Lecture 24 - Immune Memory Flashcards
What did Thucydides say about Immune memory in ‘History of the Peloponnesian War’
“Only those who had recovered from the plague could nerse the sick because they could not catch the disease a second time … this altered state is specific”
Why is immune memory vital for immunity?
Ability to resist infection after previous exposure
Describe what was seen in 18th and 19th century Measles epidemics
1781: First measles epidemic
• Entire population suffered disease
• Some survived
1846: Second measles epidemic
• Those who had survived from the previous epidemic did not develop disease
• Those who had not previously exposed got the disease
Immune memory can last this long (65 years)
Describe what was done by Jenner
18th century; ‘first vaccination’
Smallpox virus infection → fatal disease
Cowpox virus infection → mild disease
People vaccinated against cowpox virus had cross-reactive protection for the smallpox virus
How did vaccination get its name?
Vaccinia: cowpox
Vacca: cow
Since the first vaccination was against cowpox virus
When did WHO officially declare that Smallpox was eradicated?
1979
Upon which immunological principle are vaccines based?
Describe this principle
Immune memory:
- (Macfarlane Burnet’s) Theory of Clonal selection and expansion
- Differentiation into effector cells
- Contraction into memory cells
- Long term immunity
- Next time the immunogen is seen, the specific memory cells are activated
Compare the following in Primary and Immunological Memory responses: • Magnitude • Kinetics • Affinity • Isotype
Magnitude:
• 1°: normal
• 2°: heightened
Kinetics:
• 1°: slow
• 2°: fast
Affinity:
• 1°: low
• 2°: high
Isotype:
• 1°: IgM > IgG
• 2°: IgG, IgA
What are the components of immunological memory?
How long do each of these components last?
- Ab
• Stable titre in blood
• up to 60 years
• Long lived plasma cells - Memory T-cells
• Slow decay
• Half life 10-15 years
• Some still present after 30 years
Even without re-exposure, these components remain in the body
Describe the required interactions for long-lived humoral immunity
Interaction between T(fh) and B cells in the MZ of the B cell follicle
T(fh) stimulate B cells to form a germinal centre, in which CSR, SHM and formation of memory B cells and long lived plasma cells occurs
Those B cells that don’t go into the germinal centres form plasmablasts that are short lived and don’t make great Ab
Where do memory B cells reside?
- BM
- LNs
- Spleen
Where do long lived plasma cells hang out?
BM
How are newborns protected from infection?
Maternal antibodies passively delivered to foetus:
• IgG cross the placenta
• IgA present in breast milk
These persist for up to 6 months
What is the mechanism of protection in most clinically effective vaccines?
What are some exceptions?
What is required for control of these pathogens?
Antibody mediated humoral immunity
Some pathogens escape humoral immunity • HIV • Influenza virus • M. tuberculosis T cell mediated cellular immunity required for control
Compare the following in Primary and Memory responses:
• T cell frequency
• T cell effector activity
• T cell location
- T cell frequency
• 1°: Low
• 2°: Elevated - T cell effector activity
• 1°: Slow
• 2°: Fast - T cell distribution
• 1°: Lymphoid
• 2°: Lymphoid and peripheral
Describe differentiation of T cells after activation
What are the fates of these cells?
Simultaneous generation of both:
• Effector T cells
- perform function
- undergo apoptosis at the end of the immune response
• Memory T cells
- survive and persist
Which receptors do memory T cells express in particular?
Which receptor do they down regulate?
Upregulation:
• IL-7R
• IL-15R
Down regulation
• IL-2R
Which cell is required for CD8+ T cell memory formation?
Describe this interaction
CD4+ T cells - DC licensing - “ménage-à-trois”
Interaction through DC licensing:
- DC stimulates CD4+ T cell (Antigen presentation, co-stimulation, cytokines etc.)
- CD40-CD40L interaction between CD4+ T cell and DC
- DC is now “Licensed”; expressing specific surface molecules
- DC able to stimulate CD8+ T cells to form memory cells
Direct stimulation:
• CD4+ T cell releases IL-2 onto IL-2R on T cell
• (they are in close contact, because they are both interacting with the same DC)
Compare location of:
• Effector Memory T cells
• Central Memory T cells
• Tissue-resident Memory T cells
- T(EM):
• Lymphoid organs (BM, LNs, spleen)
• Blood - T(CM)
• The periphery (gut, liver, lungs, skin)
• Blood - T(RM)
• Epidermis of skin
• Non-lymphoid tissues (gut, skin, brain, glands, lungs)
• High numbers only at sites of previous inflammation
• After inflammation, remain there
Compare surface molecules of memory T-cells, T(EM), with various tissue tropisms
- Skin tropic
• CLA
• CCR4 - Gut tropic
• α4β7
• CCR9
What is CLA?
On which memory T cells is it found?
Cutaneous Leukocyte antigen
It is an E selectin ligand
Found on memory T cells that are Skin-Tropic
What are the two major subsets of memory T cells?
Any recent additions?
- T(CM)
- T(EM)
• T(RM): tissue-resident memory T cells
Compare functional properties of T(CM), T(EM) and T(RM): • Proliferative potential • IL-2 • Recirculation • Effector function • Early / late memory
- Proliferative potential
• T(CM): great
• T(EM): low
• T(RM): low (?) - IL-2 production
• T(CM): great
• T(EM): low
• T(RM): low - Recirculation
• T(CM): great
• T(EM): great
• T(RM): NONE - Effector function
• T(CM): low
• T(EM): great
• T(RM): great - Early / late memory?
• T(CM): Late
• T(EM): Early
Compare movement of CD4+ and CD8+ memory T cells in skin
CD8+ T cells:
• Epidermis
• Very slow moving, barely moving at all
- CD4+ T cells
• Dermis
• Much movement