Lecture 3 - Antigens Flashcards
What is the fn of the immune system?
to protect the body against invading organisms
What is an antigen?
any substance that can induce antibody generation (induce specific immune responses - can be bound by B or T cell receptors)
-also called immunogens
What do B cell receptors (Ab) recognize?
peptides sugars, lipids, nucleic acids and hormones
What do T cell receptors recognize?
only peptides that have been processed or degraded
-gamma/delta T cells recognize lipids directly on pathogen surface
what is an allergen?
antigen that induces an allergic reaction/immune response
What are epitopes?
smaller portions of large molecules that have the structure bound by the Ab or T cell receptor
-also called an antigenic determinant
Can an Ag contain more than one epitope?
each Ag contains many epitopes individually able to bound by Ab or T cell receptors
What is multivalency?
when epitopes are repeated several times on a macromolecule
How do antigenic-specific cells (B and T cells) recognize epitopes?
B cells have receptors (Ab) that can bind directly to the native Ag
- T cells require presentation of the epitope by an MHC molecule
- different lymphocytes/receptors can recognize different epitopes on the same Ag
What influence does spatial arrangement of epitopes on a single Ag have?
it affects how Abs can bind to the macromolecule
-ususally Ab epitopes are limited to those accessible to the Ab, and crowding can exclude access of Ab to all epitopes
How are antigenic determinants (epitopes) limited?
limited to those portions of the Ag that can bind to MHC molecules –> differences in the responses of different individuals
What if there is no MHC mol to present a particular epitope?
can’t generate Abs for that epitope
What are haptens?
small molecules that are not normally immunogenic but become antigens when linked to another structure (carrier) –> linkage forms a new epitope which is now big enough to be bound by Ab or T cell receptors
What are common results of haptens?
drug allergies –> common due to the tendency for them to bind larger proteins
Give examples of haptens?
- penicillin –> binds to albumin
- urushiol –> toxic agent of poison ivy (converted to a reactive cmpd which reacts with skin proteins)
What are blood group Ags?
- A-type blood contains an A-type enzyme
- B-type blood contains a B-type enzyme
- AB-type blood contain both enzymes
- O-type blood lack both types of enzymes
What types of Ab do haptens generate?
1) against the carrier
2) against the hapten
3) against the new epitope generated by the hapten-carrier linkage
- normally don’t generate Abs against carrier (own RBCs)
What are T independent Ag?
Ags that are immunogenic enough that T cells are not required to activate B cells for Ab production
- usually very complex molecules
- have repeating epitopes (multivalent)
- cross-link B cell receptors (Abs) on the surface of a B cell
- stable in vivo
When can these T ind. Ags occur?
early in an immune response and assist in host clearance of certain pathogens
-B cells bind enough epitopes to Abs to activate
What makes a good Ag (generate a strong Ab response)?
- size (large)
- Complex (last long enough so immune response can be generated)
- intermediate stability (not too stable so T cells can’t break down)
- Foreign enough
- more different immunogen is from recipient –> stronger the immune response
Rate macromolecules on how good antigens they would be (proteins, simple polysacch, complex carb,, nucleic acids, lipids)
- Proteins - excellent Ags if greater than 1000Da
- Simple Polysaccharides - poor Ags (readily degraded in cells)
- Complex carb - usually good Ags (esp if bound to proteins)
- Nucleic acids - usually poor Ags (unless bound to proteins)
- Lipids - usually poor Ags (unless linked to proteins)
What influences immunogenicity?
Host factors and environmental factors
What host factors affect immunogenicity?
Genetics - genes that encode the specific antigen receptors can vary btw individuals
-MHC, T cell receptors, Abs
Age - specific immunity in particular is deficient in neonates and in senescent individuals
What environmental factors affect immunogenicity?
dose, route of exposure, adjuvants (recognition factors)
- increased: large, intermediate dose, complex, particular, denatured, multiple diffs, slow release, bacteria, effective interaction with host MHC
- decreased: small, high or low dose, simple, soluble, native, few diffs, rapid release, no bacteria, ineffective interaction with host MHC
What is cross-reactivity?
process by which one epitope is similar enough to trigger a response against another epitope, even on very different molecules –> specific immunity against apparently unrelated Ags
Give an example of cross-reactivity
blood antigens - bacteria contain glycoproteins with carb sidechains similar to those found on RBCs
Describe different situations of Ag exposure
- Ags encountered in tissues are taken up by dendritic cells (and macrophages) tehn moved to draining lymph nodes –> elicit IgG isotype Abs
- Ag encountered on mucosal surfaces are generally taken up through specialized M cells or via dendritic cells that extend through the epithelial lining –> elicit IgA and IgE isotype Abs
- diff Abs elicit diff immune responses
What is Ag processing?
degradation of proteins into peptides that can bind MHC molecules for presentation to T cells
What is Ag presentation?
display of Ags as peptide fragments bound to MHC molecules on surface of a cell
How are diff cell origins presented?
- exogenous Ags (outside cell) –> MHC class II mols
- endogenous Ags (inside cell) –> MHC class I mols
What are Antigen-presenting Cells?
highly specialized cells that can display processed Ag as peptide fragments on cell surface
What does Ag processing involve?
uses surface mols encoded by Major Histocompatibility Complex
What determines the pathway for Ag break down?
which class of MHC mols used which depends on origin of Ag
- Ags in cytosol –> MHC class I (contact cytoplasm)
- Ags from outside cell –> MHC class II (separate from cytoplasm)
What are autoantigens?
self antigens
-normally ability for immune system to recognize self proteins is blocked. If errors occur, Abs and reactive T cells canb e generated against them
Give examples of autoantigens
mitochondria, sperm, nucleic acids
-usually requires a host genetic predisposition for disease
How can pathogens induce autoimmunity?
molecular mimicry
-infection with particular pathogens is associated with immune response against self epitopes
What is molecular mimicry?
when some pathogens express proteins or carb residues that resemble host mols
What does mol mimicry result in?
activation of T cells that also recognize host cell proteins presented by normal, homeostatic MHC class I mols -sequestered self Ags may be released following damage by pathogens --> exposes them to adaptive immune cells
Name some types of Ag associated with pathogens or infections
H antigens - flagellum
F antigens - pili
K antigens - capsule
O antigens - cell wall
What are tumor antigens
self antigens used to identify tumors (not expressed often)
- presented on surface of tumor cells by MHC class I and II mols
- not found on normal cells
What are superantigens?
- usually secreted exotoxins that are highly mitogenic and stimulatory for T cells
- don’t require prior processing in order to bind to T cell receptor
- most work by cross-linking MHC and TCR to overstimulate T cells and drive hyperinflammation
- T cell thinks there’s an epitope and creates an immune response
What’s the difference btw innate and adaptive?
innate system recognizes many chemical structures or signatures without first processing a larger mol
- determinants recognized by innate immmune system differ from those recognized by adaptive immune system
- Abs, B/T cell receptors recognize discrete determinants and demonstrate high degree of specificity
- innate immune system recognize broad molecular patterns found in pathogens but NOT in host –> lack a high degree of specificity –> sometimes called Pathogen Associated Molecular Patterns (NOT antigens)
