C3 - LESSON 1: ANTIGENS Flashcards
- macromolecules capable of triggering an adaptive immune response by inducing the formation of antibodies or sensitized T cells in an immunocompetent host.
Immunogens
- substance that stimulates antibody formation and has the ability to bind to an antibody or a T lymphocytes antigen receptor but may not be able to evoke an immune response initially (e.g., haptens)
Antigens
ability to induce a humoral and/or cell-mediated immune response
Immunogenicity
ability to combine specifically with the final products of the immune response
• Antigenicity
Factors Influencing the Immune Response
- Age
- Overall health
- Dose
- Route of inoculation
- Genetic capacity
Age
a. Elderly b. Neonates
Overall health
a. Malnutrition, fatigue or stress
Route of inoculation
a. Intravenous (into a vein)
b. Intradermal (into the skin)
c. Subcutaneous (beneath the skin)
d. Oral contact
Genetic capacity
a. Linked to MHC and to receptors generated during T- and B- lymphocyte development.
b. MHC
Traits of Immunogens
Immunogens
a. Weight:
b. Best immunogens:
c. Rule of thumb:
a. Weight: 10,000 Daltons (MW)
b. Best immunogens: 100,000 Daltons
c. Rule of thumb:
Lymphocyte capable of reacting with self-antigen is normally eliminated
Foreignness
Chemical composition and molecular complexity
a. Proteins and polysaccharides are the best immunogens
b. Carbohydrates-
c. Lipids and nucleic acid-
must be subject to antigen processing which involves enzymatic digestion to create small peptides or pieces that can be complexed to MHC molecules to present to responsive lymphocytes.
The ability to be processed and presented with MHC molecules
Poor immunogen
Carbohydrates
Lipids and nucleic acid
Foreignness Rule of thumb:
Macromolecular size Rule of thumb:
Antigenic determinants
Epitopes
part of an antigen which reacts specifically with an antibody or T lymphocyte receptor
Epitopes
Epitopes may be repeating copies or they may have differing specificities:
A. SEQUENTIAL OR LINEAR EPITOPES
B. CONFORMATIONAL EPITOPES
Example: Amino acids following one another on a single chain
A. SEQUENTIAL OR LINEAR EPITOPES
Results from the folding of one chain or multiple chains, bringing certain amino acids from different segments of a linear sequence or sequences into close proximity with each other so they can be recognized together.
B. CONFORMATIONAL EPITOPES
React with both linear and conformational epitopes present on the surface of an immunogen
Recognition of Epitopes by B cells
Anything that is capable of cross-linking surface immunoglobulin molecules is able to trigger Bcell activation.
Recognition of Epitopes by B cells
immunogen does not necessarily have to be degraded first.
Recognition of Epitopes by B cells
able to recognize an immunogen it must first be degraded into small peptides by an antigenpresenting cell (APC)
Recognition of Epitopes by T cells
peptides form a complex with MHC proteins and are carried to the surface of the APC.
Recognition of Epitopes by T cells
Small organic molecules that are antigenic but not immunogenic
HAPTENS
Capable of reaction with antibody however precipitation or agglutination will not occur
HAPTENS
Coupling to a carrier: hapten-carrier conjugate
HAPTENS
The Specificity of Serological Reactions
Karl Landsteiner
He discovered that antibodies not only recognize chemical features such as polarity, hydrophobicity, and ionic charge, but the overall three-dimensional configuration is also important.
Karl Landsteiner
is a substance, distinct from antigen, that enhances T cell activation by promoting the accumulation of APCs at a site of antigen exposure and by enhancing the expression of costimulators and cytokines by the APCs.
ADJUVANT
It enhances response to immunization.
ADJUVANT
ADJUVANT
Example: (?)- used to complex with the immunogen to increase its size and to prevent a rapid escape from the tissues.
Aluminum salts
ADJUVANT Effects
o Antigen persistence is prolonged
o Co-stimulatory signals are enhanced
o Local inflammation is increased
o Non-specific proliferation of lymphocytes is stimulated
- antigens that belong to the host
Autoantigens
- from other members of the host’s species
Alloantigens
- from other species such as other animals, plants or microorganisms
Heteroantigens
- heteroantigens that exist in unrelated plants or animals
Heterophile Antigens
Relationship of Antigens to the Host
Physical Nature of Antigens
Chemical Nature of Antigens
- degree to which antigenic determinants are recognized as non-self by an individual’s immune system
Foreignness
- For an antigen to be recognized as foreign by an individual’s immune system, sufficient antigens to stimulate an immune response must be present
Degradability
- The higher the (?), the better the molecule will function as an antigen.
Molecular Weight
The number of antigenic determinants on a molecule is directly related to its size.
Molecular Weight
- If a molecule is an effective antigen (?) is mandatory.
Structural Stability
If a structure is unstable (e.g., gelatin) the molecule will be a poor antigen
Structural Stability
- The more (?) an antigen, the greater is its effectiveness
Complexity
- excellent antigens because of their high molecular weight and structural complexity
Proteins
- inferior antigens because of their relative simplicity and lack of structural complexity
Lipid
- poor antigens because of relative simplicity, molecular flexibility, and rapid degradation
Nucleic acids
- by themselves are considered too small to function as antigens
Carbohydrates (polysaccharides)
Tightly linked cluster of genes
MAJOR HISTOCOMPATIBILITY COMPLEX
Participates in the development of HMI and CMI
MAJOR HISTOCOMPATIBILITY COMPLEX
Plays a role in intracellular recognition of antigens
MAJOR HISTOCOMPATIBILITY COMPLEX
Discrimination of self from non self
MAJOR HISTOCOMPATIBILITY COMPLEX
Partly determines response of an individual to antigens of infectious disease and graft rejection
MAJOR HISTOCOMPATIBILITY COMPLEX
Implicated in susceptibility to disease and development of autoimmunity
MAJOR HISTOCOMPATIBILITY COMPLEX
Name was given by Dausset
Human Leukocyte Antigens
they were first defined by discovering an antibody response to circulating white blood cells
Human Leukocyte Antigens
Also known as MHC molecule; because they determine whether transplanted tissue is histocompatible and thus accepted or recognized as foreign and rejected.
Human Leukocyte Antigens
Main function is to bring antigen to the cell surface for recognition by T cells, because T- cell activation will occur only when antigen is combined with MHC molecules.
Human Leukocyte Antigens
Genes controlling expression of these molecules are actually a system of genes known as the
major histocompatibility complex (MHC)
a. Endogenous pathway of antigen presentation
- Class I molecules- synthesized in the rEr
a. partial digestion of proteins synthesized in the cytoplasm.
- Peptides bind with the class I molecules
b. intracellular peptides may include viral, tumor, or even bacterial antigens.
- Peptides bind with the class I molecules
c. Digestion- carried out by proteases that reside in large cytoplasmic complexes- proteasomes.
- Peptides bind with the class I molecules
- Transporters associated with antigen processing
- TAP1 and TAP2
- brings the TAP transporters into close proximity to the newly formed MHC molecules
- Tapasin
class I MHC complexes contain self-peptides- ignored by the T cells
- In healthy cells
derived from viral proteins or proteins associated with cancerous states
- Diseased cells peptides
- complex with CD8+ T cells
Class I molecules
- produces cytokines
CD8+ T cell
- cause lysis of the entire cell
CD8+ T cell
CLASS II MOLECULE
1. Class II MHC binds (?) to block binding of endogenous antigen.
2. MHC complex goes through (?).
3. Invariant chain is degraded, leaving (?).
4. Exogenous antigen taken in and degraded and routed to (?).
5. CLIP fragment exchanged for antigenic peptide.
6. (?) is transported to cell surface.
7. (?) binds to CD4 T cell.
invariant chain
Golgi complex
CLIP fragment
intracellular vesicle
Class II MHC antigenic peptide
Class II MHC peptide complex
Found virtually on all body tissue cells
Class I MHC
Platelets express primarily Class I HLA-A and HLA-B antigens
Class I MHC
Found on B lymphocytes, activated T lymphocytes, monocytes, macrophages, dendritic cells, early hematopoietic cells, and some tumor cells
Class II MHC
consist of secreted proteins with immune function.
Complement components C2, C4a, C4b, and factor B
Steroid enzymes 21hydroxylase enzyme A and 21-hydroxylase enzyme B -Inflammatory proteins TNF-α and TNF-β.
Heat shock proteins such as HSP70.
These are not related structurally to the MHC-I and MHC-II molecules.
They have no role in antigen presentation. -They do play a role in the immune response.
Class III MHC
Class I MHC
HLA-A
HLA-B
HLA-C
Class II MHC Gene products
DP
DQ
DR
Class III MHC Gene products
Complement
TNF
Heat Shock Protein
Steroid Enzymes
Antigen specificity: 8-10 amino acid peptide length
Class I MHC
Antigen specificity: 13-18 amino acid peptides
Class II MHC
Antigen presentation: CD8+ T cells
Class I MHC
Antigen presentation: CD4+ T cells
Class II MHC
Cellular location of recognition: Endogenous – (endoplasmic reticulum)
Class I MHC
Cellular location of recognition: Exogenous – (membrane receptor)
Class II MHC
Cellular location of recognition: Membrane receptor
Class III MHC
(?) will have an increased survival rate of the patient and a decreased risk of graft vs. host disease if HLA and MHC matching between donor and recipient is done.
Organ transplant & bone marrow transplant
(?) between donor and recipient is useful to patients who are retractile to random donor platelets
Platelet transfusion matching
(?) exerts the strongest influence on long-term kidney survival after a transplant.
HLA compatibility
HLA identical donors for bone marrow transplantation to reduce the frequency of (?).
graft vs. host disease
(?) for exclusion or non-exclusion.
Paternity testing
Association between HLA phenotype and some diseases
Disease association
is found in >90% of patients with ankylosing spondylitis, but in only 10% normal individuals.
HLA-B27