Immunology - Chapter 11
What can be given to a rhesus negative mother during pregnancy to prevent the generation of a primary immune response against rhesus positive fetal red blood cells (which causes hemolytic anemia of the newborn during second and subsequent pregnancies)? How does the drug prevent the primary immune response?
A controlled concentration of IgG antibody specific for the rhesus antigen on red blood cells can be given to a rhesus negative mother during the final trimester (and again after birth) to prevent the mother generating a primary response against rhesus positive fetal red blood cells. When fetal red blood cells enter the mother's circulation, they are bound by the IgG. Any maternal naïve B-cells that bind to the fetal red blood cells will also have the inhibitory IgG receptor engaged by the IgG coating the fetal blood cells, which inhibits activation of the naïve B-cell.
What is a memory response, also called a secondary immune response? Compare a memory/secondary immune response to a primary immune response regarding the speed of the response and the strength/effectiveness of the response.
A memory/secondary immune response is the adaptive immune response produced upon second and subsequent encounters with an antigen. The memory/secondary immune response is activated faster and is more effective than the primary immune response.
How is the adaptive immune system able to respond more rapidly and effectively during a secondary/memory immune response compared to a primary immune response? d. the speed of activation of memory cells versus naïve cells
As mentioned in (c), B-cell receptors have a higher affinity for antigen, so they will be activated sooner in the course of an infection (i.e., at lower antigen concentration). Central memory T-cells are also more readily activated compared to naïve T-cells (the receptor affinity hasn't changed, but they don't require a co-stimulatory signal), so they will be activated sooner in the course of an infection.
Describe the meaning of original antigenic sin. What effect does original antigenic sin have on the strength of a memory response for a pathogen that changes it surface antigens over time, such as the influenza virus.
During a memory response to a pathogen that has developed new antigens since the primary immune response, the memory response is only specific for the antigens that were present during the primary immune response, i.e., the original antigens encountered. New antigens (not present during the primary immune response) are not recognized by memory B cells. Furthermore, naïve B cells that could recognize the new antigens are inhibited from being activated by the IgG antibodies present from the primary response (which will bind the pathogen). Therefore, the memory response gets weaker over time as it remains specific only for the original antigens that were encountered during the primary response. Once none of the original antigens are present anymore, then a new primary immune response can be generated to new antigens.
How is the adaptive immune system able to respond more rapidly and effectively during a secondary/memory immune response compared to a primary immune response? a. the number of antigen-specific memory cells during a secondary immune response versus the number of antigen-specific naïve cells during a primary immune response
During a primary response, activated T-cells and B-cells undergo proliferation, and some cells differentiate to memory cells. Therefore, for each initial antigen specific naïve B cell/naïve T-cell, there are many-fold more antigen specific memory B-cells/memory T-cells. Therefore, upon subsequent exposure to the same antigen, there will be more antigen specific lymphocytes able to respond.
How can this inhibition of naïve B cells be beneficial to the immune response during a secondary immune response?
It ensures the preferential activation of memory B cells that will differentiate to plasma cells that secrete high affinity, class switched antibody. It inhibits activation of new naïve B cells that would initially differentiate to plasma cells that secrete low affinity IgM, which would not be as effective and would dilute the more effective antibody.
How is the adaptive immune system able to respond more rapidly and effectively during a secondary/memory immune response compared to a primary immune response? b. antigen-specific antibody and effector memory T cells already in circulation
Long-lived plasma cells continue to secrete a low level of antigen-specific antibody after the primary infection. Upon subsequent infection by the same pathogen, protective antibodies are already in circulation to act immediately. Effector memory T-cells are already differentiated and circulate in tissues ready to respond immediately when they encounter their antigen again
What are memory B cells and how do they differ from naïve B cells with respect to lifespan and the B-cell receptor (i.e., does the receptor have a high antigen affinity, and what immunoglobulin class is the receptor)?
Memory B-cells are long lived B-cells that differentiate from activated B-cells during a primary immune response. Naïve B-cells express relatively low-affinity IgM and IgD receptors on the surface (i.e., not class-switched). Memory B-cells are produced after activated B-cells have undergone somatic hupermutatuion and class switching in the germinal center, so memory B-cells express high affinity, class-switched receptors.
How is the adaptive immune system able to respond more rapidly and effectively during a secondary/memory immune response compared to a primary immune response? c. the affinity and class of immunoglobulin produced during the secondary response versus the primary response
Memory B-cells have already undergone affinity maturation and class switching, so they have high affinity, class switched receptors. Therefore, upon subsequent encounter with a pathogen, it takes less antigen to activate a memory B-cell receptor versus a naïve B-cell receptor, so memory B-cells are activated earlier in the course of infection. Upon activation, some memory B-cells immediately differentiate into plasma cells that secrete high affinity, class switched antibody (which is more effective than the low affinity IgM, which is initially secreted during a primary response). Other memory B-cells form a germinal center and undergo more somatic hypermutation, so affinity maturation continues throughout the secondary immune response
How is the adaptive immune system able to respond more rapidly and effectively during a secondary/memory immune response compared to a primary immune response? e. the preferential activation of memory B-cells over new naïve B-cells.
Memory B-cells that secrete more effective, high affinity, class switched antibody are preferentially activated over new naïve B-cells that would secrete lower affinity, IgM antibodies upon initial activation, which are less effective (see Q5).
What are the two broad classes of memory T cells, and how do they differ from naïve Tcells?
Memory T-cells differentiate from activated T-cells during a primary immune response. There are two broad classes of memory T-cells: a. Effector memory T-cells are long-lived effector T-cells (already differentiated to a particular T-cell subset) that circulate in peripheral tissues and can respond immediately when they encounter their antigen again in tissues b. Central memory T-cells are more like naïve T-cells in that they circulate between blood and secondary lymphoid tissues and retain the potential for proliferation and differentiation when activated to produce effector T-cells. Central memory T-cells are activated more readily than naïve T cells (and will therefore differentiate into effector T-cells earlier in the course of an infection).
How are naïve B cells inhibited by IgG antibodies that were produced during a primary immune response?
Naïve B cells have an inhibitory Fcγ receptor (a receptor that binds IgG), which prevents activation of naïve B-cells when IgG antibody binds to it. During a primary response, there is no antigen-specific IgG antibody in circulation, so the inhibitory Fcγ receptor is not engaged, and naïve B-cells are activated. During a memory/secondary response, antigen is bound by the long-lived IgG that remains in circulation after the primary response. Therefore, during a memory/secondary response, a naïve B-cell that binds antigen with its B- cell receptor will simultaneously bind the IgG coating the antigen with its Fcγ receptor, which will inhibit activation of the naïve B cell.
