Johnson & Johnson, Explanations for Clotting ? – Part 5

To the specialist:  This article attempts to make some very inaccessible material accessible. The simplifications are abbreviations for what the specialist already knows.  Plain language is used even when concise language is available. The innate and adaptive systems are now known to be so intermingled, they aren’t really separate systems, just different types of responses.

3.5 billion years ago, the first living organism successfully closed its “self” off from a  ancient ocean, with a stockade in the form of a fatty membrane. This captured, for all descendants, including you, the salty chemical balance of that ocean: the chloride salts of sodium and potassium. As the ancient sea was less salty than it is now, so your blood is less salty. This is your most ancient inheritance, from a time before time.  DNA may have come a little later.

In your salty inner sea, some molecules gain or lose electrons to other molecules, acquiring an electric charge. The cell walls of many bacteria are covered with polyanions, long chains of molecules that have gained electrons. This is used as a danger signal by oldest part of the immune system, the innate, which came about  with evolution of multicellular life,about 1.5 billion years ago. Heparin has an extremely high negative charge.

Without training or prior exposure, the innate immune response uses the bacterial polyanions to identify bacteria as pathogens. This is called a danger pattern or signal, one of many, for which the innate immune response has a repertoire of responses. Some  of these responses involve recruitment of the adaptive immune system.

Unlike the ancient innate response, the newer adaptive immune response has no immediate defense against a novel pathogen. It requires a sample of possibly alien substance, which it compares to a huge library of patterns, called epitopes. If found in the library, and detailed tests show it isn’t a legitimate part of you, production of antibodies commences. When in a normal state of vigilance, the immune system does not attack “self”tissue. This is called tolerance.

Burnet’s  1957 theory of clonal selection , still foundational, implies:

  • A mistake occurs when antibodies are generated that respond to “self”. This failure of tolerance results in an autoimmune disorder.
  • This mistake is  a binary outcome: it happened, or it didn’t.
  • The above is now known to be too simple.  There is a legitimate need, on occasion, for the immune system to  attack “self” tissue. A failure of tolerance can be induced for good purpose.

In wars of the 20th century, the final, desperate tactic of a trapped unit with some fortification was to call for artillery on top of its own position. So it is when the pathogen is adept at mimicking the body’s own tissue. When  lesser responses fail, pathogen and tissue are marked for destruction by the same antibody.

From (Blood) Heparin-Induced Thrombocytopenia,

Several theories have been advanced to explain this unusually high frequency of anti-PF4/heparin antibodies. PF4 binds effectively to bacterial walls of gram-positive and gram-negative bacteria,42-44  and bacterial infection, if accompanied by platelet activation and PF4 release, may provide a sufficient priming stimulus for an immune response upon subsequent heparin exposure.42 

This is a passive note, peripheral to the subject of the paper, which is low platelet count.  Implication: Platelets are adapters from the innate to the adaptive immune system. Binding with bacteria creates a narrow class of antigen, which includes heparin/PF4, from an innate danger signal. This allows the adaptive immune response to participate without requiring a specific antibody.

For a more active voice, see (PMC) Thrombocytopenia in Virus Infections. Quoting,

3.1.3. Sequestration and Intravascular Destruction – …Furthermore, platelets can bind to neutrophils, forming platelet-neutrophil aggregates, which in turn triggers the phagocytosis of platelets [,]…Implication: Platelets actively participate in the innate immune response.

3.1.4. Platelet Expression of Pattern Recognition Receptors  – …can identify pathogen associated molecular patterns (PAMPs) from viruses and many are expressed by platelets []… This enhances … activation of leucocytes []. … may have both an immune protective mechanism, [] or be injurious to the host. Implication: Strong coupling exists between innate and adaptive immune responses.

3.1.6. Platelets Act as Antigen Presenting Cells — APCs require MHC-I molecules to present antigen to CD8+ T cells. There is evidence now that platelets…contain all the MHC-I and co-stimulatory molecules necessary for antigen presentations. ….Implication: As well as innate, platelets are part of the adaptive immune response.

It’s tempting to leap to this conclusion: COVID-19 causes clotting, so COVID holds the smoking gun.  But there isn’t enough logical glue. You might find your leap is actually a dive, and there isn’t any water in the pool.

To be continued shortly.

 

 

 

 

 

 

 

 

 

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