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J 7V z0___PPT10:___PPT9  Antibodies> "  f c    @` @ Z@1))?_J V z0___PPT10:___PPT9 Complement, others> " f c    @` @ Z"@1))?'J _V z0___PPT10:___PPT9 Blood proteins> " fc   @` @ Z`-@1))?  7J z0___PPT10:___PPT9 DLymphocytes in epithelia; antibodies secreted at epithelial surfaces>E " Df c  E  @` @ Z0@1))?_ J z0___PPT10:___PPT9 0Skin, mucosal epithelia; antimicrobial chemicals>1 " 0f c  1  @` @ ZC@1))?' _J z0___PPT10:___PPT9 Cellular and chemical barriers> " fc   @` @ Z\M@1))?' 7 z0___PPT10:___PPT9  ComponentsB "  fg   @` @ ZxP@1))? 7 z0___PPT10:___PPT9 Yes> " f c    @` @ ZHZ@1))? z0___PPT10:___PPT9 Yes> " f c    @` @ Z@]@1))?' z0___PPT10:___PPT9 Nonreactivity to self> " fc     @` @ ZPx@1))? 7z0___PPT10:___PPT9 Yes> " f c    @` @ ZHq@1))? z0___PPT10:___PPT9 None> " f c    @` @ Zq@1))?'z0___PPT10:___PPT9 Memory> " fc   @` @ Zp@1))? o7z0___PPT10:___PPT9 LVery large; receptors are produced by somatic recombination of gene segments>M " Lf c  M  @` @ ZL@1))?o z0___PPT10:___PPT9 Limited; germline-encoded> " f c &      @` @ Z@1))?'oz0___PPT10:___PPT9  Diversity> "  fc   @` @ Z\@1))? 77oz0___PPT10:___PPT9 6For antigens of microbes and for nonmicrobial antigens>7 " 6f c &!      @` @ Z@1))?7 oz0___PPT10:___PPT9 3For structures shared by groups of related microbes>4 " 3f c  4  @`  @ Z@1))?'7oz0___PPT10:___PPT9  Specificity> "  fc   @` !@ Z@1))?'+77z0___PPT10:___PPT9 CharacteristicsB " fg   @` "@  `@1))? 7+z0___PPT10:___PPT9 Adaptive: " fc   @` #@  `@1))?_ +z0___PPT10:___PPT9 Innate: " fc   @` $@  `@1))?'_+z0___PPT10:___PPT9 B " fg  @`B %@ Z8c ))?'7B &@ Z1 ))?'7B '@ Z8c ))?''+B (@ Z8c ))?77+B )@ Z1 ))?'+7+B *@ Z1 ))?'+'B +@ T1 ))?__+B ,@ T1 ))?  +B -@ Z1 ))?7+7B .@ Z1 ))?'777B /@ Z1 ))?'o7oB 0@ Z1 ))?7 B 1@ Z1 ))? 7 B 2@ Z1 ))?'7B 3@ Z1 ))?'7B 4@ Z1 ))?' 7 B 5@ Z1 ))?' 7 B 6@ Z1 ))?'J 7J B 7@ Z1 ))?_ _B 8@ Z1 ))?  B 9@ Z1 ))?'V 7V H @ 0޽h ? 33___PPT10i.+D=' = @B + ZQL0    (  /  Z11))?R )The physiologic function of immune systemL*0 2c(ce * /  0@ D E j WInnate Immunity: the early reactions Adaptive Immunity: the later responses HXZbbbb X   Z1))?"`   Z1))?"`   Z1))?"`+   ZD1))?: }#Defense against infectious microbes*$0( 2$e $    Z1))?"`   Z1))?"`+  Z1))?"`  Z1))?"`  Z1))?"`+  Z1))?"`  Z1))?"`+H  0޽h ? ̙33y___PPT10Y+D=' = @B +GvL0 y "(  x y c TA0S9781416031239-001-f001"` y Z1))?"` y Z1))?"`+ y Z1))?"` y Z1))?"`+H x 0޽h ? ay___PPT10Y+D=' = @B + L0 'P (   ~   s *|Dz'  D    Z\ D1))?/m  wInnate Immunity*0 2g      Z1))?"`   Z1))?"`   Z1))?"`+   Z1))?"`   Z1))?"`+H   0޽h ? y___PPT10Y+D=' = @B +L0  b(    Z<0D1))?ZJ zOVERVIEW6 0 cc  &  Z5D1))?|  0The first line of defense against infection An evolutionarily older defense strategy, found in all classes of plants and animals Preexist infection or exposure to foreign antigen Respond immediately after recognition of microbes Respond in essentially the same way to repeated infection "-0 2: q2% q2 q20 2,eaa[aa1aa1 a a9ac&/ *    Z1))?"`  Z1))?"`  Z1))?"`+   Z1))?"`   Z1))?"`+H  0޽h ? 33___PPT10i.|+D=' = @B +L0 `(    ZKD1))?/&  U Initial response to microbes to prevent infection with elimination of danger Innate components also important in adaptive immunity Stimulates adaptive responses h5 q! qY q q2a    ZlTD1))?w  } FUNCTIONS6 0  cc      Z1))?"`   Z1))?"`   Z1))?"`+   Z1))?"`  Z1))?"`+H  0޽h ? 33___PPT10i.(,.+D=' mw= @B +<ZL0 ;;P3m;(    Z[D1))?' "Components of innate immune system6#0( 2a"a #    `1))?9 Y   #"J>iA  C ZbD1))?6Y z0___PPT10:___PPT9  CytokinesB "  fg   @` B Z8mD1))? Y6z0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2f c   '  @` A ZeD1))? 6z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " f c &     @`  @ ZxD1))? Y z0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cf c 4  (     @` ? ZD1))?  z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "f c @       @` > Z@D1))?+ Y z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gf c &   '  @` = Z$D1))?+  z0___PPT10:___PPT9  Complement: "  b c    @` ; Z|D1))?X Y+ z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @` : Z|D1))? YX z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2f c  .  @` 9 ZlD1))? X z0___PPT10:___PPT9 NK cells> " f c    @` 8 ZD1))?kY z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bf c &    M  @` 7 Z D1))?k z0___PPT10:___PPT9  Macrophages> "  f c    @` 6 ZD1))?Ykz0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *f c &     @` 5 Z1))?kz0___PPT10:___PPT9  Neutrophils> "  f c     @` 3 Z1))?Yz0___PPT10:___PPT9 Circulating effector cellsB " fg&     @` 2 Z(1f1))?Yz0___PPT10:___PPT9 Microbial killing> " f c    @` 1 Z4f1))?z0___PPT10:___PPT9 Intraepithelial lymphocytes> " f c    @` 0 ZFf1))?1Yz0___PPT10:___PPT9 Microbial killing> " f c    @` / ZxPf1))?1z0___PPT10:___PPT9 Defensins/cathelicidin> " f c    @` . ZKf1))?cY1z0___PPT10:___PPT9 Prevent microbial entry> " f c    @` - Zff1))?c1z0___PPT10:___PPT9 Epithelial layers> " f c    @` + Zjf1))?Ycz0___PPT10:___PPT9 Epithelial barriersB " fg   @` *  `̄1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @` )  `x1))?z0___PPT10:___PPT9  Components< "  fc   @`B E Z8c ))?YB F Z1 ))? Y B G Z8c ))?B H Z8c ))?YYB K Z1 ))?YB L Z1 ))? B M T1 ))?B O Z1 ))?YY B Q Z1 ))?cYcB V Z1 ))?1Y1B X Z1 ))?cB ] Z1 ))?YB e Z1 ))?YB m Z1 ))?YB s Z1 ))?kYkB u Z1 ))?X B z Z1 ))? Y B  Z1 ))?X YX B  Z1 ))?+ Y+ B  Z1 ))? Y B  Z1 ))?+ 6B  Z1 ))? Y B  Z1 ))?6Y6H  0޽h ? 33___PPT10i.'`+D=' = @B +bL0 D(  D D c TA0S9781416031239-002-f003"`< D ZX1))?O {Epithelial barriers*0 2g   D Z1))?"` D Z1))?"` D Z1))?"`H D 0޽h ? ay___PPT10Y+D=' = @B + p\4(  \8 U \3V \ C &A0202_1 V \ C &A 0202_2"UH \ 0޽h ? 33___PPT10i.`7֓+D=' = @B +2yL0 1)p (  P  Z,1))?Z dSkin Mucosal surfaces of the gastrointestinal tracts (GI) Mucosal surfaces of the respiratory tracts2e0 2:a+a e    Z1))?,] L wPhysical barriers(0 2e     Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.(@|T=+D=' = @B +D2L0 C;p (    Z1))?,] L Antimicrobial Peptides <0 2ee  H  Z1))?zT Defensins Cystein-rich peptides with 29-34 amino acids Present in the skin and abundant in neutrophil granules Broad-spectrum antibiotics Upregulated by inflammatory cytokines Cryptocidines Secreted by the epithelium of the intestine Locally sterilize the lumen of intestine 0 2 g-cc7c c cc&cgc+ c $c$)(c(    J   %      W   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.01/+D=' = @B +L0  (  4  Z1))?,L Intraepithelial lymphocytes P0 2eee  r  Z1))?) JIntraepithelial T cells Present in the epidermis of the skin and in mucosal epithelia gd cells and NKT cells Serve as sentinels at common sites of microbial invasionn0 2g>cc9c  r  Z1))?c )i BB-1 cells Present in peritoneal cavity Produce NATURAL antibodies v'0 20( 2 gc7c c  C    Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.SO+D=' = @B +< ;;3<y;(    Z1))?' "Components of innate immune system6#0( 2a"a #    `1))?9 Y < #"J>Y  Z|1))?Yz0___PPT10:___PPT9  CytokinesB "  fg   @`  ZTp1))?Yz0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @`  Z p1))?z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`   Z p1))?G Yz0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @`   Z<p1))?G z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @`   Z2p1))? YG z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @`   Z5p1))? G z0___PPT10:___PPT9  Complement: "  bc   @`   Z\?p1))? Y z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @`   ZDKpf1))?N Y z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @`  ZdWpf1))?N  z0___PPT10:___PPT9 NK cellsB " fg   @`  Z(lpf1))? YN z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @`  Z(mpf1))? N z0___PPT10:___PPT9  MacrophagesB "  fg   @`  Z|pf1))?<Y z0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @`  Zpf1))?< z0___PPT10:___PPT9  NeutrophilsB "  fg    @`  Zpf1))?VY<z0___PPT10:___PPT9 Circulating effector cellsB " fg&     @`  Zxp1))?YVz0___PPT10:___PPT9 Microbial killing> " fc   @`  Zp1))?Vz0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @`  Zhp1))?DYz0___PPT10:___PPT9 Microbial killing> " fc   @`  Zp1))?Dz0___PPT10:___PPT9 Defensins/cathelicidin> " fc   @`  ZPp1))?vYDz0___PPT10:___PPT9 Prevent microbial entry> " fc   @`  Zp1))?vDz0___PPT10:___PPT9 Epithelial layers> " fc   @`  Zp1))?Yvz0___PPT10:___PPT9 Epithelial barriersB " fg   @`   `pp1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @`   `p1))?z0___PPT10:___PPT9  Components< "  fc   @`B  Z8c ))?YB  Z1 ))?YB  Z8c ))?B   Z8c ))?YYB ! Z1 ))?YB " Z1 ))?B # T1 ))?B $ Z1 ))?YYB % Z1 ))?vYvB & Z1 ))?DYDB ' Z1 ))?vVB ( Z1 ))?YB ) Z1 ))?VYVB * Z1 ))?<Y<B + Z1 ))? Y B , Z1 ))?< B - Z1 ))?N YN B . Z1 ))? Y B / Z1 ))? Y B 0 Z1 ))?G YG B 1 Z1 ))? B 2 Z1 ))?YB 3 Z1 ))?YH  0޽h ? 33___PPT10i.'`+D=' = @B +   v(    Z fp1))?\ ` Phagocytes& 0 2 c    Z 1))? $  `Cell types Neutrophils and Macrophages Primary functions Identify, ingest, and destroy microbesPa0 2 aaa'a&    K   Z1))?"`  Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.@p!+D=' = @B +   X(    Z)1))?  0Neutrophils Polymorphonuclear neutrophils (PMNs)H10 2 acch            c TA 0S9781416031239-002-f004"`H  0޽h ? 33___PPT10i.Ap+D=' = @B +T {s L (  L L Z51))?   ;Downloaded from: StudentConsult (on 22 April 2010 06:36 AM)&<0(2<c <  L Z:1))?Z  f 2005 Elsevier &0(2c  Y L Z?1))?2,l mThe most abundant population of circulating leukocytes Mediate the earliest phases of inflammatory responses$n0 2ncm   L ZD1))?rJ m Neutrophils$ 0 2 a     L Z1))?"`  L Z1))?"`+  L Z1))?"` L Z1))?"`+H L 0޽h ? ay___PPT10Y+D=' = @B + @ (    ZpM1))?w0  _ Macrophages$ 0 2 a    c TA 0S9781416031239-002-f005"`4/U    ZOHa1))?"`v r&Figure 2-5 Maturation of mononuclear phagocytes. Mononuclear phagocytes develop in the bone marrow, circulate in the blood as monocytes, and are resident in all tissues of the body as macrophages. They may differentiate into specialized forms in particular tissues. CNS, central nervous system.''c '   Z1))?"`   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.At+D=' = @B +& %%$(  " /I  ~ #"2&b9  L  f@a1))? I z0___PPT10:___PPT9 spleen6 " bc  Z 0 @`Q K  fa1))? <___PPT10^___PPT9@8 Sinusoidal lining cells` "  bc ff   Y 0  @` J  f41))? I z0___PPT10:___PPT9 bone6 " bc  X 0 @` I  f~1))? z0___PPT10:___PPT9  Osteoclasts6 "  bc   W 0  @` H  fP1))? I z0___PPT10:___PPT9  granulomas6 "  bc   V 0  @` G  fl1))? z0___PPT10:___PPT9 Epithelioid cellsH "  bfc   U 0  @` F  f`1))? }I z0___PPT10:___PPT9  neural tissue6 "  bc   T 0  @` E  fD1))?} z0___PPT10:___PPT9  Microglia6 "  bc   S 0  @` D  f|̅1))? jI}z0___PPT10:___PPT9 liver6 " bc  R 0 @` C  fx1))?j }z0___PPT10:___PPT9  Kupffer cells6 "  bc&   Q 0  @` B  fυ1))? VIjz0___PPT10:___PPT9 connective tissue6 " bc  P 0 @` A  f1))?V jz0___PPT10:___PPT9  Histiocytes6 "  bc   O 0  @` @  fp1))? CIVD___PPT10$r___PPT9TL fpulmonary alveolus of lungs " bcfcb c 0    M 0N 0 @` ?  f 1))?C Vz0___PPT10:___PPT9 Alveolar macrophages* " f   @` >  fp1))? /ICz0___PPT10:___PPT9 Location: " cc   @` =  f4p1))?/ Cz0___PPT10:___PPT9  Name of cell: "  cc   @`B M T1))?/I/B N T1))? I B O T1))?/ B P T1))?I/I   Z1))?"`  Z1))?"`  Z1))?"`H  0޽h ? 33___PPT10i. Y&+D=' = @B +) @80 (    Zy1))?z, U Dominant effector cells of the later stages of innate immune response Play central role in both innate and adaptive immune responsel0 2ccFc c =c@   5  >   Z`/p1))?<\ _ Macrophages$ 0 2 a    Z1))?"`   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i. $+D=' = @B + P (   z   Z6p1))?TbZR___PPT94, Active recruitment of the cells to sites of infection 2. Recognition of microbes Phagocytosis 4. Destruction of ingested microbes 61 0  1 0 +0 Taa+a4T   ,   @`   ZFp1))?9 /The steps of functional responses of phagocytes&00 20c 0    Z1))?"`   Z1))?"`   Z1))?"`H   0޽h ? 33___PPT10i. `*+D=' = @B + p d(  d d c TA 0S9781416031239-002-f007"` d Z>p1))?Z  f 2005 Elsevier &0(2c   d ZRp1))?H. oRecruitment of leukocytes&0 2c   d Z1))?"`  d Z1))?"`  d Z1))?"`H d 0޽h ? ay___PPT10Y+D=' = @B +] tlp $(  $ $ Zdp1))?Da p Phagocytosis& 0 2 c    $ Zp1))?'q  H A cytoskeleton-dependent process of engulfment of large particles Bound microbes are ingested into vesicles, where the microbes are destroyed~: q2 q28 q2 q2aa   $ Z1))?"` $ Z1))?"` $ Z1))?"`+  $ Z1))?"`  $ Z1))?"`+H $ 0޽h ? 33___PPT10i. 0u+D=' = @B +  ((  ( ( Zup1))?La $Destruction of phagocytosed microbes&%0 2%c&     ' ( Z|rp1))?<  Where Phagolysosome Killing Mechanisms 1. Reactive oxygen intermediates (ROIs) 2. Reactive nitrogen intermediates: mainly NO 3. Preformed antimicrobials 0 2ac a a ccKcc@    t   ( ZXp1))? ',  7BUT, these mechanisms also can cause host tissue injury(80 28g 8  ( Z1))?"` ( Z1))?"`  ( Z1))?"`+  ( Z1))?"`  ( Z1))?"`+H ( 0޽h ? 33___PPT10i. $+D=' = @B +k  |"(  | | c TA0S9781416031239-002-f008"`  | Z1))?"`  | Z1))?"`+  | Z1))?"`  | Z1))?"`+H | 0޽h ? ay___PPT10Y+D=' = @B +  D@(  D D c TA0S9781416031239-002-f009"`R=l  D ZpHa1))?"`v ~2Figure 2-9 Effector functions of macrophages. Macrophages are activated by microbial products such as LPS and by NK cell-derived IFN-γ (described later in the chapter). The process of macrophage activation leads to the activation of transcription factors, the transcription of various genes, and the synthesis of proteins that mediate the functions of these cells. In adaptive cell-mediated immunity, macrophages are activated by stimuli from T lymphocytes (CD40 ligand and IFN-γ) and respond in essentially the same way (see Chapter 13, Fig. 13-14).33c 3  D Z1))?"` D Z1))?"`+  D Z1))?"`  D Z1))?"`+H D 0޽h ? ay___PPT10Y+D=' = @B +M d\` (    Zp1))?j  sNatural Killer cells (NK cells)$ 0 2 a    Zp1))? \TL___PPT9.& A type of cytotoxic lymphocytes The principal physiologic role Defense against infections by viruses and some other intracelluar microbes 2. Rejection of tumors @0 2B1 20 20 2?ccQccc@    b   +  @`  Z1))?"`  Z1))?"`+   Z1))?"`   Z1))?"`+   Z1))?"`H  0޽h ? 33___PPT10i.Bʄ3+D=' = @B +   (    c TA0S9781416031239-002-f011"` &  Zp1))?_q]  Effector function40 2ac(    P  Zp1))?26  Perforin Granzyme \0 2ccc  c 4       Z1))?"`   Z1))?"`+   Z1))?"`   Z1))?"`+H  0޽h ? ay___PPT10Y+D=' = @B +< ;; 3=LT;(  L L Zp1))?' "Components of innate immune system6#0( 2a"a #  L  `1))?r9 Y? =L #"J>Y? L Zp1))?YY?z0___PPT10:___PPT9  CytokinesB "  fg   @` L Z pf1))?YYz0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @` L Z@pf1))?Yz0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`  L Zpf1))? Yz0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @`  L Zpf1))? z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @`  L Z|f1))? Y z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @`  L Z|f1))?  z0___PPT10:___PPT9  Complement: "  bc   @`  L ZL|f1))? Y z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @`  L Z!|1))? Y z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @` L Z4|1))?  z0___PPT10:___PPT9 NK cells: " bc   @` L Z|1))?Y z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @` L ZB|1))? z0___PPT10:___PPT9  Macrophages: "  bc   @` L ZT|1))?Yz0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @` L Z`,|1))?z0___PPT10:___PPT9  Neutrophils: "  bc    @` L ZXN|1))?Yz0___PPT10:___PPT9 Circulating effector cellsB " fg&     @` L Z`Z|1))?Yz0___PPT10:___PPT9 Microbial killing> " fc   @` L Zn|1))?z0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @` L Z8|1))?DYz0___PPT10:___PPT9 Microbial killing> " fc   @` L Z|1))?Dz0___PPT10:___PPT9  Defensins> "  fc    @` L Z |1))?vYDz0___PPT10:___PPT9 Prevent microbial entry> " fc   @` L Zh|1))?vDz0___PPT10:___PPT9 Epithelial layers> " fc   @` L Zв|1))?Yvz0___PPT10:___PPT9 Epithelial barriersB " fg   @` L  `|1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @` L  `|1))?z0___PPT10:___PPT9  Components< "  fc   @`B L Z8c ))?YB L Z1 ))??Y?B L Z8c ))?B  L Z8c ))?YYB !L Z1 ))?YB "L Z1 ))??B #L T1 ))?B $L Z1 ))?YY?B %L Z1 ))?vYvB &L Z1 ))?DYDB 'L Z1 ))?vB (L Z1 ))?YB )L Z1 ))?YB *L Z1 ))?YB +L Z1 ))?YB ,L Z1 ))? B -L Z1 ))? Y B .L Z1 ))? Y B /L Z1 ))? Y B 0L Z1 ))? Y B 1L Z1 ))? YB 2L Z1 ))?YB 3L Z1 ))?YYYH L 0޽h ? 33___PPT10i.'`+D=' = @B +  m(    ZT+|1))?T kThe complement system&0 2c  @  0d| q,TLD___PPT9& A complex series of some plasma proteins Pathways of complement activation Classical Pathway Alternative Pathway The lectin Pathway*qq"qq9 *b$b9b4* N    p`Pp  Z1))?"`  Z1))?"`  Z1))?"`+   Z1))?"`   Z1))?"`+H  0޽h ? 33___PPT10i., R7+D=' = @B + RJ `(  `J ` C "A 0207r_ ` Z1))?"` ` Z1))?"`+ ` Z1))?"`  ` Z1))?"`+H ` 0޽h ? 3380___PPT10.  (    c TA0S9781416031239-002-f012"`J h  Z~Ha1))?"`  rPathways of complement activation. The activation of the complement system may be initiated by three distinct pathways, all of which lead to the production of C3b (the early steps). 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(- ./ 057 BF?IK M Q R T V W PowerPoint Document(ϡDocumentSummaryInformation8 M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/LungsOPhttp://en.wikipedia.org/wiki/HistiocytesPhttp://en.wikipedia.org/wiki/HistiocytesP\http://en.wikipedia.org/wiki/Connective_tissue\http://en.wikipedia.org/wiki/Connective_tissueQRhttp://en.wikipedia.org/wiki/Kupffer_cellRhttp://en.wikipedia.org/wiki/Kupffer_cellRDhttp://en.wikipedia.org/wiki/LiverDhttp://en.wikipedia.org/wiki/LiverSLhttp://en.wikipedia.org/wiki/MicrogliaLhttp://en.wikipedia.org/wiki/MicrogliaTThttp://en.wikipedia.org/wiki/Neural_tissueThttp://en.wikipedia.org/wiki/Neural_tissueUPhttp://en.wikipedia.org/wiki/EpithelioidPhttp://en.wikipedia.org/wiki/EpithelioidVNhttp://en.wikipedia.org/wiki/GranulomasNhttp://en.wikipedia.org/wiki/GranulomasWPhttp://en.wikipedia.org/wiki/OsteoclastsPhttp://en.wikipedia.org/wiki/OsteoclastsXBhttp://en.wikipedia.org/wiki/BoneBhttp://en.wikipedia.org/wiki/BoneYNhttp://en.wikipedia.org/wiki/SinusoidalNhttp://en.wikipedia.org/wiki/SinusoidalZFhttp://en.wikipedia.org/wiki/SpleenFhttp://en.wikipedia.org/wiki/Spleen/ 0DTimes New RomanԷ80ԷǶ 0̷DArialNew RomanԷ80ԷǶ 0̷" D[SOalNew RomanԷ80ԷǶ 0̷0DVerdanaw RomanԷ80ԷǶ 0̷"@DWingdingsRomanԷ80ԷǶ 0̷PDSymbolgsRomanԷ80ԷǶ 0̷`DTahomagsRomanԷ80ԷǶ 0̷" C0.  @n?" dd@  @@``  h2 =DA=@$! / &0" ><I=Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FHV7>*$d]K3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' (- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKdǶ 0Rppp@ <4BdBd 0Tq<4!d!d 0Tqs ʚ;zLs8ʚ;<4dddd| 0___PPT10D[SOes New TTpX80pǶ 0hDArialNew TTpX80pǶ 0h" DTimes New RomanpX80pǶ 0h pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~Pr{{/0(X   M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/Lungs?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e՜.+,D՜.+,8    On-screen ShowHoechst Marion Roussel ( 0Times New RomanArialVerdana WingdingsSymbolTahomaDefault DesignSlide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9 Slide 10 Slide 11 Slide 12 Slide 13 Slide 14 Slide 15 Slide 16 Slide 17 Slide 18 Slide 19 Slide 20 Slide 21 Slide 22 Slide 23 Slide 24 Slide 25 Slide 26 Slide 27 Slide 28 Slide 29 Slide 30 Slide 31 Slide 32 Slide 33 Slide 34 Slide 35 Slide 36 Slide 37 Slide 38 Slide 39 Slide 40  Fonts UsedDesign Template Slide Titles( 8@ _PID_HLINKSAPT0http://en.wikipedia.org/wiki/Pulmonary_alveolus#http://en.wikipedia.org/wiki/Lungs)http://en.wikipedia.org/wiki/Histiocytes/http://en.wikipedia.org/wiki/Connective_tissue*http://en.wikipedia.org/wiki/Kupffer_cell#http://en.wikipedia.org/wiki/Liver'http://en.wikipedia.org/wiki/Microglia+http://en.wikipedia.org/wiki/Neural_tissue)http://en.wikipedia.org/wiki/Epithelioid(http://en.wikipedia.org/wiki/Granulomas)http    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0ppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P 0N0 (    Zw1))? C iInnate Immunity*0 2g<    Z,1))?t2 \Rui He ruihe@fudan.edu.cn Department of Immunology Shanghai Medical School Fudan University(]0( 2]cN   2      Z1))?"`)    f,1))?"`)W N$0 c     ff1))?"`Vk N$0 c H  C AFD6/H  0޽h ? 33___PPT10i.Ps:+D=' = @B +" 0SN0 ! (    Z1))?"`  6 wG bComponents of Immunityb$    Z1))?  'Innate Immunity: non-specific, also called natural or native immunity Adaptive Immunity: specific, also called acquired immunityt0 2c c6ac c(a    Z1))?"`   Z1))?"`+   Z1))?"`   Z1))?"`+H  0޽h ? 33___PPT10i.wZL+D=' = @B +`@ 0GN0 _?W?7?@>(  @td  :@ #"  @  f1))?z0___PPT10:___PPT9 (Features of Innate and Adaptive Immunity:)( " (d333a )  @`B @ T1))?B @ T1))?B @ T1))?B  @ T1))?;: '7 ?@ #":. 9 89 9 8 9'7  @ Z$+1))? V 7z0___PPT10:___PPT9  Lymphocytes> "  f c    @`  @ Z51))?_V z0___PPT10:___PPT9 ;Phagocytes (macrophages, neutrophils), natural killer cells>< " ;f c &     @`  @ ZI1))?'V _z0___PPT10:___PPT9 Cells> " fc   @` @ ZT1))? J 7V z0___PPT10:___PPT9  Antibodies> "  f c    @` @ ZN1))?_J V z0___PPT10:___PPT9 Complement, others> " f c    @` @ Z j1))?'J _V z0___PPT10:___PPT9 Blood proteins> " fc   @` @ Zn1))?  7J z0___PPT10:___PPT9 DLymphocytes in epithelia; antibodies secreted at epithelial surfaces>E " Df c  E  @` @ Zx1))?_ J z0___PPT10:___PPT9 0Skin, mucosal epithelia; antimicrobial chemicals>1 " 0f c  1  @` @ Z\1))?' _J z0___PPT10:___PPT9 Cellular and chemical barriers> " fc   @` @ Z1))?' 7 z0___PPT10:___PPT9  ComponentsB "  fg   @` @ Zp|1))? 7 z0___PPT10:___PPT9 Yes> " f c    @` @ ZT1))? z0___PPT10:___PPT9 Yes> " f c    @` @ Z81))?' z0___PPT10:___PPT9 Nonreactivity to self> " fc     @` @ Zd1))? 7z0___PPT10:___PPT9 Yes> " f c    @` @ Z1))? z0___PPT10:___PPT9 None> " f c    @` @ Z1))?'z0___PPT10:___PPT9 Memory> " fc   @` @ Z1))? o7z0___PPT10:___PPT9 LVery large; receptors are produced by somatic recombination of gene segments>M " Lf c  M  @` @ Z1))?o z0___PPT10:___PPT9 Limited; germline-encoded> " f c &      @` @ Z1))?'oz0___PPT10:___PPT9  Diversity> "  fc   @` @ Z>1))? 77oz0___PPT10:___PPT9 6For antigens of microbes and for nonmicrobial antigens>7 " 6f c &!      @` @ Z<1))?7 oz0___PPT10:___PPT9 3For structures shared by groups of related microbes>4 " 3f c  4  @`  @ Z>1))?'7oz0___PPT10:___PPT9  Specificity> "  fc   @` !@ Z>1))?'+77z0___PPT10:___PPT9 CharacteristicsB " fg   @` "@  `, >1))? 7+z0___PPT10:___PPT9 Adaptive: " fc   @` #@  `3>1))?_ +z0___PPT10:___PPT9 Innate: " fc   @` $@  `=>1))?'_+z0___PPT10:___PPT9 B " fg  @`B %@ Z8c ))?'7B &@ Z1 ))?'7B '@ Z8c ))?''+B (@ Z8c ))?77+B )@ Z1 ))?'+7+B *@ Z1 ))?'+'B +@ T1 ))?__+B ,@ T1 ))?  +B -@ Z1 ))?7+7B .@ Z1 ))?'777B /@ Z1 ))?'o7oB 0@ Z1 ))?7 B 1@ Z1 ))? 7 B 2@ Z1 ))?'7B 3@ Z1 ))?'7B 4@ Z1 ))?' 7 B 5@ Z1 ))?' 7 B 6@ Z1 ))?'J 7J B 7@ Z1 ))?_ _B 8@ Z1 ))?  B 9@ Z1 ))?'V 7V H @ 0޽h ? 33___PPT10i.+D=' = @B +  0cWN0    (  /  Z >1))?R )The physiologic function of immune systemL*0 2c(ce * /  0C> E j WInnate Immunity: the early reactions Adaptive Immunity: the later responses HXZbbbb X   Z1))?"`   Z1))?"`   Z1))?"`+   ZPR>1))?: }#Defense against infectious microbes*$0( 2$e $    Z1))?"`   Z1))?"`+  Z1))?"`  Z1))?"`  Z1))?"`+  Z1))?"`  Z1))?"`+H  0޽h ? ̙33y___PPT10Y+D=' = @B + 09qN0 y "(  x y c TA0S9781416031239-001-f001"` y Z1))?"` y Z1))?"`+ y Z1))?"` y Z1))?"`+H x 0޽h ? ay___PPT10Y+D=' = @B +  0N0 'P (   ~   s *^>z'  >    Z a>1))?/m  wInnate Immunity*0 2g      Z1))?"`   Z1))?"`   Z1))?"`+   Z1))?"`   Z1))?"`+H   0޽h ? y___PPT10Y+D=' = @B + 0N0  b(    ZPn>1))?ZJ zOVERVIEW6 0 cc  &  Zs>1))?|  0The first line of defense against infection An evolutionarily older defense strategy, found in all classes of plants and animals Preexist infection or exposure to foreign antigen Respond immediately after recognition of microbes Respond in essentially the same way to repeated infection "-0 2: q2% q2 q20 2,eaa[aa1aa1 a a9ac&/ *    Z1))?"`  Z1))?"`  Z1))?"`+   Z1))?"`   Z1))?"`+H  0޽h ? 33___PPT10i.|+D=' = @B + 0N0 `(    Z|>1))?/&  U Initial response to microbes to prevent infection with elimination of danger Innate components also important in adaptive immunity Stimulates adaptive responses h5 q! qY q q2a    Z>1))?w  } FUNCTIONS6 0  cc      Z1))?"`   Z1))?"`   Z1))?"`+   Z1))?"`  Z1))?"`+H  0޽h ? 33___PPT10i.(,.+D=' = @B +< 0N0 ;;P3`;(    ZȘ>1))?' "Components of innate immune system6#0( 2a"a #    `1))?~9 i?A  #"J>Y C Z<>1))?i=Az0___PPT10:___PPT9  CytokinesB "  fg   @` B Zt>1))? A=z0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @` A Z>1))?i =z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`  @ Z>1))? A z0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @` ? Z>1))?i  z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @` > Z>1))?n A z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @` = Z$>1))?in  z0___PPT10:___PPT9  Complement: "  bc   @` ; Z>1))?i An z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @` : ZB1))? A z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @` 9 Z8B1))?i  z0___PPT10:___PPT9 NK cells> " fc   @` 8 ZB1))?A z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @` 7 ZB1))?i z0___PPT10:___PPT9  Macrophages> "  fc   @` 6 ZB1))?Az0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @` 5 Z$;B1))?iz0___PPT10:___PPT9  Neutrophils> "  fc    @` 3 ZtGB1))?iAz0___PPT10:___PPT9 Circulating effector cellsB " fg&     @` 2 Z,PBf1))?Az0___PPT10:___PPT9 Microbial killing> " fc   @` 1 ZSBf1))?iz0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @` 0 ZleBf1))?Az0___PPT10:___PPT9 Microbial killing> " fc   @` / Z@qBf1))?iz0___PPT10:___PPT9  Defensins> "  fc    @` . Z{Bf1))? Az0___PPT10:___PPT9 Prevent microbial entry> " fc   @` - Z(vBf1))?i z0___PPT10:___PPT9 Epithelial layers> " fc   @` + ZBf1))?i8A z0___PPT10:___PPT9 Epithelial barriersB " fg   @` *  `B1))??A8z0___PPT10:___PPT9 Principal Functions> " fc   @` )  `B1))?i?8z0___PPT10:___PPT9  Components< "  fc   @`B E Z8c ))?i?A?B F Z1 ))?iAB G Z8c ))?i?i8B H Z8c ))?A?A8B K Z1 ))?i8A8B L Z1 ))?i8iB M T1 ))??8B O Z1 ))?A8AB Q Z1 ))?i A B V Z1 ))?iAB X Z1 ))? B ] Z1 ))?iAB e Z1 ))?iAB m Z1 ))?iAB s Z1 ))?iAB u Z1 ))? B z Z1 ))?i A B  Z1 ))?i A B  Z1 ))?in An B  Z1 ))?i A B  Z1 ))?n =B  Z1 ))?i A B  Z1 ))?i=A=H  0޽h ? 33___PPT10i.'`+D=' I= @B + 0N0 D(  D D c TA0S9781416031239-002-f003"`< D Z؈B1))?O {Epithelial barriers*0 2g   D Z1))?"` D Z1))?"` D Z1))?"`H D 0޽h ? ay___PPT10Y+D=' I= @B + 0 p\4(  \8 U \V \ C &A0202_1 V \ C &A 0202_2"UH \ 0޽h ? 33___PPT10i.`7֓+D=' I= @B +; 0yN0 :2p (  W  ZtB1))?Z g Skin Mucosal surfaces of the gastrointestinal tracts (GI) Mucosal surfaces of the respiratory tracts6h r2<a,a h    Z؀B1))?,] s yPhysical barriers*0 2g     Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.(@|T=+D=' I= @B + 02N0 p &(    ZB1))?,] L Antimicrobial Peptides <0 2ee    ZB1))?zT  Defensins Cystein-rich peptides with 29-34 amino acids Present in the skin and abundant in neutrophil granules Broad-spectrum antibiotics Upregulated by inflammatory cytokines Cryptocidines Secreted mlWe; :~Nn5OkkxnZ.ʝ͟A}a3 k/NFex'c^UVDVmfSw+'lj0zTz 2}=f2:ʿ?kIKU}/dՐ",gΧ Fe׺ o]m߻b/:c.e^6cfGP p75*骒Dm/}׺ UWzm/'vu$瑾-{?GseϲNMy6SkXkk*ZPߣY{ɍh)x(96?s}i->moOWΙwٮv[!Ԗ%ǹX+OUMa5<[ݷ.Zg5by the epithelium of the intestine Locally sterilize the lumen of intestine H r20 2 r2V0 2 g-cc7c c cc&cgc+ c $c$)(c(     J   %      W   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.01/+D=' I= @B +4 0N0 3+ (  4  ZB1))?,L Intraepithelial lymphocytes P0 2eee    ZB1))?) L Intraepithelial T cells Present in the epidermis of the skin and in mucosal epithelia gd cells and NKT cells Serve as sentinels at common sites of microbial invasion r20 2g>cc9c    ZY'  Z1))?Yz0___PPT10:___PPT9  CytokinesB "  fg   @`  Z1))?Yz0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @`  Z@1))?z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`   ZH/1))?G Yz0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @`   Z11))?G z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @`   ZH1))? YG z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @`   Z8@1))? G z0___PPT10:___PPT9  Complement: "  bc   @`   Z_1))? Y z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @`   Zif1))?N Y z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @`  Zjf1))?N  z0___PPT10:___PPT9 NK cellsB " fg   @`  Z䀹f1))? YN z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @`  ZXf1))? N z0___PPT10:___PPT9  MacrophagesB "  fg   @`  Zf1))?<Y z0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @`  Zf1))?< z0___PPT10:___PPT9  NeutrophilsB "  fg    @`  Zf1))?VY<z0___PPT10:___PPT9 Circulating effector cellsB " fg&     @`  ZD1))?YVz0___PPT10:___PPT9 Microbial killing> " fc   @`  Z¹1))?Vz0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @`  Z,ƹ1))?DYz0___PPT10:___PPT9 Microbial killing> " fc   @`  ZϹ1))?Dz0___PPT10:___PPT9  Defensins> "  fc    @`  Z۹1))?vYDz0___PPT10:___PPT9 Prevent microbial entry> " fc   @`  Z1))?vDz0___PPT10:___PPT9 Epithelial layers> " fc   @`  Z1))?Yvz0___PPT10:___PPT9 Epithelial barriersB " fg   @`   `l1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @`   ` l1))?z0___PPT10:___PPT9  Components< "  fc   @`B  Z8c ))?YB  Z1 ))?YB  Z8c ))?B   Z8c ))?YYB ! Z1 ))?YB " Z1 ))?B # T1 ))?B $ Z1 ))?YYB % Z1 ))?vYvB & Z1 ))?DYDB ' Z1 ))?vVB ( Z1 ))?YB ) Z1 ))?VYVB * Z1 ))?<Y<B + Z1 ))? Y B , Z1 ))?< B - Z1 ))?N YN B . Z1 ))? 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(- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0ppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P3  0 JB (    Z1))?\ ` Phagocytes& 0 2 c    Zl1))?u  ^b Cell types Neutrophils and Macrophages Primary functions Identify, ingest, and destroy microbes r20 2 r2'0 2 aaaaa'a&    L   Z1))?"`  Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.@p!+D=' = @B + 0   Z(    Z(l1))?  0Neutrophils Polymorphonuclear neutrophils (PMNs)J10 2 ccch            c TA 0S9781416031239-002-f004"` #H  0޽h ? 33___PPT10i.Ap+D=' = @B +Z 0 y L(  L L ZH3l1))?   ;Downloaded from: StudentConsult (on 22 April 2010 06:36 AM)&<0(2<c <  L Z@7l1))?Z  f 2005 Elsevier &0(2c  ] L Z$;l1))?2, o The most abundant population of circulating leukocytes Mediate the earliest phases of inflammatory responses&p r2pao   L Z@l1))?rJ o Neutrophils& 0 2 c     L Z1))?"`  L Z1))?"`+  L Z1))?"` L Z1))?"`+H L 0޽h ? ay___PPT10Y+D=' = @B + 0 @ }(    ZGl1))?w0  a Macrophages& 0 2 c    c TA 0S9781416031239-002-f005"`G?   Z1))?"`   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.At+D=' = @B +Z% 0 q$i$$(  " dbg   #"2&bdg  L  fhVl1))? H g z0___PPT10:___PPT9 spleen( " b  Z 0 @`Q K  fWl1))?dH g <___PPT10^___PPT9@8 Sinusoidal lining cells` "  bb ff   Y 0  @` J  f,pl1))? ) H z0___PPT10:___PPT9 bone( " b  X 0 @` I  fpl1))?d) H z0___PPT10:___PPT9  Osteoclasts( "  b   W 0  @` H  fl1))? ) z0___PPT10:___PPT9  granulomas( "  b   V 0  @`  G  f(l1))?d ) z0___PPT10:___PPT9  Ho 'Jq:WSd":a̱OoC1Svn}VUms~:P2ZwXG!ߴW>Ԏ;CiSSthsl!MLIHzGGʘ%$xu (k.-uwwV:SlH6˛:Ms-,dWrF .uJZC o~ӬV?Un[T.v.Muz u~lto2C>XnUM.SL-ڵ~u۳ȲWks\s˿5)هs>4_S DoY?Zߏ--lĆwk6宓*v5,cp-\z}'efmm8{{N69CginWZ?im io)uUMۮKuKsmӳhkNEpithelioid cellsL "  bfb   U 0  @` F  fАl1))?  z0___PPT10:___PPT9  neural tissue( " b   T 0  @` E  fHl1))?d z0___PPT10:___PPT9  Microglia( "  b   S 0  @` D  f̲l1))? z0___PPT10:___PPT9 liver( " b  R 0 @` C  f8l1))?d z0___PPT10:___PPT9  Kupffer cells( " b&   Q 0  @` B  fl1))? z0___PPT10:___PPT9 connective tissue( " b  P 0 @` A  fl1))?d z0___PPT10:___PPT9  Histiocytes( "  b   O 0  @` @  f(l1))? D___PPT10$r___PPT9TL bpulmonary alveolus of lungs| " bbfbb b 0    M 0N 0 @` ?  fl1))?d z0___PPT10:___PPT9 Alveolar macrophages, " f   @` >  fo1))? bz0___PPT10:___PPT9 x Location& "  `   @` =  fTo1))?db z0___PPT10:___PPT9 x Name of cell& "  `   @`B M T1))?dbbB N T1))?dg g B O T1))?dbdg B P T1))?bg   Z1))?"`  Z1))?"`  Z1))?"`H  0޽h ? 33___PPT10i. Y&+D=' = @B +r([r(0$05 ~ 7*[ /0(X   M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/LungsOPhttp://en.wikipedia.org/wiki/HistiocytesPhttp://en.wikipedia.org/wiki/HistiocytesP\http://en.wikipedia.org/wiki/Connective_tissue\http://en.wikipedia.org/wiki/Connective_tissueQRhttp://en.wikipedia.org/wiki/Kupffer_cellRhttp://en.wikipedia.org/wiki/Kupffer_cellRDhttp://en.wikipedia.org/wiki/LiverDhttp://en.wikipedia.org/wiki/LiverSLhttp://en.wikipedia.org/wiki/MicrogliaLhttp://en.wikipedia.org/wiki/MicrogliaTThttp://en.wikipedia.org/wiki/Neural_tissueThttp://en.wikipedia.org/wiki/Neural_tissueUPhttp://en.wikipedia.org/wiki/EpithelioidPhttp://en.wikipedia.org/wiki/EpithelioidVNhttp://en.wikipedia.org/wiki/GranulomasNhttp://en.wikipedia.org/wiki/GranulomasWPhttp://en.wikipedia.org/wiki/OsteoclastsPhttp://en.wikipedia.org/wiki/OsteoclastsXBhttp://en.wikipedia.org/wiki/BoneBhttp://en.wikipedia.org/wiki/BoneYNhttp://en.wikipedia.org/wiki/SinusoidalNhttp://en.wikipedia.org/wiki/SinusoidalZFhttp://en.wikipedia.org/wiki/SpleenFhttp://en.wikipedia.org/wiki/Spleen/ 0DTimes New Roman\t3 0DArialNew Roman\t3 0" D[SOalNew Roman\t3 00DVerdanaw Roman\t3 0"@DWingdingsRoman\t3 0PDSymbolgsRoman\t3 0`DTahomagsRoman\t3 0" C0.  @n?" dd@  @@``  h2 =DA=@$! / &0" ><I=V7>*$d]K3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' (- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0ppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P+ 0 B:0 (    Za1))?z, U Dominant effector cells of the later stages of innate immune response Play central role in both innate and adaptive immune responsel0 2ccFc c =c@   5  >   Z1))?"`   Z1))?"`   Z1))?"`   ZG1))?Wt  a Macrophages& 0 2 c  H  0޽h ? 33___PPT10i. $+D=' = @B +r~[~ Z[ /0(X   M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/LungsOPhttp://en.wikipedia.org/wiki/HistiocytesPhttp://en.wikipedia.org/wiki/HistiocytesP\http://en.wikipedia.org/wiki/Connective_tissue\http://en.wikipedia.org/wiki/Connective_tissueQRhttp://en.wikipedia.org/wiki/Kupffer_cellRhttp://en.wikipedia.org/wiki/Kupffer_cellRDhttp://en.wikipedia.org/wiki/LiverDhttp://en.wikipedia.org/wiki/LiverSLhttp://en.wikipedia.org/wiki/MicrogliaLhttp://en.wikipedia.org/wiki/MicrogliaTThttp://en.wikipedia.org/wiki/Neural_tissueThttp://en.wikipedia.org/wiki/Neural_tissueUPhttp://en.wikipedia.org/wiki/EpithelioidPhttp://en.wikipedia.org/wiki/EpithelioidVNhttp://en.wikipedia.org/wiki/GranulomasNhttp://en.wikipedia.org/wiki/GranulomasWPhttp://en.wikipedia.org/wiki/OsteoclastsPhttp://en.wikipedia.org/wiki/OsteoclastsXBhttp://en.wikipedia.org/wiki/BoneBhttp://en.wikipedia.org/wiki/BoneYNhttp://en.wikipedia.org/wiki/SinusoidalNhttp://en.wikipedia.org/wiki/SinusoidalZFhttp://en.wikipedia.org/wiki/SpleenFhttp://en.wikipedia.org/wiki/Spleen/ 0DTimes New Roman\t3 0DArialNew Roman\t3 0" D[SOalNew Roman\t3 00DVerdanaw Roman\t3 0"@DWingdingsRoman\t3 0PDSymbolgsRoman\t3 0`DTahomagsRoman\t3 0" C0.  @n?" dd@  @@``  h2 =DA=@$! / &0" ><I=V7>*$d]K3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' (- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0Hppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P 02N0 p <(    ZB1))?,s Antimicrobial Peptides @0 2gg    ZB1))?zT # Defensins Cystein-rich peptides with 29-34 amino acids Present in the skin and abundant in neutrophil granules Broad-spectrum antibiotics Upregulated by inflammatory cytokines Cryptocidines Secreted by the epithelium of the intestine Locally sterilize the lumen of intestine Z r20 2 r2V0 2 eg-cc7c c cc&cec+ c $c$)(c(     J   %      W   Z1))?"`   Z1))?"`H  0޽h ? 33___PPT10i.01/+D=' = @B +J 0N0 IA (  8  ZB1))?,s Intraepithelial lymphocytes T0 2gge    ZB1))?). L Intraepithelial T cells Present in the epidermis of the skin and in mucosal epithelia gd cells and NKT cells Serve as sentinels at common sites of microbial invasion r20 2ge>cc9c    Z<I=V7>*$d]K3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' (- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0ppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P' 0 >6p $(  $ $ Z6o1))?Da p Phagocytosis& 0 2 c    $ ZD=o1))?'   A cytoskeleton-dependent cellular process of phagocytes of engulfing large particles Bound microbes are ingested into vesicles called phagosome6 q2aa&     $ Z1))?"` $ Z1))?"` $ Z1))?"`+  $ Z1))?"`  $ Z1))?"`+H $ 0޽h ? 33___PPT10i. 0u+D=' = @B +%  0 <4 ((  ( ( ZIo1))?La $Destruction of phagocytosed microbes&%0 2%c&     S ( ZL?o1))?O   Where Phagolysosome Killing Mechanisms 1. Reactive oxygen intermediates (ROIs) 2. Reactive nitrogen intermediates: mainly NO 3. Preformed antimicrobials  r20 2 r2u0 2aa a a aaNa@    t   ( ZYo1))?  7BUT, these mechanisms also can cause host tissue injury*80 28g 8  ( Z1))?"` ( Z1))?"`  ( Z1))?"`+  ( Z1))?"`  ( Z1))?"`+H ( 0޽h ? 33___PPT10i. $+D=' = @B +M 0 d\` (    Zro1))?j  sNatural Killer cells (NK cells)$ 0 2 a    Zuo1))? \TL___PPT9.& A type of cytotoxic lymphocytes The principal physiologic role Defense against infections by viruses and some other intracelluar microbes 2. Rejection of tumors @0 2B1 20 20 2?ccQccc@    b   +  @`  Z1))?"`  Z1))?"`+   Z1))?"`   Z1))?"`+   Z1))?"`H  0޽h ? 33___PPT10i.Bʄ3+D=' = @B +r*  ~ ht2 /0(X   M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/LungsOPhttp://en.wikipedia.org/wiki/HistiocytesPhttp://en.wikipedia.org/wiki/HistiocytesP\http://en.wikipedia.org/wiki/Connective_tissue\http://en.wikipedia.org/wiki/Connective_tissueQRhttp://en.wikipedia.org/wiki/Kupffer_cellRhttp://en.wikipedia.org/wiki/Kupffer_cellRDhttp://en.wikipedia.org/wiki/LiverDhttp://en.wikipedia.org/wiki/LiverSLhttp://en.wikipedia.org/wiki/MicrogliaLhttp://en.wikipedia.org/wiki/MicrogliaTThttp://en.wikipedia.org/wiki/Neural_tissueThttp://en.wikipedia.org/wiki/Neural_tissueUPhttp://en.wikipedia.org/wiki/EpithelioidPhttp://en.wikipedia.org/wiki/EpithelioidVNhttp://en.wikipedia.org/wiki/GranulomasNhttp://en.wikipedia.org/wiki/GranulomasWPhttp://en.wikipedia.org/wiki/OsteoclastsPhttp://en.wikipedia.org/wiki/OsteoclastsXBhttp://en.wikipedia.org/wiki/BoneBhttp://en.wikipedia.org/wiki/BoneYNhttp://en.wikipedia.org/wiki/SinusoidalNhttp://en.wikipedia.org/wiki/SinusoidalZFhttp://en.wikipedia.org/wiki/SpleenFhttp://en.wikipedia.org/wiki/Spleen/ 0DTimes New Roman\t3 0DArialNew Roman\t3 0" D[SOalNew Roman\t3 00DVerdanaw Roman\t3 0"@DWingdingsRoman\t3 0PDSymbolgsRoman\t3 0`DTahomagsRoman\t3 0" C0.  @n?" dd@  @@``  h2 =DA=@$! / &0" ><I=V7>*$d] oZJzNV&@zZCcc]Do<'+̲t~KC;o,S+]4[CUWi8Rɗd۬,8}8ZSzmŦzmAߥ{ص`YzEW7}m\7o;خukpm鏧"1T]lWSog֪amllsv$W7b<1[ăc}N3Gγ}.C[t=جdfH2{EEc# d;}Lk8s=6[^?ڇRѸջ"܇N:k[}u`v!nk/nlIOEߊ2:!O d?\s5u_SXH&_enǀ[Kgwʷ5t?YStK3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' (- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s%t v w y { } b$ؽ)ܨKucq;vFR$ۖ\( KR$Ea1SSR$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKd3 0ppp@ <4BdBd^ 08t3<4!d!d^ 08t3s ʚ;zLs8ʚ;<4dddd٫ 0___PPT10D[SOes New Roman< 0<DArialNew Roman< 0<" DTimes New Roman< 0< pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !/h~P%  0 <4 ((  ( ( ZIo1))?La $Destruction of phagocytosed microbes&%0 2%c&     S ( ZL?o1))?O   Where Phagolysosome Killing Mechanisms 1. Reactive oxygen intermediates (ROIs) 2. Reactive nitrogen intermediates: mainly NO 3. Preformed antimicrobials  r20 2 r2u0 2aa a a aaNa@    t   ( ZYo1))?  7BUT, these mechanisms also can cause host tissue injury*80 28g 8  ( Z1))?"` ( Z1))?"`  ( Z1))?"`+  ( Z1))?"`  ( Z1))?"`+H ( 0޽h ? 33___PPT10i. $+D=' = @B +r2b~ 2 l /0(X   M^http://en.wikipedia.org/wiki/Pulmonary_alveolus^http://en.wikipedia.org/wiki/Pulmonary_alveolusNDhttp://en.wikipedia.org/wiki/LungsDhttp://en.wikipedia.org/wiki/LungsOPhttp://en.wikipedia.org/wiki/HistiocytesPhttp://en.wikipedia.org/wiki/HistiocytesP\http://en.wikipedia.org/wiki/Connective_tissue\http://en.wikipedia.org/wiki/Connective_tissueQRhttp://en.wikipedia.org/wiki/Kupffer_cellRhttp://en.wikipedia.org/wiki/Kupffer_cellRDhttp://en.wikipedia.org/wiki/LiverDhttp://en.wikipedia.org/wiki/LiverSLhttp://en.wikipedia.org/wiki/MicrogliaLhttp://en.wikipedia.org/wiki/MicrogliaTThttp://en.wikipedia.org/wiki/Neural_tissueThttp://en.wikipedia.org/wiki/Neural_tissueUPhttp://en.wikipedia.org/wiki/EpithelioidPhttp://en.wikipedia.org/wiki/EpithelioidVNhttp://en.wikipedia.org/wiki/GranulomasNhttp://en.wikipedia.org/wiki/GranulomasWPhttp://en.wikipedia.org/wiki/OsteoclastsPhttp://en.wikipedia.org/wiki/OsteoclastsXBhttp://en.wikipedia.org/wiki/BoneBhttp://en.wikipedia.org/wiki/BoneYNhttp://en.wikipedia.org/wiki/SinusoidalNhttp://en.wikipedia.org/wiki/SinusoidalZFhttp://en.wikipedia.org/wiki/SpleenFhttp://en.wikipedia.org/wiki/Spleen/ 0DTimes New Roman\t3 0DArialNew Roman\t3 0" D[SOalNew Roman\t3 00DVerdanaw Roman\t3 0"@DWingdingsRoman\t3 0PDSymbolgsRoman\t3 0`DTahomagsRoman\t3 0" C0.  @n?" dd@  @@``  h2 =DA=@$! / &0" ><I=V7>*$d]K3/5 B" o;?    &&= D    P_yh &J:A $###T >Q C $$?.<d6N+!]+1X..3$K9 *  6C(7K `,Q *II )*  y !"' 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(- ./ 057 BF?IK M Q R T V W Y Z \ ]^R`=ac e g i n o@p qr>s&t v w y { } ~$R$ۖ\( KR$1X9VrG]] R$C5ڔ3Fe<Ob$<_5pq}%V2~]A9Mcb$-VΙQ3 b$)t>FH?#R$3%%lf)I;bR$d-,_J4:BcR$PpSD:q]^b$\|3gu"./7RR$+I t)[EE7YTn <b$3೪[IFOvI$R$\S7 BTL-8iR$q;­\.  R$jKunCo$  0e0e    A AƁ1ρ ))     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| 3f3!@f[ g4KdKdǶ 0                         ! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c d e f g h i j k l m n o p q r s t u v w x y z { | } ~  Rppp@ <4BdBd 0T@7 <4!d!d 0T@7s ʚ;zLs8ʚ;<4dddd| 0___PPT10D[SOes New TTpX80pǶ 0hDArialNew TTpX80pǶ 0h" DTimes New RomanpX80pǶ 0h pp___PPT9/ 0DM$Pulmonary alveolus*N Lungs6OHistiocytesBP"Connective tissue8QKupffer cell*R Liver2SMicroglia:TNeural tissue6UEpithelioid4VGranulomas6WOsteoclasts(XBone4YSinusoidal,Z Spleen&? %O =  `j ^ FUNCTIONS COMPONENTS Innate immunity recognition The influence on adaptive immunity 8_qbEf _ q     r ux y !"/h~PH  ` 33` Sf3f` 33g` f` www3PP` ZXdbmo` \ғ3y`Ӣ` 3f3ff` 3f3FKf` hk]wwwfܹ` ff>>\`Y{ff` R>&- {p_/̴>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> zr  (    6P " `}  X Click to edit Master title style!! (  00 " `  RClick to edit Master text styles Second level Third level Fourth level Fifth level!    S   00 "^ `  n*"0 c    0З "^   p*$0 c    0 "^ `  p*$0 c  t  C >A&2007928195140760_c"u    Z1))?#" `    Z1))?#" `    f$Hi1))?#" `  N$0 c V  0޽h ?"` 3380___PPT10.oM) Default DesignL0 ?(      f |f1))?"`V N$0 c   Z!|1))? C iInnate Immunity*0 2g<    Z&|1))?t2 \Rui He ruihe@fudan.edu.cn Department of Immunology Shanghai Medical School Fudan University(]0( 2]cN   2      Z1))?"`)    f<|1))?"`)W N$0 c H  0޽h ? 33___PPT10i.Ps:+D=' = @B +SL0  Q(    6k| wG bComponents of Immunityb$    Zho|1))?  'Innate Immunity: non-specific, also called natural or native immunity Adaptive Immunity: specific, also called acquired immunityt0 2c c6ac c(a    Z1))?"`H  0޽h ? 33___PPT10i.wZL+D=' = @B +`@GL0 _?W?7?@>(  @td  :@ #"  @  fH|1))?z0___PPT10:___PPT9 (Features of Innate and Adaptive Immunity:)( " (d333a )  @`B @ T1))?B @ T1))?B @ T1))?B  @ T1))?;: '7 ?@ #":. 9 89 9 8 9'7  @ Zh|1))? V 7z0___PPT10:___PPT9  Lymphocytes> "  f c    @`  @ Z|1))?_V z0___PPT10:___PPT9 ;Phagocytes (macrophages, neutrophils), natural killer cells>< " ;f c &     @`  @ Z|1))?'V _z0___PPT10:___PPT9 Cells> " fc   @` @ Zl|1))? J 7V z0___PPT10:___PPT9  Antibodies> "  f c    @` @ Z,|1))?_J V z0___PPT10:___PPT9 Complement, others> " f c    @` @ Z`|1))?'J _V z0___PPT10:___PPT9 Blood proteins> " fc   @` @ Z|1))?  7J z0___PPT10:___PPT9 DLymphocytes in epithelia; antibodies secreted at epithelial surfaces>E " Df c  E  @` @ ZL{1))?_ J z0___PPT10:___PPT9 0Skin, mucosal epithelia; antimicrobial chemicals>1 " 0f c  1  @` @ ZL|1))?' _J z0___PPT10:___PPT9 Cellular and chemical barriers> " fc   @` @ Z({1))?' 7 z0___PPT10:___PPT9  ComponentsB "  fg   @` @ Z{1))? 7 z0___PPT10:___PPT9 Yes> " f c    @` @ Z`,{1))? z0___PPT10:___PPT9 Yes> " f c    @` @ Z &{1))?' z0___PPT10:___PPT9 Nonreactivity to self> " fc     @` @ Z0{1))? 7z0___PPT10:___PPT9 Yes> " f c    @` @ Z;{1))? z0___PPT10:___PPT9 None> " f c    @` @ Z9{1))?'z0___PPT10:___PPT9 Memory> " fc   @` @ Ze{1))? o7z0___PPT10:___PPT9 LVery large; receptors are produced by somatic recombination of gene segments>M " Lf c  M  @` @ Zg{1))?o z0___PPT10:___PPT9 Limited; germline-encoded> " f c &      @` @ Z4]{1))?'oz0___PPT10:___PPT9  Diversity> "  fc   @` @ Z{1))? 77oz0___PPT10:___PPT9 6For antigens of microbes and for nonmicrobial antigens>7 " 6f c &!      @` @ Z({1))?7 oz0___PPT10:___PPT9 3For structures shared by groups of related microbes>4 " 3f c  4  @`  @ Z{1))?'7oz0___PPT10:___PPT9  Specificity> "  fc   @` !@ Z$3{1))?'+77z0___PPT10:___PPT9 CharacteristicsB " fg   @` "@  `4{1))? 7+z0___PPT10:___PPT9 Adaptive: " fc   @` #@  `|{1))?_ +z0___PPT10:___PPT9 Innate: " fc   @` $@  `<{1))?'_+z0___PPT10:___PPT9 B " fg  @`B %@ Z8c ))?'7B &@ Z1 ))?'7B '@ Z8c ))?''+B (@ Z8c ))?77+B )@ Z1 ))?'+7+B *@ Z1 ))?'+'B +@ T1 ))?__+B ,@ T1 ))?  +B -@ Z1 ))?7+7B .@ Z1 ))?'777B /@ Z1 ))?'o7oB 0@ Z1 ))?7 B 1@ Z1 ))? 7 B 2@ Z1 ))?'7B 3@ Z1 ))?'7B 4@ Z1 ))?' 7 B 5@ Z1 ))?' 7 B 6@ Z1 ))?'J 7J B 7@ Z1 ))?_ _B 8@ Z1 ))?  B 9@ Z1 ))?'V 7V H @ 0޽h ? 33___PPT10i.+D=' = @B +>cWL0 ME (  /  Z̯|1))?R )The physiologic function of immune systemL*0 2c(ce * /  0| E j WInnate Immunity: the early reactions Adaptive Immunity: the later responses HXZbbbb X    Z1))?"`   ZГ|1))?: }#Defense against infectious microbes*$0( 2$e $   Z1))?"`H  0޽h ? ̙33y___PPT10Y+D=' = @B +39qL0 B:y (  x y c TA0S9781416031239-001-f001"`H x 0޽h ? ay___PPT10Y+D=' = @B + L0 P W(   ~   s *@z'      Z1))?/m  wInnate Immunity*0 2g      Z1))?"`H   0޽h ? y___PPT10Y+D=' = @B +sL0 rj (    Z#1))?ZJ zOVERVIEW6 0 cc  &  Z{1))?|  0The first line of defense against infection An evolutionarily older defense strategy, found in all classes of plants and animals Preexist infection or exposure to foreign antigen Respond immediately after recognition of microbes Respond in essentially the same way to repeated infection "-0 2: q2% q2 q20 2,eaa[aa1aa1 a a9ac&/ *    Z1))?"`H  0޽h ? 33___PPT10i.|+D=' = @B +/L0 .&`(    Z|B1))?/&  U Initial response to microbes to prevent infection with elimination of danger Innate components also important in adaptive immunity Stimulates adaptive responses h5 q! qY q q2a    Z<>1))?w  } FUNCTIONS6 0  cc      Z1))?"`H  0޽h ? 33___PPT10i.(,.+D=' = @B +<L0 ;;P3`;(    ZlO1))?' "Components of innate immune system6#0( 2a"a #    `1))?~9 i?A  #"J>Y C ZS1))?i=Az0___PPT10:___PPT9  CytokinesB "  fg   @` B Zf1))? A=z0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @` A Zi1))?i =z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`  @ ZHx1))? A z0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @` ? Z{1))?i  z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @` > Z,1))?n A z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @` = Z1))?in  z0___PPT10:___PPT9  Complement: "  bc   @` ; Z`1))?i An z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @` : ZD1))? A z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @` 9 Z輓1))?i  z0___PPT10:___PPT9 NK cells> " fc   @` 8 Z1))?A z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @` 7 Zړ1))?i z0___PPT10:___PPT9  Macrophages> "  fc   @` 6 Zܸ1))?Az0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @` 5 Zt1))?iz0___PPT10:___PPT9  Neutrophils> "  fc    @` 3 Z1))?iAz0___PPT10:___PPT9 Circulating effector cellsB " fg&     @` 2 Ztf1))?Az0___PPT10:___PPT9 Microbial killing> " fc   @` 1 Zأf1))?iz0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @` 0 ZLf1))?Az0___PPT10:___PPT9 Microbial killing> " fc   @` / Zf1))?iz0___PPT10:___PPT9  Defensins> "  fc    @` . Zf1))? Az0___PPT10:___PPT9 Prevent microbial entry> " fc   @` - Zxf1))?i z0___PPT10:___PPT9 Epithelial layers> " fc   @` + Zf1))?i8A z0___PPT10:___PPT9 Epithelial barriersB " fg   @` *  `1))??A8z0___PPT10:___PPT9 Principal Functions> " fc   @` )  `|1))?i?8z0___PPT10:___PPT9  Components< "  fc   @`B E Z8c ))?i?A?B F Z1 ))?iAB G Z8c ))?i?i8B H Z8c ))?A?A8B K Z1 ))?i8A8B L Z1 ))?i8iB M T1 ))??8B O Z1 ))?A8AB Q Z1 ))?i A B V Z1 ))?iAB X Z1 ))? B ] Z1 ))?iAB e Z1 ))?iAB m Z1 ))?iAB s Z1 ))?iAB u Z1 ))? B z Z1 ))?i A B  Z1 ))?i A B  Z1 ))?in An B  Z1 ))?i A B  Z1 ))?n =B  Z1 ))?i A B  Z1 ))?i=A=H  0޽h ? 33___PPT10i.'`+D=' = @B +L0 Dg(  D D c TA0S9781416031239-002-f003"`< D Z>1))?O {Epithelial barriers*0 2g   D Z1))?"`H D 0޽h ? ay___PPT10Y+D=' = @B + p\4(  \8 U \HV \ C &A0202_1 V \ C &A 0202_2"UH \ 0޽h ? 33___PPT10i.`7֓+D=' = @B + yL0  p (  W  Z1))?Z g Skin Mucosal surfaces of the gastrointestinal tracts (GI) Mucosal surfaces of the respiratory tracts6h r2<a,a h    ZH1))?,] s yPhysical barriers*0 2g  H  0޽h ? 33___PPT10i.(@|T=+D=' = @B +}2L0 |tp  (    Z|1))?,s Antimicrobial Peptides @0 2gg    Zpx1))?zT # Defensins Cystein-rich peptides with 29-34 amino acids Present in the skin and abundant in neutrophil granules Broad-spectrum antibiotics Upregulated by inflammatory cytokines Cryptocidines Secreted by the epithelium of the intestine Locally sterilize the lumen of intestine Z r20 2 r2V0 2 eg-cc7c c cc&cec+ c $c$)(c(     J   %      W H  0޽h ? 33___PPT10i.01/+D=' = @B +L0  (  8  ZJ1))?,s Intraepithelial lymphocytes T0 2gge    Z<1))?). L Intraepithelial T cells Present in the epidermis of the skin and in mucosal epithelia gd cells and NKT cells Serve as sentinels at common sites of microbial invasion r20 2ge>cc9c    Z1))?c ) C B-1 cells Present in peritoneal cavity Produce NATURAL antibodies  r20 20( 2 ec7c c  D H  0޽h ? 33___PPT10i.SO+D=' = @B +< ;;3<l;(    Zg1))?' "Components of innate immune system6#0( 2a"a #    `1))?9 Y < #"J>Y'  Zwc1))?Yz0___PPT10:___PPT9  CytokinesB "  fg   @`  Zc1))?Yz0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @`  Zl1))?z0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`   ZԲ1))?G Yz0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @`   Zܭ1))?G z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @`   Zʏ1))? YG z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @`   Z0ŏ1))? G z0___PPT10:___PPT9  Complement: "  bc   @`   Zޏ1))? Y z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @`   Zf1))?N Y z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @`  Zf1))?N  z0___PPT10:___PPT9 NK cellsB " fg   @`  Z|f1))? YN z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @`  ZT|f1))? N z0___PPT10:___PPT9  MacrophagesB "  fg   @`  Zf1))?<Y z0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @`  Zpyf1))?< z0___PPT10:___PPT9  NeutrophilsB "  fg    @`  Z yf1))?VY<z0___PPT10:___PPT9 Circulating effector cellsB " fg&     @`  Z y1))?YVz0___PPT10:___PPT9 Microbial killing> " fc   @`  Z y1))?Vz0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @`  Zy1))?DYz0___PPT10:___PPT9 Microbial killing> " fc   @`  Z$.y1))?Dz0___PPT10:___PPT9  Defensins> "  fc    @`  Zdy1))?vYDz0___PPT10:___PPT9 Prevent microbial entry> " fc   @`  ZHJy1))?vDz0___PPT10:___PPT9 Epithelial layers> " fc   @`  ZMy1))?Yvz0___PPT10:___PPT9 Epithelial barriersB " fg   @`   `Dy1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @`   `Day1))?z0___PPT10:___PPT9  Components< "  fc   @`B  Z8c ))?YB  Z1 ))?YB  Z8c ))?B   Z8c ))?YYB ! Z1 ))?YB " Z1 ))?B # T1 ))?B $ Z1 ))?YYB % Z1 ))?vYvB & Z1 ))?DYDB ' Z1 ))?vVB ( Z1 ))?YB ) Z1 ))?VYVB * Z1 ))?<Y<B + Z1 ))? Y B , Z1 ))?< B - Z1 ))?N YN B . Z1 ))? Y B / Z1 ))? Y B 0 Z1 ))?G YG B 1 Z1 ))? B 2 Z1 ))?YB 3 Z1 ))?YH  0޽h ? 33___PPT10i.'`+D=' = @B +   (    Zy1))?\ ` Phagocytes& 0 2 c    Z~y1))?u  ^b Cell types Neutrophils and Macrophages Primary functions Identify, ingest, and destroy microbes r20 2 r2'0 2 aaaaa'a&    L   Z1))?"`H  0޽h ? 33___PPT10i.@p!+D=' = @B +   Z(    Zy1))?  0Neutrophils Polymorphonuclear neutrophils (PMNs)J10 2 ccch            c TA 0S9781416031239-002-f004"` #H  0޽h ? 33___PPT10i.Ap+D=' = @B + L(  L] L Z y1))?2, o The most abundant population of circulating leukocytes Mediate the earliest phases of inflammatory responses&p r2pao   L Z,y1))?rJ o Neutrophils& 0 2 c   H L 0޽h ? ay___PPT10Y+D=' = @B + %@ (    Zpy1))?w0  a Macrophages& 0 2 c    c TA 0S9781416031239-002-f005"`G? H  0޽h ? 33___PPT10i.At+D=' = @B +# ""9"(  " dbg   #"2&bdg  L  fЮy1))? H g z0___PPT10:___PPT9 spleen( " b  Z 0 @`Q K  f y1))?dH g <___PPT10^___PPT9@8 Sinusoidal lining cells` "  bb ff   Y 0  @` J  fy1))? ) H z0___PPT10:___PPT9 bone( " b  X 0 @` I  fy1))?d) H z0___PPT10:___PPT9  Osteoclasts( "  b   W 0  @` H  fy1))? ) z0___PPT10:___PPT9  granulomas( "  b   V 0  @`  G  fy1))?d ) z0___PPT10:___PPT9 Epithelioid cellsL "  bfb   U 0  @` F  f  fY? L Z1))?YY?z0___PPT10:___PPT9  CytokinesB "  fg   @` L Zf1))?YYz0___PPT10:___PPT9 2Opsonization of microbes, activation of complement>3 " 2fc  '  @` L Zlf1))?Yz0___PPT10:___PPT9 C-reactive protein (pentraxin)> " fc&     @`  L Zf1))? Yz0___PPT10:___PPT9 COpsonization of microbes, activation of complement (lectin pathway)>D " Cfc4  (     @`  L Zxf1))? z0___PPT10:___PPT9 "Mannose-binding lectin (collectin)># " "fc@       @`  L Z`/f1))? Y z0___PPT10:___PPT9 GKilling of microbes, opsonization of microbes, activation of leukocytes>H " Gfc&   '  @`  L Z@:f1))?  z0___PPT10:___PPT9  Complement: "  bc   @`  L ZDf1))? Y z0___PPT10:___PPT9 Circulating effector proteinsB " fg&      @`  L Z 1))? Y z0___PPT10:___PPT9 2Lysis of infected cells, activation of macrophages>3 " 2fc .  @` L ZZ1))?  z0___PPT10:___PPT9 NK cells: " bc   @` L Ze1))?Y z0___PPT10:___PPT9 bEfficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation>c " bfc&    M  @` L Zp1))? z0___PPT10:___PPT9  Macrophages: "  bc   @` L Z{1))?Yz0___PPT10:___PPT9 *Early phagocytosis and killing of microbes>+ " *fc&     @` L Z`~1))?z0___PPT10:___PPT9  Neutrophils: "  bc    @` L Z1))?Yz0___PPT10:___PPT9 Circulating effector cellsB " fg&     @` L ZL1))?Yz0___PPT10:___PPT9 Microbial killing> " fc   @` L Z1))?z0___PPT10:___PPT9 Intraepithelial lymphocytes> " fc   @` L Z1))?DYz0___PPT10:___PPT9 Microbial killing> " fc   @` L Z1))?Dz0___PPT10:___PPT9  Defensins> "  fc    @` L Zt1))?vYDz0___PPT10:___PPT9 Prevent microbial entry> " fc   @` L Z1))?vDz0___PPT10:___PPT9 Epithelial layers> " fc   @` L Z1))?Yvz0___PPT10:___PPT9 Epithelial barriersB " fg   @` L  `P1))?Yz0___PPT10:___PPT9 Principal Functions> " fc   @` L  `1))?z0___PPT10:___PPT9  Components< "  fc   @`B L Z8c ))?YB L Z1 ))??Y?B L Z8c ))?B  L Z8c ))?YYB !L Z1 ))?YB "L Z1 ))??B #L T1 ))?B $L Z1 ))?YY?B %L Z1 ))?vYvB &L Z1 ))?DYDB 'L Z1 ))?vB (L Z1 ))?YB )L Z1 ))?YB *L Z1 ))?YB +L Z1 ))?YB ,L Z1 ))? B -L Z1 ))? Y B .L Z1 ))? Y B /L Z1 ))? Y B 0L Z1 ))? Y B 1L Z1 ))? YB 2L Z1 ))?YB 3L Z1 ))?YYYH L 0޽h ? 33___PPT10i.'`+D=' = @B +f }u  (    ZD1))?T kThe complement system&0 2c  @  0  TLD___PPT9& A complex series of some plasma proteins Pathways of complement activation Classical Pathway Alternative Pathway The lectin Pathway*qq"qq9 *b$b9b4* N    p`Pp  Z1))?"`H  0޽h ? 33___PPT10i., R7+D=' = @B +  `(  `J ` C "A 0207'H ` 0޽h ? 3380___PPT10.{  2(    c TA0S9781416031239-002-f012"`J h  ZHa1))?"`  rPathways of complement activation. The activation of the complement system may be initiated by three distinct pathways, all of which lead to the production of C3b (the early steps). C3b initiates the late steps of complement activation, culminating in the production of peptides that stimulate inflammation (C5a) and polymerized C9, which forms the membrane attack complex, so called because it creates holes in plasma membranes. The principal functions of major proteins produced at different steps are shown. The activation, functions, and regulation of the complement system are discussed in much more detail in Chapter 14..s"c Qc  s H  0޽h ? ay___PPT10Y+D=' = @B +  d(  dN d C &A 0208_2 O^PH d 0޽h ? 3380___PPT10.piFi x@ T(  T T ZH 1))?r Np The effect of complement activation Opsonization of pathogen Recruitment of leukocytes Killing of pathogens% q0 2K q2a$ccKa4$    > H T 0޽h ? 33___PPT10i.[U+D=' = @B + 'Q(    Z<81))?T _ Cytokines& 0 2 c    Z<1))?q PH@___PPT9" Cell source: macrophages, neutrophils, and NK cells, endothelial cells, some epithelial cells Functions Recruit and activate leukocytes Produce systemic alterations that contribute to potentiate antimicrobial responsespj0 2s1 2 cUc csc&     @`` L ZO1))? rProteins secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells. $s0 2scr   M Z1))?"`H  0޽h ? 33___PPT10i.0@:=+D=' = @B + h(  hJ h C "A 0231:V?P h s *޽h ?"` 3380___PPT10.0Džh 0%P=(  P{x jq  %P #"*,,+,,,jq  P Zb1))?"`Eq z0___PPT10:___PPT9 Control of inflammation> " fc   @` P Zd1))?"`Eq z0___PPT10:___PPT9 IL-10, TGF-> "  fc   @` P Z[1))?"`Ez0___PPT10:___PPT9 Proliferation of NK cells> " fc   @` P Z1))?"`Ez0___PPT10:___PPT9 IL-15> " fc   @`  P Z1))?"`z0___PPT10:___PPT9 PIFN- production by NK cells and T cells>) " (fc )  @`  P Z<|1))?"`z0___PPT10:___PPT9 IL-12> " fc   @`  P Z1))?"`z0___PPT10:___PPT9 Macrophage activation> " fc   @`  P Z̫1))?"`z0___PPT10:___PPT9  IFN-> " fc   @` P Z1))?"`z0___PPT10:___PPT9  Inflammation> "  fc   @` P Z1))?"`z0___PPT10:___PPT9  TNF, IL-1> "  fc   @` P Z1))?"`jz0___PPT10:___PPT9  CytokinesB "  fg   @`B P Z1 ))?jjB P Z1 ))?B P Z1 ))?B P Z1 ))?B P Z1 ))?B P Z1 ))?EEB P Z1 ))?q q B P Z1 ))?jq B P Z1 ))?q B P Z1 ))?q B P Zo ))?j  P Z1))? $  hIn severe infection, excess systemic cytokine production is harmful and may even cause death of the host`i0 2c;cg&c i H P 0޽h ? 33___PPT10i.).{+D=' = @B +  ` X (  X X Z1))?   The first line of host defense against microbes The mechanisms of innate immunity exist before exposure to microbes The components of the innate immune system include epithelial barriers,leukocytes, circulating effector proteins and cytokines Neutrophils and macrophages are phagocytes that kill ingested microbesby producing ROIs, nitric oxide, and enzymes in phagolysosomes NK cells are lymphocytes that defend against intracelluar microbes by killing infected cells and providing a source of the macrophage-activatingcytokine IFN- The complement system is activated by microbes, and products of complement activation promote phagocytosis and killing of microbes and stimulate inflammation Different cytokines of innate immunity recruit and activate leukocytes, enhance the microbicidal activities of phagocytes, and stimulate NK cells and T cell responses i n2V n2 n2c/ccC c c~cccg g $g$       3        0   M  h      H  X Z1))?"` X 6Z W cSummary f   X Z1))?"`  X Z1))?"`+  X Z1))?"`  X Z1))?"`+H X 0޽h ? 3380___PPT10.!? tC(  t  t Z|1))?X8  To be continuedB0( 2g(g(  D t S  ?"` 3380___PPT10.+rߊ`fJjq Piux @  w,o@'0R <GsMz X_pions S V/rf͏ my]dpx"