Immune memory and vaccines Flashcards
What is the hallmark of acquired immunity?
development of memory response
Describe the memory B cell response in comparison to the primary response
- long lived
- respond more quickly to subsequent infection
- high Ab titires
- makes Abs of high affinity and have class switched
Why do memory B cells respond more quickly to Ag?
- higher frequency of Ag-specific B cells
- express higher levels of MHC-II and T cell costimulatory molecules
- can get better help from T cells
- don’t require as much T cell help - memory T cells to same Ag
- larger numbers of T cells to help B cells
Describe some charactersistics of long-lived plasma cells: what type of cell they resemble, where they are found, source, lifespan, Ab properties
- resemble “memory” cells
- found = some in bone marrow, most in gut and lung mucosa
- source = primary focus and germinal centre
- lifespan = long lived (e.g. the persistence of serum Ab.s to smallpox vaccine 75 years later)
- Ab properties = do not need Ag stimulation to produce Ag-specific Abs
Describe the relationship bewteen self renewal + memory potential and differentiation status of memory T cells and Ag exposure
low Ag exposure: high ability to self-renew + memory potential, lowly differentiated
high Ag exposure: low ability to self-renew + memory potential. highly differentiated
Describe the differentiation order from low to high Ag exposure of memory T cells
naive T cell –> Tscm –> Tcm –> Tem –> Teff –> death, note: Tcm, Tem, Teff can differentiate into Trm (sits between Tem and Teff)
What are some characterisitics of Tscm cells?
- scm = stem cell memory
- found in secondary lymphoid tissue
- can develop into all other memory subsets
- self renewing
- long lasting source of T cells
What are some characterisitics of Tcm cells?
- central memory
- can go back into secondary lymphoid organs unlike other activated T cells
- travel between secondary lymphoid organs
- long lived and slowly proliferate
- rapid activation
- produce lots of IL-2
- can differentiate to various effector T cells
What are some characterisitics of Tem cells?
- em = effector mememory
- patrol tertiary sites
- proliferate very little if at all
- rapid effector response
- produce little IL-2
- commited to a specific effector lineage
What are some characterisitics of Teff cells?
- eff = effector
- e.g. CTL, Th
- do not go back into secondary lymphoid tissue
What are some characterisitics of Trm cells?
- rm = resident memory
- upregulate tissue markers –> forces rm to stay in that tissue
- permanent residents of previously infected tissues
- extremely rapid and localized effector response
What are some surface markers found on various memory T cells and what is their role? What memory T cells have which?
- CCR7 = chemokine R, homing to secondary lymphoid organs (naive, scm, cm)
- CD62L = L-selectin. adhesion protein, homing to secondary lymphoid organs (naive, scm, cm)
- CD44 = cell surface glycoprotein involved in cell adhesion, highly expressed when TCR is activated (cm, eff, em, rm)
- CD69 = C-type lectin, prevent immune cells from leaving tissues (rm)
- FAS = R for FASL (all activated T cells, not naive)
Describe T cell homeostasis between naive, effector and memory T cells
naive
- live months to years
- undergo minimal basal proliferaiton
- rely on IL-7 to maintain
effector:
- live days to weeks
- derived from both naive and memory T cells
- terminally differntiated and part of large clonal populations
memory:
- live months to years
- undergo extensive basal proliferation
- rely on IL-7 and 15
What is passive immunization, when is it needed, what are some side effects?
passive immunization = delivery of preformed Ab
conditions where this is needed:
- immune deficiency
- toxin or venom exposre with immediate threat to life
- exposure to pathogens that can cause death faster than an effective immune response can develop
side effect = can lead to type I or II hypersensitivities
What is active immunization?
immunization to induce immunity and memory
Why is the HPV vaccine important? What is the HPV vaccine?
- HPV implicated in 99% of cervical cancers
- high risk HPV (16 and 18) make up 70% of all cancers
- vaccine = Garadasil
What are the pros and cons of whole organism, live attenuated vaccines? Name some examples
pros:
- retain their ability to replicate, promoting strong humoral and cell-mediated responses
- often do not need boosters
cons:
- may revert to pathogenic form
- may have more side-effect complications
- may also require refrigeration for stability during transport
examples:
- polio, measles, mumps, rubella, TB
What are the pros and cons of whole organism. inactivated/killed vaccines?
pros:
- no reversion
- often more stable/easy to store and transport
cons:
- often require booster shots
- don’t replicate in host –> don’t induce cell mediated immunity, humoral only
- manufacturing risks to personnel
- adjuvants often required
What are adjuvants and how do they work?
- adjuvant = enhance the immune response to a vaccine especially if the Ag is a weak simulator
- promotes inflammation to recruit more immune cells to the area, enhancing effectiveness
- slows down Ag release to promote longer interactions, enhancing effectiveness
Name and describe three common adjuvants
- alum
- good at stimulating Th2, but not Th1 responses - MF39
- oil in water emulsion, slows Ag delivery - AS04
- alum + TLR4 agonist, encourages Th1 response
Describe the types, pros and cons, and name examples of purified macromolecules subunit vaccines
types:
- inactivated exotoxins/toxins
- inactivated capsular polysaccharides
- inactivated surface glycoproteins
pros/cons:
- similar to those of inactivated vaccines
examples: DTaP, HBV
Describe what purified macromolecule conjugate vaccines are/why they’re used, examples, and how we can induce CTL responses with these?
why they’re used:
- conjugate or multivalent vaccines can improve immogenicity and outcomes
- some Ag are not strong enough on their own to stimulate a good response, so they are coupled to something else that is particularly good at Ab induction
example: influenza B, pneumonia
what about CTL responses:
- simple linking of a weak Ag with a stronger one may not give the desired outcome –> Ag has to be delivered into cells for presentation on MHC-I molecules
- creation of lipid carriers known as ISCOMs for delivery into cells
Describe what recombinant vector vaccines are, the pros and cons, and examples
what they are:
- use a different attenuated pathogen and genetically engineer it to carry and express another pathogen’s genes
pros:
- all the benefits of attenuated vaccines
- fewer risks - not using the actual pathogen, but something else entirely
cons:
- some of the attenuated vaccine problems present (esp stability issues)
example: vaccina, ebola
Describe nucleic acid based vaccines: how they work, pros and cons, examples
how they work:
- DNA and mRNA encoding pathogen sequences are packaged and injected into muscle tissue
- host cells take up DNA or mRNA and express it internally
- makes protein to gen Ab response
- provides Ag for presentation via MHC-I, stimulating CTL production
pros:
- induces humoral and cell-mediated immunity
- prolongs expression, should enhance memory
- very stable and customizable
cons:
- TBD
examples: SARS-CoV 2
What are two reasons why we should be vaccinated?
- herd immunity
- fewer number of individuals who can spread an infection
- protects susceptible indiviudals –> young childre, immunocomprimised, those who have an ineffective response to vaccine - protection against the infection but also against complications for that infection
What is the Ro?
- reproduction rate
- measures how infectious a pathogen is
What is the herd immunity threshold (HIT)?
percentage of population that must be immune to stop the spread of the pathogen
