Immunological memory

Question 1

What is the difference between antigen specific memory cells before an infection compared to after an infection?

Answer 1

• 100x more specific memory cells compared to specific naïve cells before infection

Question 2

After 1st immune response 95% of lymphocytes will die but some will survive - what cells are these?

Answer 2

• plasma cells (detectable response)
• memory B lymphocytes *
• memory Th lymphocytes *
• memory Tc lymphocytes *
• = induced response

Question 3

Where are plasma cells found?

Answer 3

• spleen
• lymph nodes
• lamina propria
• bone marrow

Question 4

Depending on location what do plasma cells do?

Answer 4

• secrete Abs into bloodstream, lymph, mucosa (even not during infection)

Question 5

Why don’t you have to wait for B and T cell reactivation to get some protection?

Answer 5

• due to the response from plasma cells

Question 6

What don’t Plasma cells do?

Answer 6

• don’t class switch
• don’t undergo somatic hypermutation
• don’t function as an APC or move around
• don’t proliferate (they are fully differentiated)

Question 7

Memory B and T cells are induced what does this mean?

Answer 7

• respond when they see the antigen in a later infection

Question 8

What are common features of B and T lymphocytes?

Answer 8

• Cells are longer lasting
• less co-stimulation required than naïve
• stronger responses after activation (proliferation/cytokine production/Ab production)
• responses can occur faster

Question 9

What is immunity?

Answer 9

• protection from an infectious disease

Question 10

What are the two types of immunity?

Answer 10

• passive
• active

Question 11

What is passive immunity?

Answer 11

• protection transferred form another person or animal
• temporary protection that wanes with time, because the individual doesn’t have the ability to produce the immunity itself

Question 12

What is active immunity?

Answer 12

• protection produced by the animals own immune system
• longer-term protection

Question 13

What is transferred in passive immunity?

Answer 13

• transfer of antibodies

Question 14

When is passive immunity most important?

Answer 14

• in early childhood

Question 15

Why is passive immunity particularly important in farm animals?

Answer 15

• as there are 6 layers to their placenta so no antibodies are transferred pre-birth

Question 16

Where do farm animals get their passive immunity from?

Answer 16

• colostrum with IgG

Question 17

What does inadequate colostrum lead to?

Answer 17

• increased mortality and illness

Question 18

What serum immunoglobulins are important in chicken immunity?

Answer 18

• IgY
• IgM
• IgA

Question 19

How are IgY, IgM, IgA transported to the chick for passive immunity?
How long does this provide protection?

Answer 19

• transported from the hen sera > egg yolk (IgY)
• transported from the oviduct > albumin (IgA/M)
• protection for 10-20 days

Question 20

Why is passive immunity so important in neonates?

Answer 20

• no/very few adult-like T or B cells in peripheral lymphoid tissues at birth
  = incomplete immune system

Question 21

Passive immunity is critical in treatments of some diseases - what are some of these?

Answer 21

• Tetanus used in horses and humans
• Hepatitis A and B
• immunodeficient individuals

Question 22

Why does passive immunity eventually end?

Answer 22

• due to catabolism of antibodies

Question 23

What leads to natural active immunity?

Answer 23

• infection by a pathogen and subsequent resolution leads to the production of memory T and B cells plus plasma cells

Question 24

Want do we want to achieve with vaccination?

Answer 24

• still want strong immunological memory but no/very limited symptoms

Question 25

Why do we want to vaccinate a pregnant animal just prior to giving birth e.g., 3-12 weeks prior with cow?

Answer 25

- gives the goal of creating passive immunity for the offspring - calves take up antibody from colostrum and are protected

Question 26

Why don't we vaccinate newborns?

Answer 26

- MDA can negatively impact active immunity as if new born still has high enough levels it can impact the ability to vaccinate to create active immune response and thus memory cells and plasma cells

Question 27

What is the B cell activation response characteristic of?

Answer 27

- secondary (memory) response - faster response

Question 28

During B cell activation what happens to Abs and what type of isotype switch has occurred?

Answer 28

- more abs produced for longer - IgM/D > IgG, IgA, IgE

Question 29

What do the vast majority of vaccines depend on?

Answer 29

- antibody production

Question 30

What is serological memory reliant on?

Answer 30

- long-lived plasma cells and memory B cells

Question 31

Where do Plasma cells and B cells originate during an active immune response?

Answer 31

- germinal centres

Question 32

Where are germinal centres?

Answer 32

- within secondary lymphoid organs (lymph nodes, spleen, MALT)

Question 33

What are germinal centres the site of?

Answer 33

- B cell proliferation - Ab class switching - Affinity maturation

Question 34

What do B cells undergo as they proliferate?

Answer 34

- somatic hypermutation

Question 35

What is somatic hypermutation? What does this create

Answer 35

- mutation of BCR genes, specifically V segments - generally single nucleotide changes = creates more diversity

Question 36

The key to increased affinity is competition - What do B cells compete for? Where is this present?

Answer 36

- compete for survival signals based on recognition of antigen - present on follicular dendritic cells

Question 37

What happens as a result if somatic hypermutation?

Answer 37

- the affinity of the antibody increases and memory B cells also have: - Increased MHC class II expression - reduced requirement for T cell activation

Question 38

Memory T cells also critical in immunity - especially what type?

Answer 38

- CD4 T cells

Question 39

When activated what do memory T cells express higher levels of?

Answer 39

- adhesion molecules (important in APC interaction) - IL-4 or IFN-y (dependent on Th1 or Th2) - IL-2Rb - receptor for IL-15 (and IL-2)

Question 40

What is one way in which memory cells can last for so long?

Answer 40

- IL-15 cytokine lasts for a long time when bound to IL-2RB - allows for low level division so receptor is no internalised

Question 41

As infections accumulate over time more memory cells circulate - what does this mean for older individuals?

Answer 41

- there are more memory lymphocytes than naïve lymphocytes

Question 42

What are the different division of Memory T cell?

Answer 42

- central memory T cells * - Effector memory T cells * - tissue resident memory T cells - stem cell memory T cells

Question 43

Where are central memory T cells preferentially located?

Answer 43

- in lymphoid tissues

Question 44

What causes some central T cells to stay in the lymph node and proliferate?

Answer 44

- CCR7 binding to the chemokine CCL19 which is produced by cells within the T cell sones of lymph nodes, the spleen and other lymphoid tissue

Question 45

What are effector memory T cells specialised for?

Answer 45

- Circulate through blood, specialised for quickly entering inflamed tissue

Question 46

When do effector memory T cells develop and what do they do?

Answer 46

- Rapidly develop into effector cells following re-stimulation and quickly secrete large amounts of cytokines

Question 47

What are markers for central memory T cells?

Answer 47

- CCR7 positive (CCR7+) - CD62L high

Question 48

What are markers for effector memory T cells?

Answer 48

- CCR7 negative (CCR7-) - CD62L low