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Immunology and Haematology > Adaptive Immune System > Flashcards

Adaptive Immune System Flashcards

1
Q

What are the main cells of the adaptive immune system?

A
  • T lymphocytes
    • CD4+ Helper T lymphocytes
    • CD8+ Cytotoxic T lymphocytes
  • B cells
    • Plasma cell
    • Memory B cell
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2
Q

Describe the development of the cells of the adaptive immune system?

A
  1. Multipotent haematopoietic stem cells found in bone marrow differentiate to form common myeloid and lymphoid progenitor cells
  2. Lymphoid progenitor cells give rise to T cells, B cells and NK cells
  3. B cells mature in bone marrow, whereas T cells move and complete maturation within thymus
    1. Once in thymus T cells are termed thymocytes, where they develop specific T cell markers including the T cell receptor
  4. Both cells differentiate further within secondary lymphoid organs
    1. Positive and negative selection occurs here
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3
Q

Where do B cells and T cells mature?

A
  1. B cells mature in bone marrow, whereas T cells move and complete maturation within thymus
    1. Once in thymus T cells are termed thymocytes, where they develop specific T cell markers including the T cell receptor
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4
Q

Where do T cells recieve their TCR?

A

Thymus

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5
Q

What are T cells in the thymus termed?

A

Thymocytes

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6
Q

What does TCR stand for?

A

T cell receptor

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7
Q

Describe the formation of the TCR?

A

T cell receptor (TCR) formed during T cell development in thymus:

  • Composed of alpha and beta chains
  • Within these proteins are complementarity determining regions (CDRs)
    • Part that binds to antigens
    • V(D)J recombination occurs to create diverse selection of antigen binding sites within T cell receptors
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8
Q

What chains is the TCR composed of?

A
  • Composed of alpha and beta chains
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9
Q

What does CDRs stand for?

A

Comlementarity determining regions

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10
Q

What are CDRs?

A
  • Part that binds to antigens
  • V(D)J recombination occurs to create diverse selection of antigen binding sites within T cell receptors
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11
Q

What allows the diversity of the TCR?

A
  • V(D)J recombination occurs to create diverse selection of antigen binding sites within T cell receptors
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12
Q

What does CD refer to?

A

CD refers to cluster of differentiation:

  • All white cells have unique surface markers, named as specific CD markers
  • Cells gain and lose these as they mature, so presence or absence allows maturity of cell to be assessed
  • CD4+ and CD8+ act as co-receptors with the TCR, to allow TCR to interact with MHC more effectively
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13
Q

What does the presence of CD markers allow to be assessed?

A
  • Cells gain and lose these as they mature, so presence or absence allows maturity of cell to be assessed
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14
Q

What is the function of CD4 and CD8?

A
  • CD4+ and CD8+ act as co-receptors with the TCR, to allow TCR to interact with MHC more effectively
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15
Q

Where does positive and negative selection of T cells occur?

A

Thymus

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16
Q

Describe the development of T cells in the thymus?

A

In early stage of development within thymus, neither CD4 nor CD8 is expressed on T cell so they are termed double negative thymocytes (CD4- and CD8-)

They continue to develop and become double positive thymocytes (CD4+CD8+)

They then undergo positive and negative selection:

  • Positive selection – identifies T cells capable to interacting with MHC
    • If able to interact with MHC survive
    • If unable to interact with MHC are destroyed by apoptosis
  • Negative selection – identifies T cells that react to strongly to self-antigens
    • If react too strongly destroyed by apoptosis

Cells that survive this differentiate into single positive T cells (either CD4 or CD8) depending on whether TCR recognised MHC I or MHC II

Then released from thymus as naïve cells, only differentiating into Th or Tc once they have encountered complementary antigens within secondary lymphoid organs

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17
Q

What is positive and negative selection?

A
  • Positive selection – identifies T cells capable to interacting with MHC
    • If able to interact with MHC survive
    • If unable to interact with MHC are destroyed by apoptosis
  • Negative selection – identifies T cells that react to strongly to self-antigens
    • If react too strongly destroyed by apoptosis
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18
Q

What causes T cells to become CD4 or CD8?

A

Cells that survive this differentiate into single positive T cells (either CD4 or CD8) depending on whether TCR recognised MHC I or MHC II

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19
Q

What are T cells termed when they are released from the thymus?

A

Naive T cells

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20
Q

When do naive T cells differentiate into T helper or T cytotoxic cells?

A

Then released from thymus as naïve cells, only differentiating into Th or Tc once they have encountered complementary antigens within secondary lymphoid organs

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21
Q

Describe the function of cytotoxic T cells?

A
  • Recognise and destroy viral infected host cells, or any host cells showing signs of damage via their MHC I expression
  • Kill using 3 different mechanisms once activated
    • Release IFN and TNF-a which have anti-viral and anti-tumour effects
    • Release cytotoxic granules containing perforin and granzyme proteins in direction of target cells
      • Performin produces pore in target membrane allowing entry of granzyme enzymes
      • Granzymes are proteases that trigger the caspase cascade which leads to apoptosis of cell
    • Induce apoptosis via Fas and FasL interactions with target cell
      • Activated Tc cell will express FasL on surface, which binds to the Fas receptor on target cell triggering the caspase cascade and causing apoptosis
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22
Q

What are the 3 mechanisms cytotoxic T cells can use to kill?

A
  • Release IFN and TNF-a which have anti-viral and anti-tumour effects
  • Release cytotoxic granules containing perforin and granzyme proteins in direction of target cells
    • Performin produces pore in target membrane allowing entry of granzyme enzymes
    • Granzymes are proteases that trigger the caspase cascade which leads to apoptosis of cell
  • Induce apoptosis via Fas and FasL interactions with target cell
    • Activated Tc cell will express FasL on surface, which binds to the Fas receptor on target cell triggering the caspase cascade and causing apoptosis
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23
Q

What does performin and granzymes do?

A
  • Performin produces pore in target membrane allowing entry of granzyme enzymes
  • Granzymes are proteases that trigger the caspase cascade which leads to apoptosis of cell
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24
Q

How do cytotoxic T cells induce apoptosis on the target?

A
  • Activated Tc cell will express FasL on surface, which binds to the Fas receptor on target cell triggering the caspase cascade and causing apoptosis
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25
Q

What are functions of helper T cells?

A
  • Help activate other immune cells by releasing T cell cytokines
  • Responsible for B cell antibody class switching, activation and growth of cytotoxic T cells and maximise activity of phagocytes
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26
Q

What are the different types of helper T cell subsets?

A
  • Th1
    • Releases IFN-gamma to maximise activity of phagocytes and cytotoxic T cells
    • Function – cellular immunity, clearance of intracellular pathogens
  • Th2
    • Releases – IL4, IL5, IL13 to activate basophils, mast cells and eosinophils, and to promote class switching of antibodies to IgE
    • Inhibits activity of Th1, over-activity of Th1 can result in type IV hypersensitivity reactions such as in MS, but over-activity of Th2 can result in type I hypersensitivity such as asthma
    • Function – humoral immunity, clearance of certain extracellular pathogens, allergy
  • Th17
    • Releases – IL17, IL22, IL21 which are pro-inflammatory and stimulates recruitment of neutrophils and macrophages to infected tissues via CXCL-8
    • If Th17 over-active can create a chronic inflammatory state as seen in some autoimmune diseases such as rheumatoid arthritis
    • Function – tissue inflammation and autoimmunity, clearance of certain extracellular pathogens
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27
Q

For Th1:

  • releases
  • function
A
  • Releases IFN-gamma to maximise activity of phagocytes and cytotoxic T cells
  • Function – cellular immunity, clearance of intracellular pathogens
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28
Q

For Th2:

  • releases
  • function
A
  • Releases – IL4, IL5, IL13 to activate basophils, mast cells and eosinophils, and to promote class switching of antibodies to IgE
  • Inhibits activity of Th1, over-activity of Th1 can result in type IV hypersensitivity reactions such as in MS, but over-activity of Th2 can result in type I hypersensitivity such as asthma
  • Function – humoral immunity, clearance of certain extracellular pathogens, allergy
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29
Q

For Th17:

  • releases
  • function
A
  • Releases – IL17, IL22, IL21 which are pro-inflammatory and stimulates recruitment of neutrophils and macrophages to infected tissues via CXCL-8
  • If Th17 over-active can create a chronic inflammatory state as seen in some autoimmune diseases such as rheumatoid arthritis
  • Function – tissue inflammation and autoimmunity, clearance of certain extracellular pathogens
30
Q

How are T regulatory cells formed?

A

During selection in thymus, some T cells that recognise self-antigens differentiate into regulatory T cell instead of being deleted

Some of this differentiation is also induced in periphery

31
Q

Describe the functions of T reg cells?

A
  • Suppressing the activation, proliferation and cytokine production of CD4 and CD8 lymphocytes
  • Control the response to self-antigens, and so monitor self-tolerance
  • Secretes IL10 and transforming growth factor-beta (TGF-b) which are anti-inflammatory to help suppress immune response
32
Q

What cytokines do T reg cells secrete?

A
  • Secretes IL10 and transforming growth factor-beta (TGF-b) which are anti-inflammatory to help suppress immune response
33
Q

Are the cytokines that T reg cells secrete pro or anti-inflammatory?

A

Anti-inflammatory

34
Q

What kind of immunity are B lymphocytes responsible for?

A

Responsible for humoral immunity as part of adaptive immune response:

  • Acts through actions of antibodies (or immunoglobulins) directed against specific antigens
35
Q

What do antibodies do?

A

Recognise antigen and bind to it via the Fab (fragment antigen binding variable region) of antibody

Once bound communicate with other components of immune system via Fc (constant region) of antibody at the base of the Y

36
Q

How do antibodies bind to antigen?

A

Fab region of antibody

37
Q

What does Fab stand for?

A

Fragment antigen binding variable region

38
Q

What is the Fab region of antibody also called?

A

Variable region

39
Q

What are the 2 forms antibodies can be found as?

A
  • Soluble form secreted by plasma cells free-floating in bloodstream
  • Fixed form membrane bound on to surface of B cell, membrane bound antibody is also referred to as B cell receptor
40
Q

What are antibodies fixed to surface of B cells called?

A

B cell receptor

41
Q

What does BCR stand for?

A

B cell receptor

42
Q

What are the 5 different antibody isotypes?

A
  • IgA
    • Dimeric
    • Present within secretions such as tears and milk
  • IgD
  • IgE
    • Immune response to parasites, also involved in pathogenesis of allergic reactions
  • IgG
    • Main component of secondary antibody immune response to antigen
    • Only isotype able to cross placenta
  • IgM
    • Primary antibody response to antigen
    • Largest antibody with most binding sites, so more efficient at activating complement
43
Q

Which antibody is most prevalent?

A

IgG

44
Q

What is the only antibody that can cross the placenta?

A

IgG

45
Q

What antibody forms the primary antibody response?

A

IgM

46
Q

What antibody is most efficient at activating complement?

A
  • IgM
    • Primary antibody response to antigen
    • Largest antibody with most binding sites, so more efficient at activating complement
47
Q

What does the suffix of the immunoglobulin isotypes relate to?

A

Suffix relates to the heavy chain present on the isotype

48
Q

What does each antibody differ in?

A
  • Biological properties
  • Functional locations
  • Ability to deal with different antigens
49
Q
A
50
Q

What are some functions of antibodies?

A
  • Bind to antigens directly to form immune complexes which are cleared through filtration in the blood in organs like liver and spleen
  • Act as opsonins for phagocytosis
  • Activating complement cascade via the classical pathway
  • Bind to target cell and initiate a non-phagocystic cell-mediated destruction of cell, called antibody-dependent cellular cytotoxicity (ADCC)
51
Q

What does ADCC stand for?

A

Antibody-dependent cellular cytotoxicity

52
Q

What is ADCC?

A

Initiates killing of pathogens or target cells via immune cells from innate system:

  • Antibodies bind to antigen receptors on target cell via the Fab region of antibody
  • The Fc antibody receptor can then bind to a number of immune cells to activate them
    • NK cells, macrophages, neutrophils, eosinophils
  • Does not involve complement, and mechanism is not phagocytosis
53
Q

What is ADCC primariliy mediated by?

A

Primarily mediated by NK cell activation:

  • NK cells bind to FC portion of a cell-bound antibody via their FC receptor, CD16
  • Activates NK cell, causing cell mediated destruction of target cell through release of perforin and granzyme, causing apoptosis in target cell
  • Binding to FC portion of membrane bound antibody can also activate macrophages, neutrophils and eosinophils causing degranulation and toxic enzymes to facilitate extracellular destruction of target cell
54
Q

Describe the process of ADCC with NK cells?

A
  • NK cells bind to FC portion of a cell-bound antibody via their FC receptor, CD16
  • Activates NK cell, causing cell mediated destruction of target cell through release of perforin and granzyme, causing apoptosis in target cell
  • Binding to FC portion of membrane bound antibody can also activate macrophages, neutrophils and eosinophils causing degranulation and toxic enzymes to facilitate extracellular destruction of target cell
55
Q

Where does B cell development occur?

A
  • B cells express unique surface receptor called a B cell receptor, which is actually an antibody
  • During B cell development, V(D)J recombination occurs within the genes encoding the antigen binding sites of B cell receptor, creating diversity
56
Q

Where does B cell activation occur?

A

B cells circulate between secondary lymphoid organs looking for antigens that match B cell receptor, activation occurs within these secondary lymphoid organs through 1 of 3 mechanisms

57
Q

What are the 3 mechanisms of activating B cells?

A
  • Helper T cell dependent activation
  • Helper T cell independent activation
  • Memory B cell activation helper T cell dependent activation
58
Q

When does helper T cell dependent activation of B cell occur?

A

Helper T cell dependent activation occurs when antigen recognised by B cell and helper T cell

59
Q

When does helper T cell independent activation of B cell occur?

A

Helper T cell independent activation occurs when B cells are activated directly by antigens found within secondary lymphoid organs:

  • T independent antigens are usually lipids or polysaccharides where T dependent antigens are proteins
60
Q

What kind of molecules are of T independent and T dependent antigens usually?

A
  • T independent antigens are usually lipids or polysaccharides where T dependent antigens are proteins
61
Q

What happens when a memory B cell re-encounters an antigen?

A

When a memory B cell re-encounters an antigen that is able to bind to BCR (B cell receptor), the memory B cell reactivates and initiates differentiation into plasma cells, resulting in rapid release of antigen specific antibodies

62
Q

What could occur following the activation of a B cell?

A
  • B cell bound to antigen differentiates into short lived plasma cell
    • Secretes IgM and IgG antibodies specific for the antigen encountered
    • Found primarily in spleen and lymph nodes
  • Or go to germinal centre of lymph node to proliferate and develop an ability to bind to antigen with greater affinity and undergo immunoglobulin class switching
    • This is process where B cells become able to produce a different class of Ig in response to same antigen
    • After this has occurred they exit lymph node and travel to bone marrow where they differentiate into long-lived plasma cell or memory B cell
63
Q

Where do B cells go to proliferate and develop class switching?

A

Germinal centre of lymph node

64
Q

What do B cells do after undergoing immunoglobulin class switching?

A
  • After this has occurred they exit lymph node and travel to bone marrow where they differentiate into long-lived plasma cell or memory B cell
65
Q

What is immunoglobulin class switching?

A

Mechanism that changes the isotope of an antibody produced by B cells from one to another, such as IgM to IgG in primary and secondary infections:

  • Results in change of heavy chai of an antibody, whilst keeping variable region of antibody unchanged
  • Meaning new isotope acts on same antigen but with different effector cells
66
Q

What does immunoglobulin class switching allow?

A
  • Meaning new isotope acts on same antigen but with different effector cells
67
Q

Does immunoglobulin class switching change the heavy chain or light chain?

A
  • Results in change of heavy chain of an antibody, whilst keeping variable region of antibody unchanged
68
Q

Describe the speed of response of B cells when first encountering an antigen, compared to re-encountering it in the future?

A

When foreign antigen first encountered there is a lag phase whilst activated B cells are differentiating into plasma cells, no antibodies are produced here

Once plasma cells have formed a low number of IgM antibodies released to neutralise initial infection, and small amounts of IgG can also be produced

Memory B cells are produced, so if same antigen is encountered in the future the response is faster, causing quick high amounts of IgG and low amounts of IgM

69
Q

What are the typical Ig levels when a B cell first encounters an antigen?

A

Once plasma cells have formed a low number of IgM antibodies released to neutralise initial infection, and small amounts of IgG can also be produced

70
Q

What are the typical Ig levels when a B cell re-encounters an antigen?

A

Memory B cells are produced, so if same antigen is encountered in the future the response is faster, causing quick high amounts of IgG and low amounts of IgM

71
Q

What is immunological memory?

A

These long lived memory cells that enable a quick response in the future is referred to as immunological memory:

  • Memory B cells generate accelerated and more potent antibody-mediated immune response
  • Memory T cells can either express CD4 or CD8 and respond rapidly

Immunology and Haematology (23 decks)

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