The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

An antibody, in short, can be conceived as a molecule with multiple parts—the

binding prongs

and a shaft that enables it to liaise with the immune system to become a p...

if the structure of antibodies was malleable, then the genes that encoded them must also be malleable—by mutation.

Proteins don’t grow on command, but cells do.

When an antigen binds to one such B cell

it is stimulated and begins to outgrow all the others.

clonal selection: the selection of an individual cell capable of binding an antigen.

Ultimately, the B cell matures into a cell so single-mindedly dedicated to antibody production that its structure and metabolism are altered to facilitate the process. It is now a cell dedicated to making antibodies—a plasma cell. Some of these plasma cells also become long lived and retain the memory of the infection.

Rituxan was among the first monoclonal antibodies against cancer.

“Using cells to fight cells,” he marveled. “We never really thought about all that we could do when we raised that first antibody.”

these cells would become the epicenter of one of the defining epidemics in human history.

Why aren’t the chronic viruses vanquished by the immune system—especially by T cells?II

This is what viruses do: they “go native.”

What, then, prevents any virus from using every cell in our body as a perfect microbial sanctuary?

The subtle, wise, discerning T cell.

your T cells can recognize virally infected cells only if they come from your body, not someone else’s.III

It was as if the T cell was capable of asking two independent questions.

It is as if the MHC protein is a frame. Without the right frame, or context (“yourself”), the T cell cannot even see the picture, even if it is a distorted version of the “self.” And without the picture in the frame

the T cell cannot recognize the infected cell. It needs both the pathogen and the self—the picture and the frame.V

“That protein, NP, never makes it to the cell surface,”

“As far as cell surface proteins are concerned, there is nothing for a NP-detecting T cell to see,”

Rather, the cells were detecting viral peptides—small

The self, yes, but the altered self.

was actually a carrier, a peptide bearer, and a “frame.”

One part of a finger touches the self, one part makes contact with the foreign. When both are touched, recognition is achieved.

Our immune system is built on both the recognition of self and of its distortion. It is designed, by evolution, to detect the altered self.

a majority of peptides derived from pathogens outside the cell

are presented by class II MHCs.

Rather, this T cell is an orchestrator.

“helper” T cell. Its job is to bridge the innate and adaptive immune system—macrophages

There is a duality in the immune system: one recognition system needs no cellular context

while the other is triggered only when the foreign protein is presented in the context of a cell

first human disease to be characterized by the selective loss of a specific T cell subset,

the CD4 cell is not so much a helper as it is the master machinator of the entire immune system, the coordinator, the central nexus through which virtually all immune information flows.

“A clear nonconfluent margin separates different species or [even] different specimens belonging to the same species.”

It’s not invasion, the ecologists insist. It’s interconnectedness.

Even early physiologists noted that the rejection of the nonself—and the strict definition of boundaries—was a feature of human tissues.

They present peptides to a T cell so that a T cell can detect infections and other invaders and mount an immune response. And they are also the determinants by which one person’s cells are distinguished from another person’s cells, thereby defining the boundaries of an organism.

The self is defined, in part, by what is forbidden to attack it.

T cells are born in the bone marrow as immature cells and migrate to the thymus to mature.

Immunity and its opposite are twinned: the Cain of inflammation conjoined with the Abel of tolerance.

once the barrier to the self has been broken, everything that is self can be under attack.

called cancer a “distorted version of our normal selves.”

This double-headed problem—cancer’s kinship to the self and its immunological invisibility—is the oncologist’s nemesis.

increasingly imagining the immune system as a knowable machine, with movable—manipulable, decipherable, changeable—cogs, gears, and parts.

Asymptomatic/presymptomatic transmission. Exponential growth. The two critical ingredients in the recipe for a pandemic had already been established by that innocuous-seeming report.

unpredictable, mysterious deadliness.

is one of the key detectors of viral invasion.

soon after infection, the virus “reprograms” the infected cell.