Further notes about the morphostasis concept – split files

(45) Direct "pathogen"/microbe killing by the adaptive immune system

I know that this is repetitious but only constant repetition will eventually encourage people to pay attention.

The opinion – that the adaptive immune system directly attacks "pathogens" – sticks like a limpet.

Think about it.

Can lymphocytes or antibodies directly kill or eliminate anything without enlisting the co–operation of more primitive (innate) immune mechanisms?

Cytotoxic T–cells encourage cells to commit suicide when they display the Mhc/peptide debris–products derived from the processing of internal pathogenic micro–organisms (or abiotic pathogens). These cells are encouraged to sanitize their contents (a very primitive innate immune mechanism). This is NOT a direct attack on the "pathogen". Helper T–cells recognise the Mhc/peptide debris–products that APCs (phagocytes) have ingested and processed. They cannot recognise and respond directly to the "pathogen"; it MUST be processed first. When it does recognise this Mhc/peptide–debris it ramps up the local innate immune activity. The latter is what "kills" the "pathogens" (and gives local self cells a hard time too). I suspect that B–cells are specialised (targeting) phagocytes that are, probably, originally intended to target specific developmental tissue debris (eg, resorbed stuff like finger webs). This system has been "licensed" to other, more extrinsic, debris by enabling the B–cell (as an APC) to stimulate helper T–cells. Once again, what is recognised on re–encounter is the processed debris that the B–cell has ingested and then presented in the Mhc groove. It is the presence of locally processed debris, processed by an APC, that encourages a ramping up of local innate immune aggression. Again, there is no direct attack on the "pathogen". The closest we come to a direct attack is by the immunoglobulin led "opsonisation" of directly recognised "pathogen" epitopes. BUT – this simply leads to an enhanced, focalised, ramping–up of the complement (primitive innate immune) system that will still avoid excessive damage to healthy self cells (through complement inhibitors).

T-cells and antibodies do not directly attack "pathogens". They generate a large repertoire of receptors that are able to recognise cell(Mhc class I)/phagocyte(Mhc class II) processed biological debris. This processed debris is then assigned either an aggressive or a tolerant association. These can then be used to reproduce a caricatured (aggressive) inflammatory or a (tolerant) non–inflammatory milieu on any reencounter.

Isn't this incontravertible?

A useful way of regarding this is to realise that T cell receptors are predilectively focused on allo-mhc ligands (a clue that the vertebrate immune system evolved from ancient mechanisms of colony interaction – not necessarily or inevitably competition). In practice, debris is processed and presented in the peptide groove of self–mhc ligands. This produces peptide–modified–self–mhc ligands. These modified self ligands have the properties of allo-mhc ligands. It is always modified self ligands that are generated as a consequence debris processing. There is no direct T–cell attack on foreign antigens.