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Immunology > T and B Cells > Flashcards

T and B Cells Flashcards

1
Q

What are the two distinct populations of T cells that aid to defend against pathogens?

A

Helper T cells and Cytotoxic T cells.

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2
Q

How do Helper T cells function to remove extracellular pathogens, often bacteria by acting as messengers?

A
  1. TH1 cells (a subpopulation of helper T cells) activate macrophages to better remove and degrade bacteria at the site of infection.
  2. Conversely, TH2 cells activate B cells to become plasma cells, which will secrete antibodies that opsonize and neutralize.
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3
Q

What do cytotoxic cells do when they recognize specific peptides on virally infected cells or antigen presenting cells? What other cell is this action similar to?

A
  1. When cytotoxic cells recognize the specific peptides on virally infected cells or antigen presenting cells, they will RELEASE CYTOTOXIC CHEMICALS and CYTOKINES.
    This mechanism is similar to the action of natural killer cells (NK cells) which was discussed with innate immunity.
  2. Or sends a signal into the space between the two cells and the virally infected cell undergoes apoptosis.
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4
Q

What cytotoxic chemicals are released by cytotoxic T cells?

A

Granulysin, granzyme, and perforin.

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5
Q

What is the signaling pathway utilized by cytotoxic T cells called and what does it accomplish?

A

The signaling pathway utilized by cytotoxic T cells is called the Fas ligand pathway, which sends a signal to
the virally infected cell via the Fas ligand causing the cell to undergo apoptosis. This reduces the effects
on other nearby healthy cells since cytotoxic chemicals are not released.

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6
Q

What are clusters of differentiation? What is the importance of this for a T cell?

A
  1. Clusters of differentiation separate leukocytes (T cells and B cells) based on* the cell surface molecule identified by a given group of monoclonal antibodies.
  2. Since T cells function is dependent on interaction with other cells, it is imperative that the correct T cell be activated.
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7
Q

What do cytotoxic T cells and helper T cells possess to ensure they interact with the correct MHC molecule on the surface of antigen presenting cells?

A

Cytotoxic T cells possess CD8 and helper T cells possess CD4. This ensures that they
interact with the correct MHC molecule on the surface of antigen presenting cells. MHC is the major histocompatibility complex.

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8
Q

What does the T cell recognize within the MHC molecule?

A

The T cell receptor specific for a particular peptide will recognize the PATHOGEN PEPTIDE presented within the MHC molecule.

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9
Q

How are T cell receptors similar to immunoglobulins?

A

T cell receptors have a similar structure, function, and creation (from gene rearrangements)
when compared to immunoglobulins. A T cell receptor is like the arm of an immunoglobulin molecule
with one end attached to the T cell (constant region) and the other end available for peptide recognition
(variable region).

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10
Q

What is the T cell receptor comprised of? What is the final product?

A

It is comprised of an ALPHA and BETA CHAIN. The alpha chain is similar to the light chain being created from gene rearrangements of V and J gene segments. The beta chain is similar to the
heavy chain of immunoglobulins and is created from gene rearrangement of V, D, and J gene segments. The final product is an α:β T cell receptor.

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11
Q

What are the differences between B and T cell receptors?

A

Differences between B and T cell receptors include:

  1. T cell receptors only have one binding site,
  2. Peptides have to be presented by other cells as a T cell cannot interact directly with a pathogen, and
  3. A T cell receptor does not undergo somatic hypermutation and isotype switching.
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12
Q

What do T cells rely on to combat pathogens?

A

T cells rely on the presentation of pathogen peptides by other cells as they cannot directly interact with the pathogen surface. These presentation molecules are called major histocompatibility
complexes (MHC).

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13
Q

What cells present these two classes of MHC molecules discussed: MHC Class I and MHC Class II?

A

MHC Class I is presented by any cell with the exception of red blood cells.
MHC Class II is presented by professional antigen presenting cells (Dendrites, Macrophages, and B cells).

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14
Q

Why can’t red blood cells present MHC Class I molecules?

A

This is because MHC Class I molecules present viral peptides, and viruses are capable of invading any cell. Red blood
cells lack a nucleus; therefore a virus cannot invade and use the genetic material to replicate, so they do not have the capability of expressing MHC Class I.

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15
Q

Why are MHC Class II molecules only presented by professional antigen presenting cells (i.e. Dendrites, Macrophages, and B cells)?

A

MHC Class II is presented by professional antigen presenting cells (Dendrites, Macrophages, and B cells). They present peptides from bacteria; this is why
only antigen presenting cells can present MHC Class II, because THEY POSSESS PHAGOCYTIC PROPERTIES.

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16
Q

What is antigen processing and antigen presenting?

A

When a pathogen is causing an infection within tissue, resident macrophages and dendritic cells uptake the pathogen and degrade it, referred to as antigen processing. It then takes the peptides from the degraded pathogen and presents it on its surface for interaction with a T cell, referred to as antigen
presenting.

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17
Q

What cells are MHC Class I molecules presented to?

A

MHC Class 1: Specific T cell receptors on CD8 T cells (cytotoxic) from any virally infected cell.
MHC Class 2: T cell receptors on CD4 T cells (helper) within secondary lymphoid tissue from APCs coming from infected tissue.

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18
Q

What does it mean when it is said that MHC classes express promiscuous binding specificity? What is the result?

A

BOTH MHC classes express Promiscuous binding specificity:
This means that many different types of peptides can be attached to the peptide binding groove of the MHC molecule for presentation to specific T cells that
possesses the receptor for that peptide. This interaction leads to their activation into effector cells (either helper T cells or cytotoxic T cells).

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19
Q

Hematopoietic steel cells (HSCs) who express what component (?) can become what type of cell lineages?

A

HSC’s, expressing CD34, can become any cell from the three cell lineages: erythrocytes (red blood cells), leukocytes (white blood cells), and megakaryocytes (platelets).

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20
Q

Where do B cells originate from (cell and location)?

A

B cells originate, as any other hematopoietic cell, from a hematopoietic stem cell (HSC) in the
bone marrow

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21
Q

Where to B cells complete their maturation versus where T cells mature?

A

B cells complete their maturation within the bone marrow, whereas T cells complete their maturation within the thymus (hence the “T” cell).

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22
Q

What helps a lymphoid progenitor cell to turn into a immature B cell?

A

The lymphoid progenitor cell will receive support from the stromal cells of the bone marrow and growth factors such as IL-7 and stem cell growth factor. This allows the lymphoid progenitor cell to continue its maturation into an immature B cell.

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23
Q

Where is the immature B cell released to and what will have there?

A

This allows the lymphoid progenitor cell to
continue its maturation into an immature B cell, until this cell can be released from the bone marrow to secondary lymphoid tissue where it will be activated to become a plasma cell that secretes antibodies.

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24
Q

What are the six phases of development of a B cell population?

A

There are six phases of development:

a) creation of a diverse B cell population,
b) negative selection,
c) positive selection,
d) searching for pathogen,
e) finding pathogen, and
f) attacking pathogen.

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25
Q

Why does a creation of a diverse B cell population occur?

A

Because of gene rearrangements.

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26
Q

What are the 5 stages of immature B cell development (or cell names)? Note: details on what occurs later. What is the main to be or not to be scenario?

A
  1. Early Pro-B Cell
  2. Late Pro-B Cell
  3. Large Pre-B Cell
  4. Small Pre-B Cell
  5. Immature B Cell

Will the develop a functional immunoglobulin or not. If it doesn’t a survival signal is not given and the cell undergoes apoptosis (cell death). If it is functional then it goes on to become an immature B cell.

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27
Q

Describe the early Pro-B cell and Late Pro-B cell phases?

A

Early Pro-B: Diversity (D) and Joining
(J) gene rearrangements occur in the early pro-B cell stage.

Late pro-B cell:

  1. D, J, and Variable (V) gene rearrangements occur to create a functional variable region of the heavy chain.
  2. The Constant (C) gene region is added, typically a µ heavy chain.
  3. To create diversity amongst the variable regions, P (palindrome) and N (non-templated) nucleotides will be randomly inserted into the gene segments.
  4. Fate reviewed: If it is unable to make a functional heavy chain, it will not receive a survival signal, and will die via apoptosis. If the cell receives a survival signal it may continue maturation.
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28
Q

What occurs in the large Pre-B and small pre-B stage? What happens to a non-functional and functional immunoglobulin?

A

Large pre-B cell stage: the cell that is able to make a functional heavy chain will undergo several cellular divisions.

Small pre-B cell stage, the heavy chain will be combined with different light chains.

Fate reviewed: If a functional immunoglobulin cannot be created, then a survival signal will not be given, and the cell will die via apoptosis. The functional immunoglobulin will then be transported to the surface of the cell and the result will be an immature B cell.

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29
Q

What is a problem that can happen with all of the diversity created with immature B cells?

A

The immature B cell must express tolerance to self prior to being released into circulation. With all of the diversity created, there is unavoidably to be some B cells that express specificity to self.

30
Q

What are the three pathways that autoreactive B cells can be removed?

A

There are three different pathways by which autoreactive B cells can be removed: 1. receptor editing,

  1. becoming anergic, or
  2. death via apoptosis.
31
Q

What is receptor editing that occurs when a B cell expresses reactivity to self? Then what occurs?

A

Receptor Editing:
This is a process by which the light chain of the immunoglobulin is altered. Once a new immunoglobulin is created, the receptor is tested again for reactivity. If it is still reactive it will undergo apoptosis, if it does not express reactivity to self then it is released into circulation.

32
Q

What does it mean when the autoreactive B cells becomes anergic?

A

B cells can also be made anergic. This means that they are inactivated, but allowed to go into circulation. Anergic cells
typically live only 1-5 days, whereas a typical lymphocyte has a half-life of 40 days.

33
Q

What B cells are made anergic and why?

A

B cells that express reactivity to soluble self antigen will be made anergic because they will not cause any detriment to self cells.

34
Q

What happens once a B cell is no longer autoreactive?

A

Once a B cell is no longer autoreactive, it is allowed to enter circulation to take up residence in the secondary lymphoid tissue.

35
Q

What two chemokines are secreted by secondary lymphoid tissues that attract B cells?

A

Secondary lymphoid tissues, such as the lymph node, secrete two chemokines that will attract B cells. CCL19 and CCL21 are secreted by the lymph node cortex.

36
Q

What receptor do B cells contain for CCL21 (chemokines released by the lymph node cortex for example)?

A

CCR7

37
Q

Once the B cell is in the lymph node, what further draws it in and determines if the B cell will stay?

A

Once in the lymph node, the follicular dendritic cells (FDC’s) of the primary lymphoid follicle will further draw B cells by releasing chemokine CXCL13. There, B cells will await introduction to an antigen.
If the B cell is not introduced to its specific antigen, then it will detach from the FDC’s and will continue searching through the lymph and blood.

38
Q

What happens if the B cell is introduced to a particular antigen in a secondary lymphoid tissue such as a lymph node?

A

If the B cell is introduced to its particular antigen, then it will become activated and mature to a plasma cell, secreting antibodies that will opsonize or neutralize the pathogen.

39
Q

What are the two methods of introduction of the pathogen to the immature B cell? and what is the result?

A

Introduction can occur through:
1. Direct interaction with the pathogen or 2. B cell can be activated by a CD4 helper T cell with the same specificity.

Result:
Clonal expansion, the rapid division of the cell that contains a receptor with the correct specificity for the invading pathogen.

40
Q

What is the germinal center?

A

An area, that was a primary follicle that contained a variety of B cells, becomes occupied by rapidly dividing clones of a particular B cell. That area becomes a secondary lymphoid follicle or germinal center.

41
Q

What happens after clonal expansion?

A

At this point the plasma cell, having now encountered the antigen, will undergo affinity maturation. This process is marked by creating an antibody molecule that has a high affinity (strong binding) to the antigen.

42
Q

What are the two different stages to affinity maturation?

A

Somatic hypermutation
Isotype Switching

1. Somatic hypermutation involves small mutations in the variable region of the 
immunoglobulin by inserting P and N nucleotides so that a stronger antigen binding site can be created. 
2. Isotype switching is the process by which the class of immunoglobulin is changed to get the correct effector antibody.
43
Q

Give an example of isotype switching?

A

For example: IgM is the first antibody to be secreted upon exposure to an antigen,
however, if the antigen is from a parasite, then the isotype is switched to IgE as it is more efficient.

44
Q

How do B cells contribute to creating memory to a given pathogen? What particular benefit does this provide an individual?

A
  1. During the final stages of affinity maturation within the secondary lymphoid tissues, memory is created. Life long B cells are created that contain high affinity immunoglobulins so upon subsequent exposures it can easily be activated to secrete antibodies to fight the pathogen. 2. This allows for a quick response, so fast
    that the individual may not even identify that they have been exposed to the pathogen.
45
Q

What problem can result from the high incidence of gene rearrangement that occurs with B cells/plasma cells?

A

Mutations can easily result and can manifest themselves in several different
disease states. The diagnosis is based on the stage of B cell development in which the mutation has occurred.

46
Q

Give two examples of diseases as a result of B cell development mutations?

A
  1. Acute Lymphoblastic Leukemia (ALL) results from rapid and uncontrolled
    division of lymphoid progenitors cells,
  2. Multiple Myeloma that results from the rapid and uncontrolled division of plasma cells.
47
Q

Based on Figure 3 Summary of B Cell development, what stage name corresponds to these events:

a) a repertoire of B cells occur
b) autoreactive B cells get edited
c) B cells released to secondary lymphoid tissues
d) recirculation of B cells
e) activation of B cells by pathogen or CD4 T cells
f) somatic hypermutation and isotype switching to create high effective antibodies

A

a) Creation of Diverse B Cell Population
b) Negative Selection
c) Positive Selection
d) Searching for Pathogen
e) Finding Pathogen
f) Attacking Pathogen

48
Q

Where does an undifferentiated T cell leave from and enter?

A

T cells begin down a very similar path as B cells. They begin their development within the bone marrow from hematopoietic stem cells. However, they do not complete their maturation there. An undifferentiated cell will leave the bone marrow and enter the thymus.

49
Q

What does the undifferentiated T cell interact with to become a thymocyte?

A

This cell will then interact with IL-7 within the thymus which will cause the loss of CD34 from the surface of the hematopoietic stem cell causing it to become a thymocyte.

50
Q

Why makes a T cell a double negative thymocyte?

A

At this point it will not be displaying CD4 or CD8, so it is referred to as a double negative thymocyte.

51
Q

How does the thymocyte become a CD4 or CD8 cell?

A
  1. The thymocyte, displaying the generic T cell markers CD2 and CD5, will undergo several gene rearrangements of the alpha and beta chains of its receptor in order to create a population of T cells with different specificities.
  2. While it is creating a functional receptor it will also display CD4 AND CD8, making it a double positive thymocyte. So, how does it choose?
  3. The double positive thymocyte will go through a process of positive selection.
  4. Within the thymus, the cell will interact with thymic epithelial cells displaying self-peptide in MHC class I and II molecules. This process will help determine if the thymocyte can create a functional receptor. There is only self-peptide available, so in this case the thymocyte needs to respond to self in order to determine that the receptor will work within circulation.
  5. If the double positive thymocytes binds to MHC class I on thymic epithelial cells then it will display CD8,
  6. If it binds to MHC class II on thymic epithelial cells then it will display CD4.
  7. If the double positive thymocyte does not have a receptor that is functional then it will undergo apoptosis.
52
Q

What does the single positive thymocyte display?

A

The now single positive thymocyte, will display either CD4 or CD8.

53
Q

Why does the single positive thymocyte go through negative selection and how?

A

The now single positive thymocyte, which will display either CD4 or CD8, will then go through negative selection.

Why: This is to remove any T cells that will be autoreactive within circulation.

How: Any T cells that have a specificity for self after it has been determined that their receptor is functional are tested against MHC class I and II molecules on the surface of macrophages and dendrites in the thymus. If they are autoreactive they are removed via apoptosis.

54
Q

What happens to single positive thymocytes with autoreactive receptors? What does positive selection determine?

A

They are removed via apoptosis.

Positive selection determines whether the
receptor works, and negative selection removes any autoreactive T cells prior to entering peripheral circulation.

55
Q

Where does a functional T cell go and what attracts it there?

A

A functional T cell will find a home within the secondary lymphoid tissue, attracted by the same chemokines that attracted B cells to the lymph node, CCL19 and CCL21.

56
Q

What are regulatory CD4 T cells and what is their purpose?

A

Regulatory CD4 T cells are a subset of T cells and will express CD25 to separate them from helper cells.

The purpose of these regulatory cells is to remove the autoreactive CD4 T cells.

57
Q

What is the implication of regulatory CD4 T cells’ purpose in removing autoreactive CD4 T cells?

A

The regulatory cells need to be
autoreactive and carry the same specificity for the antigen presenting cells as the autoreactive CD4 T cell
that it is trying to remove. When binding occurs to the same antigen presenting cell the regulatory cell will send signals to the autoreactive cell to undergo apoptosis.

58
Q

What cells perform cell mediated immunity?

A

Cell mediated immunity is an area of the adaptive immune response that is dominated by the action of T cells. T cells, even though they are unable to interact and remove the pathogen directly
serve a wide array of functions in the eradication of infection. The two populations of T cells, cytotoxic
and helper, work against intracellular (viral) and extracellular (bacterial), respectively.

59
Q

Where do T cells go after they have passed the stringent process of selection within the thymus?

A
  1. Allowed to enter peripheral circulation.
  2. Single positive thymocytes (CD4 or CD8) take residence in 2ndary lymphoid tissue throughout the body. Occupy specific T cell area & await APCs.
  3. Some (small #’s) take residence w/in a variety of tissues throughout the body ready to act when a pathogen is present.
60
Q

What happens when T cells awaiting dendrites is not activated?

A

If a T cell is not activated in
one lymph node then it will leave via the efferent lymphatic vessel to the next lymph node “downstream”, and arrive via the afferent lymphatic vessel.

If an antigen is met then a different process
will follow.

61
Q

What happens when a dendrite presents a peptide in MHC class I to a CD8 cytotoxic T cell in the medullary area of the lymph node?

A 
If a dendrite presents a peptide in MHC class I to a CD8 cytotoxic T cell in the medullary area of the lymph node then the T cell will be activated, will leave the lymph node, and migrate to the area of 
infection to fight off the virus through the release of cytotoxic chemicals. The conclusion is the destruction of virally infected cells that show the same peptides as the initial dendrite.
62
Q

What happens when a dendrite presents a peptide in MHC class II to a CD4 helper T cell in the medullary area of the lymph node? What are the two types of activations?

A

If a dendrite presents a peptide in MHC class II to a CD4 helper T cell in the medullary area of the lymph node then the T cell will be activated.
a) If a TH1 cell is activated, it will leave the lymph node, and
migrate to the area of infection in order to activate macrophages, which will result in better removal of the bacteria through phagocytosis.
b) If a TH2 cell is activated, it will stay in the lymph node, activate B cells in the medullary area, the B cells will be activated resulting in its maturation to plasma cells which secrete antibodies to opsonize and neutralize the pathogen.

63
Q

What is clonal selection and what is the result?

A

When the lymphocyte that carries the correct receptor is activated via the interaction with an
antigen presenting cell, this is called clonal selection. A specific receptor (and therefore the lymphocyte
– or clone) is selected based on the specific pathogen peptide. To create more of this clone is order to
fight off the pathogen clonal expansion must occur. Clonal expansion is the proliferation of the clone
that has been selected. This means that there will be more of the lymphocyte available to deal with the
large amount of pathogen that is causing the infection.

64
Q

Can T cells cause their own clonal expansion? How?

A

Remarkably, T cells can cause their own clonal expansion. When a T cell is activated it will release IL-2. IL-2 can then attach to IL-2 receptors that are on the surface of the same cell. This ensures that the specific clone is receiving the “expansion” signal.

65
Q

What are naive T cells?

A

Naïve T cells, ones that
have not come into contact with their specific antigen, can arrive to the lymph node via high endothelial
venules (circulation) or via the afferent lymphatic vessel. Even though the majority of lymphocytes are
maintained within secondary lymphoid tissue, T cells do undergo circulation between the blood and the
lymph to ensure that they have opportunity to be activated. T cells are attracted to the lymph node by
the cytokines CCL19 and CCL21, this ensures they make it to the right place.

66
Q

What immune response is dominated by B cells?

A

Humoral immunity

67
Q

What happens when B cells are activated?

A

They mature to plasma cells and secrete antibodies which will opsonize or neutralize the pathogen.

68
Q

What is opsonization?

A

The process by which antibodies coat the pathogen to enhance its phagocytosis or to activate the complement cascade.

69
Q

What is neutralization? Which antibodies are very efficient at it?

A

Neutralization is the process by which
antibodies bind to the virus, bacteria, or toxin to prevent its interaction with healthy cells.

IgA and IgG are both very efficient at neutralization.

70
Q

How is humoral immunity by B cells different from cell mediated immunity by T cells?

A

Cell mediated immunity is dominated by T cells, not antibodies.

Immunology (12 decks)

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