4 basic immunology

8/17/2019 4 Basic Immunology

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Immunology is the study of the ways in which the body

defends itself from infectious agents and other foreign

substances in its environment. The immune system

protect us from pathogens. It has the ability todiscriminate (differentiate) between the individual`s

own cells and harmful invading organisms.

Immune system has two lines of

defense:

a. Innate (non specific) immunity

a. Adaptive (specific) immunity


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1.Innate

immunity: Characters1 1st line of defense

2 apid defense

! The same on re"

e#posure to Ag

$ %o memory cell

& ecogni'e and

react againstmicrobes only

loc* entry of microbes and eliminate

succeeded microbes which entered the host


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Components:

1 Barriers:

a. Physical barriers: protect against invasion of microbes

eg epidermis !eratinocyte epithelium of mucusmembrane cilia b "echanical barrier : longitudinal flow of air and fluid movement of

mucus by cilia

c Chemical barriers:

#$!in: % & defensin

lyso'yme ase *ase#esp +ract: & defensin

#,I+: % defensin pepsin

lyso'yme

#-C of stomach: !ill ingested

microbes

#+ears in eye: lyso'yme d. Biologicalbarriers: commensal microbes or flora

inhibit growth of pathogenic bacteria


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2.Innateimmunecells:phagocytes("acrophage

neutrophil ) / cells

.0Cyto!ines: + I1 I12 I3 chemo!ines

.4Complement: 5lternative pathway lectin pathway

.67ther plasma proteins (acute phase response):

8"annoseBindingectin:participateinlectin

pathway of complement8C eactive Protein: coat microbes and help in

phagocytosis

B: ecognition of microbes by the innatesystem: the cells(pathogen#recognition

structurescalled pathogen#receptorsreceptors)

associated

of innaterecogni'e

molecular patterns(P5"Ps)sharedbydifferent microbes


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5daptive immunity:

Characters

12nd line of defense

2+elayed as response to infection

!,pecific for microbes - Antigen(can

differentiate Antigen)

$as memory cell which remember

microbes and give strong

immune response on re"e#posure


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components (se9uential phases)

1Ag recognition by lymphocyte through specific receptor to

Ag

2Activation of lymphocyte / proliferation/ differentiationinto memory cell - effector cell

!0limination of microbes

$+ecline - Termination of immune response

&ong lived memory cell

Cells of adaptive immunity1B lymphocyte : produce antibodies that neutrali'e and

eliminate etracellular microbes and toins(humoral

immunity)2+ lymphocyte: eradicate intracellular microbes (cell

mediated immunity


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Hematopoitic stem cell in the bone marrow givea. Lymphoid progenitor: give

T

lymphocyte

B

lymphocyte

NK cell

b. Myeloidprogenitor:give

Leucocytes

(neutrophils&


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$tem cells

,tem cells are undifferentiated (unspeciali'ed) cells which

possess 1,elf"renewal and can be maintained in undifferentiated state.

23otency " the capacity to differentiate into speciali'ed cell typese.g. muscle cell4 a red blood cell4 nerve cell or a brain cell.

Types of mammalian stem cells5

!0mbryonicstemcells(isolatedfromtheinner cellmass

of blastocysts)$Adult stem cells (umbilical cord blood and bone marrow).

"edical importance:•as the potential to treatment of human diseases.

•6ould be used in the generation of cells and tissues

for transplantation.

•one marrow transplants that are used to treat

leu*emia.

•3ossible to be introduced into damaged tissue in order to treat

a disease or in7ury e.g. cancer4 type1 diabetes mellitus 48


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o ymphocytes are the only cells with specific receptors for antigensand are the *ey mediators of adaptive immunity.

o Theycan be distinguished bysurface proteinsidentified by

monoclonal

antibodies......thestandardnomenclaturefotthese proteinsis

the96+9

(cluster of differentiation)and a number : for e#ample 6+14 6+24

6+!4

;.etc.o

ymphocytes include: lymphocytes5 mediators of humoral immunity

T lymphocytes5 mediators of cell"mediated immunity.

%atural *iller cells5 cells of innate immunity

B l h t + l h t


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B lymphocyte + lymphocyte

arise from one marrow

mature in one marrow Thymus

ame one marrow lymphocytes Thymus derived lymphocytes

; of total blood 1< 1& = >a7ority

lymphocyte

$teps in maturation ,tem cell / lymphoid progenitor / pre cell ,tem cell / lymphoid progenitor / immature T cell / leave bone

/ immature cell / mature?na@ve cell /

leave bone marrow to meet antigen in the 2ndmarrow to thymus gland / maturation - selection / mature?na@ve T

cellslymphoid organs T helper (6+$)

T cytoto#ic (6+)/ leave thymus to meet antigen in the 2 nd lymphoid organs

phenotypicmar!ers

1. 6+ 1B - 6+ 21 1. 6+ !

2. Cc receptor 2. 6+ $ or 6+

!. class II >6 molecule !. T cell receptor (T6)

unction Antibody production (humoral immunity) 6ell mediated immunity

5ntigen recogni'ed 3rotein 4 polysaccharide4 lipid4 nucleic acid 3rotein only

and small chemicals (free - soluble) " 6+$ cell recogni'e / peptide D >6 II molecule

" 6+ cell recogni'e / peptide D >6 I molecule

5ntigen recognition B cell receptor (BC)5 membrane +C 5 2 types E?F T6 - G?H T6

receptor Immunoglobulin (Ig > - Ig +) %


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Are large lymphocytes with numerous cytoplasmic granules

% cells comprise about 16 I molecules on its surface

unction of / cells:

Activated by I"12/

•illing tumor cells.•illing virus"infected cells.

•3roduce IC%"G which activate macrophages.

Antibody"dependent cellular cytoto#icity(A+66


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Fig.6 Nk cells


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+hese include:

a+endritic cells

b.>acrophages

c. lymphocytes7ccurance: in the epithelium of the s!in> gastrointestinal

tract> respiratory tract (the common portal of entry of

microbes).unctions:

a6apture and transport antigens to the peripheral lymphoidtissues

b process antigens

3resent the peptides derived from these antigens to

T lymphocytes


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They are rich in class II "-C

molecules Pathways of antigen processing

presentation:a 6lass II >6 pathway5i3rotein antigen ta*en from e#tracellular environment.

i3roteins are degraded by lysosomal proteases.

The resulting peptides are presented to 6+$D cells withclass II >6 molecules.

b 6lass I >6 pathway5i6ytosolic proteins e.g. intracellular microbes.

i3roteins are degraded by a structure called proteosome.

iThe resulting peptides are presented to 6+D cells

withclass I >6 molecules.


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Defnition: Cells which can recognie &ingest & !ill microbes &"oreign bo#ies

Types:

eutrophil "acrophage

; in blood >ost numerous

J6s

K in acute infection

ew

$i'e $mall arge - mononuclear

ife ew hours *ays


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They are rich in class II "-C

molecules Pathways of antigen processing

presentation:a 6lass II >6 pathway5 i3rotein antigen ta*en from e#tracellular environment.

i3roteins are degraded by lysosomal proteases.

The resulting peptides are presented to 6+$D cells with

class II >6 molecules. b 6lass I >6 pathway5

i6ytosolic proteins e.g. intracellular microbes.

i3roteins are degraded by a structure called

proteosome.

iThe resulting peptides are presented to 6+D cells with

class I >6 molecules.


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Defnition: Cells which can recognie &ingest & !illmicrobes &"oreign bo#ies

Types:

eutrophil "acrophage

; in blood >ost numerous

J6s

K in acuteinfection

ew

$i'e $mall arge - mononuclear

ife ew hours *ays


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1 +elivary of

phagocytic

cell to site if infection5

*iapedisis: histamine ? stimulates phagocytes to migrate through wallof blood vessel to enter tissue

Chemotais : chemotactic factors as chemo!ines complement (C0a

C4a C6a) attract phagocytes towards microbes in tissue2 ecognition of microbes5

3hagocytes can recogni'e and bind microbes through receptor on its outer surface eg

mannose receptor - Toll"i*e receptor

!dhAerence to target (opsoni'ation)>icrobe coated with IgL or complement (6!b)

IgL or 6!b bind with their receptors on phagocytic cells,o they bring microbe near phagocytic cell /easy 4 helped phagocytosis.

7psonins: antibodies (Ig,) or C0b which are capable of of enhancingphagocytosis.

$ Ingestion of

target "6ell membrane of phagocytes invaginate to enclose microbe / microbe become in cytoplasms surrounded by cell membrane (vacuole) phagosome

13h l f ti


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13hagolysosome formation

Phagosome fuses with lysosome forming phagolysosometo !ill microbe2 Intracellular *illinga) 72 dependent system ( espiratory bursts ):

-M2 free radicals as 2M2 4 M2 - M.-To#ic nitrogen o#ide.

b) 72 independent agents

"ysosomal granules: basic ptn ? damage

permeability barrier in bacteria fungi virus

"actoferrin / chelating iron ptn ? @ iron ? @

bacterial

growth

"ysosomal en'ymes / as lyso'yme nuclease phospholiase

N.+igestion by macrophage

"icrobes now are digested into small antigen peptides which


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$row at sites which phagocyte can%t reachCapsule prevent phagocytosis

Can !ill phagocyte either be"ore or a"ter

phagocytosis Can survive insi#emacrophage as intracytoplasmicpathogens


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1ry lymphoid organ 2nd lymphoid organ

Bone marrow +hymus gland " ymph

node

" $pleen

" +onsils

" PayerAs

patches

,ites for contact

between lymphocyte -

Antigen to initiate

immune response

- cell

maturation

- lood cell

generation iehematopioesis

- + cell maturation

- ducate + cell how to differentiate

between self Antigen (>6

peptide) - non selfAntigen

- + cell selection :

Positive selection: only T cell which

can bind with >6 is allowed to

grow

egative selection: only T cell which

bind efficiently with >6 (auto"

reactive T cell)is eliminated by

apoptosis as it is a dangerous cell


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5ntigen:$ubstancerecogni'edbyimmunesystemwhich may be

-,imple or comple#-6arbohydrate4 lipid4 protein4 nucleic acid4 phospholipids

- cell recogni'e any biological Ag-T cell recogni'e peptide Ag presented on >6

pitopes (antigenic determinants):-Tcell•,mallest partonAgwhich bindwith6

receptors•determines the specificity of Ag

•if Ag contain multiple epitopes 4 it is called multivalent

Ag


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a. Immunogens

arge Ag with epitopes capable of binding with immune receptor -inducing immune response.

Always a macromolecule (protein4 polysaccharide).

%otice thatnot all antigens are immunogens

b.-aptensA small Ag with epitopes capable of binding with immune receptor - without

inducing immune response

OT can produce immune response only whenconugated with large carrier molecule (as aprotein) ?

immune response againstepitopesof hapten carrier.

c.+olerogens,elf Ag (>6) normally not stimulate immune system

ac* of immune response against self Ag called self

tolerance

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1$i'e: proteins D 1E /*s are more immunogenic.

2Compleity:comple proteins with numerous> diverse

epitopes are more to induce an immune response than are

simple peptides that contain only one or few epitopes.

0Conformation and accessibility: epitopes must be Fseen byGand be accessibile to the immune system.

4Chemical properties:"A protein is good immunogens.

">any charbohydrates4 steroids4 and lipids are poor immunogens.

Amino acids and haptens are4 by themselves4 not immunogenic


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Types o Antigens

.1T-cell independent antigens

( T' activate B cells without help"rom T cell

;e)g) polysacchari#es(Pneumococcalpolysacchari#e* LP+(

.T-cell dependentantigens: !e"#ires T cellhelp or $ cell activation%

e.g. proteins (microbial


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Proteins pro#uce# by pathogens.Not processe# by antigen presenting cells.

ntact protein bin#s to variable region o" , chainon TC- o" T cells an# to .HC class on antigen

presenting cells They in#uce massive T cellactivation

Large numbers o" activate# T cells releaselarge amount o" cyto!ines lea#ing to systemic

to/icity an# s!in syn#rome#iseases.


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+taphylococcal enteroto/ins+taphylococcal to/ic shoc! syn#rome to/in01(T++T01'

A)s and diseases:

+taphylococcal to/ic shoc! syn#rome)+taphylococcal scal#e# s!in syn#rome)


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2$ 1 +3$+


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2$) 1 +3$+A*T+),* $+*D+*) ML,/L, 0 T,+MM/*, 2T,M

mmunoglobulins(gs':

T cell receptors

(TC-':

.HC molecules.


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Immunoglobulins (Igs) (antibodies)which mediate*ef :Immunoglobulinsareglycoproteins

humoral or antibody mediated immunity

3roduction - distribution of antibodies

•In lymph node / antigenic stimulation of cells with help of Thelper cyto*ines / cell proliferate / differentiate into

plasma cell which secrete antibodies / enter circulation / site

of infection•Also mature cell in one >arrow e#press membrane bound

antibodies (6)•,o antibodies are produced in lymphoid tissue - bone

marrow


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>embrane bound Ig ,ecreted Ig

0#pressed on cell surface (Ig> - Ig+)as 6 for Ag

If bind with Ag / initiate

cell response

" in plasma - mucosa - interstitial fluidsof tissues


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•P shaped molecules of $ polypeptide chains•2identical heavy chain / each chain / 1 variable

domain (Q) - ! or $ constant domains (6)

•2identical light chain / each chain / 1 variable

domain (Q) - 1 constant domains (6)

•0ach variable domain (Q or Q) contains !hypervariable regions called complementary

determining repeats (6+)•+isulfide bond connect heavy chain with light chain

- heavy chain with heavy chain


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C terminal en# o" heavy chain may be anchore#in plasmamembrane o" B cell (g. & g4' / act as BC-

ab H fragment 5g binding c H fragment crystalline -inge region

6ontain whole light chain D Q

D 61

2 in number

3art for Ag recognition and

binding

Tend to crystalli'e in solution

Mne in number

6ontain remaining of both

heavy chains 6 domain

Live effector -

biological function of antibody

" Cle#ible region lies between

Cab - Cc to give mobility to

both Cab to accommodate

different Ag


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3) mmunoglobulin classes

mmunoglobulins /#ivi#e# into 5ve #i6erent classes/ accor#ing to the #i6erence in structure inconstant #omains o" heavy chain

)1$amma heavy chains / g$

)73lpha heavy chains / g3

)8.u heavy chains / g.

)9Epsilon heavy chains / gE

):4elta heavy chains / g4

4i6erent classes an# subclasses o" antibo#iesper"orm #i6erent e6ector "unctions (table 1'.

There are two types o" light chains* calle# ; (!appa'an# < (lamb#a') 3n antibo#y has either two ; lightchains or two < light chains.


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eavy chain class (isotype' s3itching: is theswitch "rom one g isotype to another) 3"teractivation o" B lymphocytes* the antigen0speci5cclone o" B cells proli"erate an# #i6erentiate intoprogeny that secrete antibo#ies= some o" theprogeny secrete g.* an# other progeny o" thesame B cells pro#uce antibo#ies o" #i6erent

isotypes to me#iate #i6erent "unctions an#combat #i6erent types o" microbes.


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Isotype $ubtypes - chain $erum conc.

mg


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Defnition: i#entical monospeci5c antibo#iesthat are pro#uce# by one type o" imm#necell that are all clones o" a single parentcell.

+n contrast4 antibodies obtained rom theblood o an imm#ni5ed host are calledpolyclonal antibodies.

http://en.wikipedia.org/wiki/Monospecific_antibodyhttp://en.wikipedia.org/wiki/Monospecific_antibodyhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/Cloninghttp://en.wikipedia.org/wiki/Cloninghttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/Monospecific_antibodyhttp://en.wikipedia.org/wiki/Monospecific_antibody


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$teps:1A mouse is immuni'ed with the antigen of interest

2 cells are isolated from the spleen of the animal

! cells (Ab"producing cell) are then fused with myeloma cells

(malignant cell) in vitro by using a fusion agent as poly"ethylene glycol4

a virus.

The cell fusion form an immortali'ed antibody"producing cell

Rhybridoma9.

&ybrids (fused cells) are selected for growth in special culture media. The cells that fuse with another cell or do not fuse at all die because theydo not have the capacity to divide indefinitely. Mnly hybridomas between

cells and myeloma cells survive.

ybridomas4 secrete a large amount of mAbs.


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Fig.13 Hybridoma


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1Todefineclustersof differentiation(6+mar*ers)onlymphocytes

2+iagnosis of many viral4 bacterial and fungal infections by using their

specificmonoclonal antibodies.

!+iagnosis and treatment of cancer

$Treatment of autoimmune diseases as rheumatoid arthritis

&3revention of graft re7ection


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umoral immunity is mediated by secreted antibodies

Its physiologic function is defense against e#tracellular

microbes and microbial to#ins


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1eutrali'ation of microbes and microbial toins:aAntibodies bloc*s and prevent binding of microbe to cells i.e. prevent infection of cells

bAntibodies inhibit the spread of microbes from an infected cell to an ad7acent cell.

Antibodies bloc* binding of to#in to cellular receptors4 and thus inhibit pathologic effectsof the to#in.

27psoni'ation and phagocytosis:

Antibodies of IgL isotype opsoni'e (coat) microbes and promote their phagocytosis by

binding to Cc receptors on phagocytic cells

05ntibody#dependent cell#mediated

cytotoicity (5*CC):

aIgL antibodies bind to infected cells are

recogni'ed by Cc receptors on % cells./

activation of % cells / *illing of antibody"

coated cells.

bIg0 antibodies bind to helminthic parasites4 and are recogni'ed by Cc receptors oneosinophils / activation of eosinophils /release their granule contents4 / *illing of parasites.

5ctivation of the complement by Ig, and Ig"


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+he primary response

Mhen we are eposed to an antigen for the first time> there

is a lag of several days (1E days) before specific antibody

becomes detectable. +his antibody is Ig". 5fter a short

time> the antibody level declines.+he secondary response

If at a later date we are re#eposed to the same antigen>

there is more rapid appearance of antibody> and in

greater amount. It is of Ig, class and remains detectablefor months or years.


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Primary esponse $econdary esponse

• $low in 7nset

• ow in "agnitude

• $hort ived

• Ig"

• apid in 7nset

• -igh in "agnitude

• ong ived

• Ig, (7r Ig5> or Ig)

This phenomenon is possible beca#se the imm#ne systempossesses specifc imm#nologic memory or antigens.

D#ring the primary response4 some $ lymphocytes4 becomememory cells 3hich are long lived. Th#s 3e can see that thesecondary response re"#ires the phenomen 6no3n as classs3itching (+gM to +g)'.


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*ef.: group of genes on short arm of chromosome Nwhich produce "-C molecules present on cell

surfaces and responsible for display of protein 5g to +

cell

5lso called human leucocytic 5g H -5


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lass + M genes / HL303 & HL30B & HL30C/

role in 3g presentation to Tc

lass ++ M genes / HL304 region (HL304-

& HL304P & HL304>' / role in 3gpresentation to Th

lass +++ M genes / lies between class & & not pro#uce .HC but pro#uce some

complement components & TN20?.

Class I molecules Class II molecules

http://www.cehs.siu.edu/fix/medmicro/cment.htmhttp://www.cehs.siu.edu/fix/medmicro/cment.htmhttp://www.cehs.siu.edu/fix/medmicro/cment.htmhttp://www.cehs.siu.edu/fix/medmicro/cment.htm


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tructure • 2 poly peptide chain

• α chain → (α1 & α2 & α3 domains) encoded by

MHC I genes

• ß2-micoglob!lin → not encoded by MHC genes

• 2 poly peptide chain (encoded by

MHC II)

• α chain → (α1 & α2)

• " chain → ("1 & "2)

!roo"eo# $g presentation bet#een α1 & α2 domain ( ) " 1 & α1 domain

%istribution $ny n!cleated cell in body $g % C (macophage & denditic &

cells)&resent$g to 'c (C) 'h (C*)


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A system of circulating and membrane"associated proteinsthat function in both the innate and adaptive branches of

the immune system.


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♣ 6omponents 61 6B 4 factor 4 +4 and 3.

♣

Cragments of complement components5 each componentcan be cleaved into 2 fragments indicated by a lowercase

letter (e.g. 6&a4 6&b 4 6$a4 6$b;).

♣ A hori'ontal bar above a component or comple#

indicate en'ymatic activity e.g. 6$b2b S 6! convertaseen'yme.


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1In innate immunity, complement can be activated in twoways: via the alternative pathway or via the mannan-

binding lectin pathway .

Inadaptiveimmunesystem:Complement canalsobe

activated via the classical pathway


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3ctivate# by antigen0antibo#y (g$* g.'comple/.

C1(C1@*r*s' complement component bin# 3g03b

comple/* lea# toactivation o" C1.C1 act as an enyme an# cleave both C7

an# C9.

C9b A 7b * "orm the C8 convertaseC9b7b which cleaveC8

Bin#ing o" C8b to C9b7b lea# to the "ormation

o" C9b7b8b which is the C: convertase that


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.BL are serum proteins bin# to speci5ccharbohy#rates

This pathway is activate# by bin#ing o" .BL tomannose

resi#ues o" glycoproteins on certain microbes.nce .BL bin# to mannose* it interact with 7

.BL-activate# serine protease (.3+P1 & .3+P7'.

3ctivation o" .3+P lea# to activation o" C7*C9*an# C8 in the same li!e the classicalpathway.


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nitiate# by cell0sur"ace components o" microbesthat are recognie# as "oreign to the host asLP+

+pontaneous brea!#own o" C8* the mostabun#ant serumcomplement component

C8b attaches to receptors on the sur"ace o"microbes

C8b bin# to "actor B2actor B is cleave# by "actor 4 to pro#uce

C8bBb* anunstable C8 convertaseC8bBb bin#s proper#in "actor ("actor P' to

pro#uce stabilie# C8 convertase.3##itional C8b "ragments are a##e# to

"orm C: convertase


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6an be entered from the classical4 >4 or classical pathway of complement activation. Attachment of 6&b to the bacterial

membrane initiate the formation of the membrane attac*

comple# (>A6) and lysis of the cell. •lysis.•

6&b attach to the cell membrane•Addition of components 64 6N4 6 to form 6&bN.

•,ubseuent addition of multiple molecules of 6B (poly 6B) to

form pores in the cell membrane of microbe and lytic death

of the cell.•The >A6 is 6&bNB(n).

•6B is homologous to Rperforin9 found in Tc and % cellgranules


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♥ Mpsoni'ationand phagocytosis56!b(or 6$b)actasopsonins

♥ 6omplement"mediated lysis5 the membrane attac*

comple# >A6 creates pores in cell membranes and

induce osmotic lysis of the cells.♥ ,timulation of inflammatory reactions5 6&a4 6!a4 and 6$a

bind to receptors on neutrophils and stimulate

inflammatory reactions that serve to eliminate microbes.

Also4 6&a4 6!a and 6$a are chemoattractants toneutrophils.

♥ 3roviding stimuli for cell activation and the humoral

immune response.


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*ef:proteinssecretedbyimmunecellsinresponseto

microbes

ole of cyto!ines:

1,timulate growth - differentiation of lymphocyte

2Activates immune cells to eliminate microbes - Ag!,timulate hematopoiesis

$Osed in medicine as therapeutic agent


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*omenclat#re accor#ingpro#ucing cell Mono6ines "rom

macrophagemonocyte

Lympho6ines "rom lymphocyte

+nterle#6ins "rom leucocytes & act on otherleucocytes eg L01 & L07 & L08…..

$iologic response modifer cyto!ine

which use# clinically to A or 0 immunity

,eneral Properties:


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1 %ot stored in

granules2 Action5 either Pleotropism: act on different cells giving different effects

edundancy: multiple cyto!ines act on 1 cell giving

same

effect! >ode of action55utocrine : act on same cell that produce it

Paracrine: act on adacent cell

ndocrine:act on distant cell at distant site

$ind with specific receptor on target cell

&The effect on target cell / alter gene e#pression / new

protein


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"ediators and regulators of innate immunity:produced mainly by

macrophages> and / cells.Tumor necrosis factor T%C"E ;.. activation of neutrophils

-inflammation.I"1;;.activation of neutrophils and inflammation

I"12;..activation of T - % cells

Interferon IC%"E and IC%"F;..antiviral action and

increase e#pression of class I >6in all cells.6hemo*ines ;;;chemota#is - migrationof leu*ocytes

into tissues

"ediators and regulators of adaptive


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"ediators and regulators of adaptive

immunity: produced by + lymphocytes.I"2;;.proliferation of T4 %4 and cells.

I"$;;. cell isotype switch to Ig0 and mast cell

proliferation.

I"&;;. cell proliferation and eosinophils

activation.IC%"G;..macrophage activation and increase microbicidal

functions.$timulators of hematopoiesis:

Lraulocyte"monocytes colony stimulating factor L>"6,C.

I"! and I"N.

Cyto!ine Profiles of +h1 and +h2

$ b


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$ubsets

1#+h1: Induced by IC%"G and I"12

3roduce 5 IC%"G4 I"24 T%C4 TCunction5 cell"mediated immune response.

2#+h2:Induced by5 I"$

3roduce 5 I"$4 I"&4 I"1


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0radicates infections by intracellular microbes.6onsist of the activation of na@ve T cells to proliferate and

differentiate into effector cells (6+$D T helper cells and

6+D cytolytic cells: 6Ts) and the elimination of the

intracellular microbes.


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1C*4O + cells: activate macrophages to !ill ingestedmicrobes that are able to survive inside phagocytes.

+-1 activate macrophages by secretion of the

macrophage#activating cyto!ine> I#3.

2C*=O + cells !ill any cell containing microbes ormicrobial proteins in the cytoplasm (intracellular) by

direct cell cytotoicity> thus eliminating the

reservoir of infection.


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5ctivated by two signals:•+he 1st signal : peptide O "-C on the surface of 5PCs

recogni'ed by +C#C*0

•+he 2ndco#stimulatory signal: is the interaction of BQ

molecule on 5PCs with C*2= on + cells.

In absence of 2nd signal> eposure of + cells to antigen

lead to anergy (unresponsiveness


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16Tsrecogni'eclassI>6D peptidesonthesurfaceof Rtarget9 cell.

Cormation of tight adhesions Rcon7ugates9 with these cells.

16Ts are activated by I"2 - IC%"G to release their granule

contents toward thetarget cell i.e. granule e#ocytosis.

$The granules contents include5a3erforin4 which form pores in the target cell membrane

bLran'ymes4 enter the target cells through these pores andinduce apoptosis through the activation of caspases.

&+etachment of 6T from target cells to *ill other target

cell.

+eath of target cell by apoptosis.


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Every immune response is a comple/ an# highly regulate#se@uence o" events involving several cell types that interact

with each other either #irectly or through cyto!ines) (2ig)1D'

3PCs capture a minute amount o" the antigen by phagocytosis.3ntigenprocessing3PCsprocesstheantigentoverysmall

"ragments (pepti#es'3ntigenpresentationthe3PCspresentpepti#esplusclass.HC

molecules to T helpercell. pepti#e0.HCcomple/to TC-s/activationo" helper TBin#ingo"

lymphocytes +ecretion o" cyto!ines inclu#ing L07 by the activate# TH cells that

act on thepro#ucing TH cells themselves lea#ing to their proli"eration an#

activation.2N0 activates macrophages & phagocytosis.

3ctivation o" B lymphocytes nee# 7 signals) The 5rst signal is

bin#ing o" the antigen to BC-*an#the secon#one is provi#e#by helper "actors

)cyto!ines(secreted by TH cells e.g.IL-2, IL-4, IL-5. The second signl is

clled T cell hel! .

B cell proli"eration an# #i6erentiation into either memory Blymphocytes or plasma cells which secrete antibo#ies.

3ctivation o" cytoto/ic T cells Tc lymphocytes recognie antigen on

the sur"ace o" target cell (e)g)virus0in"ecte# cell' which e/press


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3#Fustment o" the immune response to a#esire# level,

as in immunopotentiation* orimmunosuppression.


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Defnition enhancement o" the immune response by increasing its rateor prolonging its #uration by the a#ministration o" another substance(an a#Fuvant ')Ad7#vant: an agent that stimulate the immune system an# increasethe response to a

"ccine,without having any speci5c antigenic e6ect by itsel" :

norganic a#Fuvants li!e aluminium

salts rganic a#Fuvants li!e

s@ualene

il0base# a#Fuvants li!e

complete "reun#Gs a#Fuvant ncomplete "reun#Gs a#Fuvant

irosomes 3 virosome is a phospholipi# bilayer vesicle containing

hepatitis 3 an# inIuena antigensCyto!ines "or e/ample L017,

Mechanisms o action o ad7#vants:

Prolong retention o" the immunogen

ncrease the sie o" immunogen an# so promote phagocytosis an#presentation by macrophages

+timulate the inIu/ o" macrophages an# other immune cells to theinFection site

ncrease local c to!ine ro#uction

Immunosuppression

*ef.:$uppression of immune system

http://en.wiktionary.org/wiki/adjuvanthttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Lipid_bilayerhttp://en.wikipedia.org/w/index.php?title=Vesicle_(lipidomics)&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Vesicle_(lipidomics)&action=edit&redlink=1http://en.wikipedia.org/wiki/Lipid_bilayerhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wiktionary.org/wiki/adjuvanthttp://en.wiktionary.org/wiki/adjuvant


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*ef.:$uppression of immune system

Indications:

1ypersensitivity responses.

2Autoimmune disease.

!After transplantation to prevent re7ection.

Induction:

$+rugs.

&adiation.N5nticancer drugs

"ethods of immunosuppression:1 6yclosporine - tacrolimus

2A'athioprine - mycophenolate!6orticosteroids

$Anti 6+! monoclonal antibodies

&Anti"I2 receptor antibody


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FProgrammed Cell *eathGApoptosis is self suicide of cells when they are no longer

needed or if they become damaged and cannot be repaired. e.g.

modeling of tissues - organs during embryogenesis : and

shedding of uterine lining each month in females

cells normally die and eliminated by phagocytosis

In the immune system4 apoptosis is important for elimination ofunwanted and harmful lymphocytes during maturation and after

activation at the end of an immune response to return the

immune system bac* to its resting state after elimination of the

antigen. Also apoptosis is essential in elimination of infectedcells.

Apoptosis is induced by the activation of proteolytic en'ymes

4 basic immunology

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