7: Immunological memory 🏁

Question 1

Immunogical memory consists of 2 parts. Name both parts and their effector cells / molecules

Answer 1

Reactive memory
- expanded poulation of antigen specific B memory cells expressing antibodies of increased affinity and switched isotypes
- expanded population of antigen specififc CD4+ and CD8+ memory cells remebering their original cytokine expression profile

Antibody memory
specific antibody persisiting for years after antigenic stimulation

Question 2

Characteristics of reactive immunological memory

Answer 2

selectiv
- against pathogens recognized by B and T cells at the same time

specific
- for one pathohen/antigen

strong
- increased number / reactivity of memory cells
- stronger IgG signal compared to IgM/IgD signal of naive B cells

fast
- memory cells exhibit lower activation thresholds than naive cells

optimized
- affinity maturated antibodies, optimized antibody class, selective cytokine production

Question 3

Characteristics of antibody memory

Answer 3

specific
for one pathogen/antigen

immidiately protective
already present in serum at time of reinfection

very long-lasting
persists for years/decades

Question 4

Immunological memory protects …. (4)

Answer 4

• newborns (memory antibodies transferred from mother)
• against reinfection
• after immunization/vaccination
• weak individuals of community via herd immunity

Question 5

Generation of immunological memory

Answer 5

expanded population of B and T memory cells
antigenic stimulation drives clonal expansion

memory cellls react faster and stronger than naive cells
- IgM/IgD of naive cell results in weaker signal compared to IgG of memory cell (lower activation threshold)
- antibodies of memory B cell in general are more sensitive to lower concentration

memory T cells respond with selective and optimized cytokine production
- remember their cytokine profile (imprinted by histone methylation)

B memory cells exhibit an altered homing potential
can migrate to different tissues and organs compared to naive B cells
- naive B cells found in follicle
- memory B cells in marginal zone for antigen encouter with higher rate and earlier

T memory cells exhibit an altered homing potential
- naive T cells need to access lymphoid tissue to become stimulated
- memory T cells can migrate to site of inflammation or to folicles to help B cells
- memory T cells are believed to have potential to relocate to site of original activation

Long/lived plasma cells provide humoral antibody immune response
- reactived memory cells form plasma blast that can migrate to deposit tissue to differentiate into long-lived plasma cells with continous antibody secretion without need for reactivation

Question 6

Different CD4 subsets based on cytokines and function

Answer 6

TH1
- intracellular pathogen
- autoimmunity
- B cell help
- e.g. IFN-G,IL-2

TH2
- extracellular parasites
- allergy / asthma
- B cell help
- e.g. IL-4,IL-13

T(reg)
- immune tolerance, regulation of immune response
- e.g. TGF-ß

TH17
- extracellular bacteria, fungi
- autoimmunity
- e.g. IL-17

TFH
- Germinal center
- e.g. IL-21

Question 7

Formation of B memory cells
where, how, which cell types are involved

Answer 7

Mechanism

Dark zone (proliferating)
- only Re-circulating B-2 cells pass through lymphoid organs
- Re-encountering of antigen leads to crosslinking of B cell receptors
- result in trapping
- germinal centers formation: specialized structures that contain highly proliferating B cells, called centroblasts
- activates hypermutation and affinity maturation

Light zone (non proliferating)
- upregulation of surface Ig, stop dividing and receiving costimulatory singnals from T cells and follicular DCs
- Apoptosis of unselected cells / no costimulatory signal
- Selected cells leave lymph node as memory cells or plasma cells

Question 8

How do dendritic cells capture and release antibodies?

Answer 8

Antigen enters germinal centre in form of immune complex (C3b and anibodies)

Immune complex binds to Fc and complement receptors on dendrites

Dendrites developes bead with thin layer of immune complexes

Release of beads as Iccosomes

Iccosomes bind to and are taken up by B cell surface immunoglobulin

Question 9

How does hypermutation work and what is the consequence?

Answer 9

T helper signal promotes somatic hypermutation in the CDR encofing parts responsible for antibody specifcity

multiple B cell clones with different mutations arise that produce antibodies with higher, lower and no affinity

Affinity maturation: only high affinity B cells survive because low affinity Ig presents Ag inefficiency to T cells, but T helper signal (CD40) is important for B cells to survive

Question 10

Can the autoreactive memory be harmfull?
If yes, give an example, explain why and is there a treatment that overcomes the harm?

Answer 10

Yes, it can contribute to pathogenesis and therapy resistance of autoimmune diseases

e.g. Systemic lupus erythematosus where autoantibodies are only incompletely supressed by immunosupressive drugs because long-lived plasma cells are roboust against the treatment

Long-lived plasma cells hide in microenviromental niches that provide anti-apoptotic signals mediating the resistance against the drug

Proteasome inhibitor Bortezomib depletes long-lived plasma cells and prevents severe symptoms