16 - Immunological Memory

Question 1

Linked recognition

Answer 1

T cells and B cells must recognise antigens contained within the same molecular complex in order to interact

Question 2

Immunological memory

Answer 2

• Does not require repeated exposure to original antigen
• Memory cells may be sustained by cytokines produced in response to infection with other, unrelated pathogens

Question 3

Naive T cells in lymph nodes

Answer 3

Naive T cells activated in the T cell rich area of lymph node by DC become follicular T helper cells, express CXCR5 and move towards B cell zone where they attach to activated B cells via linked recognition

Question 4

Primary focus

Answer 4

• Formation takes about 5 days
• B cells activated in the primary foci move to adjacent follicles to become germinal centre (GC) B cells, or the medullary cords of LN to become plasma cells in situ
• Surviving GC B cells that have undergone class switching and affinity maturation will become either high affinity memory B cells or long lived plasma cells

Question 5

Plasma cells in situ

Answer 5

Secrete antibody for a few days, then undergo apoptosis

Question 6

high affinity memory B cells/long lived plasma cells

Answer 6

Become resident in bone marrow where they continue to secrete antibodies into the blood for months - years

Question 7

Memory B cells

Answer 7

• Divide very slowly
• Express surface Ig but do not secrete antibody
• May differentiate into plasma cells, allowing long term production of antibody

Question 8

Repeated immunisation

Answer 8

Leads to increasing affinity of antibody due to somatic hypermutation and selection by antigen in germinal centers

Question 9

Memory B cells during secondary exposure

Answer 9

During secondary exposure to antigen, antibodies persisting from primary immune response immediately bind to pathogen to initiate phagocytosis and complement pathway

Question 10

Primary response

Answer 10

• Following activation of naive cells
• Consists of antibodies derived from diverse population of precursor B cells specific for different epitopes
• Low affinity with few somatic mutations
• Isotype is IgM class switching to IgG

Question 11

Secondary response

Answer 11

• Mediated by memory cells
• Derived from high affinity B cells which have undergone significant clonal expansion
• High affinity antibodies with extensive somatic mutation
• Isotype is IgG and IgA
• More intense and effective response

Question 12

How do naive T cells home to lymph nodes

Answer 12

Through binding of L selectin (CD62L) to sulphated carbohydrates (e.g. CD34) displayed on surface of HEV

Question 13

How can naive T cells be identified

Answer 13

CD45RA

Question 14

How can effector T cells be identified

Answer 14

CD45RO

Question 15

Receptors expressed on the surface of effector T cells and their ligands

Answer 15

• Lose expression of L selectin
• Express LFA-1 which binds to ICAM-1
• Express VLA-4 which binds to VCAM-1

Question 16

Signals required for T cell survival

Answer 16

Restimulation with IL-7, IL-15 and with self antigens presented by MHC

Question 17

what do naive T cell differentiate into

Answer 17

Effector T cell or memory T cell

Question 18

Why are elderly more susceptible to infection

Answer 18

• Capacity to produce naive cells is lost with age, must rely on memory cells
• Problem when new strain arises

Question 19

Memory T cells

Answer 19

• TCR does not undergo class switching or somatic hypermutation
• Identified via expression of cell surface molecules

Question 20

Marker of T cell activation

Answer 20

CD69

Question 21

Marker of activated T cell

Answer 21

CD44

Question 22

Two types of memory cells that CD4 and CD8 cells differentiate into

Answer 22

• Effector memory cells (Tem)
• Central memory cells (Tcm)

Question 23

Effector memory cells (Tem)

Answer 23

• Rapidly differentiate into effector T cells after restimulation, and secrete large amounts of IFN-gamma, IL-4, IL-5
• Lack chemokine receptor CCR7
• Express high levels of integrins such as LFA-1
• Specialised for rapidly entering inflamed tissues

Question 24

CCR7

Answer 24

(required for entry of naive T cells into HEV, therefore Tem cells are excluded from lymph nodes

Question 25

Central memory T cells (Tcm)

Answer 25

• Express CCR7 and can enter lymphoid tissue, as do naive T cells
• On stimulation with antigen, rapidly lose expression of CCR7 and differentiate into Tem cells

Question 26

Further differentiation of Tem cells

Answer 26

Further differentiate into Th1 or Th2 cells, determining the cytokines these cells produce

Question 27

CD4 T cells

Answer 27

• Promote the maintenance of CD8 memory cells
• In absence of MHC class 2 proteins, CD4 T cells fail to develop in thymus

Question 28

Tissue resident memory (TRM) T cells

Answer 28

• Major immune compartment that surveys peripheral tissues for reinfection
• Activated CD8 and CD4 T cells enter dermis and other peripheral tissues (via CXCR3)
• induction of CD69 expression on T cells leads to their retention in dermis

Question 29

Original antigenic sin

Answer 29

When individuals who have been infected with one variant of influenza virus are infected with a second or third variant, they make antibodies only against epitopes that were present on the initial virus

Question 30

Tools for measuring antigen specific T cells

Answer 30

• Tetramers are reagents used in flow cytometry to identify and track antigen specific T cells
• The combination of MHC class 1 and antigen peptide must be known (synthesised)
• This MHC/peptide complex is labeled with a fluorophore, and added to the T cells being analysed
• Attachments of the tetramer to a T cell indicates the presence of an antigen specific T cell
• Detection of other markers (e.g. CD45RO) indicates effector or memory phenotypes