Immunogens Or Antigens

Francis Ian L. Salaver, RMT Irene Chris F. Acua, RMT

Antigen
* Antigens have the ability to combine/bind specifically with antibodies produced or sensitized T-lymphocytes. Immunogen * A foreign substance, when introduced into human body, stimulate formation of specific antibodies or sensitized lymphocytes

All immunogens are antigens but not all antigens are immunogens.

Haptens:
- Low molecular weight substances - These substances not immunogenic by itself - If coupled with a larger carrier molecule (albumin, globulins), they become immunogenic. - Examples : simple chemicals and drugs: penicillin, sulphonamide, aspirin, cosmetic, tranquillizers, neomycin skin ointment

Sites on or within antigen with which antibodies react Molecular shapes or configurations that are recognized by B or T cells. Different types (structure): sequential/linear or conformational

A single antigen may have multiple epitopes

Antibodies are specific for epitopes

Portion of the Ig that binds to epitope is concentrated in hypervariable regions that forms the CDR (Complementarity-determining region)

Structure of epitopes
1 Sequential or linear epitope
A sequential amino acid fragment, single chain

2 Conformational epitope
Nonsequential polypeptides or polysaccharide on the surface of the molecules Folding of one chain or multiple chainsbringing a.a from diff segments of a linear sequence into close proximity w/ each other so they can be recognized.

Conformational and Linear Epitope

 Antigen
Characteristic

recognition by B and T cells

B cells B-cell receptor binds Ag Protein, polysaccharide, lipid T cells T cell receptor binds Ag + MHC peptide

Antigen interaction Nature of antigens

Binding soluble antigens

Epitopes recognized

yes
Accessible, sequential, or conformational

no
Internal linear peptides produced by antigen processing (proteolytic degradation)

 B-cells

recognize and bind to free antigen in solution. epitopes are exposed and easily accessible. Immunogen does not need degradation first

cell recognizes an epitope only as part of a complex formed w/ MHC proteins on the surface of the APC. APC must process and degrade immunogen first for it to be recognized by T cells.

 1.
2. 3.

Factors related to the antigens

Factors related to the host Factors related to the exposure

1.
2. 3. 4. 5.

Foreigness Degradability Molecular Weight Structural Stability Chemical Complexity

 The

immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. = the degree to which antigenic determinants are recognized as nonself by an individuals immune system
Substances that never contact with lymphocytes in embryo period.

Foreigness

Greater

phylogenic difference, greater immunogenecity.

A.1

Autologous antigens - found within the same individual; ones own antigen; would stimulate the production of autoantibodies (SLErythematosus) A.2 Syngeneic antigen- found between genetically identical individuals; twins A.3 Allogeneic/Homologous Ag- found between individuals of the same species (blood transfusion; tse transplant)
A.4

Sequestered antigens- antigens that are not exposed to antibody-producing cells (ex.cornea, sperm) A.5 xenogeneic or Heterogeneic (Heteroantigens)occur to unrelated animals and plants species. Good example is the cardiolipid from the beef heart muscle and Ab against T. pallidum * Identical or closely related in structure so that the antibody
to one will cross react with antigen of the other.

Principle: antibody induced by one will also bind to another antigen

e.g. smallpox cowpox Beef heart muscle T. pallidum Proteus rickettsiae (weil-felix test) EBV sheep red cells

 Antigens

that are easily phagocytosed are generally more immunogenic.

order for most antigen to stimulate IR, interaction between APC & helper T cells must occur. is because for most antigens the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

In

This

 The

higher the molecular weight, the better the molecule will function as antigen.
number of antigenic determinants is directly related to its size. weight of 10,000 daltons or

The

Molecular

higher.

Hapten: Small foreign molecule that is not antigenic. Must be coupled to a carrier molecule to be antigenic. Once antibodies are formed they will recognize hapten.

 For

a molecule to become an effective antigen, structural stability is mandatory.

 Use

of adjuvant.

An agent that when mixed with immunogen will enhance the IR against the immunogen. Can an adjuvant cause IR on hapten? Can a hapten with a carrier molecule cause IR? Use in vaccine = Vaccine adjuvant Aluminum potassium sulfate (alum) only adjuvant used for licensed human vaccine in the US. Alum causes Ag to precipitate when injected, the precipitated Ag is released more slowly but continuously, to stimulate the macrophage to take up, process, and present antigens to T lymphocytes.

 "An

immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."

 The

more complex the substance (Ag) is chemically the more immunogenic it will be. Complex proteins are better Ag large, repeating polymers such as lipids, CHO, and nucleic acids, are poor antigens. Ex. Poly-D-glutamic acid capsule of B. anthracis (50,000 Da) not immunogenic bec it is not chemically complex but if it is attach to a moieties (dinitrophenol) w/c by themselves are not immunogenic the entire macromolecule becomes immunogenic

A. Proteins All proteins are immunogens. These may be pure proteins or they may be glycoproteins or lipoproteins. the more complex the protein the more immunogenic proteins are multideterminant (multiepitope) antigen B. Polysaccharides Pure polysaccharides and lipopolysaccharides are good immunogens but not always immunogenic. Ex. Capsule of Bacillus anthracis
C. Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when conjugated to protein carriers. Ex. Anti-DNA antibodies in patients w/ SLE D. Lipids In general lipids are non-immunogenic, although they may be haptens.

 A.

20,000 Kd protein from the same person B. 5,000 kD toxin from bacteria C. 10,000 kD cholesterol from another human

1. Genetic background 2. Age,Sex 3. Overall health

 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). Ex. allergies

 Age

can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount and immune response to an immunogen.
INCREASED PREDISPOSITION TO INFECTION

Old Very

young

 Malnourished,

fatigued, or stressed unlikely to mount a successful immune response

1. Dosage of antigen threshold amount

Very large can result to T and B cell tolerance memory cells become overwhelmed & nonresponsive

2. Number of injections repeated administration = strong immune response (memory) 3. Pathways of immunization * intravenous Ag are carried first to spleen * intradermal * subcutaneous travel to locally & drains lymph nodes * oral 4. Adjuvant

Active at very low concentration They activate multiple clones of T-lymphocytes The massive T-cell activation causes release of large amounts of cytokines w/c leads to systemic toxicity It does not lead to acquired immunity i.e no memory

Examples: * Bacterial toxins of: Staphylococcus aureus Streptococcus pyogenes

* They have the ability to bind both class II MHC molecules and TCR chain * They act as a clamp between the two, providing a signal for T-cell activation

Complete Antigen Incomplete Antigen/ Hapten

 TD-Ag
TI-Ag

(thymus dependent Ag )
(thymus independent Ag)

TD-Ag can stimulate B cell to produce Ab with the help of T cell

Most of TD-Ag are protein Have many kinds of determinants Stimulate B cell to produce :IgG, IgM, IgA Have immune memory

TI-Ag can stimulate B cells to produce Ab without the help of T cell

Most are polysaccharide (capsule) These antigens are characterized by the same antigenic determinant repeated many times Only induce B cell to produce IgM Can not induce CMI No immune memory

Why all of this is important to know??????

Common etiologic agents of diseases in newborns Streptococcus pneumoniae Haemophilus influenzae Neisseria meningitidis Streptococcus agalactiae

If there are antibodies, how come those organisms still manage to cause disease esp NB?
The reason that new-borns cannot adequately make antibodies to repeating polysaccharide epitopes due to immaturity of receptors of the innate immune system. may also be due to most of their B cells being immature and unable to respond to B cell receptor crosslinking (Janeway et.al, 2005). The ability to respond to polysaccharide antigens is developed by 18months 2years of age.

1.Unideterminant, Univalent antigens- there is only one epitope present

2.Unideterminant, Multivalent- there is only one type of epitope present but many such epitopes on each molecule 3.Multideterminant, Univalent- there are many types of epitopes but only one of each kind per molecule 4.Multideterminant, Multivalent- there are many different kinds of epitopes and many of each kind per molecule

 An

immunologic reaction in w/c the immune components, either cells or antibodies, react with 2 molecules that share similar epitopes but are otherwise dissimilar. Example: Tetanus toxoid and tetanus toxin

Toxoid is a toxin that is modified in nontoxic form but still maintains its immunochemical cx. Immunization with toxoid will still induce IR against C. tetani toxin because the toxoid still shares similar epitopes with the native toxin. Epitopes are not destroyed during modification.

 Homologous

substance used to induce IR is similar from the actual immunogen. Heterologous substance used to induce IR is different from the actual immunogen

May or may not react with the immune component If IR do take place there is immunologic crossreactivity

mitogen is a protein substance that encourages a cell to commence cell division,triggering mitosis. Mitogens are often used to stimulate lymphocytes and therefore assess immune function.
Mitogenesis

is the induction (triggering) of mitosis, typically via a mitogen.

 Acts

upon T cells

Phytohaemagglutinin (PHA) Concavanalin A Pokeweed seed antigen

Acts

upon B cells

Lipopolysaccharide Pokeweed seed antigen