Primary vs. Secondary Immune Response

The initial encounter of a naïve immune-competent lymphocyte with an antigen induces a primary immune response; a later contact of the host with the same antigen will induce a more rapid and heightened secondary immune response.

Differences in the Primary and Secondary Immune Response. Image source: Abbas et. al: Cellular and Molecular Immunology

The amplified population of memory cells accounts for the rapidity and intensity distinguishing a secondary response from a primary one.

We apply the concept of immune response to produce needed immunity in a host through vaccination. Antigens administered in the body via vaccination imitate the infectious agent; thus body produces T-lymphocyte, B-lymphocyte, and antibodies against it. If a vaccinated person encounters infection later in life (by the same pathogen), the memory B cells and T cells fight off the infection rapidly and in heightened response, thus giving protection.

In some vaccines, the first dose (primary response) does not provide needed immunity, and that immunity may begin to wear off after a certain period. In such cases, we provide more shots and even booster doses to keep immunity at the needed level (i.e., to maintain the population of memory cells).

Major characteristics/differences between primary and secondary immune responses are summarized in this table:

 Primary Immune Response Secondary Immune Response
DefinitionImmune response against primary antigenic challengeImmune response against subsequent antigenic challenge
ResponseLow, sluggish (appear late), and short-livedPrompt,  powerful, and prolonged (long-lasting)



Antibody producing cellsNaïve B cellsMemory B cells
Peak ResponseSmallerLarger
Antibody levelsAntibody levels peak in the primary response at about day 14 and then begin to drop off as the plasma cells begin to die.Because there are many more memory cells than naïve B cells for the primary response, more plasma cells are generated in the secondary response, and antibody levels are 100 to 1000 fold higher.
Lag periodThe lag period is longer (4-7 days)
This lag is the time required for the activation of naive B cells by antigen and TH cells and the subsequent proliferation and differentiation of the activated B cells into plasma cells.
The lag period is absent or short (1-3 days)


The secondary response reflects the activity of the clonally expanded population of memory B cells. These memory B cells respond to antigens more rapidly than naïve B cells.

Negative phaseNo negative phaseA negative phase may occur
Antibody IsotypeThe antibody is produced in low titer and is of IgM type.


The disease diagnosis presence of IgM is suggestive of a recent primary infection.

Antibody is produced in high titer and mainly IgG type (IgA or IgE in certain situations). In the diagnostics, the presence of IgG should be interpreted cautiously as it may be because of previous vaccination or subsequent sub-clinical infections (local cut-off titer or previous infections with the same agent). 
Specificity of AntibodyAntibodies are more specific but less avidAntibodies are less specific but more avid
Antibody AffinityLower average affinity, more variable



Higher average affinity (affinity maturation)
Induced byAll immunogens (Both T-dependent and T-independent antigens are processed by primary immune response)Only protein antigens  

(Only T dependent antigens are processed)


  1. Kuby Immunology, 8th Edition
  2. Roitt’s Essential Immunology, 13th Edition

Nisha Rijal

I am working as Microbiologist in National Public Health Laboratory (NPHL), government national reference laboratory under the Department of health services (DoHS), Nepal. Key areas of my work lies in Bacteriology, especially in Antimicrobial resistance.

One thought on “Primary vs. Secondary Immune Response

  1. how do you activate your secondary response as stronger – immune stimulating supplements ????

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