Lecture 12 (6B) - Immunological Memory

Question 1

Immunological memory

Answer 1

the ability of the immune system to respond quicker and better to pathogens that have been encountered previously

Question 2

Damage and infection stimulates

Answer 2

inflammation

Question 3

Inflammation

Answer 3

damaged tissues make proinflammatory cytokines
• macrophages in
• TNFα, IL-1, IL-6, IL-8
• the wound bleeds to wash out foreign bodies
• resident macrophages and the injured tissues initiate an inflammatory response

Question 4

Inflammation first drives

Answer 4

the innate immune response
• clot forms to seal the wound
• macrophages
• NK cells
• neutrophils
• fluid enters the site
• IgM

keep under control until adaptive

Question 5

Dendritic cells initiate

Answer 5

adaptive immunity
• DC gets pieces of pathogens and
• have TLR/pathogen recognition receptors on surface so can respond /recognize pathogens
• acts as danger signal
• upregulates B7 and CD40 on DC -> signal T cells to proliferate

Question 6

Immature DC –> Mature DC

Answer 6

• in the tissues is scanning, finds danger signals
• maturation on meeting a microbial challenge (danger signals)
• becomes a mature dendritic cell that goes to the lymphatics and lymph nodes
• upregulates B7 and CD40 - the signal for the T cells to proliferate
• when mature starts chopping up bits of proteins , upregulates MHC on surface, puts protein in MHC, turns on B7 and CD40, goes to lymph nodes (primed DC)

Question 7

Dendritic cells go to the lymph nodes

Answer 7

activates naive T cells - passes protein to other DC, they interact with naive T cells - find one that recognizes the MHC+peptide
• in through afferent lymphatics
• activate/prime T cells that proliferate
• TH1 helper T cells and cytotoxic T cells leave through efferent to the site of infection =

Question 8

Cell-mediated immunity

Answer 8

clones of T cells leave lymph node back to site of problem

• CD4 or CD8
• CD8 kill directly - with perforin and granzymes
• Th1 cells support cytotoxic T cells and macrophages = cell mediated response, good for getting rid of pathogens that infect cells
• Th2 cells

Question 9

Humoral immunity

Answer 9

Th2 cells help B cells make antibodies which are good at catching big pathogens

Question 10

B cells become plasma cells

Answer 10

which produce huge amounts of diverse antibodies
• IgM - makes this first, low affinitiy
• IgG - blood
• IgE - mast cells, allergies
• IgA - mucosal

make a lot of IgG to send to site of infection

Question 11

A fraction of the activated T and B cells become

Answer 11

memory cells and provide long-lasting immunity to that infection

Question 12

A fraction of the activated T and B cells become memory cells and

Answer 12

provide long-lasting immunity to that infection
• cytotoxic T cells
• helper T cells
• B cells
- in an active immune response, there’s lots
- lots are left after an immune response, but not enough storage, so just want to keep the useful ones

Question 13

After an active immune response

Answer 13

effector cells are stored for rapid deployment if infection re-occurs
• memory cytotoxic T cells
• memory helper T cells
• memory B cells

• still have more than the original, faster
• pathogens would also have to proliferate to keep up, but can’t –> can’t beat memory

Question 14

Immunological memory can be maintained WITHOUT

Answer 14

continued exposure to the pathogen

• it is maintained by long-lived antigen-specific lymphocyte that persist for many years

Question 15

Immunological memory is maintained by

Answer 15

long-lived antigen-specific lymphocytes that persist for many years
• can be maintained without continued exposure to the pathogen

Question 16

Demonstrating immunological memory

Answer 16

1. infect animal with virus
2. animal survives
3. 1 month later take the white blood cells
4. transfer lymphocytes - T and B cells - to a mouse that has never seen the virus
5. it is protected so when challenged with the virus, it doesn’t develop disease

Question 17

Spanish flu (1918-1919)

Answer 17

• more recorded deaths than any other infectious disease ever
• 25 million people (estimates up to 100 million)
• most people who died were
- very young (immune system not fully developed)
- very old (immune system deteriorates)
• people who survived the russian flu had active memory for the spanish flu

Question 18

B cell memory

Answer 18

• 100-fold more antigen-specific memory B cells than naive B cells
• antibody produced with higher affinity for antigen
(high affinity of antibody, high somatic hypermutation)
• higher MHC-II and increased B7.1 and B7.2

Question 19

Higher affinity antibodies in

Answer 19

secondary immune response
• primary infection - made different antibodies, some with low, medium, or high affinity
• secondary infection - antibodies made from primary still there, but low affinity antibodies are outcompeted (B cell that makes it won’t make much)
• tertiary infection - almost no antibodies with low affinity, make less of medium affinity, those with high affinity are boosted (B cell selected for)
–B cells will mutate to make higher affinity
– B cells improve affinity of antibody

Question 20

Somatic hypermutation in the germinal centers of lymph nodes

Answer 20

the process of directed mutation to the variable region of the antibody molecule, followed by selection for high affinity antibody/antigen interactions results in the progressive improvement of antibody affinities

Question 21

Memory T cells

Answer 21

• increased frequency of cells (100-1000 fold higher)
• increased survival characteristics eg increase in Bcl-2
• can be re-stimulated much more easily - the requirement for costimulation is much reduced
(originally hard to activate because only want proinflammatory when super necessary)
• rapidly proliferated and rapidly produce effector cytokines (eg IFN-γ)

Question 22

Memory t cells can be identified by their

Answer 22

surface molecules
• CD44
• CD45RO
• DD45RA
• CD26L - some
• CCR7 - some
• CD69 - none
• Bcl-2
• interferon-γ

Question 23

2 types of memory T cells

for both CD4 and CD8

Answer 23

• effector memory T cells

* central memory T cells

Question 24

Effector memory T cells

Answer 24

• rapidly mature to secrete IFN-γ, IL-4 and IL-5
• lack the LN-homing receptor CCR7
• have tissue-homing receptors (CCR5) and inflammatory cytokine receptors

TISSUE MEMORY CELLS
RAPID-RESPONSE UNIT

• need CCR7 to go to lymph node
• no CCR7 = goes to tissue so there when an infection comes to tissue

• CCR5 = gut homing receptor

• when activated don’t proliferate but send out cytokines
• rapid response unit

have inflammatory cytokine receptors, TCR, CCR5

Question 25

Central memory T cells

Answer 25

• express CCR7 and reside in secondary lymphoid tissue
- CCR7 = go to lymph nodes
• expand into effector cells rapidly and in large numbers

PROVIDE REINFORCEMENTS IN LARGE NUMBERS
• help effector memory T cells

have CCR7, TCR, L-selectin