To understand the history of HDFN due to anti-D, it is useful to review the immune response.
A primary (1°) immune response is the response that occurs following the first exposure to a foreign antigen.
A secondary (2°)/anamnestic immune response occurs following subsequent exposures.
The main differentiating features as related to producing anti-D during pregnancy are shown in the table and figure.
| 1o immune response | 2o immune response |
| 1. Following the first exposure to the D antigen, a lag phase occurs in which no anti-D is produced, but activated B cells differentiate into plasma cells. The lag phase can be as short as several days, but often is longer. | 1. When exposure to D occurs in subsequent pregnancies, the lag phase is short (3–7 days) due to the presence of memory B cells that quickly differentiate into antibody-secreting plasma cells. |
| 2. Depending on the antibody detection method, it often takes 5–15 weeks before anti-D is detectable in serologic tests. | 2. An increase in anti-D is usually detectable within days. |
| 3. The amount of anti-D produced is relatively low. | 3. The amount of anti-D rises to a higher level. |
| 4. Anti-D titers decline fairly rapidly and may become undetectable. | 4. Anti-D titers tend to remain higher for longer but eventually decline. |
| 5. The first anti-D produced is mainly IgM (although small amounts of IgG are usually also produced). | 5. The main type of anti-D produced is IgG (although small amounts of IgM may be produced). |
