IMMUNOLOGY AND SEROLOGY

LECTURE / WEEK NO.2/ MACARUBBO L.

NATURE OF ANTIGENS AND THE MAJOR TRAITS OF IMMUNOGENS

HISTOCOMPATIBILITY COMPLEX
 Immunogenicity – ability of an immunogen to
I. Factors influencing the immune response stimulate a host response.
II. Traits of immunogens  Immunogenicity depends on:
III. Epitopes, haptens, and adjuvants o Macromolecular size
IV. Relationship of antigen to the host  At least 10,000 daltons to be
V. Major histocompatibility complex (MHC) and its recognized
role in the immune response  Most active are at least 100,000
daltons
FACTORS INFLUENCING THE IMMUNE RESPONSE  Foreignness (substances that is not normally found in
 Lymphocytes are the key cells that are responsible the body)
for the specificity, diversity, and memory that o The more taxonomically different, the more
characterize adaptive immunity. successful it is as an immunogen
 Immunogens – macromolecules capable of LEVELS OF PROTEIN ORGANIZATION
triggering an adaptive immune response by inducing
the formation of antibodies or sensitized T-cells in an  Protein structure - made up of amino acids that is
immunocompetent host. attached to one another.
 Proteins (powerful immunogens since it is made up of
 Age units amino acids) and polysaccharides are most
o Older individuals—decreased response to effective immunogens.
antigenic stimulation (geriatric patient)  Primary structure – determines secondary structure
o Neonates—immune system not fully developed  Tertiary structure – embodies the spatial or 3D
orientation of the entire molecule.
 Overall health  Quaternary structure – association of two or more
o Malnutrition chains into a single polymeric unit.
o Fatigue
o Stress

 Route of inoculation (ways of exposure)

o Intravenous -
reins

o Intradermal - skin

o Subcutaneous -
beneath skin

o Oral -

mouth

 Also determines which cell populations

will be involved in the response.

 Dose
o The larger the amount of immunogen exposed
to, the greater the immune response
o Very large doses can induce tolerance

 Genetic capacity (predisposition)

IMMUNOLOGY AND SEROLOGY: NATURE OF ANTIGENS AND THE MAJORHISTOCOMPATIBILITY COMPLEX 1

 IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.2/ MACARUBBO L.

EPITOPE Antibody –
B cell
 The key portion of the immunogen recognized in the receptor
Haptens
immune response. Known as determinant site or
epitopes.
 Only a small part of immunogen is recognized in the
immune response.
 Linear epitopes
o Sequential ADJUVANTS
o Example: amino acids following one another on  Can make immunization more effective
a single chain.
 Work by targeting APCs (Antigen Presenting Cells) —
 Conformational epitope important to the adaptive immune response
o Has folding of one or more chains
 Administered with an immunogen that increases the
o Allows amino acids from different segments to
immune response in order to provide immunity to a
come into close proximity.
particular disease.
 Trait
 Protect immunogens from degradation
1. Macromolecular size
 Allow a longer response time that attracts more immune
2. Foreignness
cells to injection site
3. Chemical composition and molecular
 Used to accelerate immune response and increase
complexity
duration of protective immunity.
4. Ability to be processed and presented with MHC
molecules. RELATIONSHIP OF ANTIGENS TO THE HOST

 Autoantigens
o Belong to the host
o Do not usually evoke an immune response
o If immune response occurs, an autoimmune
condition is likely.
 If an immune response does occur to
autoantigens, it may result in an
autoimmune disease.
HAPTENS
 Alloantigens
 Non-immunogenic materials that create new antigenic o From other members of host species (such as in
determinants when combined with a carrier transplantation and blood transfusion)
 Haptens are antigens but not immunogens.  Heteroantigens
 Can react with the antibody, even without being o From other species, such as animals, plants, or
complexed to a carrier molecule microorganisms
 When bound to carriers, contribute to the development  Heterophile antigens
of interconnected lattice that serves as the basis for o Exist in plants or animals but are identical to or
precipitation and agglutination reactions closely related in structure so that antibody to
 Karl Landsteiner conducted the study of haptens in 1917. one will cross-react with antigen of the other
 Antibody not only recognize chemical features such as o Example: antigen from pneumococci bacteria
polarity, hydrophobicity, and ionic charge but overall 3D cross-reacting with type B blood group antigen
configuration is important.

IMMUNOLOGY AND SEROLOGY: NATURE OF ANTIGENS AND THE MAJORHISTOCOMPATIBILITY COMPLEX 2

 IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.2/ MACARUBBO L.

MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES Class I MHC Molecules

 Linked to the genetic capability that allows the body to  Expressed on all nucleated cells
mount an immune response.  Differ in level of expression
 Have been found on all nucleated cells in the body o Highest on lymphocytes and myeloid cells
 Play a pivotal role in the development of humoral and o Lowest or undetectable on liver hepatocytes,
cellular immunity. neural cells, muscle cells, and spermatozoa
 Determine whether transplanted tissue is  Glycoprotein dimers made up of two non-covalently
histocompatible and accepted or recognized as foreign linked polypeptides.
and rejected.
 Bring antigens in the body to the surface of cells for
recognition by T cells.
 When combined with antigen on the surface of other
cells, activate T cells.

GENES CODING FOR MHC MOLECULES

\
 Found in humans on the short arm of chromosome 6
 Divided into three categories or classes:
o Class I: found on three different loci (designated
as A, B, and C) Class II MHC Molecules
o Class II: found on the D region (designated as DR,
 Found primarily on APCs
DQ, and DP)
 Include:
o Class III: found in a region between class I and II
o B lymphocytes
 Codes for C4A, C4B, C2, and B
o Monocytes
complement proteins
o Macrophages
 Alleles are alternate forms of a gene that code for a
o Dendritic cells
slightly different variety of the same product.
o Thymic epithelium
 The MHC system is described as polymorphic because
 DP, DQ, DR
there are so many possible alleles at each location.
o Major class II molecules
 HLA-A has over 2,000 different alleles
o Two non-covalently bound polypeptides that
 HLA-B has over 2,600 different alleles are encoded by separate genes in the MHC
 HLA-C has over 1,500 different alleles complex
 Because the MHC genes are closely linked, inheritance
for the grouping is known as a haplotype
 One haplotype is inherited from each parent
 Each inherited chromosomal region consist of a package
of genes A, B, C, DR, DP, Q. The full genotype would
consist of two of each gene at a particular locus.
 MHC type is about as unique as fingerprint.

IMMUNOLOGY AND SEROLOGY: NATURE OF ANTIGENS AND THE MAJORHISTOCOMPATIBILITY COMPLEX 3

 IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.2/ MACARUBBO L.

ROLE OF CLASS I MOLECULES IN THE IMMUNE RESPONSE SUMMARY

 Class I MHC–peptide interaction  Adjuvants are substances that can be mixed with antigen
o Molecules process endogenous antigens to enhance the immune response.
o Peptides are approximately 8 to 11 amino acids  Autoantigens belong to the host.
in length  Alloantigens are from the same species as the host but
o Transporters associated with antigen are not identical to the host.
processing (TAP1 and TAP2) transport antigenic  Heteroantigens are from other species.
peptides to the endoplasmic reticulum, where  Heterophile antigens exist in unrelated species, but their
they bind to MHC class I molecules structure is so similar that antibody formed to one will
cross-react with antigen from a different species.
ROLE OF CLASS II MOLECULES IN THE IMMUNE RESPONSE
 The MHC encodes class I and class II molecules, which
 Class II MHC–peptide interaction play a major role in antigen presentation to T cells.
o Molecules participate in the exogenous pathway  Class I and class II molecules bind peptides within cells
of antigen presentation and transport them to the plasma membrane, where the
o Molecules are synthesized in the endoplasmic peptides can be recognized by T cells.
reticulum and associated with a protein called  Class I molecules present antigen to CD8+ T cells,
the invariant chain (Ii) triggering a cytotoxic reaction.
o Ii is cleaved to form a fragment, CLIP, which is  Class II molecules present antigen to CD4+ T cells, which
exchanged for the antigenic peptide are helper cells involved in antibody production.
o The MHC II peptide complex is transported to
the cell surface.

CLINICAL SIGNIFICANCE OF MHC

 Important in tissue transplant procedures

 Classes I and II can induce graft rejection
 Appear to play a role in development of autoimmune
diseases

SUMMARY

 Immunogens are macromolecules that elicit formation of

immunoglobulins or sensitized cells in an
immunocompetent host.
 An antigen denotes a substance that does not elicit a
host response but reacts with antibody once it has been
formed.
 Immunogenicity is influenced by factors such as age,
health, route of inoculation, and genetic capacity.
 An epitope is a determinant site of an immunogen and is
recognized by B or T cells.
 Haptens are non-immunogenic substances that must be
combined with a carrier to provoke an immune response.

IMMUNOLOGY AND SEROLOGY: NATURE OF ANTIGENS AND THE MAJORHISTOCOMPATIBILITY COMPLEX 4