Losing and recovering your immunological memory

03 January 2014

Research by scientists from NIMR has shown that immunological memory can be temporarily lost but then recovered. The work is published in PLOS Pathogens.

Antibody responses to infectious pathogens are critical in host survival, recovery and protection from reinfection; they also correlate with the success of vaccination. The immune response to infections that have previously been encountered is faster and more effective. This effect is known as immunological memory. The mechanisms that maintain immunological memory over time are unknown.

It is currently thought that long-term antibody responses are maintained over long periods of time by specialised antibody-secreting plasma cells, known as memory B cells (MBCs) and long-lived plasma cells (LLPCs). MBCs and LLPCs occupy distinct anatomical locations in the spleen and bone marrow, respectively. However, subsequent infection with different pathogens may cause the loss of previously established immunological memory.

Jean Langhorne, in NIMR’s Division of Parasitology, and George Kassiotis, in the Division of Immunoregulation, have used a mouse model to examine the maintenance of long-term humoral immunity to Influenza A virus. They infected mice with a mild strain of Influenza and waited until the animal had made a stable protective neutralising antibody response to flu before giving them a malaria infection. The amount of flu-specific antibody and number of specific plasma cells were then measured for several weeks after the mice had recovered from the malaria infection.

George Kassiotis and Jean Langhorne

George Kassiotis and Jean Langhorne

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The researchers found that a single malaria episode caused the loss of pre-existing plasma cells and serum antibodies and increased susceptibility to Influenza A re-infection. However, Influenza-specific immunity does eventually recover in these animals with the replenishment of plasma cells by B cells over the course of several weeks.

These findings directly demonstrate how an acute infection such as malaria can cause attrition of existing immunity to other infections. This might mean that there are periods when an otherwise protective vaccine is no longer protective. However, this is transient as memory B cells replenish the pool of cells making protective antibody. A large pool of memory B cells therefore is very important for maintaining and recovering protective antibody responses after vaccination. This has implications for understanding the longevity of protective efficacy of vaccinations in countries where continuous infections are endemic.

Jean Langhorne

The bone marrow cells responsible for antibody memory to influenza infection, which were previously thought to be irreplaceable, appear to be constantly replenished by splenic memory B cells. As a result, immunity to influenza can recover over time, even following severe heterologous infections, such as malaria, which causes considerable loss of bone marrow, but not splenic cells.

George Kassiotis

Original article

Dorothy H. L. Ng, John J. Skehel, George Kassiotis and Jean Langhorne (2013)

Recovery of an antiviral antibody response following attrition caused by unrelated infection

PLOS Pathogens 10(1): e1003843 Article fulltext

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