Immunology 7: Requirements for the Induction of Antibody Responses Flashcards
Scientists thought induction of a precursor cell occured when?
Antigen interacted with precursor’s antibody-like receptor
“interaction of antigen with precursors antibody-like receptor was thought to lead to multiplication of precursor cell and differentiation of its descendants into antibody producing cells” Describes what idea?
→ direct binding model for precursor cell activation
Substance that induces antibodies is said to be?
Immunogenic
Hapten molecules
→ small, non-immunogenic molecules that are chemically conjugated to large foreign molecule thats immunogenic can have antibodies raised against it
Hapten-carrier conjugate
→ hapten conjugated to an immunogenic macromolecule
Presence of antibody to the hapten can be demonstrated how?
→ showing that a precipitin reaction occurs when hapten-P complex is added to immune serum, but not when just P is added.
Evidence against direct antigen binding model
Observations that do not fit with model:
→ macromolecular haptens exist
→ requirement for 2 cell types to obtain an antibody response
Macromolecular haptens are evidence against direct antigen binding model why?
→ some foreign macromolecules were haptenic (could not induce antibodies) but an antibody could be induced if they were chemically conjugated to an immunogenic carrier
→ ex, synthetic protein poly-L-lysine: antibody is present in the immune serum when PLL was with bovine serum albumin (carrier) - then, if PLL is added by itself (it is haptenic) it can precipitate, so it could bind PLL but PLL can’t induce the formation of antibody, carrier has to do that → mere binding of antigen to antibody-receptors of precursor does not result in antibody induction
Why is requirement for 2 cell types to obtain an antibody response evidence against direct antigen binding model?
→ if precursor cells are irradiated (X-ray) daughter cells will die. in mice: this destroys ability of precursors to produce progeny and antibodies
→ removal of thymus gland from mice within 24h of birth removes ability to mount immune responses (immunoincompetent) as adults – thymus cells might be precursor cells
EXPERIMENT:
→ mice then given diff potential sources of precursor cells and antigen
→ even if irradiated mice given thymus cells and antigens, no antibodies made
→ possible that bone marrow has precursor cells, but when irradiated mice given bone marrow cells and antigen, no antibodies
When irradiated mice given both thymus and bone marrow cells and an antigen, a very substantial and brisk response formed! So both thymus and bone marrow cells needed for inducing antibodies
After experiment with bone marrow and thymus cells, which is the precursor cell?
→bone marrow cells have antibody receptors on surface
→ thymus cells have antigen Thy1
→ cells corresponding to bone marrow and thymus cells found in spleen carry immunoglobulin receptors and Thy1 antigen on their surface too
→ thymus cells present in thymus (or thymus-derived cells in lymphoid organs) needed to allow antigen to induce bone marrow precursor cells to help produce antibody secreting progeny = HELPER/INDUCER T CELLS
Why do B cells need inducer T cells to be activated by antigens?
→ T cells are antigen-specific and only to foreign, not self, antigens
→ some antigens can’t induce antibodies unless conjugated to carrier that is immunogenic
**B cell can be induced by antigen if second cell (inducer T cell) also binds to antigen *helper T cells only exist for foreign antigens: explains why PLL lacks response if absent from helper T cells
Antigen bridge model
hypothesis that interaction between B and helper T cells is required to form antibody formation
→ explains lack of response to PLL as being due to absence of sufficient helper T cells specific for antigen PLL: induction of antibody to PLL only occurs when animal is immunized with conjugate PLL_BSA bc there are many more helper T cells specific for carrier BSA than PLL
→ idea is consistent since its possible to sensitize animals so their T cells proliferate to BSA but not PLL
→ basically B and T cells go on either side of antigen and make it a “bridge” b/n them
When did the antigen bridge model become modified?
→ when it became apparent that CD4+ T cells don’t bind intact antigen, but a peptide derived from the antigen that is bound to an MHC class 2 molecule, AND that B cells express MHC class 2 antigens on their surface
Modified antigen bridge model: a B cell with antibody receptors specific for PLL had to bind what to be induced?
→ bind with its receptors on PLL end of the PLL-BSA conjugate (BSA is the carrier)
→ upon binding, conjugate then aggregates cells anti-PLL antibody receptor and resulting complex is endocytosed into B cell
→ inside B cell, PLL-BSA complex is degraded and resulting BSA-derived peptide brought into contact with MHC class 2 molecules
→ peptides bind MHC class 2 molecules and peptide-MHC complex inserts into B cells membrane
→ complex is recognized by specific helper T cells
Model for modified antigen bridge model is called?
what does it account for?
→ called MHC-restricted B cell/T helper cell interaction model
→ takes into account that helper T cells can’t recognize antigen directly like B cells do, but can recognize peptide that is bound to MHC molecule
