:

thymic

stromal

cells

(TSC)epithelial

cells,

monocytes

(macrophage),

TDCthymocytes T

cell(+)Structure:

cortex---immature

thymocytesmedulla---mature

thymocytesM,

TDCFunction:

It

is

the

site

of

T

cell

maturation/selection;It

determines

the

specificity

of

theTCR

expressed

on

the

T

cells

releasedto

peripheryIntroductionThe

thymus

is

a

primary

lymphoid

organ

and

the

seat

of

Tlymphocyte

differentiation

and

selection. It

is

a

bi-lobedorgan

located

just

under

the

sternum

and

is

largest

in

pre-puberty.

It

involutes

with

age.The

lymph

nodeHuman:2-10mm

meterround

and

kidney

shapedConsists

of

:

cortex

(B-cell

area)paracortex

(T-cell

area)central

medulla

(B-cell

area)IntroductionIntroductionThe

lymph

node180-250ggerminal

center

(B)the

white

pulpperiarterial

lymphatic

sheath(T)the

red

pulp

(B)function:

destroy

the

Ag,

aged

pla

etsimmune

responseIntroductionThe

spleenIntroductionThe

spleenMucosal

immune

system(MIS)non-encapsulated

lymphoid

tissue

in

thelamina

propria

and

submucosal

areas

ofthe

gastrointestinal,

respiratory

andgenitourinary

tracts.tonsil,

appendix,

Peyer’s

patches3.

B

cellIELIgAAdaptive

immunity,

T

cell(Intraepithelial

lymphocytes)4.

function:

local

(mucosal)

immunityIntroductionMucosal-associated

lymphoidtissue

(MALT)Lymphocyte

recirculationLymphocytes

leave

the

blood

via

high-walled

endothelium

of

the

post-capillaryvenulesLymphocyte

trafficking

exposes

antigento

a

large

numbe