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Year 2 MIS > Cells of adaptive immune response > Flashcards

Cells of adaptive immune response Flashcards

1
Q

What are the 2 main cells of the adaptive system?

A
  • B and T cells
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2
Q

Where are T cells created and matured?

A
  • created in bone marrow from hematopoietic lineage forming common lymphoid progenitor cell
  • immature T cells then travel to thymus to mature
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3
Q

When an immature B cells has gone through its development, is it self-reactive?

A
  • no

- means it will not reactive with ‘self’ antigen on cells of the body

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4
Q

How are B cells not self reactive?

A
  • they possess human DNA to that the cell is able to distinguish self from foreign
  • also undergo self tolerance using autoimmune regulatory gene (AIRE) checks self antigens against the B cell
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5
Q

Where are B cells created and where do they mature?

A
  • both in bone marrow

- remember B for B cell and Bone marrow

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6
Q

The B cells both possess a heavy and light chains, which associate with the constant, variable, antigen bridging sites and bridges. Label the B cell receptors in the image below:

heavy chain
light chain
constant region
variable region
antigen binding site
disulphide bridge
A 
1 = antigen binding site
2 = variable region
3 = constant region
4 = disulphide bridge 
5 = light chain
6 = heavy chain
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7
Q

The variable region of the heavy and light chains posses different segments. What segments are located on the heavy and light chains?

1 - heavy and light
2 - heavy and dark
3 - light and dark
4 - heavy and long

A

1 - heavy and light

  • heavy contains = variable, diversity and joining areas hence we call it heavy
  • light = variable and joining
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8
Q

How do the B cells have so many different B cell receptors (antibodies) on different B cells?

1 - constantly testes against foreign antigens
2 - transcription of new receptors continues from birth
3 - V and J segments on light segment diversify
4 - V, J and D segments on heavy segment diversify

V = variable segment (44 of these)
J = joining segment (27 of these)
D = diversity segment (6 of these)
A

4 - V, J and D segments on heavy segment diversify

  • 2 alleles for V, D and J segments inherited from parents encoding B cells
  • V, D and J segments can be arranged in a myriad of orders meaning lots of variable receptors and specific to a specific antigen
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9
Q

B cell receptors/antibodies contain a variable and constant region. What are the functions of each of these?

1 - variable = antigen binding site, constant = antigen binding site
2 - variable = antibody class, constant = antigen binding site
3 - variable = antigen binding site, constant = antibody class
4 - variable = antibody class, constant = antibody class
A

3 - variable = antigen binding site, constant = antibody class

  • VDJ recombination determines the variable region giving antigen specificity
  • constant region can undergo class switching determining the class of antibody (IgA, IgM etc..)
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10
Q

What determines the specificity of B cell receptors that can then be specific to antigens?

1 - gene variation
2 - VDJ segments
3 - gene variation and VDJ arrangement

V = variable segment (44 of these)
J = joining segment (27 of these)
D = diversity segment (6 of these)
A

3 - gene variation and VDJ arrangement
- variability of genes inherited combined with the various arrangement of V, D and J segments on the variable regions of the heavy and light chains

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11
Q

What is the function of recombination-activating genes (RAG 1 and 2) that synthesis RAG 1 and RAG 2 enzymes?

1 - removed damaged VDJ segments
2 - check VDJ segments have been arranged correctly
3 - help D and J segments get spliced together
4 - develop new VDJ segments

V = variable segment (44 of these)
J = joining segment (27 of these)
D = diversity segment (6 of these)
A

3 - help D and J segments get spliced together

  • formation of early pro B cell from the common lymphoid progenitor cell
  • the splicing is a race between the chromosome from mum and dad, which ever does this phase 1st will code for the B cells
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12
Q

Once RAG 1 and Rag 2 have successfully spliced together segments D and J the B cell becomes a late pro B cell. What must happen next for the late pro B cell to become a large pre B cell?

1 - VDJ recombinase splices together the DJ segment with V giving us VDJ
2 - VDJ recombinase checks the DJ segment and may replace damage segments
3 - B cell will move to secondary lymphoid tissue

V = variable segment (44 of these)
J = joining segment (27 of these)
D = diversity segment (6 of these)
A

1 - VDJ recombinase splices together the DJ segment with V giving us VDJ

  • forms the VDJ segment of the heavy chain antigen binding site
  • VDJ segment is combined with mu gene which codes for the constant region
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13
Q

Once the VDJ segment which makes up the antigen binding site of the heavy chain and constant region is complete, the cell is considered a large pre B cell. The heavy chain then needs to be tested to see if it is functional and if the B cell should continue with its development or be destroyed. How is the variable region of the light chain created?

1 - light chain goes through VJ arrangement
2 - VDJ segment is copies for form a similar VJ segment
3 - surrogate light chain composed of lamba and V pre B proteins is attached to VDJ segment

V = variable segment (44 of these)
J = joining segment (27 of these)
D = diversity segment (6 of these)
A

3 - surrogate light chain composed of lamba and V pre B proteins is attached to VDJ segment
- this is then transported to the cell surface in a vesicle a

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14
Q

Once a surrogate light chain is bound to VDJ heavy chain it is then transported to the cell surface in a vesicle to the cell surface. How does this confirm if the VDJ segment on the heavy is functional?

A
  • receptor binds close to immunoglobulin side chain alpha and Beta
  • if the surrogate light chain and heavy chain successfully make a functional heavy chain on the surface of the large pre-B cell, these side chains send down a signal to the nucleus
  • the cell then rapidly proliferates and each daughter cell, containing the same variable region on the heavy chain
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15
Q

Once a large pre B cell has created functional heavy chains using the surrogate light chains, the large pre B cell proliferates into small pre B cells. How do these small pre B cells then create a light chain?

1 - VDJ segment is formed and J segment is removed
2 - VJ segments are formed from left over VDJ segments
3 - kappa or lamba chains are copied if they bind well with antigens
4 - V and J segments are re-arranged forming kappa or lamba light chains

A

4 - V and J segments are re-arranged forming kappa or lamba light chains

  • if kappa and lamba light chains do not function correctly the cell is killed off
  • then released as an immature B cell and released into the circulation
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16
Q

Which immunoglobulin is produced first in B cell production?

1 - IgD
2 - IgA
3 - IgG
4 - IgM

A

4 - IgM

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17
Q

How does the body identify which B cells are self reactive?

1 - B cells circulate of period if they bind self antigens they undergo apoptosis
2 - B cells move to secondary lymph tissue and randomly sample tissies
3 - auto immune regulator gene (AIRE) located in primary lymphoid tissue throughout the body

A

3 - auto immune regulator gene (AIRE) located in primary lymphoid tissue throughout the body

  • various self antigens will be tested on the B cell to assess if it is self reactive
  • if a small pre B cell has strong affinity to a self antigen it will undergo apoptosis
  • if a small pre B cell has an intermediate affinity to a self antigen the light chain will be re-arranged so that it doesn’t recognised self antigens at all
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18
Q

There are 2 main types of T cells, CD4+ and CD8+. What are the more common names for these 2 types of T cells?

A
  • CD4 = T helper cells

- CD8 = cytotoxic T cell

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19
Q

The T cell contains 2 T cell receptors. What are they called?

1 - alpha and gamma chains
2 - alpha and beta chains
3 - gamma and beta chains
4 - gamma and delta chains

A

2 - alpha and beta chains

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20
Q

The T cell contains 2 T cell receptors, alpha and beta chains. The beta chains contain 3 segments. What are they?

1 - heavy, light, variable
2 - light variable, joining
3 - variable, diversity, heavy
4 - variable, diversity, joining

A

4 - variable, diversity, joining

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21
Q

In addition to T cell receptors the T cells also contain CD3 as that is part of the T cell receptors. The T cell will then also express a specific CD molecule once it matures. What are these 2 CD molecules that will be present in a mature T cell?

1 - CD8 and CD10
2 - CD4 and CD8
3 - CD4 and CD10
4 - CD4 and CD11

A

2 - CD4 and CD8

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22
Q

When a common lymphoid progenitor cell arrives at the thymus, does it contain anything on its cell surface?

A
  • no
  • CD3-, CD4- and CD8-
  • called the double negative stage
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23
Q

Once a T cell begins its development it will go from nothing on its self surface to contain 3 CD molecules. What are these 3 CD molecules?

1 - CD3, CD8 and CD10
2 - CD1, CD4 and CD8
3 - CD3, CD4 and CD8
4 - CD4 and CD11

A

3 - CD3, CD4 and CD8

- called double positive stage

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24
Q

When a common lymphoid progenitor cell arrives at the thymus, it does not contain anything on its cell surface, including T cell receptors, CD3-, CD4- and CD8- molecules, called the double negative stage, which can be further subdivided in DN1, DN2, DN3 and DN4. What happens in the DN1 stage?

1 - IL-2 and IL-7 are secreted stimulating RAG-1 and 2
2 - IL-2 signals for T cells to develop CD3 receptors
3 - IL-2 signals T cells to secrete CD4 and CD8 receptors
4 - RAG1 and 2 stimulate B cell receptor development

A

1 - IL-2 and IL-7 are secreted stimulating RAG-1 and 2

  • T cell moves to DN2 stage where RAG 1 and RAG 2 splice together D and J segments
  • which ever chromosome splices first will be expressed
  • the T cell then moves to stage DN3 with a functional Beta chain
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25
Q

One the T cell at the DN3 stage of T cell development has formed D-J segments on the Beta chain. What occurs to move the T cell onto DN4 stage?

1 - VDJ recombinase splices DJ segment with V segment forming VDJ segment
2 - VDJ recombinase checks the DJ segment and may replace damage segments
3 - T cell will move to secondary lymphoid tissue

A

1 - VDJ recombinase splices DJ segment with V segment forming VDJ segment

  • VDJ segment is the complete antigen binding site (variable region) of the B chain of the T cell receptor
  • the VDJ segment is then bound to the constant region of the B chain
26
Q

Once a T cell beta chain receptor is at the DN4 stage with its complete VDJ antigen binding site, what happens next?

A
  • beta chain functionality is assessed
  • invariant pre-T alpha chain is produced to see if the beta chain is able to bind with it
  • if it does they are both transported to the cell surface in a vesicle
27
Q

Once a T cell beta chain receptor is at the DN4 stage with its complete VDJ antigen binding site, the beta chain functionality is assessed. An invariant pre-T alpha chain is produced to see if the beta chain is able to bind with it, and if it does they are both transported to the cell surface in a vesicle. Once on the surface what else must be present?

A
  • a second invariant pre-T alpha chain bound to the beta chain, receptors are dimers so we always need 2
  • flanked either side of the 2 receptors is CD3
  • the cell recognises this and begins to proliferate creating daughter cells
  • all daughter cells contain the same Beta chain
28
Q

Once a T cell has begun proliferating from stage DN4 what is present in the surface of the daughter cells and what are these cells then called?

A
  • contains 2 copies of the invariant pre-T alpha chain bound to the same beta chain
  • flanked either side of the 2 receptors is a CD3 molecule
  • CD4 and CD8 molecules
  • these T cells are now called DP cells
29
Q

Once we have DP cells which contain the following on their cell surfaces:

  • 2 copies of the invariant pre-T alpha chain bound to the beta same chain
  • flanked either side of the 2 receptors is a CD3 molecule
  • CD4 and CD8 molecules

What happens to the alpha chains?

A
  • begin to arrange the V and J segments
  • this means they will all have the same beta chain VDJ (variable region), but a unique VJ segment (variable region) on the alpha chain
30
Q

What happens if the alpha chain does not bind with the beta chain or the T cell is self-reactive?

A
  • T cell undergoes apoptosis
31
Q

In addition to lymphoid epithelial cells that presenting antigens, what other cell presents antigens to developing T cells in the thymus?

1 - eosinophils
2 - dendritic cells
3 - neutrophils
4 - macrophages

A

2 - dendritic cells

32
Q

Are T cells able to become active if they do not bind with a suitable major histochemical complex molecule?

A
  • no
  • T helper CD4 = MHC-II
  • cytotoxic cell CD8 = MHC-I
33
Q

T cells receptors need to bind with antigens and MHC before they can become active. How do they do this?

A
  • antigen presenting cells (macrophages, dendritic cells, and B cells) presents antigen as a peptide on its MHC-I or MHC-II receptors
  • CD4+ will bind with MHC-II receptors
  • CD8+ will bind with MHC-I receptors
34
Q

T cells must undergo a process called central tolerance, what is this?

1 - process of allowing B and T cells to be released into circulation
2 - process of eliminating self reactive B and T cells
3 - process of B and T cells maturing back in bones

A

2 - process of eliminating self reactive B and T cells

  • must ensure T cell receptors can bind with MHC molecules called POSITIVE SELECTION
  • must not bind too strongly to MHC molecules called NEGATIVE SELECTION, which could become self reactive and attack self antigens so these cells undergo apoptosis
35
Q

In positive selection as part of T cell development, which cells survive and which undergo apoptosis?

A
  • those that bind to MHC survive

- those that don’t bind to MHC undergo apoptosis

36
Q

In negative selection, there is a gene present in lymphoid tissue that allows antigens to be presented to immature T cells in a controlled fashion to assess for self reactivity. What is this gene called?

1 - T cell VDJ recombinase
2 - T cell recombinase
3 - T cell refractase
4 - autoimmune regulator gene (AIRE)

A

4 - autoimmune regulator gene (AIRE)

  • expressed in lymphoid tissue
  • allows controlled presentation of antigens to immature T cells
37
Q

In negative selection, AIRE is present in lymphoid tissue, allowing antigens to be presented to immature T cells in a controlled fashion to assess for self reactivity. What happens to T cells that bind strongly to MHC molecules?

A
  • undergoes apoptosis
38
Q

In negative selection, AIRE is present in lymphoid tissue, allowing antigens to be presented to immature T cells in a controlled fashion to assess for self reactivity. What happens to T cells that bind strongly to MHC molecules but do not recognise the self-antigen that is present on the MHC molecule?

1 - undergo apoptosis
2 - down regulate CD4 and CD8 receptors
3 - develop into a single positive T cell

A

3 - develop into a single positive T cell

- involves down regulation of either the CD4 or CD8 receptor

39
Q

When a T cell develops into a single positive T cell, down regulating either the CD4 or CD8 molecules, how does it determine if it is the CD4 or CD8 molecule that it down regulates?

A
  • depended on the strength of the binding between the T cell receptor and MHC molecules
  • strong/intermediate binding of CD4 molecules = down regulation of CD8 molecules
  • strong/intermediate binding of CD8 molecules = down regulation of CD4 molecules
40
Q

Once the T cell has down regulated the CD4 or CD8 molecules on its surface, what are these T cells then referred to as?

A
  • single positive CD4+ T cell

- single positive CD8+ T cell

41
Q

Once the T cell has down regulated the CD4 or CD8 molecules on its surface, they are referred to as a single positive CD4+ T cell or single positive CD8+ T cell. These cells are then recognised as naive T cells and travel where and what for?

A
  • travel to secondary lymphoid tissues (spleen, lymph nodes)

- deal with antigens presented on MHC molecules like dendritic cells

42
Q

From CD4 and CD8 T cells, which is a helper cell and which is a cytotoxic cell?

A
  • CD4 = helper cell

- CD8 = cytotoxic cell

43
Q

From CD4 and CD8 T cells, which bind with MHC-I and MHC-II?

A
  • CD4 = MHC-II (4 / 2 = 2)

- CD8 = MHC-I (1 x 8 - 8)

44
Q

Organise the basic order of the T cell development below:

positive selection
re-arrange beta chain
negative selection
re-arrange alpha chain

A 
1st = re-arrange beta chain
2nd = re-arrange alpha chain
3rd = negative selection
4th = positive selection
45
Q

There are a number of ways in which B and T cells are able to produce unique receptors. One of these is called VDJ recombination. What is this?

A
  • random arrangement of the VDJ segments on the variable regions of the heavy and beta chains
  • on the heavy chain for B cells
  • on the beta chain for the T cells
  • this creates receptors for specific antigens
46
Q

When we look at an antibody produced by a B cell, there are 2 main parts. The constant and variable regions. Which part relates to determining the the class of the antibody, such as IgG, IgM, IgA, IgD or IgE?

A
  • constant region
47
Q

There are a number of ways in which B and T cells are able to produce unique receptors. One of these is somatic hypermutation, which occurs only in B cells. What is somatic hypermutation?

A
  • process where B cells are able to switch between antibody classes
  • this is based on the antigen that they come into contact with
  • ensure the immune system is specific to the foreign antigen
48
Q

There are a number of ways in which B and T cells are able to produce unique receptors. One of these is somatic hypermutation. Somatic hypermutation is a process where B cells are able to switch between antibody classes (IgG, IgM, IgE, etc..), based on the antigen that they come into contact with. This ensures the immune system is specific to the foreign antigen. Does this occur in B and T cells?

A
  • no

- only B cells produce antibodies and needs to be activated by T cells to do this

49
Q

There are a number of ways in which B and T cells are able to produce unique receptors. One of these is somatic hypermutation, which occurs only in B cells. Somatic hypermutation is a process where B cells are able to switch between antibody classes (IgG, IgM, IgE, etc..), based on the antigen that they come into contact with. This ensures the immune system is specific to the foreign antigen. This occurs only in B cells. What must happen to the B cell in order for somatic hypermutation to occur?

A
  • B cell binds an antigen
  • B cell expresses CD40 on cell surface
  • helper T cell with CD40 ligand (CD40L) binds to CD40 receptor on B cell, B cell up-regulates cytokine receptors
  • helper T cell expresses cytokines
  • cytokines expressed determine the class switch to a specific antibody
50
Q

In somatic hypermutation once B cell binds an antigen, the B cell expresses CD40 on cell surface and a helper T cell with CD40 ligand binds to CD40 receptor on B cell. This causes the B cell to up-regulate cytokine receptors and then the helper T cell expresses cytokines that cause changes in the B cell, called class switching and change the antibody they are producing. One of the first changes is the activation of an enzyme. What is this enzyme called?

1 - autoimmune regulatory gene (AIRE)
2 - activation Induced cytidine deaminase (AID)
3 - lactate dehydrogenase
4 - creatine kinase

A

AID

51
Q

IIn somatic hypermutation once B cell binds an antigen, the B cell expresses CD40 on cell surface and a helper T cell with CD40 ligand binds to CD40 receptor on B cell. This causes the B cell to up-regulate cytokine receptors and then the helper T cell expresses cytokines that cause changes in the B cell, called class switching and change the antibody they are producing. One of the first changes is the activation of an enzyme called activation Induced cytidine deaminase (AIR). What is the function of the AID enzymes?

A
  • allows B cell to make cuts in its DNA

- B cell can then class switch from IgM to IgG, IgA, or IgE depending on the cytokines stimulation

52
Q

In somatic hypermutation once B cell binds an antigen, the B cell expresses CD40 on cell surface and a helper T cell with CD40 ligand binds to CD40 receptor on B cell. This causes the B cell to up-regulate cytokine receptors and then the helper T cell expresses cytokines that cause changes in the B cell. One of the first changes is the activation of an enzyme called activation Induced cytidine deaminase (AIR). The AIR enzymes allows B cell to make cuts in its DNA and therefore switching antibody class switch from IgM to IgG, IgA, or IgE depending on the cytokines stimulation. If a patient does not have the AIR enzyme, what can this cause?

1 - autoimmune disease
2 - AIR mutations
3 - hyper IgM immunodeficiency
4 - hyper somatic mutations

A

3 - hyper IgM immunodeficiency

  • AIR allows switching between antibody class, without it, the B cell cannot switch between classes
  • IgM is the first antibody produced so they have lots of IgM
53
Q

During somatic hypermutation the enzyme activation Induced cytidine deaminase (AIR) is expressed and is able to bind directly with DNA, but only when B cells are activated and proliferating. Once bound to DNA it causes a change in one of the bases of the single stranded DNA. What change does this induce?

1 - cytosine to guanine
2 - cytidine to adenine
3 - thymine to uridine
4 - cytidine to uridine

A

4 - cytidine to uridine

54
Q

During somatic hypermutation the enzyme induced cytidine deaminase (AIR) is expressed and is able to bind directly with DNA, but only when B cells are activated and proliferating. Once bound to DNA it causes a switch from cytidine to uridine in the single stranded DNA. Uridine is only present in RNA and will not be able to remain once the DNA recombines. What does the cell then do to fix this problem?

A
  • repairs DNA via bases excision or mismatch repair
  • mismatch repair changes the DNA resulting in mutations
  • base excision results in a new base pair in the DNA
  • BOTH CAUSE RANDOM MUTATIONS RESULTING IN UNIQUE ANTIGENS IN DAUGHTER CELLS
55
Q

During somatic hypermutation the enzyme induced cytidine deaminase (AIR) is expressed and is able to bind directly with DNA, but only when B cells are activated and proliferating. Once bound to DNA it causes a switch from cytidine to uridine in the single stranded DNA. Uridine is only present in RNA and will not be able to remain once the DNA recombines, so the DNA is repaired via bases excision or mismatch repair:

  • mismatch repair changes the DNA resulting in errors
  • base excision results in a new base pair in the DNA
  • BOTH CAUSE RANDOM MUTATIONS RESULTING IN UNIQUE ANTIGENS IN DAUGHTER CELLS

These mutations can result in changes in the affinity of the antibody binding site of the heavy chain of the B cell. Do all mutations increase the affinity?

A
  • some mutations increase antigen affinity called affinity maturation
  • some mutation reduce antigen affinity (if low affinity the B cell will not be activated and die)
56
Q

Somatic hypermutation results in a point mutation within the B cells DNA. What does this cause?

A
  • results in diversity of antigen binding site on the heavy chains of B cell receptors
57
Q

What is class switch recombination?

A
  • a B cells ability to change the type of immunoglobulin

- for example IgM to IgG

58
Q

In class switch recombination a B cell is able to change the type of immunoglobulin, for example IgM to IgG. Does this require change in both the variable and constant regions?

A
  • no
  • variable region does not change
  • constant region changes
59
Q

What 2 immunoglobulins can naive B cells produce?

1 - IgM and IgE
2 - IgM and IgD
3 - IgM and IgA
4 - IgG and IgM

A

2 - IgM and IgD

60
Q

Naive B cells are able to produce 2 different antibodies, IgM and IgD. The antibodies are able to change, called class switch recombination (CSR). What is the purpose of changing antibodies?

A
  • some antibodies bind better to different microorganisms
  • antibodies produced are dependent on the foreign body and other antibodies have more functions
  • higher affinity means the antibodies bind better and allow cytotoxic T cells to destroy it

Year 2 MIS (48 decks)

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