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Why can the human immune system only recognize some pathogens? What are the limitations?
A new study by the University of Pittsburgh in the United States may have overturned the previous understanding of the immune system:

How powerful is this discovery?

Refresh the current cognition of innate immune response, that is to say, the problems related to immunity may have to "start over" again.

It is expected to solve the problem of immune rejection that has plagued organ transplantation for more than 60 years in one fell swoop.

On the issue of cancer and autoimmune diseases, new insights may emerge.

The top journal Science published this heavy article on immunology (* * * is also a China scholar). The core point is that innate myeloid immune cells such as macrophages and monocytes can also produce antigen-specific immune memory.

It seems that this time, the immunology textbook will be revised. Netizens also seconded this, saying that this research will change textbooks.

Different immune systems

We all know that the immune system is divided into two parts:

One is innate immunity, including myeloid cells such as macrophages and monocytes, and innate lymphocytes such as NK cells;

The other is adaptive immunity, such as well-known T cells and B cells.

In the face of foreign "invaders", these two little guys have their own duties.

Congenital immune cells, like sentinels, are the first cells to find foreign organisms in the body. If they find something abnormal, they will go back to adaptive immune cells and say, "Brother, it's your turn."

△ working cells: macrophages vs staphylococcus aureus

When adaptive immune cells are activated, they will stimulate a strong immune response.

Adaptive immune cells have a unique skill-immune memory. Once you meet an intruder, you will remember what it looks like.

If you dare to invade again next time, adaptive immune cells will quickly identify and launch a more violent attack.

This is what we used to know about the immune system.

So, does immune memory really only have adaptive immune cells?

This is a problem to be solved by researchers at the University of Pittsburgh and Cornell University. They found that macrophages and monocytes, two innate immune cells, also have the same function.

In other words, we thought they were just "sentinels" before, but we never expected that they would also have the stunt of "immune memory".

What is even more unexpected is that the combat effectiveness is almost out of the chart, and it also plays a very key role in the "host defense" mission.

Simply subverting cognition!

At present, the main cause of organ transplantation failure is immune memory, so this discovery fundamentally provides a new insight for solving organ transplantation problems.

As Dr. Martin H. Oberbarnscheidt, one of the first papers, said:

It is expected to solve the problem of immune rejection that has plagued organ transplantation for more than 60 years in one fell swoop. So, how is such a breakthrough experiment done?

Experimental results refresh cognition

First, the researchers arranged mice lacking B cells, T cells, NK cells and other innate lymphocytes, and transplanted allogeneic spleen cells after irradiation.

Then, after 7 days, 28 days and 49 days, spleen cells homologous to the above immune spleen cells or third-party allogeneic spleen cells were transplanted again.

The results showed that, on the 7th or 28th day, mice transplanted with allogeneic spleen cells showed more obvious and strong immune response compared with non-immunized mice and mice transplanted with third-party spleen cells.

This immune response is dominated by monocyte-derived dendritic cells (Mo-DC) and macrophages.

This enhanced reaction disappeared after 49 days.

Later, the researchers used another immune deficiency model (Figure B above) to do the same experiment on mice, and the results were the same.

Moreover, the researchers also ruled out the possibility that the enhanced response originated from the persistence of antigens.

Because no donor spleen cells or complete donor MHCI molecules were detected in the circulatory system or spleen of the host.

This also shows that macrophages and monocytes in mice may have acquired specific memory of antigens.

In addition, the specific recognition of antigens by mouse and human immune cells depends on MHC (major histocompatibility complex). In order to find out the truth further, the researchers searched the 17 mouse genome database to test whether the memory of monocytes/macrophages depends on the detection of non-self MHC molecules.

Therefore, they found many protein molecules that can be expressed on the surface of bone marrow cells and can bind MHC-I.

Among them, paired immunoglobulin-like receptor -A(PIR-A) has been proved to be the MHC-I receptor needed by macrophages and monocytes for memory response. The corresponding human receptor is LILRs.

In further experiments, the researchers tried to block PIR-A and knock out PIR-A gene with antibodies respectively, and found that without PIR- 1, the monocytes and macrophages of mice would not have specific immune memory of antigens.

In other words, the immune memory of monocytes and macrophages is mediated by PIR-A.

Therefore, the researchers also proved through experiments that knocking out the gene encoding PIR-A in the receptor or blocking the combination of PIR-A and MHC-I in the donor can block immune memory and weaken the rejection of allograft.

This means that this new study extends the classical research field of immune memory to congenital bone marrow cells, and may improve the survival rate of allogeneic organ transplantation.