1) Tabulate the differences of the 5 classes of immunoglobulins.

Properties IgG IgM IgA IgD IgE

Structure
Monomer Pentamer Dimer Monomer Monomer

(1)Providing (1) (1) Patrol (1) May (1) Appears

immunity for Complement mucosal play a role to be a
the newborn fixation surfaces and in B-cell nuisance
because IgG (2) act as a first activation antibody, it
can cross the Agglutination line of defense (2) may serve
placenta (3) (2) It plays an Susceptible a protective
(2) Fixing Opsonization important role to role by
complement (4) Toxin in neutralizing proteolysis triggering
(3) Coating neutralization toxins an acute
antigen for produced by inflammator
enhanced microorganism y reaction
phagocytosis s that recruits
(opsonization) (3) It helps to neutrophils
(4) prevent and
Major Neutralizing bacterial eosinophils
Functions toxins and adherence to to the area
viruses mucosal to
surfaces help destroy
(5) invading
Participating in antigens that
agglutination have
and penetrated
precipitation IgA
reactions defenses
(better at
precipitation
reactions than
at
agglutination)

Molecular 150,000 900,000 160,000– 180,000 190,000

 weight
Sedimentatio 8S
7S 19 S 7S 7S
n coefficient
Heavy chain γ μ α δ ε

α1, α2
( IgA2 is the
predominant
form in
γ1 (67 %), γ2
Heavy chain secretions at None
(22 %), γ3 (7 None None
subclasses mucosal
%), γ4 (4 %)
surfaces, while
IgA1 is mainly
found in serum
)
Heavy chain 70,000–
molecular 50,000–60,000 70,000 55,000–60,000 62,000 75,000
weight
Constant
domains 4
3 4 3 3
(Heavy
chain)
Macrophages, Basophils
Macrophages,
monocytes, and tissue
Fc binds to monocytes,
and mast cells
and neutrophils
neutrophils
Total Ig (%) 70-75 10 10-15 <1 0.002

Serum
concentratio 800-1600 120-150 70-350 1-3 0.005
n (mg/dL)
Serum half- 2-3
23-25 6 5 1-3
life (days)
Carbohydrat
e content 12
2-3 12 7-11 9-14
(weight
percent)
Electrophore γ1
γ2–α1 γ 1–β12 γ2–β2 γ1
tic migration
Complement No
Yes Yes No No
fixation
Crosses No
Yes No No No
placenta

Researcher: Santos, Mariel Lynne

Reference: Stevens, C.D. EdD, MT(ASCP). Clinical Immunology and Serology: A

LABORATORY PERSPECTIVE (3rd ed). p. 58-62.

2) Describe the different immunoglobulin variants (Isotype, Allotype, Idiotype)

ISOTYPE: The isotypic class of antigenic determinants is the dominant type found on
the immunoglobulins of all animals of a species. The heavy-chain, constant region
structures associated with the different classes and subclasses are termed isotypuc
variants.genes for isotypic variants are present in all healthy members of a species.
Determinants in this category include those specific for each Ig class, such as gamma (γ)
for IgG, mu (µ) for IgM, and alpha (α) for IgA, as well as the subclass-specific
determinants κ and λ. H chain sequencing demonstrated the presence of domains similar
to those in the L chains—that is, variable and constant regions. The first approximately
110 amino acids at the amino-terminal end constitute the variable domain, and the
remaining amino acids can typically be divided up into three or more constant regions
with very similar sequences, designated CH1, CH2, and CH3. Constant regions of the H
chain are unique to each class and give each immunoglobulin type its name. Hence, IgG
has a γ H chain, IgM a µ chain, IgA an α chain, IgD a δ chain, and IgE an ε chain. Each
of these represents an isotype, a unique amino acid sequence that is common to all
immunoglobulin molecules of a given class in a given species.

ALLOTYPE: The second principal group of determinants is found on the

immunoglobulins of some, but not all, animals of a species. Antibodies to these allotypes
(alloantibodies) may be produced by injecting the immunoglobulins of one animal into
another member of the same species. The allotypic determinants are genetically
determined variations representing the presence of allelic genes at a single locus within a
species. Typical allotypes in humans are the Gm specificities on IgG (Gm is a marker on
IgG). In humans, five sets of allotypic markers have been found- Gm, Km, Mm, Am, and
Hv. Minor variations of these sequences that are present in some individuals but not
others are known as allotypes (Fig. 4–3). Allotypes occur in the four IgG subclasses, in
one IgA subclass, and in the kappa light chain. These genetic markers are found in the
constant region and are inherited in simple Mendelian fashion. Some of the best-known
examples of allotypes are variations of the γ chain known as G1m3 and G1m17.
IDIOTYPE: A result of the unique structures on light and heavy chains, individual
determinants characteristics of each antibody are called idiotypes. The idiotypic
determinants are located in the variable part of the antibody associated with the
 hypervariable regions that form the antigen-combining site. The variable portions of each
chain are unique to a specific antibody molecule, and they constitute what is known as
the idiotype of the molecule. The amino terminal ends of both L and H chains contain
these regions, which are essential to the formation of the antigen-binding site. Together
they serve as the antigen recognition unit.

Researcher: Santos, Mariel Lynne

Reference: M. L. Turgeon, Immunology and Serology in Laboratory Medicine, pages 17-
18

3) Identify and describe the different kinds of antibodies.

IgM

 Largest of all the antibody molecules, consists of five of the basic units (pentamer)
mu heavy chains joined together by a structure known as J-chain.

 Accounts for about 5-10% of the immunoglobulin pool.

 Restricted almost entirely to the intravascular space due to its large size.

 Fixes complement, much more efficient than IgG in the activation of complement
and agglutination.

 First antibody to be produced and is of greatest importance in the first few days of a
primary immune response to an infecting organism.

 Does not cross the placenta.

 Many blood group antibodies that are capable of agglutinating antigen positive RBCs
suspended in saline in tests performed at 22 C are IgM causing visible agglutination,
ie, ABO antibodies.

 IgM antibodies are potent agglutinators that activate complement very efficiently.
IgG

 Most abundant of the immunoglobulins in the plasma

 One basic structural unit, i.e. Y-shaped molecule having 2 light chains and 2 Gamma
heavy chains.

 Produced in response to a wide variety of antigens, including bacteria, viruses and

RBC and WBC allo-antigens.

 Coats organisms to enhance phagocytosis by neutrophils and macrophages.

 Through its ability to cross the placenta, maternal IgG provides the major line of
defense against infection for the first few weeks of a baby's life.

 It is the predominant antibody produced in the secondary response.

 The serologic behavior and characteristics of IgG antibodies make them one of the
most clinically significant in blood banking.

 Most blood group antigens capable of eliciting an immune response result in the
production of IgG antibodies.

 These antibodies are detected by serologic test procedures based on their

behavior characteristics, such as reactivity at 37 C, complement activation,
indirect agglutination and hemolysis.

 Much of routine blood banking involves serologic test procedures designed to

detect and identify IgG antibodies.

 Four subclasses which differ in their heavy chain composition and in some of their
characteristics such as biologic activities. IgG1, IgG2, IgG3 and IgG4.

IgA

 Found in saliva, tears, colostrum breast milk and in nasal, bronchial and
intestinal secretions.

 IgA present in large quantities in colostrum and breast milk, is transferred across the
gut mucosa in the neonate and plays an important role in protecting the neonate from
infection.
 Produced in high concentrations by lymphoid tissues lining the gastrointestinal,
respiratory and genitourinary tracts.

 Plays an important role in protection against respiratory, urinary tract and bowel
infections and preventing absorption of potential antigens in the food we eat.

 Represents 10 to 15% of the total circulatory immunoglobulin pool.

 In plasma IgA may exist as a single basic structural unit or as two or three basic units
joined together.

 The IgA present in secretions exists as two basic units (a dimer) attached to another
molecule know as secretory component.

 1) This substance is produced by the cells lining the mucous membranes.

 2) It is thought to protect the IgA in secretions from destruction by

digestive enzymes.

 IgA does not cross the placenta and does not bind complement.

 For blood banking, an IgA deficient individual may produce anti-IgA which can cause
severe, life-threatening anaphylactic reactions during transfusion. Once identified
these individuals must be transfused with blood and components which lack IgA.

The dimeric IgA molecule.

 1 H-chain,

 2 L-chain,

 3 J-chain,

 4 secretory component
 IgE

 Trace plasma protein (only about 0.004%) in the plasma of non-parasitized

individuals.

 Major importance mediating some types of allergic reactions and is generally

responsible for an individual's immunity to invading parasites.

 Fc region binds strongly to a receptor on mast cells and basophils and, when antigen
is bound it causes the basophil (or mast cell) to release histamines and heparin from
these cells, resulting in allergic symptoms.

 Clinical effects of IgE mediated reactions include increased vascular permeability,

skin rashes, respiratory tract constriction (wheezing), and increased secretions from
epithelium (watery eyes, runny nose).

 Not much else is known about its biologic role.

 IgE does not fix complement and does not cross the placenta.

 No blood group antibodies have been reported to belong to this class.

IgD

 Accounts for less than 1% of the total immunoglobulin pool.

 This is primarily a cell membrane immunoglobulin found on the surface of B

lymphocytes.

 IgD does not fix complement and does not cross the placenta.

 Little is known about the function of this class of antibody.

 No blood group antibodies have been reported to belong to this class.

Researcher: Joves, Yasmeen

References:
http://www.austincc.edu/mlt/bb/bb_unit3Immunology/bb_Unit3Part2Immunology/bb_unit3i
mmunologyPart2Spring2011.ppt
4) Tabulate the proteins involved in the complement system and their biologic functions

Researcher: Castro, Sheanalene

References: Stevens, C. D. (2010). Clinical Immunology and Serology: A Laboratory

Perspective (3rd ed.). Philadelphia: F.A Davis Company.
 5) Identify the disorders associated with deficiencies of the different components of the
complement system.

Classical pathway component deficiencies (C1, C4, C2)

 Individuals are prone to immune complex disease, commonly systemic lupus

erythematosus (SLE). The reason for this is thought to be that the complement
deficiency leads to an inability to clear circulating immune complexes. This in turn
leads to their deposition in tissues and an associated inflammatory response.Reduced
clearance of apoptotic cells by the complement system may also lead to the
development of auto antigens.
 C2 deficiency is also associated with recurrent bacterial infection and an increased
risk of cardiovascular disease. It is thought to influence the development
of atherosclerosis.

*Systemic lupus erythematosus (SLE) is a heterogeneous, inflammatory, multisystem

autoimmune disease in which antinuclear antibodies occur (often years before clinical
symptoms). Lupus erythematosus describes the typical rash of SLE and the term
systemic emphasises the potential for multi-organ involvement. The cause of SLE is
unknown.

MBL deficiency

 Classically presents with recurrent pyogenic infection in childhood.

 Deficiency of MBL increases susceptibility to Saccharomyces cerevisiae infection as
well as pneumococcal and neisserial infection.Pneumococcal infection is particularly
common.
 There is also an association with SLE and possibly atherosclerosis.

Alternative pathway component deficiencies (properdin, factor B and factor D)

 Affected individuals are prone to pneumococcal and meningococcal infections.

 With properdin deficiency, there is a particular risk of overwhelming neisserial
infection.

C3 deficiency

 C3 is required for opsonisation (the coating of pathogenic cells with opsonin to

facilitate phagocytosis).
 A defect in the pathway that results in deficiency of C3 can lead to problems with
opsonisation. There may be a deficiency of C3 itself or a deficiency of other
complement components in the classic, alternative or MBL pathways (ie above C3 in
the cascade).
 Primary C3 deficiency tends to present in early life with overwhelming infection with
encapsulated organisms.
  There is also a tendency to connective tissue diseases.

MAC deficiencies (C5-C9)

 Recurrent infections are again a feature.

 Infection with Neisseria meningitidis is particularly common. More rare serotypes of
this organism such as Y and W135 tend to cause the infection.

Leiner's disease

This is a paediatric condition associated with a deficiency of C5. It has also been reported
with C3 and C4 deficiency.

 It causes wasting, chronic diarrhoea and widespread seborrhoeic dermatitis.

*Seborrhoeic dermatitis is a type of skin rash. It is sometimes called seborrhoeic eczema. It

most often occurs in young adults but can occur at any age. About 1-3 in 100 adults develop
this condition. It is more common in men than in women. Some babies have a similar
condition that usually clears within a few months which is sometimes called cradle cap.

Dermatitis means inflammation of the skin, and seborrhoeic means it affects the areas where
there are sebaceous glands. These are the glands that make the oil (sebum) for the skin.

The exact cause of seborrhoeic dermatitis is not known. It is thought that yeast germs from
the Malassezia species may be involved. However, it is not just a simple skin infection and
you cannot catch this condition from others (it is not contagious). The germs live in the
sebum of human skin in most adults. In most people they do no harm. But some people may
react to these yeast germs, making the skin become inflamed.

Complement regulatory protein deficiency

 If the proteins that regulate the complement cascade are deficient, the complement
system can become over-activated.
 C1-inhibitor (C1-INH) is an inhibitory protein that regulates the classical pathway.
Deficiency results in angio-edema. C1-INH deficiency can be hereditary, resulting
in hereditary angio-edema, or acquired.
 Paroxysmal nocturnal haemoglobinuria can also occur as a result of over-activation of
the complement system.

*Angio-oedema is a local, non-inflammatory, self-limiting oedema that is circumscribed,

and is a result of increased leakage of plasma from the capillaries located in the deep layers
of the skin and the mucosae
  *Paroxysmal nocturnal haemoglobinuria

There is an acquired haemolyticanaemia due to the susceptibility of the erythrocyte

membrane to the haemolytic action of complement.

There are thromboses in large vessels, such as hepatic, abdominal, cerebral and
subdermal veins.

There is deficient haematopoiesis that may be mild or severe and cause a

pancytopenia with aplastic anaemia.

Researcher: Agsano, Alffy Maegan

Reference: https://patient.info/doctor/complement-deficiencies