Lecture 24 - Immune Memory Flashcards
Example of ancient documentation of immunological immunity
Thucydides documented immunological memory in his History of the Peloponnesian war
Treating plague
What is immunity?
The ability to resist infection after previous exposure
Persists due to immune memory
Classic epidemiological study demonstrating immune memory
Faroer Islands
Two measles epidemics. The survivors of the first didn’t get infected during the second
When was smallpox officially eradicated?
1979
Other successful vaccine campaigns
1)
2)
3)
1) Corynebacterium diphtheriae
2) Polio virus
3) Measles virus
Difference in memory between humoral and cellular arms of the immune system
Humoral immunity remains constant (stable antibody titres over time)
Cellular immunity declines, with a half life of 10-15 years
Cells which a germinal centre B cell can differentiate into
1)
2)
1) Bone marrow plasma cell
2) Memory B cell in lymph nodes or speen
Which cell becomes the effector in short-lived extrafollcular antibody production?
Plasmablast
Tfh and germinal centre B cell interactions required for immunological memory development 1) 2) 3) 4)
1) CD40/CD40L
2) ICOS/ICOSL
3) TCR/MHC
4) IL21/IL21R (IL21 R on B cell)
Frequency of cognate B cells in a primary B cell response
1:10^4 - 1:10^5
Frequency of cognate B cells in a secondary B cell response
1:10^2 - 1:10^3
Main antibodies produced in a primary response
IgM, later IgG
Main antibody isotypes produced in a secondary response
IgG, IgA
Antibodies in breastmilk
IgA
How long after birth until serum IgG levels reach those of an adult?
~10 years
Immune response that most successful vaccines work through
Antibody response
Examples of infections that aren’t immunised against using a vaccine that elicits an antibody response
1)
2)
3)
1) HIV
2) Mycobacterium tuberculosis
3) Influenza virus
Location of naive T cells
Lymphoid
Location of memory T cells
Lymphoid and tissues
Role of maternal IgA
Protects the GIT of neonate
Which cells can an activated T cell differentiate into?
1)
2)
1) Terminal effector cell (90% of T cells become these)
2) Memory cell
Phenotype of terminal effector cells
1)
2)
1) IL-7R-
2) KLRG1+ (killer cell lectin-like receptor subfamily G1)
Experiment demonstrating the importance of IL-7R and IL-15R 1) 2) 3) 4)
1) Mice infected with an antigen
2) Take IL-7+, IL-7- memory cells from mouse, place into new mice
3) Infect new mice with the same antigen
4) Mice that received IL-7R+ and expressed IL-15 generated stable memory. Mice that received IL-7R+ and didn’t express IL-15 had memory die off quickly.
Cell surface receptor expressed by effector cells, not memory cells
IL-2R
Helpless memory
Poor memory response when DC licensing is blocked (CD40/40L blocked)
Subsets of memory T cells
1)
2)
1) Central memory T cells (in lymphoid organs)
2) Effector memory T cells (extra-lymphoid tissues)
Phenotype of skin-tropic circulating memory T cells
1)
2)
1) CLA+
2) CCR4+
Phenotype of GIT-tropic circulating memory T cells
1)
2)
1) Alpha4:beta7 integrin
2) CCR9+
CLA
Cutaneous leukocyte antigen.
An E-selectin ligand expressed by skin-tropic T cells in humans
Central memory T cell phenotype
1)
2)
1) CCR7+
2) CD62L+
Effector memory T cell phenotype
1)
2)
3)
1) CCR7+/-
2) CD62L-
3) CCR5+
Central memory T cell location
1)
2)
3)
1) Blood, lymphoid tissues
2) Lymph nodes
3) Spleen
4) Bone marrow
Effector memory T cell location 1) 2) 3) 4) 5)
1) Blood, non-lymphoid tissue
2) Skin
3) Lungs
4) GIT
5) Liver
Central memory T cell functional properties 1) 2) 3) 4)
1) Proliferative potential
2) IL-2 expression
3) Recirculation
4) Poor effector function
Effector memory T cell functional properties 1) 2) 3) 4)
1) Poor proliferative potential
2) No IL2 expression
3) Recirculation
4) Effector function
Acute infection memory T cell response
Mostly effector memory T cells
Late memory T cell makeup
Almost all central memory T cells
In the skin, where do memory CD8+ T cells cluster?
Epidermis
In the skin, where do memory CD4+ T cells cluster?
Dermis, hair follicles
Difference in migration patterns in tissue-resident memory T cells
1)
2)
1) CD8+ are fairly static
2) CD4+ move around a lot
CD8+ T cells found in the skin
Permanently tissue-resident CD8+ memory cells
Permanently tissue-resident CD8+ memory cell phenotype 1) 2) 3) 4)
1) High CD103
2) High CD69
3) CD62L-
4) CCR7-
CD103
Adhesion molecule
CD69
Involved in migration
Comparison between phenotypes of T effector memory and T tissue-resident memory
Similar, but T effector memory have CCR5, and T tissue-resident memory express CD103 and CD69
Tissue-resident memory T cell location 1) 2) 3) 4) 5) 6)
1) Mainly non-lymphoid tissues
2) Skin
3) GIT
4) Lungs
5) Brain
6) Particularly common in areas after local inflammation
Tissue-resident memory T cell functional properties 1) 2) 3) 4)
1) Probably don’t have proliferative potential
2) No IL-2
3) No recirculation
4) Effector function
Probable role of tissue-resident memory T cells
1)
2)
1) Sit in places (EG: epidermis) where circulating memory T cells don’t go
2) Control persistently or recurrently occurring infections
Example of infection controlled by tissue-resident CD8+ memory cells
Herpes simplex virus
Latent in dorsal root ganglia, constant viral reactivation, but controlled by tissue-resident T cells
