Immunological memory and the secondary immune response Flashcards
Deficiencies in innate mechanisms are _____
Rare
Adaptive
- specificity
- memory
- affinity maturation (B cells)
- make possible vaccination
Acute infection
Establishment of infection –> induction of adaptive response –> adaptive immune response –> immunological memory
Extracellular
- interstitial spaces, blood, lymph = antibodies, complement, phagocytosis, neutralization
- epithelial surfaces = antibodies (IgA), antimicrobial peptides
Intracellular
- cytoplasmic = cytotoxic T cells, NK cells, helper T cells
- vesicular = T cell and NK cell dependent macrophage activation
Different types of immune effector mechanisms are effective against various pathogens
- viruses: humoral immunity (Ig) and cell-mediated immunity (CD4, CD8
- bacteria: humoral immunity (some cell-mediated)
- fungi: humoral and CD4
- protozoa: humoral and CD4
- worms: CD4
Successful primary immune response
- clears the infection
- temporarily strengthens defenses to prevent re-infection
- establishes a long term immunological memory to ensure that subsequent infections with the same pathogen will provoke a faster, stronger, secondary immune response (memory)
After successful termination of infection by the primary response, elevated levels of _____ will be present in blood/lymph , or at mucosal surfaces
High-affinity pathogen-specific antibody
______ produced during a primary immune response
Effector and memory B and T cells
- most activated T cells become effector cells
- some activated and/or effector cells become long-lived memory cells
Cell-cell interactions in a secondary immune response
- effector memory T cells can be activated directly at the site of infection by DC and macrophages
- activation requirements are less demanding since they do not require co-stimulation
Unimmunized donor primary response
- frequency of specific B cells: 1:10^4-1:10^5
- isotype of antibody produced: IgM>IgG
- affinity of antibody: low
- somatic hypermutation: low
Immunized donor secondary response
- frequency of specific B cells: 1:10^3
- isotype of antibody produced: IgG, IgA
- affinity of antibody: high
- somatic hypermutation: high
The _____ and ____ of antibody increases after successive immunizations with the same antigen
Amount; affinity
Smallpox vaccine
Persistance of immunological memory in the absence of antigen
How does IgG antibody suppress the activation of naive B cells?
Cross-linking BCR and FcgR on B cells
Primary response
Naive B cell binds pathogen –> naive B cell is activated and becomes antibody producing plasma cell –> production of low-affinity IgM antibodies
Secondary response with naive B cell
Bind pathogen coated with specific antibody –> negative signal is given to naive B cell to prevent activation –> no production of low affinity IgM antibodies
Secondary response with memory B cell
Binds pathogen coated with antibody –> memory B cell is activated and becomes an antibody producing plasma cell –> production of high affinity IgG, IgA, and IgE antibodies
How does influenza escape from immunological memory?
Highly mutable, undergoes original antigenic sin
Original antigenic sin
The first influenza strain to infect an animal constrains the immune response to other strains
- virus will drop old epitopes and add new ones, which induces a new primary response
How does influenza enter the cell?
Uses hemagglutinin protein to bind to sialic acid attached to human cell-surface proteins
- vaccines prevent this by presence of neutralizing antibodies against viral hemagglutinin
Cytomegalovirus infection
Latent virus, goes thru periods of activation that are quelled by immune responses
- increase in viral load triggers rapid increase in numbers of virus specific effector T cells
- numbers fall back once virus is under control, leaving a sustained lower-level of long-lived, virus specific memory T cells
Why is it difficult to detect T cell receptors?
They are membrane bound and never secreted
T cell differentiation
Naive T cell sees antigen
- memory cells may derive directly from activated naive T cells –> central memory cells express CCR7 and remain in lymphoid tissue –> effector memory cells lack CCR7 and migrate to tissues
- effector T cells differentiate, secrete cytokines, and express receptors –> some effector cells may become quiescent memory cells –> most effector cells die
Ubiquitous responses of innate immunity (0-4 hrs)
Infection –> recognition by preformed, nonspecific effectors –> removal of infectious agent (no clinical signs)
Induced responses of innate immunity (4-96 hrs)
Infection –> recruitment of effector cells –> recognition, activation of effector cells –> removal of infectious agent
Adaptive response (>96 hrs)
Infection –> transport of antigen to lymphoid organs –> recognition by naive B and T cells –> clonal expansion and differentiation to effector cells –> removal of infectious agent
Protective immunity
Re-infection –> recognition by preformed antibody and effector T cells –> removal of infectious agent
Immunological memory
Re-infection –> recognition by memory B cells and T cells –> rapid expansion and differentiation to effector cells –> removal of infectious agent
____ and ___ accumulate in the course of the primary immune response
Effector T cells and antibodies
Antibodies in the secondary immune response
Are of higher affinity than in the primary immune response and are of isotypes other than IgM
Only ____ are activated
Memory lymphocytes
- activation of naive cells is suppressed
Secondary immune response, immune system devotes resources to producing _____
High affinity antibodies and antigen-specific T cells that rapidly clear the invading pathogen before
Maintenance of memory cells
Does not require persistance of the original antigen
- survival signals are provided by cytokines IL-7 and IL-15
