BMLS 3 Antigens

8/13/2019 BMLS 3 Antigens

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Immunogens Or Antigens

Francis Ian L. Salaver, RMT

Irene Chris F. Acua, RMT


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Antigen

* Antigens have the ability to combine/bindspecifically with antibodies produced or

sensitized T-lymphocytes.

Immunogen

* A foreign substance, when introduced intohuman body,stimulateformation of specificantibodies or sensitized lymphocytes


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All immunogens are antigens but

not all antigens are immunogens.


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Haptens:- Low molecular weight substances

- These substances not immunogenic by itself

- If coupled with a larger carriermolecule(albumin, globulins), they become immunogenic.

- Examples :

simple chemicals and drugs:

penicillin, sulphonamide, aspirin, cosmetic,tranquillizers, neomycin skin ointment


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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


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


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1 Sequential or linear epitopeA sequential amino acid fragment,

single chain

2 Conformational epitopeNonsequential 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.

Structure of epitopes


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Conformational and Linear Epitope


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Antigen recognition by B and T cells

Characteristic B cells T cells

Antigen interaction B-cell receptor binds Ag T cell receptor binds Ag +MHC

Nature of antigens Protein, polysaccharide,

lipid

peptide

Binding soluble antigens yes no

Epitopes recognized Accessible, sequential, or

conformational

Internal linear peptides

produced by antigen

processing (proteolytic

degradation)


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B-cells recognize and bind to free antigen insolution.

epitopes are exposed and easily accessible.

Immunogen does not need degradation first

T cell recognizes an epitope only as part of a

complex formed w/ MHC proteins on thesurface of the APC.

APC must process and degrade immunogenfirst for it to be recognized by T cells.


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1. Factors related to the antigens

2. Factors related to the host

3. Factors related to the exposure


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1. Foreigness

2. Degradability

3. Molecular Weight4. Structural Stability

5. Chemical Complexity


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The immune system normally discriminatesbetween self and non-self such that onlyforeign molecules are immunogenic.

Foreigness = the degree to which antigenicdeterminants are recognized as nonself byan individuals immune system

Substances that never contact with lymphocytesin embryo period.

Greater phylogenic difference, greaterimmunogenecity.


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A.1 Autologous antigens- found within the sameindividual; ones own antigen; would stimulate theproduction of autoantibodies (SLErythematosus)A.2Syngeneic antigen- found between genetically identicalindividuals; twinsA.3 Allogeneic/Homologous Ag- found between individualsof the same species (blood transfusion; tse transplant)

A.4 Sequestered antigens- antigens that are notexposed to antibody-producing cells (ex.cornea, sperm)

A.5 xenogeneic or Heterogeneic (Heteroantigens)-

occur to unrelated animals and plants species. Goodexample is the cardiolipid from the beef heart muscleand Ab against T. pallidum

* Identical or closely related in structure so that the antibodyto one will cross react with antigen of the other.


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Principle: antibody induced by one will also

bind to another antigen

e.g. smallpox cowpoxBeef heart muscle T. pallidum

Proteus rickettsiae (weil-felix test)

EBV sheep red cells


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Antigens that are easily phagocytosed aregenerally more immunogenic.

In order for most antigen to stimulate IR,interaction between APC & helper T cellsmust occur.

This is because for most antigens thedevelopment of an immune response requiresthat the antigen be phagocytosed, processedand presented to helper T cells by an antigenpresenting cell (APC).


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The higher the molecular weight, the betterthe molecule will function as antigen.

The number of antigenic determinants isdirectly related to its size.

Molecular weight of 10,000 daltons or

higher. Hapten: Small foreign molecule that is notantigenic. Must be coupled to a carrier moleculeto be antigenic. Once antibodies are formed theywill recognize hapten.


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For a molecule to become an effective

antigen, structural stability is mandatory.


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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 adjuvantused for licensed human vaccine in the US.

Alum causes Ag to precipitate

when injected,the precipitated Ag is released more slowly butcontinuously, to stimulate the macrophage totake up, process, and present antigens to Tlymphocytes.


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"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."


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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 isattach to a moieties (dinitrophenol) w/c by

themselves are not immunogenic the

entire macromolecule becomes immunogenic


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A. ProteinsAll 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. PolysaccharidesPure 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 maybecome immunogenic when conjugated to protein carriers.

Ex. Anti-DNA antibodies in patients w/ SLE

D. LipidsIn general lipids are non-immunogenic, although they may be haptens.


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A. 20,000 Kd protein from the same person

B. 5,000 kD toxin from bacteria

C. 10,000 kD cholesterol from another human


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1. Genetic background

2. Age,Sex

3. Overall health


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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


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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.

Old

Very young

INCREASED PREDISPOSITION

TO INFECTION


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Malnourished, fatigued, or stressed unlikely

to mount a successful immune response


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1. Dosage of antigenthreshold amountVery 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 & drainslymph nodes

* oral

4. Adjuvant


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Active at very low concentration

They activate multiple clones of T-lymphocytes

The massive T-cell activation causes release oflarge 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


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* 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


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Complete Antigen

Incomplete Antigen/ Hapten


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TD-Ag (thymus dependent Ag )

TI-Ag (thymus independent Ag)


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TD-Agcan stimulate B cell to produce Abwith

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


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TI-Agcan stimulate B cells to produce Abwithout the help of T cell

Most are polysaccharide (capsule)These antigens are characterized by the

same antigenic determinant repeatedmany times

Only induce B cell to produce IgM Can not induce CMI

No immune memory


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

Common etiologic agents of diseases in

newbornsStreptococcus pneumoniae

Haemophilus influenzae

Neisseria meningitidis

Streptococcus agalactiae


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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 receptorcrosslinking (Janeway et.al, 2005).

The ability to respond to polysaccharide antigens is

developed by 18months 2years of age.


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1.Unideterminant, Univalent antigens- there is only oneepitope present

2.Unideterminant, Multivalent- there is only one type

of epitope present but many such epitopes on eachmolecule

3.Multideterminant, Univalent- there are many types ofepitopes but only one of each kind per molecule

4.Multideterminant, Multivalent- there are manydifferent kinds of epitopes and many of each kind permolecule


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An immunologic reaction in w/c the immunecomponents, either cells or antibodies, reactwith 2 molecules that share similar epitopesbut 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 IRagainst C. tetani toxin because the toxoid stillshares similar epitopes with the native toxin.

Epitopes are not destroyed during modification.


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Homologous substance used to induce IR is

similarfrom the actual immunogen.

Heterologous substance used to induce IR is

differentfrom the actual immunogen May or may not react with the immune

component

If IR do take place there is immunologic cross-

reactivity


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A mitogenis a protein substance thatencourages a cell to commence cell

division,triggering mitosis.Mitogens are often used to stimulate

lymphocytes and therefore assess immune

function.

Mitogenesisis the induction (triggering) ofmitosis, typically via a mitogen.


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BMLS 3 Antigens

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