Initiation for B Cells and Memory Flashcards

1
Q

What are the two initiation processes for B cells?

A

B cells are capable of interacting directly with the pathogen that they possess the specific receptor for. However, the majority of B cells are activated by interaction with TH2 cells. These two initiation processes are referred to as 1) thymus independent and 2) thymus dependent.

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2
Q

What does it mean to be initiated ‘thymus independent’ versus ‘thymus dependent’?

A
Thymus independent activation occurs as a result of direct interaction with the pathogen surface, no T cells are necessary. 
Thymus dependent activation of B cells occurs in the lymph node as a result of the B cell displaying MHC class II peptides to the TH2 cell that possesses a receptor with the same specificity.
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3
Q

What are the two different antigens that stimulate humoral immunity?

A

There are two different antigens that stimulate humoral immunity.

  1. Thymus independent antigens-1 are the lipopolysaccharides on the surface of gram negative bacteria.
  2. Thymus independent antigens-2 are repetitive carbohydrates or proteins that are on the surface of pathogens.
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4
Q

When is there no isotype switching? What is the implication of that (i.e., what antibody is used)?

A

When humoral immunity is stimulated directly from the pathogen surface and T cells not involved, there is no isotype switching. This means that only IgM will be produced in response to the pathogen.

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5
Q

What causes isotype switching?

A

The change in antibody class is the result of cytokines being released by the T cell to cause isotype switching in the B cell, resulting in the production of IgA, IgE, and IgG.

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6
Q

What occurs with Thymus dependent activation? Describe the Primary focus and the Secondary focus?

A

The B and T cell will form a conjugate pair within the medullary area of the lymph node and clonal expansion of the B cells will occur in two different stages. The primary focus is the rapid division of B cells within the medullary area to become plasma cells and secrete IgM that will travel back to the site of infection and try to remove the pathogen. Next is the secondary focus. This is when affinity maturation, somatic hypermutation and isotype switching, occurs to create a more efficient antibody molecule with high binding affinity. Affinity maturation results in different antibody classes (for example, IgA or IgG) because the T cell secretes cytokines that drive the activity of the B cell, unlike in thymus independent activation.

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7
Q

Where does Thymus dependent activation and subsequent affinity maturation occur?

A

This occurs in the follicle of the lymph node.

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8
Q

What is the follicle called when there is no B cell division?

A

When there is no B cell division the follicle is called a primary follicle.

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9
Q

What happens once activation of a B cell has occurred?

A

Once activation has occurred and the plasma cells are rapidly dividing due to an infection, the primary follicle will become a secondary follicle, or a germinal center. The secreted antibody will be carried through circulation to the site of infection where it can work to remove the pathogen. Different receptors will aid in the effector function and transportation of specific antibodies, see table 3-3. The antibody receptors listed are FcRN, Brambell receptor, Poly-Ig receptor, FcγRI (g is gamma), and FcεRI (e is epsilon).

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10
Q

How is humoral immunity in babies different than in an adult?

A

Humoral Immunity in Neonates Humoral immunity present in neonates is greatly different than that of a healthy adult. During pregnancy, maternal IgG antibodies can cross the placenta and protect the baby from specific pathogens. Once the baby is born these antibodies will still be present, but will gradually decrease over time. If a baby is breast fed, IgA antibodies will be passively transferred via the breastmilk and will result in IgA coating the mucosal membranes which will be able to neutralize many pathogens.

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11
Q

When will the baby start to develop its own antibodies and become competent? Which are the first ones to develop?

A

The baby will also start to develop its own IgM and IgG antibodies as it is exposed to different antigens. At approximately 1 year of age, a child’s immune system will start to become competent. This is why many immunization programs start at 2 months of age, so that the spread of communicable diseases can be prevented within these “immunocompromised” individuals.

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12
Q

Why is immunological memory referred to as the secondary immune response or the anamnestic response?

A

To fight off a pathogen, the primary immune response has had to complete a very laborious and complex process. In order to provide life-long protection to prevent the pathogen from causing disease again in the same individual, immunological memory is created. Immunological memory is also referred to as the secondary immune response or the anamnestic response. It is defined as the ability of the immune system to provide a quicker and stronger adaptive immune response to subsequent encounters with the same antigen.

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13
Q

Where is immunological memory or secondary immune response located?

A

This immunity is provided in all of the secondary lymphoid tissues of the body and these cells can also circulate to the site of infection, in order to provide unified protection.

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14
Q

Summarize what happens in the primary immune response when most cells are activated to become effector cells?

A

During the primary immune response most cells are activated to become effectors cells. B cells will become plasma cells to secrete antibodies which will opsonize and neutralize. T cells can be CD8 cytotoxic T cells to kill virally infected cells, TH1 cells to activate macrophages, or TH2 cells to activate B cells with the same specificity.

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15
Q

What is the final result of a primary immune response on B and T effector cells?

A

During this response to remove the infecting pathogen, memory cells are also created. Memory B and T cells receive cytokine survival signals in order to be long lived, so if the pathogen is encountered again, they can become activated and remove the pathogen.

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16
Q

What are important features for memory B and T cells?

A

It is imperative that memory B and T cells be:

a) sensitive,
b) easily activated (display more MHC class II),
c) abundant, and
d) have already thoroughly completed affinity maturation for the antigen they are specific for.

17
Q

When will immunological memory be activated?

A

Immunological memory will only be activated once innate immunity has been breached.

18
Q

Where can activation occur for B and T cells?

A

Activation can occur within the secondary lymphoid tissue or within circulation and once activated they can “jump” into action immediately.

19
Q

Can memory B cells get stronger after initial maturation?

A

Memory B cells can even undergo affinity maturation again to produce an antibody molecule that has even stronger affinity.

20
Q

Why are naïve B and T cells suppressed with the memory response?

A

Naïve B and T cells are suppressed so that they do not interfere with the memory response.

21
Q

What benefit does an individual gain from immunological memory?

A

Because immunological memory is so quick and efficient at fighting infection, an individual may not even be aware that they have come into contact with a pathogen (they are asymptomatic).

22
Q

How do vaccinations provide life-long immunity protection?

A

Vaccinations provide life-long protection for an individual through artificial active immunity. A manufactured product made of benign antigens is safely administered to an individual in order to stimulate their immune system. Memory is created, so upon subsequent exposures, the memory response is activated to fight the pathogen.

23
Q

If vaccinations provide life-long immunity protection why are some vaccinations like the flu-shot given annually?

A

Some vaccinations, such as the flu shot, are given annually. This is because influenza is able to escape memory due to frequent mutations. These genetic mutations result in different antigenic expression, therefore, the specific antibodies that were created through vaccination could be different then the influenza that is invading.
Another example of how immunological memory can be manipulated is in the prevention of Hemolytic Disease of the Fetus and Newborn (HDFN).

24
Q

What makes a mother at risk of developing Hemolytic Disease of the Fetus and Newborn in her second child?

A

In order for a woman to be at risk of developing HDFN they must be Rh negative. Rh is a blood group system that presents itself as antigens on the red blood cell surface. An Rh negative woman would possess NO Rh antigen on her red cells; therefore, if she were exposed to red cells that were Rh positive, she would be able to produce antibodies to Rh. These antibodies are called anti-D, as D is the major immune stimulating antigen in the Rh blood group system. These antibodies are IgG, therefore, they are capable of crossing the placenta and attaching to fetal red cells – leading to their destruction and resulting in a hemolytic anemia in the newborn or fetus. The first pregnancy is not usually an issue, as the placenta does not allow for blood exchange. If mom is exposed to the foreign blood due to trauma or during delivery, then she can produce the antibody. Because the baby is usually born at this point it is not a problem. However, for the second pregnancy if the baby is once again Rh positive then maternal anti-D can cross the placenta and attack fetal red cells.

25
Q

What is done to prevent Hemolytic Disease of the Fetus and Newborn?

A

To prevent HDFN women are given a shot of Rh immunoglobulin (RhIg) at 28 weeks gestation and within 72 hours of delivery. RhIg is a commercial suspension of anti-D. If fetal red cells are introduced into maternal circulation then the RhIg attaches to the fetal red cells. This mimics a memory response and mom’s immune system is prevented from creating an immune response to the foreign red cells. Mom must receive at least two shots because these passive immunoglobulins will eventually deteriorate over time.