100 Specific (Adaptive) Primary and Secondary Immune Responses

Immunological Memory

Building immunological memory against pathogens that are prevalent in the environment is an important strategy that can save the body from re-occurring damage and can also help the body to preserve energy by being strategic with its resources.

Primary Immune Response

As we have discussed in the previous two sections, the role of Class I and Class II MHC is vital in developing what is termed a primary adaptive immune response.  This adaptive immune response involves the activation of both T and B lymphocytes that are able to specifically bind to non-self antigens belonging to an infecting pathogen.  During the primary immune response, the amplification of cytotoxic T cells and antibodies which target the infecting pathogen for destruction play a crucial role in eliminating pathogens and their toxins.  Cytotoxic T cells and antibodies provide assistance to the innate immune response conducted by other white blood cells (WBCs, leukocytes) such as Natural Killer cells (NK cells) and the phagocytic neutrophils, macrophages, monocytes, and eosinophils.

Secondary Immune Response

When T and B cells are activated during the primary response, a pool of memory B and T cells is created that continually replenishes itself over the course of many years providing ‘memory’ of the pathogen, specifically memory of the pathogen’s antigens.   This memory pool is advantageous, as these memory cells can be very quickly activated during subsequent infections by the same pathogen.  In fact, subsequent infections provoke a ramped-up production of T and B cells from these memory cells.  In comparison to a primary immune response, the secondary immune response involves a much stronger and faster amplification of cytotoxic T cells, B cells, and antibodies.  Additionally, after the infection is eliminated, the pool of memory B cells continues to produce serum pathogen-specific antibodies at a low level which will provide immediate defense upon future exposure to the same pathogen.

Vaccinations

The premise of vaccines is to take advantage of the body’s ability to develop a tremendously effective secondary immune response.   Vaccines such as the MMRV that protects against 4 potentially debilitating and deadly viruses (Measles, Mumps, Rubella, and Varicella), work by injecting viral antigens (weakened attenuated virus) which stimulate a primary immune response against the viral antigens, without causing infection.  The benefit of this lies in the fact that memory B and T cells will be produced against all 4 viruses.  This means that should the person ever be exposed to the real virus; their memory B and T cells will ramp up production of cytotoxic T cells and antibodies during what would be termed a Secondary Immune Response.  It is likely that this secondary immune response is so quick, that the individual may not even know they were infected, as the pathogen can often be eliminated before it has had a chance to cause much in the way of damage.

Today, most viral vaccines consist of weakened (attenuated) viruses, however the SARS-CoV-2 vaccines that protect against COVID19 uses a new method of development which involves delivering only the mRNA of the virus, rather than the whole weakened virus.  The SARS-CoV-2 mRNA construct chosen for the vaccine codes for a specific viral antigen (the spike protein in the case of SARS-CoV-2).  Most bacteria vaccines are comprised of acellular or bacterial toxin components (i.e., bacterial antigens rather than the whole bacteria).  The goal of vaccine development is that the vaccine elicits a protective adaptive immune response without causing harm.

For example, the MMRV vaccine protects against 4 highly contagious viruses that are easily spread through contact and respiratory droplets.  Similar vaccines are freely available in Canada.  Check with your doctor and Immunize Canada for more information.  Currently vaccines are available against the following pathogens:

Why is it challenging or impossible to develop vaccines against some pathogens?

Pathogens such as HIV are associated with antigenic diversity, through frequent mutations.  This means that pools of memory T and B lymphocytes are no longer effective at binding to the pathogen’s antigens.  Basically, the memory T and B cells have already gone through a selection process, in terms of which memory cells are able to bind the last version of the pathogen, having what could be termed affinity maturation.  The new antigens of the more recent versions of the pathogen require different T and B lymphocytes to be selected for amplification base on those that have T cell receptors (TCRs) and B cell receptors (BCRs) that are complimentary to and can bind the pathogen antigens.  This new version of the pathogen is stimulating a primary immune response rather than a secondary immune response.

Can you list other pathogens that frequently mutate?  

Influenzae virus, SARS-CoV-2, rhinovirus, hepatitis C virus,

What are the differences between primary and secondary immune responses?

Primary immune responses take more time and result in a lower level of serum antibody produced.  The antibody titre (serum concentration levels) peak approximately 7-10 days after infection (or inoculation).  The majority of antibodies produced by plasma cells (differentiated B cells) are IgM and IgG, with IgM antibody levels typically increasing first, in a primary immune response.   IgG antibody levels increase more slowly, but reach slightly higher levels than IgM levels.

Secondary immune responses occur more quickly and result in a much higher level of serum antibodies produced.  The antibody titre peaks approximately 3-5 days after infection.  Memory B cells exist in lymphoid organs and tissues and also circulate the blood stream.  Once stimulated in a secondary immune response, Memory B cells proliferate and differentiate into plasma cells, which produce a large amount of IgG antibodies.  At the same time, there is an increase in IgM serum levels, which peak at similar concentration levels as was observed in the primary immune response.  In a Secondary Immune Response, the antibody serum levels of IgM and IgG remain high for a longer period of time than in the primary immune response, and include small amounts of IgA, IgD and IgE.

Summary of Serum Antibody Levels in Primary and Secondary Immune Responses:

Both IgG and IgM antibodies increase in number during both primary and secondary adaptive (specific) immune responses.  While IgM antibodies are the first to increase in number during a primary immune response, IgG concentrations rise to significantly higher levels than IgM levels in secondary immune responses and provide the most protection from the infecting agent.  

Summary

Immunological Memory

• Importance
  • Prevents reoccurring damage from pathogens
  • Saves energy by strategically utilizing resources
• Primary Immune Response
  • Activation of T and B lymphocytes to bind non-self antigens of the pathogen
  • Amplification of cytotoxic T cells and antibodies
  • Supports the innate immune response by aiding NK cells, neutrophils, macrophages, monocytes, and eosinophils
• Secondary Immune Response
  • Uses the memory B and T cells that were created during the primary response
  • Memory cells provide quick activation during subsequent infections
  • Stronger and faster response than the primary immune response
  • Continuous low-level production of specific antibodies by memory B cells for immediate defense
• Vaccinations
  • Utilize the body’s ability to develop a strong secondary immune response
  • Examples: MMRV vaccine (Measles, Mumps, Rubella, Varicella)
    • Injects weakened viral antigens to stimulate primary response without causing infection
    • Produces memory B and T cells for rapid response upon real infection
  • SARS-CoV-2 vaccines (COVID-19)
    • Uses mRNA to deliver specific viral antigens (spike protein) instead of whole virus
  • Bacterial vaccines
    • Use acellular or bacterial toxin components to stimulate immune response without harm
• Available Vaccines
  • Protect against highly contagious viruses spread through contact and respiratory droplets
  • Check with healthcare providers or Immunize Canada for more information on available vaccines in Canada

Challenges in Developing Vaccines Against Certain Pathogens

• Antigenic Diversity
  • Pathogens like HIV frequently mutate
  • Memory T and B cells become ineffective against new antigen versions
  • New pathogen variants stimulate a primary immune response rather than a secondary one
• Pathogens That Frequently Mutate
  • HIV
  • Influenza virus
  • SARS-CoV-2
  • Rhinovirus
  • Hepatitis C virus

Differences Between Primary and Secondary Immune Responses

• Primary Immune Response
  • Takes more time to develop
  • Results in lower serum antibody levels
  • Antibody levels peak 7-10 days after infection/inoculation
  • Majority of antibodies are IgM and IgG
  • IgM levels increase first, followed by IgG
• Secondary Immune Response
  • Occurs more quickly
  • Results in higher serum antibody levels
  • Antibody levels peak 3-5 days after infection
  • Memory B cells rapidly differentiate into plasma cells, producing large amounts of IgG at much higher levels than in the primary immune response
  • IgM levels also increase, peaking at similar levels as in primary response
  • Higher and prolonged antibody levels, including IgA, IgD, and IgE

Summary of Serum Antibody Levels

• Primary Immune Response
  • IgM increases first
  • IgG levels rise more slowly, reaching slightly higher levels than IgM
• Secondary Immune Response
  • Both IgG and IgM levels increase
  • IgG levels rise significantly higher than IgM
  • Provides most protection against the infecting agent
  • Antibody levels remain high for a longer period