Transcript Immunoglobulins - Khyber Girls Medical College

Dr Nayyer uz Zaman
Lecturer Biochemistry
KGMC
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Antibodies are globulin proteins
(Immunoglobulins) that react specifically with
the antigen that stimulated their production.
They make up about 20% of the protein in
blood plasma
Blood contains three types of globulins:
alpha, beta and gamma
Antibodies are gamma globulins
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There are five classes of immunoglobulins
(Antibodies):
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IgG
IgA
IgM
IgE
IgD
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Immunoglobulins are glycoproteins made up
of LIGHT (L) and HEAVY (H) polypeptide
chains
The terms light and heavy refer to the
molecular weight
Light chains have a molecular weight of about
25,000 while heavy chains have a molecular
weight of 50,000 to 70,000
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The simplest immunoglobulin molecule has a
“Y” shape and is made up of four polypeptide
chains: Two “H” chains and two “L” chains.
The four chains are linked by disulfide bonds
An individual antibody molecule always
consists of two identical H chains and two
identical L chains
Membrane-bound
receptor
Soluble
antibody
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L and H chains are sub-divided into “variable”
and “constant” regions
The variable regions are responsible for
antigen binding
The constant regions are responsible for
various biological functions such as
complement activation and binding to cell
surface receptors
Disulfide bond
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Variable(V) &
Constant (C)
Regions
◦ VL & CL
◦ VH & CH
Carbohydrate
CL
VL
CH2
CH1
VH
Hinge Region
CH3
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Also known as antibody-mediated immunity
It is directed primarily against
◦ Toxin induced diseases
◦ Infections by encapsulated organisms (eg
pneumococcus, Haemophilus etc)
◦ Certain viral infections
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THE PRIMARY RESPONSE:
◦ When an antigen is first encountered, the
antibodies are detectable in the blood after a long
lag period i.e. 7-10 days.
◦ A small clone of B cells or plasma cells specific for
the antigen is formed
◦ The first antibodies to form are IgM, followed by
IgG or IgA
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THE SECONDARY RESPONSE:
◦ When there is a second encounter with the same
antigen, months or years after the primary
response, there is a RAPID antibody response with
HIGHER levels of immunoglobulins (antibodies) and
a shorter lag period (only 3-5 days)
◦ There is a much larger amount of IgG made than
IgM, although IgM is first to be made in the
secondary response.
◦ This is due primarily to the “memory” B-cells that
were formed during the primary response.
◦ This is the basis for the concept of vaccination as
well
IgG
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Each IgG molecule consists of two L chains
and two H chains linked by disulfide bonds
There are 4 subclasses IgG1 – IgG4 (with IgG1
making up most i.e. approx 65% of total IgG)
IgG is the predominant antibody in the
secondary immune response and constitutes
and important defense against bacteria and
viruses
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IgG is the only antibody that can cross the
placenta, therefore it is the most abundant
antibody in newborns
IgG is one of two antibodies that can activate
the complement system (IgM is the other one)
IgG is the immunoglobulin that opsonizes i.e.
it can help enhance phagocytosis
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IgA is the main immuoglobulin in secretions
such as colostrum, saliva, tears and
respiratory, intestinal and genital tract
secretions
It prevents attachment of micro-organisms
e.g. bacteria and viruses to mucous
membranes.
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IgM is the main immunoglobulin produced in
the primary immune response.
It is present as a monomer on the surface of
virtually all B-Cells where it functions as an
antigen binding receptor.
It is a pentamer
It is the most efficient immunoglobin in
agglutination, complement fixation, and
other antibody reactions and is important in
defense against bacteria and viruses.
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It can be produced by the fetus in certain
infections
Does not cross the placenta
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This immunoglobulin has no known antibody
function but may function as an antigen
receptor
It is present on the surface of many Blymphocytes
It is present in small amounts in serum
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IgE is medically important for two reasons
◦ It mediates immediate hypersensitivity
(anaphylaxis)
◦ It participates in host defenses against certain
parasites, e.g. helminths (worms)
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IgE (Fc portion) of IgE binds to the surface of
mast cells and basophils.
Bound IgE serves as a receptor for antigens
(allergen) and this antigen-antibody complex
triggers allergic responses of the immediate
(anaphylactic) type through the release of
mediators e.g. histamine
Although it is present in trace amounts in
normal individuals, its levels are raised in
persons with allergies
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IgE is the main host defense against certain
important helminth (worm) infections, such
as strongyloides, trichinella, ascaris and the
hookworms.
The serum IgE level is usually increased in
these infections.
Because worms are too large to be ingested
by phagocytosis, they are killed by
eosinophils that release worm-destroying
enzymes
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IgE specific for worm protiens binds to
receptors on eosinophils, triggering the
antibody-dependent cellular cytotoxicity
(ADCC) response.
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CRP is a major component of acute phase proteins . It is
produced in the liver and is present in the circulation in
minute concentration (< 1 mg/dl). C-creative protein (C
strands for carbohydrate to which it binds on the capsule
of pneumococi) is involved in the promotion of immune
system through the activation of complement cascade.
Estimation of CRP in serum is important for the evaluation
of acute phase response. In a normal surgery, serum CRP
increases and returns to normal level within 7-10 days. If
the recovery is complicated by any infection, it will be
reflected by the continuous elevation of CRP which
requires further treatment.
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Multiple myeloma, a plasma cell cancer constitutes about
1% of all cancers affecting the population. Females are
more susceptible than mates for this disorder and it
usually occurs in the age group 45-60 years.
Abnormal Ig production: Multiple myeloma is due to the
malignancy of a single clone of plasma cells in the bone
marrow . This results in the overproduction of abnormal
immunoglobulins mostly (75%) IgG and in some cases
(25%) IgA or IgM IgD type multiple myeloma. In patients
of multiple myeloma, the synthesis of normal
immunoglobulins is diminished causing depressed
immunity. Hence recurrent infections are common in
these patients.
Electrophoretic pattern: The plasma of multiple myeloma
patients show a characteristic pattern of electrophoresis .
There is a sharp and distinct band (M band , for myeloma
globulin ) between ß-and γ-globulins. Further, this M
band almost replaces the γ-globulin band due to the
diminished synthesis of normal γ-globulins.
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Bence jones proteins: Henry Bence Jones first described
them in 1847. There are the light chains (k or γ) of
immunoglobulins that are synthesized in exces. Bence
Jones proteins have a molecular weight of 20,000 or
40,000 (for dimer). In about20./. Patients of multiple
myloma.
Bence Jones proteins are excreted in urine which often
damges the renal tubules.
2. The classical heat test involves the precipitation of
Bence Jones proteins when slightly acidified urine is
heated to 40-50 0 C . This precipitate redissolves on
further heating of urine to boiling point. It reappears
again on cooling urine to about 700 C.
3. Bradshaw`s test involves layering of urine on
concentrated HCL that forms a white ring of precipitate if
Bence Jones proteins are present.
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