Transcript 1) if the response to an antigen

Immunochemistry
The immune system
The body has two different types of immune response:
1) if the response to an antigen (foreign body) is the production
of soluble antibodies in the body fluids, it is called: Humoral
immunity.
2) if the response is through cytotoxic or killer T cells, then the
immunity is known as cell-mediated.
These two mechanisms complement each other.
The challenge for the immune system is to be able to provide
antibodies to interact with the antigens or foreign cells (both
known as non-self) that invade the body, but not to interact
with the body’s own proteins (known as self).
Antibodies (Immunglobulins (Igs)
A- Definition:
 Immunoglobulins are a group of proteins (gamma globulins)
produced by the body from B lymphocytes and plasma cells in
response to presence of foreign bodies.
 There are 5 basic types: G, M, A, E and D.
 All of immunoglobulins have a similar basic structure.
B- Basic structure of immunoglobulins:
 The basic unit of all Igs molecules consists of 4 polypeptide
chains linked by disulfide bonds:
a- 2 polypeptide chains of low molecular weight called light
chains (L)
b- 2 polypeptide chains of high molecular weight called heavy
chains (H)

Both H and L chains have 2 regions
a- C-terminal constant regions: having a constant amino
acid sequence within a class or type.
b- N-terminal variable (v) regions: with considerable
variation in amino acid sequence from molecule to
another.

Antigen- binding sites: This the part of antibody molecule
which combines with antigens. It is formed by a few amino
acids in the variable (v) region of H and L chains at the Nterminal.
Enzymes such as papain cleave IgG into 3 fragments: 2
Fab fragments and one Fc fragment. The Fab Fragment is
the part of the antibody molecule which combines with
antigen.

Classes of L and H chains:
a- Only 2 major types of L chains in man, Kappa (k) and
lambda (λ) chains. Approx. 70% of the human Ig
molecules carry k light chains and 30% carry λ light
chains.
b- H chain is unique to the class. In IgG, the H chains is
termed γ chain, in IgA, an α chain. In IgM a μ chain, in
IgD, a δ chain and an έ chain.

Igs contain CHO residues (2 to 12%). These are either
mannose, galactose, fructose or N-acetyl neuraminic acid.
They are attached to polypeptide chains.

Types of immunoglobulins:
1. IgG:
a- It forms 70-75% of the total serum Igs.
b- It is the only Ig which can cross the placenta.
c- It is the major Ig during secondary immune response
(i.e. prolonged stimulation of lymphocytes) with long
half life (about 30 days) if compared with other
immunoglobulins.
d- It is of low molecular weight formed of one unit only
(monomer), and contain 2-4% CHO.
2. IgA:
a- in serum present as monomer. In body fluids as diamer. In
diameric IgA, the molecules are joined by a small polypeptide
chain called J chain linked to Fc regions.
3. IgM:
a- It is present in serum and has the highest molecular
weight among all Igs as it is formed of 5 basic
subunits (pentamer)
b- Ig subunits are joined together by disulfide bonds
in a circular-fashion to form star.
c- It is the major Ig during the primary immune
response i.e. it is thr first of the antibodies which
act on introduction of foreign antigen into plasma.
Its present indicates recent infection.
d- It can not cross the placenta.
e- IgM contains 10% CHO and has a realatively short
half life.
4. Ig E: a- It is present in very low concentration in serum and
has the shortest half life (2-3 days). b- It is largely
responsible for immunity against parasites
c- Ig E ,in the presence of antigen, binds to mast cells and
basophils causing release of histamine and other
substances from mast cells. These substances result in
allergic manifestations.
5. Ig D: a- It is present in a very low concentration in serum.
b- It can not across placenta.
c- Ig D has activity against thyroid tissue, insulin,
penicillin and diphtheria toxoid

Antigens (Immunogens)
Definition: Antigens are substances when introduced to
the body will stimulate an immune response i.e. antibodies
production. Proteins, polysaccharides and other synthetic
polymers are good antigens.
 Lipids are not antigenic unless they are combined with
proteins or polysaccharides.
 Haptens: are small molecules that can not by themselves
induce antibody formation but can do so when covalently
linked to larger molecules
Hapten
+ lymphocytes → No antibodies
Hapten + protein + lymphocytes → antibodies against
hapten

Properties of antigens:
1- High molecular weight: thus proteins of molecular wt
greater than 100,000 are the most potent antigens.
2- Foreign to the body: Under normal conditions, tissues or
fluids of the body can be recognized by immune system as
self ( i.e. own tissues), and so do not stimulate immune
response.
 If foreign substances are introduced in the body, immune
system recognizes them as nonself and immune response
will occur.
3- Structural complexity: A molecule must posses a certain
degree of complexity to be antigenic. Immunogenicity
increases with structural complexity.

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Initiation of Ig production requires binding of the antigen
to the lymphocyte surface:
Antigen + lymphocyte surface → Ig
Antigens are bound to antigen receptors located on the
surface of lymphocytes.
In other words, presence of antigen stimulates and
activates B lymphocytes which are then be mature and
differentiated into plasma cells which produce antibodies.
Antigenic determinant: This the portion of antigen that
binds with the antigen receptors.
Immunopotency: It is the capacity of the region of the
antigenic determinant to induce the formation of specific
antibodies.


Neonatal and infant antibody production:
The human fetus is able to synthesize only a small amount of
Ig M and to a lesser degree, Ig A. Ig G has lower molecular
wt than Ig M and is easily able to cross the placenta.. Ig G is
also transferred from mother to baby in breast milk.
Transplacental and\breast milk-derived Ig G offer the baby a
passive immunologic protection until the endogenous Ig G
production takes place. The half life of Ig G is about 30 days
and with prolonged breast –feeding, the infant can derive
additional protection.
Immunity disorders:
1- Overproduction of Igs (hypergammaglonlinemia):
Due to increased synthesis. There are two types:
a- Diffuse hypergammaglobulinemia: when all Ig classes
are increased.
b- Discrete hypergammaglobulinemia (paraproteinemia):
when a single Ig or Ig fraction ( e.g. light chain) is
increased.
2- Underproduction of Igs (Hypogammaglobulinemia):
It may be congenital or acquired due to delayed onset of Ig
production
of
unknown
etiology
leading
to
immunodeficiency and recurrent infection.
3- Agammaglobulinemia (Bruton’s disease): Complete
absence of gamma globulins occur in boys (X-linked
disorder) in which patients have no B lymphocytes and so
low levels (or none) of all endogenous Ig subclasses are
produced. The disease leads to recurrent febrile infection in
early life, most infection in lower and upper respiratory
system resulting in otitis, pneumonia, sepsis, osteomyelitis
(inflammation of bone marrow) and meningitis.
Without early γ globulin therapy, these children die from
respiratory complications.
Other immune pathways are normal in these children.
4- Severe Combined Immune Deficiency (SCID): occur in
infants who lack both humoral (Abs) and cellular pathways
(NK cells) for killing bacteria and viruses. These children are
at risk of severe infection each time they are exposed to
infectious agents. The disease may be X-linked (in boys only)
or autosomal ( inherited in girls also).
Causes: i- aplasia of B. M. or Failure of lymphocyte
development and maturation in which both T-cells and B cells
(if present) are not functional.
ii- genetic disorder of purine metabolism: genetic deficiency
of adenosine deaminase leading to elevated levels of
adenosine in body fluids leading to failure of DNA synthesis
and so no protein synthesis. In this case the treatment is
enzyme replacement therapy or gene therapy.
Main treatment: 1-boy in the bubble i.e. in complete sterile
environment to avoid contact with any bacteria or viruses.
2- Bone marrow replacement. 3- interferon may be useful
 Other
components of immune system
1- Skin: is effective barrier to most microorganisms, but in
premature babies, this barrier is less well developed
2- Lysozyme: is an enzyme widely distributed in different
secretions and is capable of partially digesting a chemical
bond in the membrane of many bacterial cell wall.
3- Macrophages: In the presence of foreign organism,
monocytes are derived from B. M. and then are developed
into macrophages that subsequently engulf and digest
organism.
4- Natural killer (NK)cells or cell-mediated immunity: which
are leucocytes (lymphocytes) capable of recognizing cell
surface changes on host cells infected by virus particles .
The
infected host cells release interferon
which
stimulates NK cells production which subsequently bind to
these host cells and kill virus.
Interferon is also capable of providing resistance to infection
in host cells not virally infected.
5- Acute Phase proteins: which are defense proteins produced
by the liver in response to infection, particularly bacterial
infection. The most significance acute phase protein is called
‘ C-reactive protein’ (CRP). Letter C is added as it is capable
of binding to C-protein of pneumococci .
Acute phase proteins are the main components of complement .
Complement system: consists of at least 20 proteins most of
which are acute phase proteins.
Complement is produced as a result of antigen-antibody
reaction and aids antibodies in killing foreign bodies.
So, antibodies, acute phase proteins and complement coordinate
with each other to ultimately destroy bacteria and viruses.