immune system vip

8/12/2019 Immune System Vip

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Ib-202-18

Immune system continued

(Chapt 43 all)


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Antigen Recognition by

ymphocytes

! "he #e$teb$ate body is populated by t%o main types o&

lymphocytes

' lymphocytes ( cells) and " lymphocytes (" cells) %hich

ci$culate th$ough the blood In mic$oscope can*t telldi&&e$ence

! "he plasma memb$anes o& both cells

and " cells--

' ha#e about 100+000 embedded antigen $ecepto$s that all$ecogni,e the same epitope (speci&ic) the$ cells

$ecogni,e othe$ epitopes "he$e a$e enough di&&e$ent cells

%ith di&&e$ent speci&icities to $ecogni,e most allthe epitopes

p$esent in the mic$obial %o$ld


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B Cell Receptors for Antigens! bind to speci&ic+ intact antigens eithe$ in solution o$ ones that a$e

pa$t o& a &$agment o& a mic$obial cell %all

' A$e o&ten called memb$ane antibodies o$ memb$aneimmunoglobulins because they a$e embedded in the cellmemb$ane the$ antibodies ci$culate as &$ee molecules inthe blood

Figure 43.8a

Antigen-

binding

site

Antigen-

binding site

Disulfidebridge

Light

chain

Heavy chains

Cytoplasm of B cell

V

A B cell receptor consists of two identical heavy

chains and two identical light chains linked by

several disulfide bridges.

(a)

ariable

regions

Constant

regions

!ransmembrane

region

"lasma

membrane

B cell

VV

C

C C

C

V


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Antigen-

Binding site

chain

Disulfide bridge

chain

! cell

A ! cell receptor consists of onechain and one chain linked bya disulfide bridge. #!C$%

(b)

ariable

regions

Constant

regions

!ransmembrane

region

"lasma

membrane

Cytoplasm of ! cell

T Cell Receptors for Antigens and the Role of the

MHC! .ach " cell $ecepto$ consists o& t%o di&&e$ent

polypeptide chains embedded in the " cell memb$ane

Figure 43.8b

V V

C C


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! " cells bind to small &$agments o& antigens' "hat a$e bound to no$mal cell-su$&ace p$oteins called /C

molecules (mao$ histocompatibilty comple) amed sobecause only identical t%ins could tole$ate sin g$a&ts5i&&e$ent /Cs caused g$a&t $eection

! /C molecules' A$e encoded by a &amily o& genes called the mao$

histocompatibility comple "he$e a$e t%o types+ /C I

' and /C II


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! 6i$us in&ected cells p$oduce /C molecules

(/C I)' 7hich bind to antigen &$agments &$om deg$adationo& the antigen p$oteins and then a$e t$anspo$ted tothe cell su$&ace in a p$ocess called antigen

p$esentation "he antigens a$e peptides o& about -11 amino acids de$i#ed &$om the &o$eign p$otein

! A nea$by cytotoic " cell' Can then $ecogni,e the antigen &$agment displayed

on the cell*s su$&ace by means o& its speci&ic " cell$ecepto$


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Cytoto*ic ! cell

"erforin

+ran(ymes

CD,!C$

Class & 'HC

molecule

!arget

cell "eptide

antigen

"ore

$eleased

cytoto*ic

! cell

Apoptotic

target cell

Ca!cer

cell

Cytotoxic

T cell

A specific cytoto*ic ! cell binds to a

class & 'HCantigen comple* on a

target cell via its !C$ with the aid of

CD,. !his interaction) along with

cytokines from helper ! cells) leads to

the activation of the cytoto*ic cell.

1 !he activated ! cell releases perforin

molecules) which form pores in the

target cell membrane) and proteolytic

en(ymes #gran(ymes%) which enter the

target cell by endocytosis.

!he gran(ymes initiate apoptosis within the

target cells) leading to fragmentation of the

nucleus) release of small apoptotic bodies)

and eventual cell death. !he released

cytoto*ic ! cell can attack other target cells.

3

1

3

Figure 43.1"

! "he acti#ated cytotoic " cell

' :ec$etes p$oteins that dest$oy the in&ected ta$get

cell


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/C II! Class II /C molecules+ located mainly on dend$itic

cells+ mac$ophages+ and cells' 5isplay antigens to helpe$ " cells

1

Figure 43.9b

'icrobe Antigen-

presenting

cell

Antigenfragment

Class II MHC

molecule

! cellreceptor

Hel#er T cell

A fragment of

foreign protein

#antigen% inside thecell associates with

an 'HC molecule

and is transported

to the cell surface.

1

!he combination of'HC molecule and

antigen is recogni(ed

by a ! cell) alerting it

to the infection.

(b)

!hese cells

engulf antigens)

degrade them

and display

peptide

fragments on

their 'HC &&molecules at the

surface.


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13

B cell

Bacterium

"eptide

antigen

Class &&

'HC

molecule

!C$

Helper ! cell

CD

Activated

helper ! cell Clone of memory

B cells

Cytokines

Clone of plasma cells/ecreted antibody

molecules

0ndoplasmic

reticulum of

plasma cell

'acrophage

After a macrophage engulfs and degrades

a bacterium) it displays a peptide antigen

comple*ed with a class && 'HC molecule.

A helper ! cell that recogni(es the displayed

comple* is activated with the aid of cytokinessecreted from the macrophage) forming a

clone of activated helper ! cells #not shown%.

1 A B cell that has taken up and degraded the

same bacterium displays class && 'HCpeptide

antigen comple*es. An activated helper ! cell

bearing ! cell receptors specific for the same

antigen displayed on the macrophage antigenbinds to the B cell. !his interaction) with the aid

of cytokines from the ! cell) activates the B cell.

!he activated B cell proliferates

and differentiates into memory

B cells and antibody-secreting

plasma cells. !he secreted

antibodies are specific for thesame bacterial antigen that

initiated the response.

3

Figure 43.1$


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Clonal Selection of Lymphocytes

! In a p$ima$y immune $esponse

' inding o& antigen to a matu$e lymphocyte

induces the lymphocyte*s p$oli&e$ation anddi&&e$entiation+ a p$ocess called clonal

selection


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' Clonal selection o& cells

' ;ene$ates a clone o& sho$t-li#ed acti#ated e&&ecto$

cells and a clone o& long-li#ed memo$y cells

Figure 43.1

Antigen molecules

Antigen

receptor

B cells that

differ in

antigen

specificity

Antibody

molecules

Clone of memory cellsClone of plasma cells

Antigen molecules

bind to the antigen

receptors of only one

of the three B cells

shown.

!he selected B cell

proliferates) forming

a clone of identical

cells bearing

receptors for the

selecting antigen.

/ome proliferating

cells develop into

short-lived plasma

cells that secrete

antibodies specific

for the antigen.

/ome proliferating cells

develop into long-lived

memory cells that can

respond rapidly upon

subse1uent e*posure

to the same antigen.


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! "he $ole o& helpe$ " cells in ac


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ymphocyte de#elopment! e%ly &o$med lymphocytes a$ise &$om bone

ma$$o% stem cells and a$e all alie' ut they late$ de#elop into cells o$ " cells+ depending

on %he$e they continue thei$ matu$ation

Figure 43.1

Bone marrow

Lymphoid

stem cell

B cell

Blood) lymph) and lymphoid tissues

#lymph nodes) spleen) and others%

! cell

!hymus

Circulating

lymphocytes

appear the same in

the microscope) but

are functionally

different.


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Generation of Lymphocyte Diversity by Gene

Rearrangement

ymphocytes a$ise &$om plu$ipotent stemcells in the bone ma$$o% .a$ly in

de#elopment+ $andom+ pe$manent gene$ea$$angement taes place' =o$ms &unctional genes encoding the o$ "

cell antigen $ecepto$ chains


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Testing and Removal of Self

Reactive Lymphocytes! As and " cells a$e matu$ing in the bone and

thymus thei$ antigen $ecepto$s a$e tested &o$

possible sel&-$eacti#ity! ymphocytes bea$ing $ecepto$s &o$ antigens(sel& p$oteins o$ &$agments o& p$oteins) al$eadyp$esent in the body a$e dest$oyed by apoptosis

o$ $ende$ed non&unctional! /C I and II cells a$e both ep$essed at high

le#els in the thymus and bone ma$$o%


18/43

Immuni,ation! In the seconda$y immune $esponse

' /emo$y cells &acilitate a &aste$+ mo$e e&&icient

$esponse

Antibody

concentration

#arbit

raryunits%

26

264

263

262

266

6 ; 2 32 3, 47 3 5 7irst

e*posure to

antigen A

1 Day 3,=

/econd e*posure

to antigen A: first

e*posure to

antigen B

3 2eco!'ary res#o!seto anti-

gen A produces antibodies

to A: #rimary res#o!seto anti-

gen B produces antibodies to B

4

"rimary

response of

antigen B

same as

primary

response of A

even though

secondary

response of A

is much

greater.

8ote log

scale?


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! Concept 433? umo$al and cell-mediated

immunity de&end against di&&e$ent types o&th$eats

! Ac


20/43

! "he $oles o& the mao$ pa$ticipants in the

acirst e*posure to antigen

&ntact antigensAntigens engulfed and

displayed by dendritic cells

Antigens displayed

by infected cells

Activate Activate Activate

+ives rise to +ives rise to +ives rise to

B cellHelper

! cellCytoto*ic

! cell

"lasma

cells

'emory

B cells

Active and

memory

helper

! cells

'emory

cytoto*ic

! cells

Active

cytoto*ic

! cells

/ecrete antibodies that defend against

pathogens and to*ins in e*tracellular fluid

Defend against infected cells) cancer

cells) and transplanted tissues

/ecreted

cytokines

activate

Humoral @ blood?

cell and

helpe$ " cell$ecogni,e same

antigen so latte$

stimulates the

&o$me$9


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Antibody Classes

! "he &i#e mao$ classes o& antibodies+ o$

immunoglobulins

' 5i&&e$ in thei$ dist$ibutions and &unctions%ithin the body


22/43

! "he &i#e classes o& immunoglobulins

Figure 43.18

>irst &g class produced after initial e*posure to

antigen: then its concentration in the blood declines

'ost abundant &g class in blood: also present in

tissue fluids

nly &g class that crosses placenta) thus conferringpassive immunity on fetus

"romotes opsoni(ation) neutrali(ation) and agglutination

of antigens: less effective in complement activation than

&g' #see >igure 4.25%

"resent in secretions such as tears) saliva) mucus)

and breast milk

!riggers release from mast cells and basophils of

histamine and other chemicals that cause allergic

reactions #see >igure 4.36%

"resent primarily on surface of naive B cells that havenot been e*posed to antigens

IgM

#pentamer%

Ig

#monomer%

Ig*

#dimer%

Ig(mo!omer)

chain

/ecretory

component

chain

!ransmembrane

region

Ig&

#monomer%

"romotes neutrali(ation and agglutination of

antigens: very effective in complement activation

#see >igure 4.25%

"rovides locali(ed defense of mucous membranes by

agglutination and neutrali(ation of antigens #see

>igure 4.25%

"resence in breast milk confers passive immunity on

nursing infant

Acts as antigen receptor in antigen-stimulated

proliferation and differentiation of B cells #clonalselection%


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! Antibody-mediated mechanisms o& antigendisposal

,i!'i!g o+ a!tibo'ies to a!tige!s

i!acti5ates a!tige!s by

Viral !eutrali6atio!

(bloc7s bi!'i!g to 0ost)

a!' o#so!i6atio! (i!creases

#0agocytosis)

*ggluti!atio! o+

a!tige!-beari!g #articles

suc0 as microbes

reci#itatio! o+

soluble a!tige!s

*cti5atio! o+ com#leme!t system

a!' #ore +ormatio!

Bacterium

irus Bacteria

/oluble

antigens >oreign cell

Complement

proteins'AC

"ore

0nhances

0agocytosis

Leads to

Cell lysis

'acrophageFigure 43.19


25/43

Acti#e and @assi#e Immuni,ation! Acti#e immunity

' 5e#elops natu$ally in $esponse to an in&ection

' Can also de#elop &ollo%ing immuni,ation+ also called#accination

! @assi#e immunity+ %hich p$o#ides immediate+sho$t-te$m p$otection' Is con&e$$ed natu$ally %hen Ig; c$osses the placenta

&$om mothe$ to &etus o$ %hen IgA passes &$om mothe$

to in&ant in b$east mil' Can be con&e$$ed a$ti&icially by inecting antibodies

into a non-immune pe$son Immunoglobulins &o$snae bites (anti $attle snae se$um) to t$eat #ictims o&snae bites eed to no% %hat ind o& snae

inected the #enom


26/43

! In immuni,ation

' A nonpathogenic &o$m o& a mic$obe o$ pa$t o&

a mic$obe elicits an immune $esponse to animmunological memo$y &o$ that mic$obe


27/43

! Concept 434? "he immune system*s ability todistinguish sel& &$om nonsel& limits tissue

t$ansplantation

! "he immune system' Can %age %a$ against cells &$om othe$ indi#iduals

! "$ansplanted tissues

' A$e usually dest$oyed by the $ecipient*s immunesystem


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lood ;$oups and "$ans&usions

! Ce$tain antigens on $ed blood cells' 5ete$mine %hethe$ a pe$son has type A+ +

A+ o$ blood


29/43

! Antibodies to non-sel& blood types

' Al$eady eist in the body p$obably &$om

eposu$e to saccha$ides on bacte$ial %alls! "$ans&usion %ith incompatible blood

' eads to dest$uction o& the t$ans&used cells


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! Recipient-dono$ combinations

' Can be &atal o$ sa&e

Table 43.1


31/43

"issue and $gan "$ansplants! /C molecules

' A$e $esponsible &o$ stimulating the $eection o& tissueg$a&ts and o$gan t$ansplants

! "he chances o& success&ul t$ansplantation a$einc$eased' I& the dono$ and $ecipient /C tissue types a$e %ell

matched

' I& the $ecipient is gi#en immunosupp$essi#e d$ugs

! ymphocytes in bone ma$$o% t$ansplants' /ay cause a g$a&t #e$sus host $eaction in $ecipients


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! Concept 43? .agge$ated+ sel&-di$ected+ o$

diminished immune $esponses can cause disease

! I& the delicate balance o& the immune system is

dis$upted

' "he e&&ects on the indi#idual can $ange &$om mino$

to o&ten &atal conse


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! In locali,ed alle$gies such as hay &e#e$

' Ig. antibodies p$oduced a&te$ &i$st eposu$e toan alle$gen attachs to $ecepto$s on mast cells

! "he net time the alle$gen ente$s the body

' It binds to mast cell'associated Ig. molecules! inding causes the mast cells to $elease

histamine and othe$ mediato$s

' "hat cause #ascula$ changes and typicalsymptoms


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! "he net time the alle$gen ente$s the body

' It binds to mast cell'associated Ig. molecules

! "he mast cells then $elease histamine and othe$mediato$s

' "hat cause #ascula$ changes and symptoms typical

o& hay &e#e$ (%eeping mucous memb$anes+ s%elling

o& mucous memb$anes etc)


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! "he alle$gic $esponse

Figure 43.

&g0 antibodies produced in

response to initial e*posure

to an allergen bind to

receptors or mast cells.

1 n subse1uent e*posure to the

same allergen) &g0 molecules

attached to a mast cell recog-

ni(e and bind the allergen.

Degranulation of the cell)

triggered by cross-linking of

ad9acent &g0 molecules)

releases histamine and other

chemicals) leading to allergysymptoms.

3

1

3

Allergen

&g0

Histamine

+ranule

'ast cell


36/43

! An acute alle$gic $esponse sometimes leads toanaphylactic shoc because o& massi#e $elease o&histimine 5ilates #asculatu$e lood pools incapilla$y beds leading to blood p$essu$e d$ops lo%enough so that the hea$t has no blood to pump' Can occu$ %ithin seconds o& eposu$e to an alle$gen

"$eat %ith epineph$in to counte$act the e&&ect o&histamine

' Alle$gies to bees stings+ peanuts and ce$tain shell &ish

p$otein :ome people ha#e such an alle$gy topenicillium


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Autoimmune 5iseases

! In indi#iduals %ith autoimmune diseases

' "he immune system loses tole$ance &o$ sel&

and tu$ns against ce$tain molecules o& thebody


38/43

! Rheumatoid a$th$itis

' Is an autoimmune disease that leads to damage

and pain&ul in&lammation o& the ca$tilage and

bone o& oints

Figure 43.1


39/43

! the$ eamples o& autoimmune diseases include' :ystemic lupus e$ythematosus ($eaction against

histones and 5A leads to &e#e$+ a$th$itis and idneydys&unction)

' /ultiple scle$osis ($eaction against myelin sheath o&the ne$#ous system leads to loss o& moto$ cont$ol o&muscles)

' Insulin-dependent diabetes (dest$uction o& eta cellsin panc$eas leads to child onset diabetes Can*t

cont$ol blood suga$ le#el at 100 mg>100ml blood


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Immunode&iciency 5iseases! An inbo$n o$ p$ima$y immunode&iciency

' Results &$om he$edita$y o$ congenital de&ects that

p$e#ent p$ope$ &unctioning o& innate+ humo$al+ and>o$

cell-mediated de&enses

! In se#e$e combined immunode&iciency (:CI5)

' oth the humo$al and cell-mediated b$anches o&

ac


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! Ac


42/43

! Ac


43/43

:ome d$ug a#ailable to p$e#ent $eplication

o& #i$us+ but #i$us eeps mutating and

becomes d$ug $esistant

1mFigure 43.

immune system vip

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