BMLS 3 Antigens
Transcript of BMLS 3 Antigens
-
8/13/2019 BMLS 3 Antigens
1/51
Immunogens Or Antigens
Francis Ian L. Salaver, RMT
Irene Chris F. Acua, RMT
-
8/13/2019 BMLS 3 Antigens
2/51
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
-
8/13/2019 BMLS 3 Antigens
3/51
All immunogens are antigens but
not all antigens are immunogens.
-
8/13/2019 BMLS 3 Antigens
4/51
-
8/13/2019 BMLS 3 Antigens
5/51
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
-
8/13/2019 BMLS 3 Antigens
6/51
-
8/13/2019 BMLS 3 Antigens
7/51
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
-
8/13/2019 BMLS 3 Antigens
8/51
Portion of the Ig that binds to epitope is concentrated in hypervariable regionsthat forms the CDR (Complementarity-determining region)
-
8/13/2019 BMLS 3 Antigens
9/51
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
-
8/13/2019 BMLS 3 Antigens
10/51
Conformational and Linear Epitope
-
8/13/2019 BMLS 3 Antigens
11/51
-
8/13/2019 BMLS 3 Antigens
12/51
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)
-
8/13/2019 BMLS 3 Antigens
13/51
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.
-
8/13/2019 BMLS 3 Antigens
14/51
1. Factors related to the antigens
2. Factors related to the host
3. Factors related to the exposure
-
8/13/2019 BMLS 3 Antigens
15/51
1. Foreigness
2. Degradability
3. Molecular Weight4. Structural Stability
5. Chemical Complexity
-
8/13/2019 BMLS 3 Antigens
16/51
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.
-
8/13/2019 BMLS 3 Antigens
17/51
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.
-
8/13/2019 BMLS 3 Antigens
18/51
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
-
8/13/2019 BMLS 3 Antigens
19/51
-
8/13/2019 BMLS 3 Antigens
20/51
-
8/13/2019 BMLS 3 Antigens
21/51
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).
-
8/13/2019 BMLS 3 Antigens
22/51
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.
-
8/13/2019 BMLS 3 Antigens
23/51
For a molecule to become an effective
antigen, structural stability is mandatory.
-
8/13/2019 BMLS 3 Antigens
24/51
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.
-
8/13/2019 BMLS 3 Antigens
25/51
"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."
-
8/13/2019 BMLS 3 Antigens
26/51
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
-
8/13/2019 BMLS 3 Antigens
27/51
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.
-
8/13/2019 BMLS 3 Antigens
28/51
A. 20,000 Kd protein from the same person
B. 5,000 kD toxin from bacteria
C. 10,000 kD cholesterol from another human
-
8/13/2019 BMLS 3 Antigens
29/51
1. Genetic background
2. Age,Sex
3. Overall health
-
8/13/2019 BMLS 3 Antigens
30/51
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
-
8/13/2019 BMLS 3 Antigens
31/51
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
-
8/13/2019 BMLS 3 Antigens
32/51
Malnourished, fatigued, or stressed unlikely
to mount a successful immune response
-
8/13/2019 BMLS 3 Antigens
33/51
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
-
8/13/2019 BMLS 3 Antigens
34/51
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
-
8/13/2019 BMLS 3 Antigens
35/51
* 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
-
8/13/2019 BMLS 3 Antigens
36/51
Complete Antigen
Incomplete Antigen/ Hapten
-
8/13/2019 BMLS 3 Antigens
37/51
TD-Ag (thymus dependent Ag )
TI-Ag (thymus independent Ag)
-
8/13/2019 BMLS 3 Antigens
38/51
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
-
8/13/2019 BMLS 3 Antigens
39/51
-
8/13/2019 BMLS 3 Antigens
40/51
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
-
8/13/2019 BMLS 3 Antigens
41/51
-
8/13/2019 BMLS 3 Antigens
42/51
-
8/13/2019 BMLS 3 Antigens
43/51
Why all of this is important to know??????
Common etiologic agents of diseases in
newbornsStreptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Streptococcus agalactiae
-
8/13/2019 BMLS 3 Antigens
44/51
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.
-
8/13/2019 BMLS 3 Antigens
45/51
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
-
8/13/2019 BMLS 3 Antigens
46/51
-
8/13/2019 BMLS 3 Antigens
47/51
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.
-
8/13/2019 BMLS 3 Antigens
48/51
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
-
8/13/2019 BMLS 3 Antigens
49/51
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.
-
8/13/2019 BMLS 3 Antigens
50/51
-
8/13/2019 BMLS 3 Antigens
51/51