11 - Immunological Memory & Vaccination (Exam 3)

T/F: One goal of vaccination is to generate memory to a disease.

True

When a T cell undergoes asymmetric division, the __________ cells gets the mTORC1 proteins and becomes a __________ cell.

A) proximal, effector

B) proximal, memory

C) distal, effector

D) distal, memory

A) proximal, effector

Which of the following is not a reason why secondary immune responses and faster and more potent.

A) innate immune response remembers pathogen, fast respond

B) adaptive immune response can enhance innate responses

C) memory B cells have class switched high affinity receptors

D) memory T cells at be activated directly at the site of infxn 

A) innate immune response remembers pathogen, fast respond

Why do specifically IgG antibodies target naive B cells for apoptosis late during infection?

A) IgG is present in the blood, most likely to interact w/ Ag & naive B cells

B) only Fc gamma receptors have inhibitory actions other Fc receptor activate cells

C. IgG is the most abundant

D. IgG is good at neutralization

B) only Fc gamma receptors have inhibitory actions other Fc receptor activate cells

T/F: Variolation is more effective than the vaccine for smallpox

False

What type of protection does the smallpox vaccine provide?

steady state protection

• high number of Abs upon vaccination

• number drops as clear infxn (vaccine)

• steady state level

• helpers decrease over time but exist

• cytotoxic stay the same 

What is the steady state level?

Abs made by long-lived plasma cells in BM 

What is the primary response?

delay upon exposure while mounting response, 1st infxn

• effector T cells decrease following infxn because of Tregs shutting them off

• Abs maintained from long-lived plasma cells 

What occurs b/w the primary & secondary infxn?

low level of steady state Abs

• comes from long lived plasma cells in BM

What are aborted infxns?

high steady state of Abs prevents infxns

• few months after primary infxn

• Abs neutralized microbe

When is the peak of the primary response?

at 10 days

Why does the primary response eventually plummet?

Due to the decline of activated B cells, anergy, & the decrease in antibody production after the initial infection is resolved

T/F: The half life of an Ab is longer than a T cell.

True; antibodies generally have a longer half-life compared to T cells, which are more transient & go after clearing infxn

What is the secondary infxn?

T cells & Abs shoot up immediately from memory cells being activated at site of infxn

Why is the secondary infxn bigger & faster?

Abs are high affinity, already did somatic hypermutation & class switching in 1st infxn 

• don’t need license to kill, programmed to secrete correctly

How do the primary & secondary response compare to e/o?

The primary response is slower and less intense as it generates new B and T cells, while the secondary response is faster and more robust due to the presence of memory cells and pre-existing antibodies.

Which cells contribute to memory?

long lived plasma cells, memory B cells, memory T cells

What are long-lived plasma cells?

in BM secreting ABs for rest of life

• Abs in circulation for next time see infxn 

• in BM, create steady state Ab levels

What are memory B cells?

maintain BCR, immediately class switch, make Abs upon encountering Ag

• become IgG/A/E plasma cell

• primed for class switching

What are memory T cells?

already associated w/ effector functions when encounter Ag

• immediately activated, can do effector functions 

Which 2 subsets of plasma cells are made during the primary infxn?

short lived & long lived

What are short lived plasma cells?

in lymphoid tissue (medullary chords), make up most of primary response

What happens after switching Abs?

shut off further activation of naive cells

• no more activation of B cells needed 

What happens early in primary response?

early in primary response, IgM binds to B cell, induces activation of low affinity IgM plasma cell

What happens in late primary response?

late in primary response, class switch to IgG

Which receptor prevents B cell activation?

The inhibitory Fc receptor, FcγRIIB, prevents B cell activation by sending inhibitory signals when bound to IgG

• late stages of infxn

• IgG also binds microbe, inhibits activation

Why does IgG bind to the microbe & inhibit activation?

don’t want to activate naive B cells, unnecessary at that point of infxn

How does naive B cell shut off happen in the secondary response?

IgG binds FcγRIIBon B cells, prevents activation

• already have high affinity IgG for that microbe, no more Abs needed

• instead, memory cell binds Ag & becomes a plasma cell 

When does blood mixing occur?

• during birth

• complications w/ placenta

T/F: When a mother is pregnant, there is no sharing of blood b/w her & the fetus.

True, during pregnancy only giving nutrients, filtering blood

What can happen when a mother is O- /RhoD-?

• 1st baby = is RhoD+, blood mixes during birth

  • mom’s B cells make Abs to Rhod (IgG)

• 2nd baby = RhoD+, but mom passes IgGs, Rhod- specific IgG targets & kills fetal RBCs

What occurs in the first pregnancy with the RhoD- mother?

during birth, blood mixing occurs

1. primary response (maternal)

2. B cell activation against RhoD

3. anti-RhoD IgG Abs made 

4. healthy baby

What occurs in the second pregnancy with the RhoD- mother?

1. anti-RhoD memory cells get activated

2. IgG crosses placenta

3. destroys fetal RBCs

4. baby born w/ anemia

What can be done to prevent anemia in newborns?

give RhoD- women anti-RhoD Abs → RhoGAM

• given early during every pregnancy & at time of birth, don’t always know if father is actually the fetus’ father

• lower concentration of IgG

How does the treatment given to RhoD- moms work?

1. blood mixing during birth

2. B cells have IgG bound to FcyRIIB

3. IgG binds RBC

4. no response occurs, naive B cell apoptoses

5. health baby

What is original antigenic sin?

block B cell activation even though surface Ags change

• no response, IgG blocks activation

• degenerative immune response, gets worse over time 

What occurs in the primary infection during original antigenic sin?

viral strain w/ markers A, B, C, D (Ab epitope specificity)

• make Abs against all 4 surface markers 

• sick for about 2 weeks as making Abs 

What occurs in the 2nd infection during original antigenic sin?

strain w/ markers A, B, C, E

• won’t make response to E, IgG binds FcyRIIB1 & blocks

• responses from memory cells for A, B, C

• infxn cleared, respond to 3/4 markers

What occurs in the 3rd infection during original antigenic sin?

strain w/ markers A, B, E, F

• IgG for A & B blocks B cell activation for E & F

• sick but recover

What occurs in the 4th infection during original antigenic sin?

strain w/ markers A, E, F, G

• IgG for A blocks B cell activation for E, F, G

• longer infxn

What occurs in the 5th infection during original antigenic sin?

strain w/ markers E, F, G, H

• like never seen before

How can original antigenic sin be overcome?

getting vaccinated annually w/ diff versions so Abs made for diff markers

• important for RNA viruses mutating a lot 

Why are all T cells long lived?

production of T cells decreases significantly w age

• naive & memory T cells are long lived

What is starvation metabolism?

breakdown/catabolism cellular components to release/maximize energy

• mitochondrial oxidate phosphorylation

• fatty acid oxidation

• autophagy (self eat)

• mitophagy (breakdown mitochondria, = energy)

What gives rise to memory T cells?

asymmetric division

• make effector & memory T cell based on location in relation to DC

How does asymmetric division occur?

1. naive T cell interacting w/ DC presenting Ag

2. Dc gives signals to increase mTORC1

3. T cell divides

4. proximal T cell becomes effector T cell, keeps mTORC1, regular metabolism

5. distal T cell becomes memory T cell, no mTORC1, does starvation metabolism

6. both T cells leave DC to site of infxn

What do naive T cells express?

CD45RA

• longer, has harder time binding to CD3 = weaker signaling

What do effector & memory T cells express?

CD45RO

• shorter splice variant of CD45RA

• stronger binding to CD3 = stronger signaling

Why do naive T cells need costimulation?

need to get strong signals, CD45R doesn’t amplify signaling

Why don’t effector & memory T cells need costimulation?

have CD45RO strong signaling

What are the T cell memory subsets?

TCM, TEM, TRM

What is the TCM subset?

central memory T cells

• stay in secondary lymphoid tissue

• mostly TFH cells, low threshold of activation

• only helper T cells w/ effector function in secondary lymphoid tissue 

What is the TEM subset?

effector memory T cells

• circulation

• move into infected tissue upon secondary/next exposure

• CD4 (TH1, TH2, TH17) & CD8 T cells

What is the TRM subset?

resident memory T cells

• in tissues & mucosa

• move to site of primary infxn during repair of tissue

• stay until subsequent infxn

• ex → get flu = deposit TRM in lungs 

What is the order of activation for the T cell memory subsets?

1. TRM

2. TEM

3. TCM

What is unique about primary immune response to a pathogen?

• small number of pathogen specific cells

• delay before specific Abs made

• start w/ IgM of low/med affinity

• high activation threshold

• delay before effector T cells activated, enter infected tissues

• innate immunity works alone until adaptive response is activated & ongoing

What is unique about secondary immune response to a pathogen?

• large number of pathogen specific cells

• specific Abs present

• Abs are isotype switched & high affinity

• low activation threshold

• effector T cells present & activated in infected tissue

• close cooperation b/w innate & adaptive immunity from infxn start

T/F: Elements of adaptive immunity aid in enhancing innate immunity in secondary infxn. 

True, the elements of adaptive immunity, such as antibodies and memory T cells, work together with innate immune responses to provide a more effective defense against subsequent infections.