17. Immunological memory, primary and secondary immune response
Recall the extrafollicular and germinal centre reaction, mainly that only T-dependent antigens like peptide antigens induce immunological memory, affinity maturation and isotype switching. The formation of immunological memory is essential as it makes it much easier for the immune system to battle the same pathogen if it should infect the body later.
We still don’t quite know how memory cells are kept alive so long. For immune cells to live, their receptor must bind an antigen once in a while, and we aren’t sure where these memory cells find antigens to keep them alive when the body is not infected.
We call the immune response that occurs when the body first meet a specific antigen the primary immune response, and every time the body meets with the same antigen after this the secondary immune response. The differences between them is summarized in the table below.
| Property | Primary immune response | Secondary immune response |
|---|---|---|
| B-cell type involved | Naïve B cell | Memory B cell |
| Response begins how long after pathogen infection? | 4-7 days | 1-3 days |
| Time of peak response | 7-10 days | 3-5 days |
| Size of antibody response | Depends on antigen | 100-1000 times higher than primary response |
| Antibody isotype produced | Mainly IgM | Mainly IgG |
| Antigens | T-dependent and T-independent | T-dependent |
| Antibody affinity | Lower | Higher |
What makes the secondary immune response more effective?
While naïve B-cells only have IgM and IgD on their surface, memory B-cells can have every immunoglobulin isotype on their surface, which makes them more equipped to handle different pathogens than naïve B-cells. Memory B-cells also have more complement receptors and since they have undergone affinity maturation, have much higher affinity to the antigen than naïve cells.
Memory T-cells are also different than naïve T-cells. CD45 is a surface protein that is involved in cell activation and is found on all leukocytes. Naïve T-cells have the CD45RA isoform on their surface, while memory T-cells have CD45R0. The CD45R0 protein is much shorter than CD45RA, which makes it easier for the protein to associate with TCR and activate the cell.
Because the memory B-cells have higher affinity for the antigen than naïve B-cells, they will bind and phagocyte the antigen much quicker than the naïve B-cells could. Because B-cells are APCs, they can present the antigen to memory T-cells much faster than naïve B-cells.
Two cytokines are important for memory T-cells. They’re dependent on IL-15 to proliferate, and on IL-7 to survive.
Memory cells have a different recirculation pattern than naïve lymphocytes. The memory B-cells and T-cells will migrate to the place of inflammation and live in the tissue there. Naïve cells circulate in the circulation and into the secondary lymphoid organs. Memory cells upregulate certain adhesion molecules, among them CD44, which binds to a molecule found in extracellular space called hyaluronic acid.