Clinical Immunology & Serology

A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC

Complex
Chapter Three

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Immunogens are macromolecules capable of
triggering an adaptive immune response by
inducing the formation of antibodies or
sensitized T cells in an immunocompetent
host.
 Immunogens can then specifically react with
such antibodies or sensitized T cells.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

These three factors are
 The nature and complexity of the immunogen
itself
 The genetic coding of MHC molecules that
must combine with an immunogen before T
cells are able to respond to the ag
 Immunogen processing and presentation to T
and B cells

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Antigen refers to a substance that reacts with
antibody or sensitized T cells but may not be
able to evoke an immune response in the first
place.
 This response is actually caused by a
combination of three factors.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

In general, the ability of an immunogen to
stimulate a host response depends on the
following characteristics
 Macromolecular size
 Chemical composition and molecular
complexity
 Foreignness
 The ability to be processed and presented with
MHC molecules
Copyright © 2010 F.A. Davis Company
Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Haptens are nonimmunogenic materials that,
when combined with a carrier, create new
antigenic determinants.
 Poison ivy contains chemical substances
called catechols, which are haptens.
 Once in contact with the skin, these can
couple with tissue proteins to form the
immunogens that give rise to contact
dermatitis.
Copyright © 2010 F.A. Davis Company
TYPES OF ANTIGEN

1. Autoantigen – antigen derived from the same

individual
2. Alloantigen – antigen derived from different
individual from same species
3. Heteroantigen/Xenogeneic – antigen derived
from different species.
4. Heterophile antigens - exist in unrelated
plants or animals that are either identical to or
closely related in structure
Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 An adjuvant is a substance administered with
an immunogen that increases the immune
response.
 It acts by producing a local inflammatory
response that attracts a large number of
immune system cells to the injection site.
 Aluminum salts are the only adjuvants
approved for clinical use in the United States.

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 MAJOR HISTOCOMPATIBILITY
COMPLEX

formerly named as Human leukocyte antigen

(HLA)
a group of molecules which has genetic
capability to mount an immune response
changed to MHC molecules -- because they
determine whether transplanted tissue is
histocompatible and thus accepted or
recognized as foreign and rejected
are actually found on all nucleated cells in the
body and they play a pivotal role in the
development of both humoral and cellular
immunity
encoded by the MHC genes onto the cell surfaces.
 FUNCTION

1. function as antigens when transplanted from one individual to

another
2. MAIN FUNCTION: to bring antigen in the body to the surface of
cells for recognition by T cells
 TYPES
1. MHC Class I
expressed on ALL NUCLEATED CELLS
recognized by CD8+ T CELLS
2. MHC Class II
found primarily on ANTIGEN-PRESENTING CELLS
(APCs)
recognized by CD4+ T CELLS

Main Role: ANTIGEN PRESENTATION

M H C I in action
M H C I I in action
Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Class I and II gene products are involved in antigen recognition
and influence the repertoire of antigens to which T cells can
respond.
 Class III proteins are secreted proteins that have an immune
function, but they are not expressed on cell surfaces.
 See Figure 3-4.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Class I MHC molecules are expressed on all
nucleated cells, although they differ in the level
of expression.
 They are highest on lymphocytes and low or
undetected on hepatocytes, neural cells,
muscle cells, and sperm.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Class II MHC molecules are found primarily
on antigen-presenting cells, such as B
lymphocytes, monocytes, macrophages, and
dendritic cells.
 The major class II molecules—DP, DQ, and
DR—consist of two noncovalently bound
polypeptide chains that are both encoded by
genes in the MHC complex.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

Figure 3-6

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Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Different class I molecules will have slightly
different binding affinities; these small
differences determine to which particular
antigens one individual will respond.
 Display of hundreds of class I molecules
complexed to antigen allows CD8 positive T
cells to continuously check cell surfaces for
the presence of nonself antigens. (T cells are
known as surveillance cells).
Copyright © 2010 F.A. Davis Company
Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Unlike class I molecules, class II molecules
must be transported from the endoplasmic
reticulum (ER) to an endosomal compartment
before they can bind peptides.
 Dendritic cells are the most potent activators
of T cells, and they are excellent at capturing
and digesting exogenous antigens such as
bacteria.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 Once binding has occurred, the class II
protein-peptide complex is stabilized and is
transported to the cell surface. (See Fig. 3-6.)
 On the cell surface, class II molecules are
responsible for forming a trimolecular
complex that occurs between antigen, the
class II molecule, and an appropriate T-cell
receptor.

Copyright © 2010 F.A. Davis Company

Clinical Immunology & Serology
A Laboratory Perspective, Third Edition

Nature of Antigens and the MHC Complex

 If binding occurs with
a T-cell receptor on a
CD4-positive T cell,
the T helper cell
recruits and triggers a
B-cell response,
resulting in antibody
formation. (See Fig.
3-8.)

Copyright © 2010 F.A. Davis Company

• HLA-DR3 - SLE and Autoimmune Thyroid Disease
•HLA-DR4 - Rheumatoid Arthritis
•HLA-B51 - Behcet's Disease (Infection of all blood cells in the body)
•HLA-B8 - Myasthenia gravis and Celiac Disease
•HLA-DR, DQ - Type 1 DM and Multiple Sclerosis
TYPES OF GRAFTS

1. Autograft – graft derived from same

individual
2. Isograft/Syngraft – graft derived from
different class but identical individual
(eg.identical twins)
3. Allograft – found on different individual but
same species (The Basis of Transplantation)
4. Heterograft/Xenograft – from different
species