Immune Memory, 2Ndary Immune Response

Front 1

What sustains immunological memory?

Back 1

Clones of long-lived memory T and B cells (NOT antibody); constant exposure to low antigen levels

Front 2

What is the difference in the amount of time between primary and secondary immune response?

Back 2

Primary response takes a long time, up to a week, allowing the organism to get sick. Secondary response is almost immediate.

Front 3

What is the role of existing antibodies in immunological memory?

Back 3

Antibody levels can be maintained for several months after infection by plasma cells. Reinfection during this time will be destroyed very quickly thru neutralization, opsonization, and complement activation.

Front 4

Of neutralization, opsonization, and complement activation, which is a) independent of Ig class and b) Fc region dependent?

Back 4

A)Neutralization
B) Complement activation (can sometimes punch hole in antigen) and opsonization

Front 5

Most activated T and B cells become ___________ while fewer become ___________.

Back 5

short-lived effector cells; long-lived memory cells

Front 6

Properties of 2ndary immune response:
1) Memory lymphocytes (more or less) abundant than naive

2) Memory lymphocytes have (higher or lower) affinity antigen receptors than naive.

Back 6

1) More
2) Much higher. This allows them to act to a lower concentration of pathogen. They've already undergone isotype switching and affinity maturation.

Front 7

Are memory cells more likely to be IgM or IgG? Why?

Back 7

IgG. It has undergone isotype switching and affinity maturation. It works better than IgM.

Front 8

Only memory B cells, and not naive B cells, participate in the secondary immune response. WHY?

Back 8

Immune complexes bind to the BCR of pathogen-specific naive B cells and also to inhibitory Fc receptor (FcγRIIB1) which is expressed by naive B cells but not memory B cells.

This cross-linking <b>transmits a negative signal that inhibits activation of the naive B cell, even though it is pathogen-specific.</b>

Front 9

What is FcγRIIB1?

Back 9

A receptor that is only expressed by naive B cells. When it binds complexes composed of pathogen coated with a more specific antibody (from the memory B cell), it sends negative signals that inhibits activation of the naive B cell, even though it is pathogen-specific.

Front 10

What is the benefit of negative regulation/suppression of activation of naive B cells?

Back 10

Prevents production of low-affinity IgM antibodies that would be a wasteful and interfering recapitulation of the primary response.

Front 11

What is hemolytic disease of the newborn? How does it result?

Back 11

Occurs when father is Rh+ and mother is Rh- during <b>second or later pregnancy.</b>

During the first Rh+ pregnancy, fetal RBCs cross the placenta, get into mother's blood, and stimulate anti-Rh antibodies.

These are low affinity and so cause little harm to fetus.

During a second pregnancy that's Rh-, fetal red cells cross the placenta and induce a secondary response to Rh which is now high-affinity IgG. These coat fetal RBCs and cause them to be cleared. Babies have severe anemia when born.

Front 12

How is hemolytic disease of the newborn prevented?

Back 12

<b>Trick mother's immune system into responding to the primary exposure as if it were a secondary exposure. </b>During 28th week of pregnancy, give the mother a shot of anti-Rh IgG (before they've had a chance to make anti-Rh IgG). This is sufficient to coat all the fetal red cells that cross placenta to enter maternal circulation. Activation of mother's Rh-specific naive B cells is prevented!

Front 13

When Rh- woman is ABO compatible with Rh+ fetus, there is increased risk to develop Rh alloimmunization to fetus. Why?

Back 13

ABO incompatible RBCs that sneak over from fetus to mother don't survive long. ABO compatible, in contrast, have a better chance of staying around long and thus inducing antibody production.

Front 14

What are some drawbacks of suppressing naive B cells activation during 2ndary immune response?

Back 14

If you get a pathogen that is similar but not exactly the same (e.g., a flu virus that has mutated), a potentially higher-affinity antibody-producing B cell may be suppressed.
(this is the original antigenic sin)

Front 15

What is original antigenic sin?

Back 15

The phenomenon whereby the first flu strain to infect a person constrains/prevents development to future response to OTHER (similar) strains

Front 16

What cell surface markers distinguish memory T cells from naive T cells?

Back 16

CD45<b>RO</b> made by memory T cells, CD45<b>RA</b> made by naive T cells.

Memory cells express different cytokines, in general, that naive cells (don't need to memorize list).

Front 17

What are two types of memory T cell function?

Back 17

1) Effector memory T cells: quickly differentiate into potent effector T cells making lots of cytokines, and depending on the cytokine envt, can differentiate into Th1, Th2, or Th17.

2) Central Memory T cells: specialized towards entering T cell zones of secondary lymphoid tissue. rapidly express CD40L and itneract with B cells. Some become follicular helper cells.

Front 18

What are Central Memory T cells?

Back 18

specialized towards entering T cell zones of secondary lymphoid tissue. rapidly express CD40L and itneract with B cells. Some become follicular helper cells.

Front 19

What are Effector memory T cells?

Back 19

quickly differentiate into potent effector T cells making lots of cytokines, and depending on the cytokine envt, can differentiate into Th1, Th2, or Th17.

Front 20

What does CCR7 do in terms of memory T cells?

Back 20

Central memory T cells express it and remain in lymphoid tissue. Effector memory T cells lack it and migrate out to other tissues.

Front 21

Is maintenance of immunological memory dependent on antigen?

Back 21

This is controversial.
Quite low levels of antigen can remain in germinal centers attached as immune complexes on follicular dendritic cells (FDCs). These could periodically restimulate.

Front 22

What are FDCs?

Back 22

follicular dendritic cells (NOT same as dendritic cells that activate T cells). They activate B cells.

Front 23

How are antigens retained for long periods of time on FDCs? What are implications of this?

Back 23

in form of immune complexes.

FDCs express high levels of Fc and C3 (complement) receptors that bind Antigen/Antibody complexes for a long time.

Implications are allowance for continual restimulation of B cells. B cells can restimulate Ts as well.