Immunogenicity

Lecture 5

Wesam Mohammed Emharib

Introduction
*Immunogenic substance and antigenic substance are closely related terms, but it is more
appropriate to use immunogenic term to describe state in which a substance induce immune
response. And antigenic term used when the substance able to react with immune response
products

*Immunogenic substance is more general term, thus all the immunogenic substances are
antigenic substances and the reverse is not accurate.

*Hapten is an example because it is antigenic substance and lacks the immunogenicity. In

other word, hapten are antigenic substances but unable by themselves to produce immune
response

* The immune response products are effector cells e.g. (plasma cell, T helper and T cytotoxic,
and memory cells) or effector molecules e.g. (antibodies and surface receptor of effector cells)

*The immunologist rank the protein as potent immunogenic then polysaccharide. In contrast
lipid and nucleic acid are not immunogenic unless they coupled with protein or polysaccharide

* There are factors affect the immunogenicity, these factors organized into two groups:
nature of immunogenic substance and biological system of host.

 Factors affect immunogenicity

 Nature of immunogenic substance
 Foreignness
*First of all any substance induce immune response must be recognize as non-self-material.
* The extent of immunogenicity is depending on the extent of foreignness
* The difference between two species mean more structural difference thus more
immunogenicity

*Bovine serum albumin (BSA) is not immunogenic in cow, less immunogenic in goat and more
immunogenic in rabbit and chicken

* Collagen and cytochrome are highly conservative molecules, thus these molecules consider
as an exception for the pervious rule because these molecules showing very small
immunogenicity through different species.

* Also some sequestered antigen (sperm and cornea) exhibit greater immunogenicity even in
their original species when they injected into the host.

Molecular size
* The immunogenicity increase with molecular size, large molecules are more immunogenic
*The immunologist propose that molecules tend to have greater immunogenicity if their
molecular mass 100.000 Da or more. Small molecules with molecular mass between 5000 and
10,000 Da are less immunogenic.

Chemical composition or complexity of structure

*Proteins are immunogenic in all its form primary, secondary, tertiary, and quaternary
* Lipids are non-immunogenic (Haptens) and must be attached to suitable molecules such as
proteins to form lipoprotein which an immunogenic molecule

* By using this approach we can obtain antibodies against lipid part of lipoprotein and this
approach was used to measure amount or indicate presence of many clinically important lipid
such as ( steroids – fatty soluble vitamins –steroids )

*glycolipid and phospholipid recognized by immune system when coupled with closely related
MHC (Major –Histocompatibility -Complex ) molecules called CD1

 Processing and presentation

* processing and presentation of antigen on MHC enhance development of humoral
“antibody” and cellular immunity (more immunogenicity )

* usually the large molecule easily engulfed and presented on MHC than small ones, this is
because the large molecules insoluble in nature whereas small molecules are soluble.
*Also immunologist noted that large molecules which poorly engulfed and presented by
phagocytes are poor immunogenic

Biological system and immunogenicity of given substance

 Genetic of the host
* Quantity and quality of immune response after introducing of antigen depend on genotype
of the host

*Some studies demonstrate that different strain of same species respond differently to the
same immunogenic substance and genetic analysis shows that region in MHC responsible on
this variation in immunological response

* MHC gene coding glycoprotein called MHC which presenting the antigen to B or T cells thus
affecting quantity and quality of response

* The immunogenicity of macromolecules also affected by gene encoding T and B cell

receptors any genetic variation in these gene will combined with variation in immune response

 Dose and route of introducing immunogenic substance into the host

* immunological response curve of given substance determined by route and dose of
administration.

*Level of specific antibodies and number of specific T cells in serum of immunized person with
given immunogen used for measurement of immune response.

* Inadequate dose cannot induce immune response there are two explanations for this
phenomena, first the dose insufficient to stimulate enough effector cells and the second low
dose induce state of immune unresponsiveness called tolerance

* Also the high dose induce state of tolerance.

* The booster dose which mean repeated exposure to same immunogenic substance over
period of weeks augment the immune response and increase effector cells proliferation and
production of effector molecules.
* There are five route of administration intravenous, intradermal, subcutaneous,
intramuscular, and intraperitoneal

* Route of administration effects on which lymphoid organ will involve in immune response
for example spleen will deal with intravenous immunogenic substance and local lymph node
will deal with immunogenic substance injected through subcutaneous or intradermal route.

 Adjuvants
* It is substance augment immune response to antigen when mixed with it
* Usually used in two situation; first when the antigen has low immunogenicity and the
second when the antigen available in small amount

* Adiuvants enhance the immune response by one of the following mechanism:

1- persistence of antigen for long period of time
2- Enhance the co-stimulatory signal of T cell activation
3- enhance the local inflammatory reaction
4- encouragement of none specific proliferation of lymphocyte

* Aluminum potassium sulfate (Alum) is an example for adjuvants, it is keep the antigen in
tissue for long time by reduction rate of release from site of injection, thus prolonged exposure
time to immune effector mechanisms . Also alum precipitate enhances the phagocytosis by
increasing size of given antigen’

 Super antigen
* It are proteins produced by bacteria and viruses able to activate all T cells regardless antigen
specificity.

*Usual antigen activates T cells which have TCR specific to it.

* Super antigen and usual antigen, both of them presented on MHC of antigen presenting cell
to TCR of T cell, but super antigen bind to common (nonspecific) site on T cell receptor.
*concluding mark; super antigen causing polyclonal activation of T cells
Epitopes
*Effectors cells and molecules of immune system react against specific site in immunogen
called epitopes or antigenic determinants

* studies demonstrate that T and B cells may recognize different epitopes in the same
immunogenic molecule, e.g mice injected with human glucagon show humoral (antibody)
immune response against amino end of glucagon and cellular ( T ) response against carboxyl
end.