33 - B cells: B & T cell Memory, immunization Flashcards
B cell Memory
Quantitative & qualitative differences:
Primary response
Most IgM-producing cells (Some IgD) come from primary focus
Some B cells go to germinal center and undergo somatic hypermutation & class switching late in response
-Better affinity
B cell Memory
Quantitative & qualitative differences:
Secondary response
Some memory B cells make IgM
Most memory B cells express IgG (Some IgA & IgE) & will undergo further somatic hypermutation
-Re-enter GM & secrete larger # Ab
Repeated immunization leads to:4
Increasing affinity of Abs due to somatic hypermutation & affinity maturation –” can re-enter the GC
Memory B cells also express class-switched surface Ig isotype (IgG bearing memory B cells)
Memory B cells express higher levels of MHC class II, CD40 & receptors for survival & proliferation than naïve B cell
-Helps memory B cells to acquire & present Ag more efficiently to TFH than naïve B cells
-Increases Ab production
Memory B cells circulate through the blood & take up residence in spleen & lymph nodes
Memory T cells, how to disitnguish?
Surface marker used to distinguish naïve/effector & various memory T cell subset
after pathogen is cleared (T cell memory)
At least 90% of effector cells die by apoptosis after pathogen is cleared – leaving behind Ag-specific memory T cells
memoty T cells are phenotypially unique
Phenotypically unique: closer to effector T cells than naïve T cells
-Less requirement for activation + express unique set of receptors
–Different surface adhesion molecules, costimulatory receptors
—No need for strong co-stimulatory signal or cytokines
—-Memory T cells have large expression of CD28 (signal 2)
–Still require contact with p:MHC but more sensitive to stimulation & response more quickly
-Become effector upon reactivation
Memory T cells location & function , what are 3 types
TCM cells – central memory T cells TEM cells – effector memory T cells
TRM cells—permanent residents of previously infected tissue
TCM cells –
central memory T cells
Reside in/travel between secondary limonoid tissues
Rapidly reactivated by 2nd Ag exposure
Can differentiate into several subset types depending on cytokine environment
Always know they if they are becoming TCM cells
TEM cells –
effector memory T cells
Travel to/between tertiary tissues
Contribute better to 1st line defenses
-Can interact with local APCs
Shift right back into effector function on 2nd Ag exposure
TRM cells—
permanent residents of previously infected tissue
Respond upon reinfection
CD8+ TRM found in multiple tissues
Memory T cells * Fate determinants
cytokines (IL-7, IL-15), Notch 1, strength of Ag interaction
IL-7: pro-survival cytokine increased expression of Bcl-2 (anti-apoptotic factor)
-Can stay alive even if not expressed for years
Memory CD8+ T cells = more abundant than memory CD4+ T cells
Memory CD8+ T cells still require help of CD4+ T cells for longevity
Expression of IL-7R⍺ is
downregulated during effector T cell differentiation but retained/reacquired by cells destined to become memory T cells
Decrease in memory CD8 T cells from mice that don’t have
CD4+ T cells
-CD8 need licensing from CD4
Conclusion of experiment:
o Need CD4+ T cells & MHC II to maintain CD8+ T cells
o CD4+ T cells activation by MHC II impact quality & quantity of CD8+ T cells
Memory & SARS-CoV2
Memory response can
vary for different people
Immunize:
make someone/animal resistant to a particular infectious disease/pathogen
Protective immunity – can be achieved by
active/passive immunization
Passive immunity:
Temporary adaptive immunity conferred by transfer of immune products from an immune individual to a nonimmune one
-Example of immune product: Antibody (antiserum)
-Example: monoclonal therapy for SARS-CoV-2 or breastmilk from mom to newborn
Active immunity:
Adaptive immunity induced by natural exposure to a pathogen or by vaccination
Passive immunization
Several conditions still warrant this method
by delivery of pre-formed Ab
Several conditions still warrant this method
-Immune deficiency
-Toxin/venom exposure with immediate threat to life
-Exposure to pathogens that can cause death faster than an effective immune response can develop
Passive immunization doesn’t activate host natural immune response
-Doesn’t generate memory response
-Protection NOT permanent
Passive transfer of Ab to non-immunized animal prevents
activation of naïve B cells
Implication for early childhood vaccinations= Ab acquired through passive transfer via placenta & breastfeeding
Original antigenic sin:
Once we have an effective response, memory cells are enlisted rather than activating naïve cells that target new, unique epitopes
Can happen to both passive & active immunization
-bad in the situation of viruses, as it is constantly changing
Original antigenic sin: step by step example
- 1st infection – Ag epitope specificity determined
- Second infection – memory response
a. Purple/yellow kill before naïve B cell tarted to blue can get activated - 3rd infection – memory response
a. Purple clear infection before the naïve B cell targeted for the other colour - 4th infection – primary response – targeted as new pathogen
a. If memory cell weren’t so quick, there could been memory cell from light & dark blue
Active immunization = induce
immunity & memory
* Can be achieved by natural expose to infectious agent/acquired artificially (vaccines)
* Vaccines: specific immune response (With memory) induced on purpose by exposing a person to an altered & non-dangerous form/component of infectious agent
* Elicits B cell & T cell response
Adjuvants
included to enhance immune response to a vaccine (chemicals that can help)
-What if your Ag is a weak stimulator?
Promoting some inflammation can recruit more immune cells to the area – enhancing effectiveness
Slowing down Ag release can promote longer interactions, enhancing effectiveness
Attenuated vaccines
weakened form of virus:
Virus has multiple mutations that prevent it from causing a productive infection in immunocompetent humans
-Exception: immunocompromised individuals
Vaccines have built in adjuvants = PAMPs from virus trigger immune response
Immunization is a unique social contract
- Healthy individuals are asked to accept an intrusion on their body
- for a Personal & societal good with no guarantee of:
o Personal benefit
No vaccines are 100% effective
o Freedom from harm
No vaccines are 100% safe
Herd immunity:
When majority of population is immune to an infectious agent, thus significantly reducing pathogen reservoir due to low chance of a susceptible individual contacting an infected individual
