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Aryssa Lagman; BMLS-3D  The immune system is supposed to identify and attack only

“non-self” invaders from the outside world or modified/harmful


Lecture 5: Antigens and Immunogens substances present in the body under distressed conditions

Self Tolerance

 Failure (a good thing) to attack the body’s own proteins


and other antigens. If the immune system should respond
to “self,” an autoimmune disease may result.

Lecture 6: Types of Antigens

1. Autoantigens
2. Alloantigens
Old VS New Concepts 3. Heteroantigens
4. Mitogens
𝑇ℎ1  recruits other T cells
5. Superantigens
M Th and macrophages
6. Exogenous & Endogenous Antigens
𝑇ℎ2  B cells  plasma cells 7. T-cell dependent & T-cell independent antigens
= Ab production 8. Sequestrated antigens

𝑇ℎ1  recruits other T cells and


1. Autoantigens
macrophages
M Th  An antigen that is a normal bodily constituent and against
 B cells = plasma cells = IgM/IgG which the immune system produces (“self-antibodies”)
 Histocompatibility Antigens:
𝑇ℎ2  B cells  plasma cells = IgE
 The major histocompatibility complex (MHC) is a set of
genes that encodes cell surface molecules which
𝑇ℎ2 > 𝑇ℎ1 = allergic reactions controls a major part of the immune system in all
vertebrates by determining histocompatibility.
𝑇ℎ1 > 𝑇ℎ2 = autoimmune disorders
 The molecules responsible for rejection of transplants
Antigen VS Immunogen are well known to be major histocompatibility complex
(MHC.)
 Antigen: Substance that 2. Alloantigens
stimulates antibody
formation and has the ability
to bind to an antibody;
“anti(body)-gen(erating)”

 Immunogen: Macromolecules
capable of triggering an
adaptive immune response by
inducing formation of
antibodies or sensitized T
cells in an immunocompetent
host
 Hapten
 Alloantigens are from other members of the host’s
species, and these are capable of eliciting an immune
response
 They are important to consider in tissue
transplantation and in blood transfusions
3. Heteroantigens / Heterologous Antigens

o Example of antigen that is not an immunogen


o Low molecular weight particles that can bind to an
antibody but must be attached to a macromolecule
and a carrier to stimulate a specific immune response
o By themselves are not immunogenic , <10,000 Da
 Methyldopa
o Example of a hapten; antihypertensive drug

 GLIADIN—Component of GLUTIEN
methyldopa red blood cell  Example: Celiac disease, intolerant to:
DRUG INDUCED HEMOLYTIC ANEMIA o Wheat & Glutien
o Milk products (Casein)
 Anti-red cell  Antigens that exist in unrelated plants or animals but
 Anti-methyldopa which are either identical or closely related in
 Anti-methyldopa + red cell structure so that antibody to one will cross react with
antigens of the other
Self-Antigens vs Non-self Antigens 4. Mitogen
 The immune system usually does not react to self-antigens  T cell + B cell + Ag = immune response = immunogen
under normal homeostatic conditions due to negative selection  T cell + B cell + Ag = proliferation = mitogen
of T cells in the thymus  Recall mitogens for: B cell and T cell
B Cells: 8. Sequestered Antigens
 Pokeweed seed
Lipopolysaccharide
Lymphocyte Dextron

Mitogen T Cells:

 Pokeweed seed
Concanavalin A
Phytohemagglutinin

5. Superantigen

 Superantigens (SAgs)  Cellular constituents of tissue separated anatomically


are microbial products from the lymphoreticular system during embryonic
that have the ability to development and thus thought not to be recognized
promote massive as “self”
activation of immune  Should such tissue be exposed to the lymphoreticular
cells system during adult life, an autoimmune response
would be elicited
 Leads to the release of  Examples: cornea, sperm cells
inflammatory
mediators that can Epitopes
ultimately result in
hypotension, shock,
organ failure, and
death

6. Exogenoous & Endogenous Antigens

 The distinct surface features of an antigen, it’s antigenic


determinant
 Antigenic molecules usually present surface features that
can act as points of interaction for specific antibodies
 Sites in antigens, where antibodies attach
 Epitopes are recognized by B cells differ frim those
recognized by T cells. T cell cannot recognize both, unless
7. T cell Dependent & T cell independent Antigens with an APC

Classification of Epitopes

 Linear epitopes are short and continuous. After


denaturation the linear epitopes may still be able to bind
the antibody. (Continuous)
 Conformational epitopes are domains of proteins
composed of specific regions of protein chains. After
denaturation the discontinuous epitopes can no longer
bind the antibody. (Discontinuous)

Accessible = Surface vs Inaccessible = Intracellular


 Determinant: type or structure 4. Degradability
 Valence: number of antigen binding sites  Most protein antigens
1. Unideterminant, univalent need to be processed
and presented by
2. Unideterminant, multivalent antigen presenting cells
 The digested fragments
3. Multideterminant, univalent become bonded to “MHC”
proteins (or MHC
4. Multideterminant, multivalent antigens) on the surface
of the APC and this whole
complex then binds to
T-cells
Stability and Degradability

 Structurally unstable
ORALLY
Ag Damaged by HCl =  Easily destroyed
 Cannot enter body
further

 If Ag is undegradable
ORALLY
Ag Not damaged by HCL = o No AP
o No IR
Traits of Immunogens

ORALLY
Ag Not damaged by HCL but degradable =

M T B-P

5. Antigenic Chemical Complexity


 Proteins – Excellent antigens because of their high
molecular weight and structural complexity
(composed of 21 amino acids)
1. Foreignness  Carbohydrates – by themselves considered too small
 Degree to which epitopes are recognized as non-self to function as antigens (example: glycolipids and
by an individual’s immune system glycoproteins)
a) Autologous antigens: “self” antigens  Nucleic acids – poor antigens because of relative
b) Syngeneic/Isogenic: antigens having the same simplicity and rapid degradation
genetic constitution (e.g. twins)  Lipids – considered inferior antigens due to relative
c) Allogenic/Homologous: antigens shared by simplicity and lack of structural stability
individuals of same species (e.g. ABO blood group)
Adjuvants
d) Xenogenic/Heterologous: antigens shared by
individuals of unrelated species (e.g. cowpox +
smallpox = cross-reactivity)

 T. pallidum + cardiolipin
(Ag from bovine) = RPR &
VDRL
 EBV + sheep red cells =
Paul-Bunnell test
 Rickettsia + Proteus =
Weil Felix test
 S. pyogenes (M protein)
+ heart valves = RHD
 Substance administered with an immunogen that
increases the immune response
2. Molecular Weight  Usually accompanies vaccine
 Enhance immune response by:
 The higher the MW, the better the molecule will  Prolonging the existence of immunogen
function as an antigen  Increasing the effective size of the immunogen
 The number of epitopes on a molecule is directly  Increasing the number of macrophages involved in
related to its size antigen processing
 Proteins are effective antigens because of a large MW
o > 10,000 daltons = immunogenic
o <10,000 daltons = hapten
3. Structural Stability
 Solidity and strength of molecule makes it an
effective antigen
 If unstable (e.g. gelatin) = poor antigen
 If inert (static) molecules = poor antigens
 Important in cases where goal is to elicit a patient
antibody response when administering a vaccine

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