Immunology Ch. 11

What are conjugate vaccines and why are they used for infants?

A conjugate vaccine consists of a polysaccharide antigen (from a bacterial capsule) linked to a protein antigen (which may or may not be from the same pathogen). Because the two antigens are linked, the carbohydrate antigen will activate B cells and the protein antigen will activate T cells. T cells will then activate their conjugate B cells to produce antibody against the polysaccharide antigen.

What is an adjuvant and in what type of vaccines is it necessary?

An adjuvant is a component that is added to a vaccine to activate the innate immune response. Some subunit vaccines may need an adjuvant if the subunit contains antigens that effectively activate the adaptive immune response (B and T cells receptors), but do not contain pathogen associated molecular patterns that can be recognized by innate immune cells. Live-attenuated and inactivated vaccines contain whole pathogens that will contain pathogen-associated molecular patterns that will activate the innate immune response.

What are a) live attenuated vaccines b) inactivated vaccines and c) subunit vaccines?

Live attenuated vaccines use a live form of the pathogen that has acquired mutations that make it non-pathogenic (unless it subsequently develops reversion mutations). Inactivated vaccines use whole pathogen cells (viral cells or bacterial cells) that have been inactivated (killed). The inactivated cells don't have the ability to replicate and cause infection. Subunit vaccines do not use whole cells; they use only the most antigenic components of a pathogen (the components that are best able to illicit a host immune response).

How are live-attenuated pathogens produced?

Live-attenuated pathogens are produced by growing the pathogen in cells that are not host cells. The pathogen develops mutations that make it better adapted to the non-host cells, but less well-adapted to the host cells.

What type of vaccine(s) is expected to best mimic a natural infection? What type of vaccine(s) are safest? (ex. have the least potential to inadvertently cause disease)?

Live-attenuated vaccines are expected to most closely mimic a natural infection because they retain the ability to infect cells as the natural pathogen would. Live-attenuated vaccines sometimes carry the risk that the pathogen may develop mutations that revert it back to a pathogenic form. Inactivated and subunit vaccines do not have the potential to cause disease, but the host immune response against the antigens may still produce side effects.

What are memory B cells and memory T cells and how do they differ from naive B cells and naive T cells?

Memory B cells are long lived B cells that differentiated from activated B cells during the primary immune response. Memory B cells underwent class switching and affinity maturation during the primary immune response, so they have a higher affinity for antigen. Memory T cells differentiated from activated T cells during the primary immune response. There are two types of memory T cells: 1) Effector memory T cells are effector T cells that circulate in tissues and can respond rapidly to antigen encountered in tissues. 2) Central memory T cells are more like naive T cells in that they circulate in the secondary lymphoid tissues and retain the potential for activation, proliferation, and differentiation to produce more effector T cells.

How are naive B cells inhibited by IgG antibodies that were produced during a primary immune response? Why might this inhibition of naive B cells be beneficial to the host? When might this inhibition of naive B cells be detrimental to the host?

Naive B cells have an inhibitory IgG receptor. A naive B cell is inhibited when it is simultaneously bound by antigen and antigen specific IgG. This is supposed to be beneficial to the host because it ensures the activation of memory B cells that will secrete high affinity antibody and prevents activation of naive B cells that will initially secrete low affinity IgM, which will not be as effective. It may be detrimental to the host when faced with pathogens that can mutate and change their surface antigens, such as the influenza virus. Upon secondary exposure to influenza, the new, mutated antigens may no longer be recognized as effectively by memory B cells. Naive B cells that can effectively recognize the new antigens are inhibited from being activated by the IgG antibodies from the primary response. The memory response remains specific for the original antigens that were first encountered.

What is immunological memory?

The ability of the immune system to produce a faster and more efficient immune response upon subsequent exposure to a pathogen

What is a secondary immune response and how does it differ from a primary immune response?

The immune response generated upon secondary and subsequent encounters with a pathogen

What is herd immunity and why is it important?

The majority of vaccinated individuals protect the minority of unvaccinated individuals by reducing the chances that an unvaccinated individual will come into contact with an infected person. As herd immunity decreases, there is more opportunity for a chain of transmission to be maintained because there is increased likelihood that an infected individual will come into contact with an unvaccinated individual.

What is vaccination and why is it performed?

Vaccination is the deliberate immunization of an individual with pathogen antigens that can provoke the immune response, but have minimal potential to cause harmful infection. It is performed so that an individual will have immunological memory if they ever encounter the live pathogen. Their immune system will generate a fast and effective secondary immune response.

How is the adaptive immune system able to respond more rapidly and efficiently during a secondary immune response compared to a primary immune response? (There are several reasons: Think about a) the number of antigen-specific memory cells compared to the number of antigen-specific naive cells b) the antigen specific antibody already in circulation c) the affinity of the B cell receptor/antibody during the secondary vs. primary response d) the primary antibody class secreted during the secondary vs. primary response and e) effector T cells already in circulation in the tissues.

a) During the primary response, activated T cells and B cells underwent clonal expansion, and some cells differentiated to memory cells. Therefore, for every one initial antigen specific naive B cell/T cell, there are many-fold more antigen specific memory B cells/T cells. Upon subsequent exposure to the pathogen, there will be more antigen specific lymphocytes in circulation as compared to the primary response. b) Long-lived plasma cells continue to secrete a low level of antigen-specific antibody after the primary infection. Upon subsequent invasion by the same pathogen, protective antibodies are already in circulation. c) B memory cells have undergone somatic hypermutation and affinity maturation, so they have high affinity receptors and will differentiate to plasma cells that secrete higher affinity antibody. Upon subsequent encounter with a pathogen, it will take less antigen to activate memory B cells, so they will be activated sooner and will secrete higher affinity antibody. Affinity maturation continues throughout the secondary and subsequent immune responses. d) B memory cells have already undergone class switching, so upon activation they will immediately secrete high affinity class switched antibody. e) Secondary responses don't have to wait for T cells to undergo activation proliferation, and differentiation. Some effector T cells are already circulating in tissues and can respond rapidly to pathogen.