Biomedical Science 2

Makassar, 11th March 2011

Ika Yustisia
Department of Biochemistry
Faculty of Medicine UNHAS
 Introduction
 Structure and function of antibody
 Structure and characteristic of
antigen
 Structure and function of
complement
 Introduction to cytokines
 Immunological Methods
 Major molecules in Immune
system:
 Antibody
Antigen
 Complement
 Cytokine
The Immunoglobulin Superfamily
 Cell surface and soluble molecules
that mediate recognition, adhesion,
or binding functions
 Share partial amino acid sequence
homology and tertiary structural
features
• Ig heavy and light chains
 MHC: Major histocompatibility complex
(=HLA/ Human Leukocyte Antigen)
IgG: Immunoglobulin G
TCR: T-cell receptor
Other Ig superfamily: CDs, adhesion
TCR molecules
 Immunoglobulin = antibody
 Soluble antigen receptors, which are
formed by activated B cells (=plasma
cells) and released into the blood
 Important part of the humoral immune
defense system
 Antibody molecules are glycoproteins
composed of two light chains (L) of
identical sequence combined with two
identical heavy chains (H) to form the
structure (LH)2
 In IgG
• The H chains: 440 aa (50 kDa)
• The L chains: 220 aa (25 kDa)
 The four chains are covalently
interconnected by sulfide bonds
 Sequence of the NH2-terminal half of L
chains and the NH2-terminal quarter of
H chains are highly variable
 VH and VL
 Within this domain certain regions are
hypervariable
• 5 – 7 aa residues in VL
• 6 – 17 aa residues in VH
 Hypervariable = complementarity-
determining regions (CDRs)
 Forming the antigen-binding site
complementary to the topology of the
antigens
 The COOH-terminal three quarter of H
chains and the COOH-terminal half of L
chains are homologous in sequence with
other H or L of the same class
 CH and CL
 CH regions
• determining the antibody class
• profiding binding of complement proteins
• containing the site necessary for Ig to cross
placental membrane
Properties of human Igs
Major functions of human Igs
 Immunogen is a substance that
induces a specific immune response
 Antigen (Ag) is a substance that
reacts with the products of a specific
immune response
 Epitope or antigenic determinant is
that portion of an antigen that
combines with the products of a
specific immune response
 Macromolecules typically contain
multiple antigenic determinants
referred as polyvalency or
multivalency
 Haptens are small molecules which
could never induce an immune
response when administered by
themselves but which can when
coupled to a carrier molecule
 Haptens have the property of
antigenicity but not immunogenicity
 An antigen is any substances that
may be specifically bound by an
antibody molecule or T cell receptor
 Antibodies can recognize
 almost every kind of biologic molecule
 simple intermediary metabolites, sugars, lipids,
hormons
 complex molecules (carbohydrates,
phospholipids, nucleic acids, and proteins)
 T cells recognize only peptides
Factors Influencing Immunogenicity
Contribution of the Immunogen
 Foreignness
• self and non-self molecules
 Size
• in general, the larger the molecule the more
immunogenic it is likely to be.
 Chemical Composition
• In general, the more complex the substance
is chemically the more immunogenic it will be
Factors Influencing Immunogenicity
Contribution of the Immunogen
 Physical form
• In general particulate antigens are more
immunogenic than soluble ones and
denatured antigens more immunogenic than
the native form.
 Degradability
• Antigens that are easily phagocytosed are
generally more immunogenic
Factors Influencing Immunogenicity
Contribution of the Biological System
 Genetic Factors
• Some substances are immunogenic in one
species but not in another. Similarly, some
substances are immunogenic in one individual but
not in others (i.e. responders and non-responders)
 Age
• Usually the very young and the very old have a
diminished ability to mount and immune response
in response to an immunogen.
Factors Influencing Immunogenicity
Method of Administration
 Dose
• There is a dose of antigen above or below which
the immune response will not be optimal.
 Route
• Generally the subcutaneous route is better than
the intravenous or intragastric routes
 Adjuvants
• Substances that can enhance the immune
response to an immunogen
 The complement system consists of
several plasma proteins that are
activated by microbes and promotes
destruction of the microbes and
inflammation
 At least 11 distinct complement
protein exist in plasma
 Many complement proteins are
inactive precursors of proteolytic
enzymes
 Activating a succeeding protein of the
pathway by cleavage of a specific
peptide bond, leading to a cascade
effect
 Cytokines are polypeptides produced
in response to microbes and other
antigens that mediate and regulate
immune and inflammatory reactions
Functional catagories of Cytokines
 Mediators and regulators of innate
immunity
 Mediators and regulators of innate

immunity
 Stimulators of hematopoiesis
 Because of their great specificity,
antibodies form the core of many
important analytical and preparative
biochemical procedures
 Monoclonal antibodies
 Koolman, J.; Roehm, KH. Color Atlas of
Biochemistry, 2 ed. Thieme, 2004; 266-273; 306-
315
 Mathews, CK., van Holde, KE., Ahern, KG.
Biochemistry, 3 ed. Addison-Wesley PC, 2000
 Abbas, AK., Licthman, AH. Cellular and Molecular
Immunology, 5 ed. Elsevier, 2005
 Abbas, AK., Licthman, AH. Basic Immunology, 5 ed.
Elsevier, 2009
 Schultz, RM. Protein II: Structure-function
relationships in protein families in Textbook of
Biochemistry, 6 ed., Delvin, TM (editor), Wiley Liss,
2006
 Murray, RK. Plasma Proteins and Immunoglobulins
in Harper’s Ilustrated Biochemistry, Murray, RK.,
Granner, DK., Rodwell, VW(editors), 28th ed., 2009