Antibodies

Abs or Igs are glycoproteins which fall in the

gamma-globulin fraction of the serum.

They are present both intra and extra-

vascularly.

They are produced by plasma cells in

response to Ags and they react specifically
with them.

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

IgM, IgE and IgD.
 Structure of
Immunoglobulins
Properties of Different Ig
Classes
IgG:
- Monomeric, consists of 2 H and 2 L chains,
bivalent.
- 4 subclasses: IgG1,2,3, and 4.
- 75% of total serum Igs.
- It fixes complement.
- Predominant Ab in secondary immune
response.
- The only Ig which crosses the placenta.
IgM:

- Pentameric, 10 H and 10 L
chains.
- About 7% of total serum Igs.
- Predominant in the primary
immune response.
- Most efficient in agglutination,
opsonization and activating
complement.
IgM Structure
IgA:
- 2 subclasses: IgA1 and 2.
- It is present in 2 forms:
Serum IgA: monomeric, forms 15% of
serum Igs.
Secretory IgA: dimeric, predominant
in secretions e.g. saliva, tears, milk,
colostrum, bronchial, genitourinary and
intestinal secretions, has a protective
role against invading pathogens.
Secretory IgA
IgD:

- Less than 1% of total serum Igs.

- Monomeric.
- Present on the surface of B-cells
and acts as a B-cell receptor.
- Exact function not known.
IgE:

- Present in trace amounts in normal

serum.
- Monomeric.
- Associated with atopic diseases, e.g.
bronchial asthma, serum IgE level
increases in allergic individuals.
- Called cytotropic Ab, and plays a role
in type I hypersensitivity.
- Serum IgE level is very much
increased in parasitic infections.
The rate of antibody production
 The rate of antibody production
Primary response: The first encounter with an antigen
produces Abs (mainly IgM), which appear in the serum
after 7-12 days. Their concentration rises slowly to a low
peak, and then declines.
Secondary response: , A second encounter with the same
antigen results in initial drop in Ab level due to neutralization
of the already present Ab, followed by a very rapid and
intense rise due to presence of immunologic memory. Abs
(mainly IgG) will rise to a higher peak and will stay longer
than in the primary response.
The same occurs with subsequent encounters with Ag till a
hyperimmune state is reached where there is no further
increase in Ab level. This is the main reason for giving
booster injections after an initial vaccination.
Response to multiple simultaneous Ags:

- When 2 or more Ags are administered at the

same time, the host produces Abs to each of
them.

- This is applied in combined immunization e.g.

DPT vaccine used for protection against
diphtheria, whooping cough, and tetanus.
 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.
+ 

Agglutinins
Opsonins
 Incomplete or blocking Abs
Coombs (Antiglobulin(Tests
• Direct Coombs Test
– Detects antibodies on erythrocytes

+ 

Patient’s RBCs Coombs Reagent

(Antiglobulin)
 Coombs (Antiglobulin(Tests
• Indirect Coombs Test
– Detects anti-erythrocyte antibodies in serum

Step 1
+ 
Patient’s Target
Serum RBCs

Step 2

+ 
Coombs Reagent
(Antiglobulin)
 Protective Effects of
Antibodies
 Neutralization of bacterial toxins or
enzymes.
 Bacterial lysis in the presence of
complement.
 Blocking the infecting ability of the
organisms.
 Opsonization of the micro-organisms
facilitating their phagocytosis.
 Clumping of the bacterial cells,
fascilitating their uptake by
 Monoclonal Antibodies
 Highly specific Abs produced against a
single epitope.
 Applications:
- Diagnostic: e.g.
- lymphocyte subset determination,
- HLA typing.
- Therapeutic: e.g.
- antitumour therapy.
- immunosuppressive therapy to
prevent graft rejection.
The Complement
System
The complement system is a
complex group of serum proteins,
present in low concentration in
normal serum, that interact
together in a cascading fashion to
protect against infectious agents. It
also includes membrane-bound
proteins.
Synthesis:
- By many cells: hepatic parenchymal
cells, monocytes, macrophages, and
intestinal epithelial cells.
Nomenclature of complement
proteins:

Classical pathway:
C1,C2, C3…etc…………C9.
Upon cleavage the large fragment is
given the suffix “b”, and the small
fragment the suffix “a”.
e.g. C5  C5a and C5b.

Alternative pathway:
Factor B, factor D..etc
 Pathways of Complement
Activation
- 2 main pathways:- The classical and the
alternative complement pathways.

The classical pathway is triggered by Ag-Ab

complexes.

The alternative pathway is triggered by

aggregated IgA, endotoxin of Gram -ve
bacteria, and yeast zymosan.
- Activation ccurs in a sequential fashion,
each component activating the following.
Pro-enzymes  cleavage  enzymes.

Both pathways lead to formation of C3

convertase  C3 cleavage and activation 
end in formation of MAC  cell lysis.
 C3 activation is the common
central event. After that,the 2
pathways proceed in the same
fashion together through binding of
the late acting components to form a
membrane attack complex(MAC)
which becomes inserted in the lipid
bilayers of foreign membranes,
ultimately causing cell lysis.
The activation of alternative pathway
occurs in the absence of Ab, and thus
helps in the first line of defence
against microorganisms (innate
immunity) and mediates an
inflammatory response.
 The Membrane Attack
Complex
C5a

C5

70-100 Å

C6 C5b C7
C9
C9
C8 C9 C9

C9
C9C9

C9C9
C9
C9
 Biologic Functions of the
Complement System
1- Cell lysis: including bacteria, tumour cells,
erythrocytes, protozoa, enveloped viruses.
2- Opsonization: C3b acts as an opsonin.
3- Inflammatory function: due to generation of
peptide fragments.
a) Chemotaxis: e.g. C5a which attracts polymorphs
to the site of inflammation.
b) Anaphylatoxins: e.g. C3a and C5a which 
degranulation of mast cells  release of
mediators as histamine and serotonin.
Opsonization
Biologic Functions of the
Complement System