Primary and Secondary Responses Differ Significantly

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The kinetics and other characteristics of the humoral response differ considerably depending on whether the humoral response results from activation of naive lymphocytes (primary response) or memory lymphocytes (secondary response). In both cases, activation leads to production of secreted antibodies of various isotypes, which differ in their ability to mediate specific effector functions (see Table 4-2).

The first contact of an exogenous antigen with an individual generates a primary humoral response, characterized by the production of antibody-secreting plasma cells and memory B cells. As Chapter 3 showed, the kinetics of the primary response, as measured by serum antibody level, depend on the nature of the antigen, the route of antigen administration, the presence or absence of adjuvants, and the species or strain being immunized.

In all cases, however, a primary response to antigen is characterized by a lag phase, during which naive B cells undergo clonal selection, subsequent clonal expansion, and dif ferentiation into memory cells or plasma cells (Figure 11-14). The lag phase is followed by a logarithmic increase in serum antibody level, which reaches a peak, plateaus for a variable time, and then declines. The duration of the lag phase varies with the nature of the antigen. Immunization of mice with an antigen such as sheep red blood cells (SRBCs) typically results in a lag phase of 3-4 days. Eight or nine successive cell divisions of activated B cells during days 4 and 5 then generate plasma and memory cells. Peak plasma-cell levels are attained at day 4-5; peak serum antibody levels are attained by around day 7-10. For soluble protein antigens, the lag phase is a little longer, often lasting about a week, peak plasma-cell levels are attained by 9-10 days, and peak serum titers are present by around 14 days. During a primary humoral response, IgM is secreted initially, often followed by a switch to an increasing proportion of IgG. Depending on the persistence of the antigen, a primary response can last for various periods, from only a few days to several weeks.

The memory B cells formed during a primary response stop dividing and enter the G0 phase of the cell cycle. These cells have variable life spans, with some persisting for the life of the individual. The capacity to develop a secondary humoral response (see Figure 11-14) depends on the existence of this population of memory B cells as well as memory T cells. Activation of memory cells by antigen results in a secondary antibody response that can be distinguished from the primary response in several ways (Table 11-4). The secondary response has a shorter lag period, reaches a greater mag-



Primary Secondary Antibody Response

Time after immunization

Time after immunization

FIGURE 11-14

Concentration and isotype of serum antibody following primary (1°) and secondary (2°) immunization with antigen. The antibody concentrations are plotted on a logarithmic scale. The time units are not specified because the kinetics differ somewhat with type of antigen, administration route, presence or absence of adjuvant, and the species or strain of animal.

Comparison of primary and secondary antibody responses


Primary response

Secondary response

Responding B cell

Lag period following antigen administration

Time of peak response

Magnitude of peak antibody response

Isotype produced


Antibody affinity

Naive (virgin) B cell Generally 4-7 days

7-10 days

Varies depending on antigen

IgM predominates early in the response

Thymus-dependent and thymus-independent


Memory B cell Generally 1-3 days

3-5 days

Generally 100-1000 times higher than primary response

IgG predominates


Higher nitude, and lasts longer. The secondary response is also characterized by secretion of antibody with a higher affinity for the antigen, and isotypes other than IgM predominate.

A major factor in the more rapid onset and greater magnitude of secondary responses is the fact that the population of memory B cells specific for a given antigen is considerably larger than the population of corresponding naive B cells. Furthermore, memory cells are more easily activated than naive B cells. The processes of affinity maturation and class switching are responsible for the higher affinity and different isotypes exhibited in a secondary response. The higher levels of antibody coupled with the overall higher affinity provide an effective host defense against reinfection. The change in isotype provides antibodies whose effector functions are particularly suited to a given pathogen.

The existence of long-lived memory B cells accounts for a phenomenon called "original antigenic sin," which was first observed when the antibody response to influenza vaccines was monitored in adults. Monitoring revealed that immunization with an influenza vaccine of one strain elicited an antibody response to that strain but, paradoxically, also elicited an antibody response of greater magnitude to another influenza strain that the individual had been exposed to during childhood. It was as if the memory of the first antigen exposure had left a life-long imprint on the immune system. This phenomenon can be explained by the presence of a memory-cell population, elicited by the influenza strain encountered in childhood, that is activated by cross-reacting epitopes on the vaccine strain encountered later. This process then generates a secondary response, characterized by antibodies with higher affinity for the earlier viral strain.

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  • Asphodel
    What antibody predominates at 3 weeks during the primary response?
    5 years ago
    Why lag phase is longer in primary immunization?
    3 years ago

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