Module 1 Unit 2 Flashcards
are related but distinct immunologic properties that sometimes are confused.
Immunogenicity and antigenicity
is the ability to induce a detectable immune response.
Immunogenicity
The immune response may be [?] which leads to production of antibodies or cellular leading to the activation of T cells, or both.
humoral
is the ability to combine specifically with the final products of the above responses (i.e., antibodies and/or cell-surface receptors of activated T cells). Although all molecules that have the property of immunogenicity also have the property of antigenicity, the reverse is not true.
Antigenicity or specific reactivity
Low molecular weight substances are [?].
nonimmunogenic
Nonimmunogenics are often referred to as partial or incomplete antigens or [?].
haptens
commonly contains only a single determinant site which prevents them from forming crosslinks.
Haptens
These antigenic molecules may be made immunogenic when it becomes conjugated with larger carrier or indicator molecules like [?]
proteins, cells or latex particles.
There are two basic components of the antigen: the [?] and the [?].
epitope and the carrier molecule
The [?] is otherwise known as the antigenic determinant, antigenic site, reactive site or haptenic portion.
epitope
This is the immunologically active portion of an antigen which can react with antibodies and T cell receptors.
epitope
Epitopes can either be [?] and [?] in form.
linear or conformational
[?] consist of sequential amino acids on a single polypeptide chain.
Linear epitopes
[?] from the folding of a polypeptide chain/s and nonsequential amino acids are brought into close proximity.
Conformation results
The linear conformation is commonly associated with [?] while the conformation is commonly associated with [?].
surface antibody recognitioin
T cell recognitioin
refers to the structural element of immunogen that interacts with T and B lymphocytes.
Immunogenic determinant
The immunogen must possess at least 2 determinants to be able to stimulate antibody formation or 1 determinant to be able to interact and trigger a [?].
T cell response
The number of distinct determinants on an antigen molecule usually varies with its
size and chemical complexity.
The carrier component of the antigen is also called the [?], It provides bulk or molecular mass to the antigen molecule. It is also important in the regulation of humoral immune response to the antigen. T cells commonly recognize this portion.
Schelepper molecule
B cells recognize the [?].
haptenic portion
The [?] may have its own set of integral epitopes as presented by antigen presenting cells.
schlepper molecule
Examples of carriers are
albumin, globulin or other synthetic polypeptide
Antigen molecules may be
a) univalent and unideterminant (?
(b) multivalent and unideterminant (?)
(c) multivalent and multideterminant (?)
- one epitope of one design or shape
- many epitopes but of only one design
- many epitopes of different designs or shape
The immune system discriminates between [?], so that only molecules that are foreign to the self are normally immunogenic.
“self” and “nonself”
The capacity to recognize nonself is accompanied by [?], a specific unresponsiveness to self-antigens.
tolerance of self
Much of the ability to tolerate self-antigens arises during [?], during which immature lymphocytes are exposed to self components.
lymphocyte development
Antigens that have not been exposed to immature lymphocytes during this critical period may be later recognized as [?], or foreign, by the immune system.
nonself
The greater the [?], the higher the [?] thus the more immunogenic.
phylogenetic distance
structural disparity
Some macromolecules (e.g., collagen and cytochrome c) have been highly conserved throughout evolution thus there is little [?] even across diverse species lines.
immunogenicity
Some self-components (e.g., corneal tissue and sperm) are effectively sequestered from the immune system, so that if these tissues are injected even into the animal from which they originated, they will function as [?].
immunogens
Substances that are altered from what is normal to the host may become [?].
immunogenic (autoantigen)
In cases of cancer cells, there is the production of [?]. These are proteins that underwent mutation.
tumor specific antigen
This refers to the heterogeneity in the building blocks that make up the antigen.
Chemical Complexity
consisting of repeating units of a single amino acids are poor immunogens regardless of size
Homopolymers
[?] of two or more amino acids are more immunogenic
copolymers
The general rule is immunogenicity increases with
structural complexity
are considered the most immunogenic. It is with many antigenic determinants and contain amino acids which are capable of binding and folding thus imparting epitopes of different specificities.
Proteins
are generally considered weak and partial immunogens because they do not possess sufficient chemical diversity. They are also rapidly degraded and thus do not come in contact with immune cells long enough to induce reaction.
Polysaccharides
found in pneumococcal capsules and lipopolysaccharides such as endotoxins of gram-negative bacteria are two of the immunogenic forms of polysaccharides.
Pure polysaccharides
are considered strong immunogens.
Glycoproteins
Immune response is directed against its
carbohydrate epitope.
ABO blood group antigens are under this category.
Glycoproteins
[?] like hormones are usually weak immunogens.
Polypeptides
in the form of RNA and DNA are usually not immunogenic however in some autoimmune disorders like SLE (Systemic Lupus Erythematosus) nucleic acids become immunogenic leading to the formation of autoantibodies.
Nucleic acids
If amino acids are found frequently in antigenic site than others these are called
“immunodominant”
enhance antigenicity.
Basic or acidic amino acids
are more “immunogenic” than DNA since they contain unpaired nucleotides that may function as antigenic determinant. The reactive group of DNA is usually hidden.
RNAs
such as triglycerides and other fatty substances are nonimmunogenic unless coupled to proteins.
Pure lipids
As a general rule, the larger the molecule the [?].
better as an immunogen
Molecules less than one kilodalton are considered
non immunogenic
Molecules more than one but less than 6 kilodalton are considered [?]. Examples under this include insulin, histones and glucagon.
weakly immunogenic
Molecules more than ten kilodalton are considered more immunogenic like [?].
albumin and gamma globulin
which is more than 1,000,000dalton is considered an excellent immunogen.
Hemocyanin
The significance of size in immunogenicity is that [?] increase proportionately with size.
number of epitopes
Large sized molecules become easily phagocytosed and processed by macrophages to become more attractive to
T cells
must be exposed and accessible to the receptors of antibodies or T cell receptors (TCR’s) so the antigen can be bound.
Epitopes
cannot be reacted upon thus pretreatment of cells may be necessary in order to bring out these epitopes to the surface so that it can be recognized and bound.
Hidden (internally located) determinant groups
This is one reason why proteins are more immunogenic than others because of their [?] which allows greater accessibility of their determinant groups.
tertiary conformational structure
Refers to the maintenance of the conformational structure of the protein antigen.
Loss, alteration or denaturation of such lead to loss of reactivity.
Rigidity
Refers to the physical state of the antigen molecule.
Insolubility
Antigens must be [?] to be immunogenic.
particulate and insoluble
[?], [?]due to heat, [?] to insoluble carrier substance contribute to immunogenicity.
Intermolecular crosslinking
aggregation
attachment of hapten
Antigen is taken up and processed by [?].
macrophages
releases hydrolytic products which are the immunogenic units rather than the intact antigen molecule. This complexes with macrophage RNA.
Macrophage processing
The [?], when released, stimulate antibody production.
macrophage RNA
[?] during processing also reveal hidden antigenic sites.
Partial digestion
Immunogenic components are coupled to [?] and antigen is presented at the surface of the macrophage to be recognized by the lymphocytes.
MHC class II molecules
Examples of good immunogens used as vaccines are
killed organisms (eg. Typhoid bacilli)
attenuated or altered bacteria (eg. Sabin polio virus)
detoxified toxins (eg. Diphtheria and tetanus toxoids)
artificially assembled microbial components (eg. Hepatitis B virus subunits)
are chemicals which when administered with antigen enhances or provokes immunity. They are commonly mixed with antigens especially for manufacture of vaccines.
Adjuvants
Mechanism of action of adjuvants include:
1. Increases the [?] of the immunogen
2. Increased [?] and local delayed released of the antigen
3. Delayed [?] of the antigen since the antigen is surrounded by the adjuvant.
4. Prolonged [?] which increases contact of antigen with
immunocompetent cells.
5. [?] which leads to the migration of leukocytes; increasing the number of leukocytes and macrophages involved in antigen processing.
6. [?] of lymphocytes are also stimulated.
- effective size
- phagocytic uptake
- destruction and elimination
- immunogen retention
- Local granuloma formation
- Nonspecific proliferation
Examples of adjuvants include [?] made up of suspension of aluminum hydroxide mixed with antigen. x
alum precipitate
The [?] precipitates the antigen which increases size and slows down release of antigen.
salt
Another is [?], a long hydrocarbon molecule present in human sebaceous gland secretions and shark liver oil and a component of [?], an immunologic potent vaccine adjuvant.
squalene
MF-59
[?] is another classic example. This could either be the complete form made of water in oil emulsion and killed Mycobacterium tuberculosis (its cell wall contains Muramyl dipeptide which activates macrophages making it more phagocytic) or incomplete form which does not contain the M. tuberculosis component.
Freund’s adjuvant
