In order for the immune system to be stimulated to produce antibodies, there must be a surface protein of the invading pathogen which binds to a receptor on B cell surface somewhat loosely. We need this first step for the initiation of the somatic hypermutation phase to produce specific antibodies.
But what if there is a pathogen which does not have such a surface protein? i.e. its surface proteins, if it has any, do not bind with sufficiently high affinity to surface proteins on existing B cells to trigger further aspects of the immune response.
One may argue that this is unlikely to be the case because:
a) naturally occurring pathogens evolve from existing ones, so the changes in the antigens will generally be minor. A new strain will have surface proteins that are similar enough to those of an existing strain for some loose affinity to present antibodies in the host.
b) I think, though am not at all sure, that pathogens need to invade cells to be dangerous.I'm not entirely sure what the nature of a pathogen which cannot invade cells would be. Perhaps not a pathogen at all? In any case, if the starting assertion is true, the dangerous pathogens have a surface receptor which binds with surface proteins on cells to enter them. What if many antibodies are based on the same proteins? (Though I have trouble believing this because the natural agonists of these cellular receptors are some biologically relevant and useful proteins, which we would not want an immune response to. For instance, a generally accepted mechanism of entry of SARS-CoV-2 into cells is by binding the ACE2 receptor, which has angiotensin II- a vasoconstrictor peptide- as an agonist.
So my questions are:
a) Could we synthesise a pathogen which has no surface proteins but which nevertheless does harm in some way? How could it do this harm?
b) Can we make a pathogen which has surface proteins such that it can enter cells or do damage that pathogens normally do, but goes undetected by the immune system?
In the above I have assumed that surface proteins (or perhaps also other surface molecular- maybe carbohydrates will do- are necessary for activating the immune response. If this is not the case, please let me know.