4 Ab,Complement 3

8/8/2019 4 Ab,Complement 3

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AntibodiesAntibodies


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Abs or Igs are glycoproteins which fall in theAbs or Igs are glycoproteins which fall in the

gamma-globulin fraction of the serum.gamma-globulin fraction of the serum.

They are present both intra and extra-They are present both intra and extra-

vascularly.vascularly.

They are produced by plasma cells inThey are produced by plasma cells inresponse to Ags and they react specificallyresponse to Ags and they react specifically

with them.with them.

There are 5 classes of Igs namely: IgA, IgG,There are 5 classes of Igs namely: IgA, IgG,

IgM, IgE and IgD.IgM, IgE and IgD.


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Structure ofStructure of

ImmunoglobulinsImmunoglobulins


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Properties of Different IgProperties of Different Ig

ClassesClassesIgG:IgG:- Monomeric, consists of 2 H and 2 L chains,Monomeric, consists of 2 H and 2 L chains,

bivalent.bivalent.

- 4 subclasses: IgG1,2,3, and 4.4 subclasses: IgG1,2,3, and 4.- 75% of total serum Igs.75% of total serum Igs.

- It fixes complement.It fixes complement.

-

Predominant Ab in secondary immunePredominant Ab in secondary immuneresponse.response.

- The only Ig which crosses the placenta.The only Ig which crosses the placenta.


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IgM:IgM:

- Pentameric, 10 H and 10 LPentameric, 10 H and 10 L

chains.chains.

- About 7% of total serum Igs.About 7% of total serum Igs.- Predominant in the primaryPredominant in the primary

immune response.immune response.

- Most efficient in agglutination,Most efficient in agglutination,opsonization and activatingopsonization and activating

complement.complement.


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IgM StructureIgM Structure


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IgA:IgA:- 2 subclasses: IgA1 and 2.2 subclasses: IgA1 and 2.- It is present in 2 forms:It is present in 2 forms:

Serum IgA:Serum IgA: monomeric, forms 15% ofmonomeric, forms 15% ofserum Igs.serum Igs.

Secretory IgA:Secretory IgA: dimeric, predominantdimeric, predominantin secretions e.g. saliva, tears, milk,in secretions e.g. saliva, tears, milk,colostrum, bronchial, genitourinary andcolostrum, bronchial, genitourinary andintestinal secretions, has a protectiveintestinal secretions, has a protective

role against invading pathogens.role against invading pathogens.


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Secretory IgASecretory IgA


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IgD:IgD:

- Less than 1% of total serum Igs.Less than 1% of total serum Igs.

- Monomeric.Monomeric.

-

Present on the surface of B-cellsPresent on the surface of B-cellsand acts as a B-cell receptor.and acts as a B-cell receptor.

- Exact function not known.Exact function not known.


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IgE:IgE:

- Present in trace amounts in normalPresent in trace amounts in normalserum.serum.

- Monomeric.Monomeric.

-

Associated with atopic diseases, e.g.Associated with atopic diseases, e.g.bronchial asthma, serum IgE levelbronchial asthma, serum IgE level

increases in allergic individuals.increases in allergic individuals.

- Called cytotropic Ab, and plays a roleCalled cytotropic Ab, and plays a role

in type I hypersensitivity.in type I hypersensitivity.- Serum IgE level is very muchSerum IgE level is very much

increased in parasitic infections.increased in parasitic infections.


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The rate of antibody production


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The rate of antibody production

Primary response: The first encounter with an antigenproduces Abs (mainly IgM), which appear in the serumafter 7-12 days. Their concentration rises slowly to a lowpeak, and then declines.

Secondary response:, A second encounter with the same

antigen results in initial drop in Ab level due to neutralizationof the already present Ab, followed by a very rapid andintense rise due to presence of immunologic memory. Abs(mainly IgG) will rise to a higher peak and will stay longerthan in the primary response.

The same occurs with subsequent encounters with Ag till ahyperimmune state is reached where there is no furtherincrease in Ab level. This is the main reason for givingbooster injections after an initial vaccination.


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Response to multiple simultaneous Ags:

- When 2 or more Ags are administered at thesame time, the host produces Abs to each ofthem.

- This is applied in combined immunization e.g.DPT vaccine used for protection against

diphtheria, whooping cough, and tetanus.


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Kinds of Antibodies(According to reaction with their antigens

1- Agglutinins.

2- Precipitins.

3- Lysins.4- Complement fixing Abs.

5- Opsonins.

6- Antitoxins.7- Neutralizing Abs.

8- Incomplete or blocking Abs.


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+

Agglutinins


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OpsoninsOpsonins


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Incomplete or blocking AbsCoombs (AntiglobulinTests

Direct Coombs TestDetects antibodies on erythrocytes

+

Patients RBCs Coombs Reagent

(Antiglobulin)


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Coombs (AntiglobulinTests

Indirect Coombs Test Detects anti-erythrocyte antibodies in serum

Patients

Serum

Target

RBCs

+ Step 1

+ Coombs Reagent

(Antiglobulin)

Step 2


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Protective Effects ofProtective Effects of

AntibodiesAntibodies Neutralization of bacterial toxins orNeutralization of bacterial toxins or

enzymes.enzymes.

Bacterial lysis in the presence ofBacterial lysis in the presence of

complement.complement. Blocking the infecting ability of theBlocking the infecting ability of the

organisms.organisms.

Opsonization of the micro-organismsOpsonization of the micro-organisms

facilitating their phagocytosis.facilitating their phagocytosis.

Clumping of the bacterial cells,Clumping of the bacterial cells,

fascilitating their uptake byfascilitating their uptake by


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Monoclonal AntibodiesMonoclonal Antibodies

Highly specific Abs produced against aHighly specific Abs produced against asingle epitope.single epitope.

Applications:Applications:- Diagnostic:Diagnostic: e.g.e.g.

- lymphocyte subset determination,- lymphocyte subset determination,

- HLA typing.- HLA typing.- Therapeutic:Therapeutic: e.g.e.g.

- antitumour therapy.- antitumour therapy.- immunosuppressive therapy to- immunosuppressive therapy toprevent graft rejection.prevent graft rejection.


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The ComplementThe Complement

SystemSystem


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The complement systemThe complement systemis ais acomplex group of serum proteins,complex group of serum proteins,

present in low concentration inpresent in low concentration innormal serum, that interactnormal serum, that interact

together in a cascading fashion totogether in a cascading fashion to

protect against infectious agents. Itprotect against infectious agents. Italso includes membrane-boundalso includes membrane-bound

proteins.proteins.

Synthesis:Synthesis:

- By many cells: hepatic parenchymal- By many cells: hepatic parenchymal

cells, monocytes, macrophages, andcells, monocytes, macrophages, and

intestinal epithelial cells.intestinal epithelial cells.


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Nomenclature of complementNomenclature of complementproteins:proteins:

Classical pathway:Classical pathway:

C1,C2, C3C1,C2, C3etcetcC9.C9.

Upon cleavage the large fragment isUpon cleavage the large fragment isgiven the suffixgiven the suffix bb, and the small, and the smallfragment the suffixfragment the suffix aa..

e.g. C5e.g. C5

C5a and C5b.C5a and C5b.

Alternative pathway:Alternative pathway:

Factor B, factor D..etcFactor B, factor D..etc

P th f C l tPathways of Complement


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Pathways of ComplementPathways of Complement

ActivationActivation- 2 main pathways:- The- 2 main pathways:- The classicalclassical and theand the

alternativealternative complement pathways.complement pathways.

The classical pathway is triggered byThe classical pathway is triggered by Ag-AbAg-Abcomplexes.complexes.

The alternative pathway is triggered byThe alternative pathway is triggered byaggregated IgA, endotoxin of Gram -veaggregated IgA, endotoxin of Gram -vebacteria, and yeast zymosan.bacteria, and yeast zymosan.


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- Activation ccurs in a- Activation ccurs in a sequential fashionsequential fashion,,each component activating the following.each component activating the following.

Pro-enzymesPro-enzymes cleavagecleavage enzymes.enzymes.

Both pathways lead to formation of C3Both pathways lead to formation of C3convertaseconvertase C3 cleavage and activationC3 cleavage and activation end in formation of MACend in formation of MAC cell lysis.cell lysis.


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CC33 activation is the commonactivation is the common

central eventcentral event. After that,the 2. After that,the 2

pathways proceed in the samepathways proceed in the same

fashion together through binding offashion together through binding of

the late acting components to form athe late acting components to form a

membrane attack complex(membrane attack complex(MACMAC))

which becomes inserted in the lipidwhich becomes inserted in the lipidbilayers of foreign membranes,bilayers of foreign membranes,

ultimately causingultimately causing cell lysiscell lysis..


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The activation of alternative pathwayThe activation of alternative pathwayoccurs in the absence of Ab, and thusoccurs in the absence of Ab, and thushelps in thehelps in the firstfirst line of defenceline of defence

against microorganisms (against microorganisms (innateinnateimmunityimmunity) and mediates an) and mediates aninflammatory response.inflammatory response.


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The Membrane AttackThe Membrane Attack

ComplexComplex

C6 C7C8

C9

C9

C9 C

9 C9

C9C9 C

9C9

C9

C9

C5

C5b

C5a

70-100


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Biologic Functions of theBiologic Functions of the

Complement SystemComplement System

1- Cell lysis:1- Cell lysis:including bacteria, tumour cells,including bacteria, tumour cells,erythrocytes, protozoa, enveloped viruseserythrocytes, protozoa, enveloped viruses..

2- Opsonization:2- Opsonization:C3b acts as an opsonin.C3b acts as an opsonin.

3- Inflammatory function:3- Inflammatory function:due to generation ofdue to generation ofpeptide fragments.peptide fragments.

a)a) Chemotaxis:Chemotaxis:e.g. C5a which attracts polymorphse.g. C5a which attracts polymorphsto the site of inflammation.to the site of inflammation.

b)b) Anaphylatoxins:Anaphylatoxins:e.g. C3a and C5a whiche.g. C3a and C5a which degranulation of mast cellsdegranulation of mast cells release ofrelease ofmediators as histamine and serotonin.mediators as histamine and serotonin.


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OpsonizationOpsonization


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Biologic Functions of theBiologic Functions of the

Complement SystemComplement System


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4 Ab,Complement 3

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