Chapter 11 - Immunological Memory and Vaccination
Which of the following describe requirements for immunological memory to be sustained?
- Appropriate cytokines and microenvironment are needed.
Which of the following cell-surface proteins are routinely used to distinguish memory T cells from naive and effector T cells?
- CD45RA - CD45RO - CCR7 - L-selectin (CD62L)
Fatima Ahmed, a 25-year-old recent immigrant from Sudan, is brought to an obstetrician by her husband Samir for a first-time visit at about 38 weeks of pregnancy. This is Fatima's first pregnancy, and she and the baby are in excellent health. She has had no previous prenatal care, fearing that if her condition had been revealed she would not have been permitted entry into the United States. She is then seen weekly by her physician and delivers a healthy baby girl without complication 18 days after the first visit. The justification for the obstetrician administering RhoGAM postnatally is that ____.
- Fatima is RhD- and the baby is RhD+ - This case involves hemolytic disease of the newborn, which is only a problem in families where the mother is negative for the Rhesus D (RhD) antigen and the father is positive. If Fatima were RhD+, there would be no risk of hemolytic disease of the newborn and no need to administer RhoGAM. If Fatima's baby were RhD-, there would also be no concern, because even if fetal blood did enter the maternal circulation. there would be no alloimmunization against the Rhesus antigen. If Samir were RhD- and the baby RhD+, then, assuming marital fidelity, Fatima must be RhD+ and thus tolerant to Rhesus antigen. If Fatima is RhD- and the baby RhD+, however, alloimmunization could occur, putting a second pregnancy with a RhD+ baby at greater risk of hemolytic disease. Maternal anti-Rh IgG alloantibodies would cross the placenta during pregnancy, enter the fetal circulation and cause hemolysis of fetal RhD+ erythrocytes, with resulting severe anemia in the newborn baby.
Why do memory cells respond more strongly during a secondary immune response than naive lymphocytes do in a primary immune response?
- Memory cells are more numerous. - Memory cells are activated more quickly. - Memory B cells have high-affinity B-cell antigen receptors.
Which of the following statements correctly describe the function of memory T cells?
- Some memory T cells are activated by dendritic cells in secondary lymphoid tissues. - Some memory T cells circulate to peripheral tissues instead of secondary lymphoid tissues.
In which way does the B-cell population that participates in a secondary adaptive immune response differ from the B-cell population that participates in a primary adaptive immune response?
- The antibodies produced in a secondary response have higher affinity for antigen than the antibodies produced in a primary response. - Antigen-specific memory B cells in a secondary response outnumber naive B cells in a primary response by 10- to 100-fold.
Madison Tavistock, a healthy 2-year-old living in Cincinnati, had attended the Wee Folks Daycare Facility for a year. Her parents joined an anti-vaccination group when she was 9 months old, 3 months before the recommended immunization schedule for the MMR vaccine, but after Madison had already been vaccinated with DTaP. They strongly believe that the unsubstantiated risk of autism reported for MMR vaccination outweighs the benefits, and consequently have opted not to have their daughter immunized. The best explanation for why Madison has not contracted measles even though she has regular contact with other children in a large city is that ____.
- The other children in the daycare center have been vaccinated and therefore she benefits from herd immunity
Which of the following biological properties of the smallpox virus influenced its successful eradication?
- The smallpox virus evolves slowly. - Smallpox infects only humans.
One SARS-CoV-2 vaccine that entered a human phase 1 clinical trial 66 days after the viral sequence was released is classified as an RNA vaccine. The RNA in the vaccine codes for the SARS-CoV-2 spike protein (S protein), which is expressed on the surface of the SARS-CoV-2 viral particle. These spike proteins look crownlike and give the virus family its name: coronaviruses. The S protein is essential for the viral replication cycle as it binds to host-cell receptors and then rearranges to cause fusion of the viral envelope with the host-cell membrane, thus allowing delivery of the viral genome into target cells. To make the vaccine, the viral mRNA is encapsulated in a lipid nanoparticle. The idea is that after injection, the lipid nanoparticle is taken up by host cells and ribosomes translate the mRNA into viral S protein, to which an immune response will be made. In an initial study, vaccinated mice produced a neutralizing antibody response, circulating antigen-specific IgG2a antibodies, increased interferon-γ as compared to IL-4, and an increase in the number of antigen-specific CD8 cytotoxic T cells.
- The study findings suggest that helper T cells specific for S protein were activated by the vaccine - The cytokine ratio of intergeron-gamma to IL-4 suggests that the vaccine induces a TH1 response - Rationale: To produce isotype-switched IgG2a antibodies, the B cells must have received 'help' from a CD4 T cell that was responding to a peptide generated by the translated S protein and presented by MHC class II. The increased production of interferon-γ suggests a TH1 response, which together with the activation of CD8 T cells indicates protective type 1 immunity. IL-4 tends to produce a TH2 response. The observation of an increase in the number of antigen-specific CD8 T cells indicates that the translated S protein was processed into viral peptides that bound to MHC class I, thus activating CD8 T cells. Neutralizing antibodies are effective not because they activate complement, but because they bind to the S proteins expressed on the virus particle surface, thus blocking the binding to host-cell receptors and preventing infection of the cell. This RNA vaccine activated B cells and T cells and therefore induced active immunity, and is not an instance of passive immunization.
Which of the following statements correctly describe long-lived pathogen-specific plasma cells?
- Their antibodies can bind to a pathogen and deliver it to an antigen-presenting cell, which then mediates a secondary immune response. - Their antibodies can bind to a pathogen and deliver it to effector cells of innate immunity. - They require IL-6 for long-term maintenance.
Which of the following are challenges faced by scientists during the development of an effective rotavirus vaccine?
- There are many natural variants of rotavirus. - The rotavirus genome consists of 11 genomic segments that can undergo reassortment.
Which of the following statements correctly describe TEM cells?
- They circulate in non-lymphoid tissues. - They undergo activation more quickly than TCM cells. - They represent the CD8 and CD4 TH1, TH2, and TH17 subsets of primary effector T cells.
Why doesn't the SARS-CoV2 vaccine require an adjuvant
- Toll-like receptors have evolved to recognize and respond to viral RNA as a danger signal - Viral RNA binding to toll-like receptors triggers an innate immune response, inducing cytokine release an expression of co-stimulatory molecules - Adjuvants mimic ligands for toll-like receptors
Which of the following statements correctly describe the current state of vaccine development for human diseases?
- Vaccines are effective only against certain pathogens. - Not every disease has a vaccine available.
Which of the following are examples of adjuvants used in human vaccines?
- alum - virosomes - MF59
Which of the following are bound together in a conjugate vaccine?
- capsular polysaccharide - immunogenic protein
Under what conditions can a vaccine cause disease?
- incomplete inactivation of a killed vaccine - back-mutation of a nucleotide in a live-attenuated vaccine after vaccination
Which of the following statements correctly describe unconjugated bacterial polysaccharide vaccines that are administered to infants?
- induce low-affinity IgM antibodies - activate T-independent B-cell responses
Which of the following are mechanisms that cause the death of plasma cells?
- induction of apoptosis through an inhibitory signal delivered through FcγRIIB1 - inhibition of contact with stromal cells in the bone marrow
A. What is an adjuvant and why are they incorporated into human vaccines? B. Provide several examples
A. Adjuvants are components included in human vaccines that are recognized by toll-like receptors and induce nonspecific antigen-independent inflammation by activating innate immune responses. This enhances the adaptive immune response to specific antigens in the vaccine and stimulates the production of memory cells. B. Examples of adjuvants used in human vaccines include alum, a form of aluminum phosphate or aluminum hydroxide; MF59 and AS03, squalene-oil-water emulsions; virosomes, liposomes containing hemagglutinin; AS04, aluminum hydroxide plus monophosphoryl lipid A, and bacterial components included as part of some vaccines, for example whole Bordetella pertussis as part of the DTP vaccine
True or False
A. Live attenuated vaccines for both bacterial and viral pathogens have been approved for human use - TRUE B. The neutralizing antibody response induced by the tetanus vaccine targets bacterial surface glycoproteins - FALSE C. Acellular vaccines have fewer side effects than cellular vaccines do - TRUE D. Most of our effective vaccines target chronic but not acute infections - FALSE E. The original meningitis vaccine did not provide long-term protective immunity because it contained bacterial proteins and lacked polysaccharides - FALSE F. Current vaccine development depends largely on the original approach of 'isolate, inactivate, and inject' - FLASE
Memory T cells ____.
ARE: - do not require co-stimulation through CD28 - do not undergo somatic hypermutation - do not undergo isotype switching ARE NOT: - must all be activated in secondary lymphoid organs - composed only f CD4 T cells - are usually short-lived
Which chemokine receptor must memory T cells express to gain entry into secondary lymphoid tissues?
CCR7
Characteristics of CD19
CD19- CD38hi CD138+ - active autophagy - plasma cells that make antibodies against slowly evolving viruses CD19+ CD38hi CD138+ - low/no autophagy - plasma cellsthat make antibodies againstrapidly evolving viruses
This series of fluorescent light micrographs shows T cells becoming activated by antigen and undergoing mitosis. Most cellular components are divided evenly among the mitotic cells; however, the T cell closest to the activating dendritic cell (not shown) preferentially inherits certain cell components that are associated with becoming an effector T cell. This unequal sharing of cellular components is termed 'asymmetric division.' Click on the two images that show evidence of asymmetric division.
CD8 and p-S6^s240/244
Which of the following statements about the inhibitory FcyRIIB1 receptor are correct?
CORERCT: - FcyRIIB1 may induce apoptosis in both naive B cells and plasma cells - FcyRIIB1 binds to IgG complexed with antigen - FcyRIIB1 expression limits subsequent immun responses to pathogens that mutate frequently FALSE: - FcyRIIB1 delivers an inhibitory signal that inactivates naive B cells by binding to membrane-bound IgM - FcyRIIB1 is expressed on memory B cells
Complete the passage using the terms provided #2
Central memory T cells (TCM cells) are activated in T-cell zones of secondary lymphoid tissues, whereas effector memory T cells (TEM cells) are activated in inflamed tissues. This differential pattern of tissue distribution of memory T cells is because of the expression of the chemokine receptor CCR7 that allows TCM cells to enter secondary lymphoid tissues.
Complete the passage using the terms provided #5
During the production of a viral vaccine, if the viral particle is completely inactivated so that it can no longer replicate, the vaccine is called a killed virus vaccine. A second type of vaccine, called a live-attenuated virus vaccine, consists of a mutant form of the virus that grows poorly in human cells and is no longer pathogenic to humans. In general, live-attenuated virus vaccines provide better protective immunity than killed virus vaccines.
All of the following contribute to the establishment and maintenance of long-lived memory B cells except ____.
EXCEPT: - long-term persistence of antigen after primary immune response DOES CONTRIBUTE: - replenishment of memory population by cell deivision - isotype switching - somatic hypermutation - interaction with stromal cells in the bone marrow
This figure depicts how memory responses to mutable viruses erode over the course of successive infections. Choose the answer choice that best describes the mechanism responsible for this phenomenon.
Engagement of FcγRIIB1 on naive B cells by high-affinity IgG prevents the activation of new antigen-specific B cells during sequential infections with variants of influenza.
Indicate whether the following statements are true or false
FALSE: - Secondary immune response take the sam amount of time as primary immune response to become effective - Only immune responses made in mucosal secondary lymphoid tissues can provide protective immunity - Plasma cells generated in a secondary immune response have longer life spans than those made during a primary immune response - During a primary immune response, only memory B cells are generated TRUE: - On secondary exposure to an infectious agent there is reduced mortality - If an individual acquires a second cold in the same season, it will mot probably be caused by a different type of virus
Which of the following is an example of a virus used for production of a subunit vaccine?
HBV
Complete the passage using the terms provided #4
Herd immunity results when unvaccinated individuals are protected from infection by a particular pathogen if most of the population has protective immunity and resists infection by the same pathogen. Such protective immunity can be a result of prior infection or artificial exposure to a pathogen through vaccination. Because of the low probability of finding a susceptible individual in the vaccinated population, the pathogen fails to cause an epidemic. Vaccination can lead to protective immunity in the population against acute infections, but vaccines have yet to be made against the pathogens that cause chronic infections.
In which way does a conjugate vaccine differ from a purified bacterial polysaccharide vaccine?
It induces activation and differentiation of TFH cells.
Which of the following is true regarding the Salk vaccine?
It is a killed vaccine
The smallpox vaccine eradicated smallpox from the planet. Similarly, poliovirus has been virtually eliminated in the United States, with the last documented case occurring in 1979. What shared feature of the polio and smallpox viruses gives researchers optimism that poliovirus can also be completely eradicated worldwide?
Like smallpox, poliovirus only infects humans.
Which of the following pairs is mismatched
MISMATCHED: - central memory T cells: restricted to non-lymphoid tissues MATCHED: - activation of memory cells: secondary immune response - protective immunity: antibodies persist after primary immune response - neutralizing antibody: coats virus and prevents infection - IL-6: sustains survival of long-term plasma cells
Which of the following lymphocytes do NOT give rise to antigen-specific memory cells?
NK cells
Matching
Naive T Cells - expresses CD45RA and has a high threshold for activation TFH Cell - participates in efficient cognate interactions with memory B cells TCM - expresses CCR7 and has a low threshold for activation TRM - remains in previously infected peripheral tissues and does not recirculate TEM - lacks L-selectin and CCR7 and recirculates to non-lymphoid tissues
Complete the passage using the terms provided #3
One objective of the primary adaptive immune response is to form memory cells, which ensure that future invasions by the same pathogen are dealt with using a heightened level of recognition and potency. These cells are long-lived, providing a robust and fine-tuned immune response to future invasions by the same pathogen. This is the basis for the secondary adaptive immune response and effective vaccination.
Complete the passage using the terms provided #1
Primary adaptive immune responses are mediated by short-lived pathogen-specific effector B and T cells, whereas secondary adaptive immune responses are mediated by long-lived pathogen-specific memory cells. Some effector cells can be long-lived, such as the plasma cell, which resides in the bone marrow and produces steady-state levels of pathogen-specific antibody.
Viruses and their description
Smallpox - vaccine composed of a replicating virus Hepatitis B Virus - recombinant subunit vaccine generated in yeast cells Rotavirus - fecal-oral route of transmission, contains 11 genomic segments of double-stranded RNA Poliovirus - fecal-oral route of transmission Influenza Virus - rapidly evolving RNA virus requiring new vaccine annually
Why is protection against smallpox virus developed after exposure to cowpox virus?
Some surface antigenic determinants of the cowpox virus are shared with the smallpox virus.
Which of the following correctly describes the nature of the metabolic reprogramming that occurs when a naive T cell becomes activated during the primary immune response to a pathogen?
T cells changes from catabolism to anabolism
Which of the following explains why it is difficult to distinguish naive, effector, and memory T cells?
T-cell receptors are not altered after T cells leave the thymus.
Synthetic conjugate vaccines link together epitopes that are recognized by what types of cells?
T-dependent B cells and T cells
All of the following statements regarding immunological memory are true except.
TRUE: - during a primary immune response, effector B cells outnumber memory cells - a small population of plasma cells secrete pathogen-specific antibody long after pathogen clearance from the body - memory T cells and memory B cells originate in secondary lymphoid tissue through clonal expansion - memory B cells generated in secondary immune responses are more effective than memory B cells and made in primary immune responses because of affinity maturation FALSE: - memory T cells are produced during secondary immune responses, but not during primary immune responses - protective immunity persists for the same period regardless of the type of pathogen
Statements about poliovirus
TRUE: - poliovirus infects both humans and cattle FALSE: - poliovirus vaccines are produced in both inactivated and live-attenuated forms - the oral poliovirus vaccine is composed of three live attenuated viral strains - if genetic revision of strain 3 occurs when the virus is replicating in vaccinated people, pathogenesis may occur - in the US< recommended vaccine for poliovirus is the inactivated poliovirus vaccine
Which of the following best explains why a healthy individual infected with a cold virus early in the winter does not initiate a new adaptive immune response when exposed to the same virus at the end of the winter season?
The antibodies made against the virus during the first round of invasion are available months later to neutralize the same virus when it invades the host again
Which of the following explains why influenza vaccines are given each year?
The immunological memory of influenza is limited because mutations affecting hemagglutinin and neuraminidase generate variant surface glycoproteins that can no longer bind to neutralizing antibodies made by memory B cells.
Explain how the right two panels of Figure 11.10 provide evidence of an asymmetric division in CD8+ T cells to form one effector and one memory T cell
The ribosomal protein S6 is a target of the mTORC1 kinase. Increased mTORC1 activity results in increased phosphorylation of the S6 protein. Both daughter cells have a similar concentration of S6 protein as shown by the similar fluorescence levels in the third panel of the figure, labeled "Total S6." However, the far-right panel indicates a much higher concentration of phosphorylated S6 protein (p-S6S240/244) in the daughter cell nearest the dendritic cell (daughter cell to right), which indicates higher mTORC1 activity. This daughter cell is destined to become an effector CD8+ T cell while the daughter cell containing less mTORC1 activity will become a memory cell. The asymmetric division of mTORC1 results in different cell fates for each of the daughter cells.
Which of the following is a characteristic of a live-attenuated virus vaccine?
a mutated form of the virus
What is included in a vaccine to improve the adaptive immune response to an antigen?
adjuvant
What is RhoGAM?
an anti-RhD IgG antibody that is infused into RhD- women during pregnancy
Which of the following combinations would be of concern to an obstetrician caring for a woman during her second pregnancy in the context of hemolytic disease of the newborn? The maternal blood type is given first, followed by the blood type of the mother's firstborn baby.
any combination of RhD− (mother) and RhD+ (baby)
What is the consequence if the Fc receptor (FcγRIIB1) and the B-cell receptor are cross-linked on the surface of an antigen-specific naive B cell?
apoptosis is induced
A new vaccine against Neisseria meningitidis was developed using reverse vaccinology. One of the three antigenic proteins in the vaccine is called fHbp and stimulates the production of antibodies that prevent infection. In unvaccinated individuals, how does fHbp mediate its virulent effect?
by inhibiting the alternative pathway of complement activation
How does RhoGAM mediate its intended clinical effect?
by preventing activation of RhD-specific naive B cells
What type of vaccine contains unlinked antigens derived from more than one pathogen to protect against more than one disease?
combination vaccine
What important feature of cowpox makes it an effective vaccine against smallpox?
cowpox has surface antigens that elicit a cross-reactive immune response
Match each phenotype listed with the correct type of T cell.
effector T cell - CD45RO+CD69+CD127− naive T cell - CD45RA+CD69−CD127+ memory T cell - CD45RO+CD69−CD127+
Description of inactivated virus vaccines
grown in cells from another animal
What is involved in the process that is used to produce attenuated vaccines?
growth in nonhuman cells
How does the RotaTeq vaccine differ from the Rotarix vaccine?
it is a mixture of nonpathogenic engineered rotavirus
What cell type remains after an adaptive immune response and is responsible for maintaining the steady-state level of pathogen-specific antibody in the circulation?
long-lived plasma cells
After antigen activation of a naive CD8 T cell, the cell undergoes an asymmetric division, resulting in one daughter cell that is an effector T cell and one that is a memory T cell. Sort the following statements according to the type of T cell that they describe.
memory T cell: - metabolic program similar to naive T cells - distal to dendritic cell effector T cell: - proximal to dendritic cell - high levels of mTORC1 activity
Which component of a conjugate vaccine is able to stimulate a CD4 TFH-cell response?
peptide
What is the term for the type of resistance provided against a pathogen months after infection by that same pathogen?
protective immunity
In order for a subunit vaccine to protect against infection by a pathogen, what must it contain?
proteins located on the surface of the pathogen
An innovative strategy based on nucleic acid sequence data is now used to develop new vaccines that use the information derived about the pathogen's physiology and its effect on the immune system. What is this approach called?
reverse vaccinology
What is the effect of sequential infections with variants of influenza virus on the nature of the antibody response that is stimulated?
the antibody response is inhibited against variant epitopes in a subsequent infection with a similar, but not identical, strain
Which of the following best describes CD45RA and CD45RO?
they are made by alternative splicing of CD45 mRNA
How do vaccines against bacterial diseases differ from vaccines for viral diseases?
they are sometimes directed against secreted toxins
Which of the following best explains why approximately half the population of the United States has immunity to smallpox even though the smallpox vaccination was discontinued in 1972?
those who were vaccinated before 1972 have immunological memory provided by a pool of memory B cells and memory T cells that are maintained for life
Match each description with the correct term.
toxoid - chemically treated but still antigenic capsule - inhibits fixation of complement by the alternative pathway typhoid fever vaccine - defective lipopolysaccharide synthesis gene Bacille Calmette-Guerin - bovine strain of Mycobacterium tuberculosis
What is the process by which anemia arises in hemolytic disease of the newborn?
uptake of opsonized erythrocytes by fetal macrophages in the spleen
When will an existing influenza-specific memory B-cell population cease dominating the immune response to subsequent influenza infections?
while an influenza strain causing new infections lacks all of the B cell epitopes of the original strain that stimulated production of the memory B cell population
