Chapter 10 Dynamics of Adaptive Immunity. This chapter tries to integrate much of what we have already covered so we can better understand how the immune system protects from infection. How infectious agents cause disease The course of an adaptive immune response Immunological memory.
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Dynamics of Adaptive Immunity
This chapter tries to integrate much of what we have already covered so we can better understand how the immune system protects from infection.
The course of a typical infection and adaptive immune responses can be divided into phases
If no innate immunity
Skin and tight junctions usually prevent penetration
*skin or mucosal surface of the respiratory, gastrointestinal, and urogenital tract which are always exposed to microorganisms.Interstitial tissues are normally free of any microorganisms (sterile)
Most pathogens have developed defenses to partially escape destruction by the innate protective mechanisms listed in boxes 1 & 2 below
Most pathogens cause disease in only one or a few related species because the pathogens can adhere to epithelial surfaces of only a few species or can escape innate immunity of only a few species.
How do infections progress in immune deficient individuals?
Adaptive immune response becomes important when innate immunity cannot deal with the infection within a couple of day
The results of an immune response vary depending on the individual and the pathogen and other factors (e.g, level of care).
NK1.1 T cell is a T cell sub-set which expresses a surface molecule usually associated with NK cells and do not express normal TCR repertoire
What governs whether a TH0 cell differentiates into TH1 or TH2?
Pathogens influence cytokines that affect TH0 differentiation into TH1 or TH2
T cell subsets produce cytokines that regulate development of other subsets
For example, TH1 inhibits TH2 and TH2 inhibits TH1.
Thus most responses are dominated by either TH1 or TH2 and are not balanced responses
Cytokines influence the CD4 T cell subset development and this can be crucial for development of an appropriate immune response
Mice normally respond inappropriately to Leishmania and thus are killed by the parasite
Effector T cells change their adhesion molecules so they can migrate to the site of an infection. That is, adhesion molecules regulate trafficking
CD4+ T cells can license dendritic cells to activate CD8+ T cells (CTLs) (figure 8.28) but some CD8+ cells can be activated by dendritic cell in the absence of CD4+ T cells
CD8 T cells can be induced to secrete INF-g in an antigen non-specific way
Peripheral lymphoid organs are the site of antigen-specific B cell activation [antigen binding (signal 1) and T cell help (signal 2)]
The book is inconsistent on the location of the primary focus
Protective immunity is the resistance to a pathogen that results from infection or vaccination. It is due to an adaptive immune response which induced immunological memory of the pathogen. Usually, there are few or no symptoms associated with a infection when it is dealt with by protective immunity
Protective immunity consists of preformed immune components and immunological memory
Immunological Memory(maintenance of memory is probably antigen-independent but there is evidence for antigen sequestration or re-exposure to maintain memory)
Primary Vs. Secondary B Cell Responses
Affinity maturation is a form of somatic selection (somatic evolution) where B cells, using their surface antibodies (BCRs), compete for limiting amounts of antigen. The B cell must compete with each other and with free antibody produced by plasma cells or plasmablasts.
Only those B cells with the highest binding affinity will be able to bind to antigen and thus remain activated.
Memory B cells have high affinity antibody and high levels of MHC so they are efficient at acquiring antigens (signal 1) and ready to get T help (signal 2)
Memory B cells have B7 on their surface so, maybe, they can activate or participate in activation of TH2 (memory) cells
Memory B cell have usually switch class from IgM so they usually have other Ig isotypes on their surface (mostly IgG)
Memory T cells remain long after the virus infection is under control* or the virus are gone
* The case shown here is the reactivation of a letent infection
Naïve T cell require contact with MHC+self peptides for survival (like positive selection in the thymus)(too weak to activate the T cell)
Antigen encounter (signal 1) plus co-stimulation (signal 2) activates the T cell (proliferation and differentiation)
Memory cells can come directly from the activated naïve cells or from the effector cells
Some differentiate into effector cells
Memory cells need cytokines but not contact with MHC+peptide for survival. This is different from the naïve T cells (top panel)
Most effectors die in a few days
Memory T cells need MHC+self peptide to proliferate (weak interactions). These remain memory T cells and do not become effectors until they bind the MHC+the correct foreign peptide (strong binding).
Naïve B cell
Memory B cells
Effector T cell
Naïve T cell
Memory T cell
CD4 T cells are required for CTL (CD8) memory but not for primary CTL response
When antigens have both epitopes that were “seen” before and new epitopes, the memory responses to the epitopes seen before will dominate and there may be no response to the new epitopes
Original antigenic sin