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Infections and Defence > Benny Chain > Flashcards

Benny Chain Flashcards

1
Q

What does an antigen bind to to cause B cells to divide?

A

The antibody

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2
Q

What transduces signals to B cells for the release of antibody?

A

Ig alpha and beta next to the antibody

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3
Q

What does an antigen bind to to cause T cells to divide?

A

The TCR (T cell receptor)

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4
Q

Where is the variable part of the TCR located on the molecule?

A

It is located furthest from the membrane.

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5
Q

What is the TCR made up of?

A

Alpha and beta chains that bind directly to the CSM.

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6
Q

Which genes recombine for variability of the TCR?

A

The VJ and VD genes

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7
Q

Can the TCR change once it has been formed?

A

No, however B cells can.

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8
Q

What are the 2 types of TCR present on cells?

A

TCR alpha beta (most T cells)

TCR gamma delta (only a few T cells on epithelial surfaces)

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9
Q

What is the target for the TCR?

A

Short peptide chains held by the appropriate MHC class.

TCR only looks at internal protein structures.

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10
Q

What is the MHC class molecule?

A 
The MHC (major histocompatibility complex) is a target cell that presents the peptide chain to the T cell.
It binds to the backbone of the protein.
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11
Q

What is required for a T cell to become activated?

A

1) Co stimulation
2) MHC presenting cells
3) Dendritic cells
4) Negative regulatory signals

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12
Q

What are the costimulatory molecules for T cells?

A

CD28, which is a receptor for CD80 and CD86.

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13
Q

What is negative regulation?

A

When there is an inhibitory response and prevention that results from the binding of a molecule.
When the molecule is no longer bound the process may take place.

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14
Q

Which molecules bound to T cells conduct negative regulation?

A

CTLA-4 and PD1.

These are important in preventing over activation, so have been beneficial in the immune responses to cancer.

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15
Q

Which CD antigen is found on T cells?

A

T cells are associated with CD3 pathways.

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16
Q

What is the role of the CD3 pathways for T cells?

A

It informs the T cell when the TCR has bound to the MHC and peptide complex.

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17
Q

What is the difference between HLA and MHC?

A

MHC genes are polymorphic, the genes only found in humans are referred to as HLA.

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18
Q

Which HLA genes make up MHC class I?

A

HLA-A
HLA-B
HLA-C

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19
Q

Which HLA genes make up MHC class II?

A

HLA-DP
HLA-DQ
HLA-DR

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20
Q

What is the main difference between antigen recognition for B cells and T cells?

A

B cell antibodies can directly recognise the shape of the antigen, but the TCR can only recognise the antigen when it has been processed into short peptides and presented to the TCR.

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21
Q

Which cells are MHC class I molecules found on?

A

All nucleated cells (not on RBCs)

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22
Q

Which cells are MHC class II molecules found on?

A

‘Professional’ antigen-presenting cells

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23
Q

List the ‘professional’ antigen presenting cells

A

1) Interdigitating dendritic cells
2) Macrophages
3) B cells

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24
Q

What are both MHC class I and MHC class II made from?

A

2 alpha helices

1 beta pleated sheet floor

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25
Q

What part of the MHC class I molecule forms the groove in which the peptide can bind?

A

The 2 outer domains of the alpha chain

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26
Q

Which molecule is necessary for the folding and surface expression of MHC class I?

A

Beta 2 microglobulin

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27
Q

What part of the MHC class II forms the groove in which the peptide can bind?

A

The outer domains of the alpha and beta chains

28
Q

What is an exogenous antigen?

A

These are antigens that enter the body from the outside.

29
Q

What is an endogenous antigen?

A

These are antigens that are produced by normal cell metabolism or when cell is infected by bacteria or viruses.

30
Q

Which T cell does MHC class I present to?

A

MHC class I activates CD8 cytotoxic T cells

31
Q

Which T cell does MHC class II present to?

A

MHC class II activates CD4 helper T cells

32
Q

What is the binding groove of both MHC class molecules made up of?

A

2 alpha helices

1 beta sheet

33
Q

Which MHC class presents endogenous antigens?

A

MHC class I presents endogenous antigens

34
Q

Which MHC class presents exogenous antigens?

A

MHC class II presents exogenous antigens

35
Q

On which chromosome in humans is the gene for MHC?

A

Chromosome 6

36
Q

How many variants of the MHC class are present in every individual?

A

12 variants (the alleles from each parent are co dominant)

37
Q

Outline the endogenous pathway of MHC class I

A

1) Viral proteins in the cell are degraded by proteolytic enzymes inside the proteasome.
2) This generates peptide 8-10 amino acids long that are transported to the endoplasmic reticulum by TAPs (transporters associated with antigen processing).
3) The peptide then binds to the MHC class I complex and this is taken to the surface of the cell in a Trans-Golgi vesicle.
4) Now CD8 T cells with a TCR specific for the peptide on that MHC class I can now kill the infected cell.

38
Q

Outline the exogenous pathway of MHC class II

A

1) Professional antigen presenting cells take in microbes and microbial components by phagocytosis or endocytosis.
2) Protein components of the microbe are degraded by proteolytic enzymes called cathespins. These are only active in an acidic pH.
3) MHC class II that has been formed in the endoplasmic reticulum is release in vesicles that can fuse with microbial peptides that are 15 amino acids long.
4) The peptide bound to the MHC class II complex is now transported to the surface of the cell.
5) Now CD4 T cells with a TCR specific for the peptide on that MHC class II can now be activated to help other cells in the immune system.

39
Q

How can cross presentation affect the exogenous and endogenous pathways?

A

This occurs when some peptides leave the phagocytic/endocytic vesicle and enters the endogenous pathway to activate CD8 cytotoxic T cells.

40
Q

How can autophagy affect the exogenous and endogenous pathways?

A

This is when endogenous antigens are able to make their way into the MHC class II pathway.

41
Q

What is the immunological synapse?

A

The contact area between the T cell and the antigen presenting cell.

42
Q

What occurs in the immunological synapse when the T cell is activated?

A

Many TCR molecules on the surface of the T cell move into the immunological synapse.
This leads to tyrosine phosphorylation of ITAMs on several CD3 chains.
This leads to activation of transcription factors that can bind to specific sites on DNA and regulate transcription of particular sets of genes.

43
Q

What is a key step that occurs in T cell activation that is important I immunosuppressants?

A

The activation of the transcription factor NF-AT can be inhibited by cyclosporine and FK506.
This can be used clinically to block transplant rejection.

44
Q

What are the differences between a primary and secondary immune response?

A

1) More antibody released in the secondary response.
2) Second response is faster.
3) Secondary responses releases antibodies with a higher affinity to the antigen.
4) Memory cells that circulate in the bloodstream can form plasma cells faster in the secondary response.

45
Q

What are soluble antibodies known as?

A

Immunoglobulins

46
Q

What is the function of the Fab region of the antibody?

A

It is the variable region that gives antigen specificity and allows the shape to be recognised.
Contains the variable domain, the first constant domain of one of the heavy chains and a light chain.
One is present on each arm of the antigen.

47
Q

What is the function of the Fc region of the antibody?

A

Attaches to Fc receptors on cells, contains the biological activity effect of the antibody.
Composed of 2 heavy chains.
Contains the constant region of the heavy chain which determines the antibody class.

48
Q

Describe the role of IgG as an antibody

A

Most common antibody found in circulation and tissues.
Only antibody that can pass across the placenta.
It is a dimer.
Has a higher affinity for antigens than IgM.
Important in opsonisation for phagocytosis and activating complement via the classical pathway.

49
Q

Describe the role of IgA as an antibody

A

Found as a monomer in circulation and as a dimer in the mucosa.
Joined by a J protein.
Common antibody in secretions.
Present in breast milk and protects the baby in early life.

50
Q

Describe the role of IgM as an antibody

A

First antibody produced in development and in the immune response.
Has a high avidity for agglutination of antigens.
Expressed on every B cell at the beginning of its life.
It is a pentamer.
Functions as a BCR on naïve B cells.
Linked by disulphide bonds and a J chain.

51
Q

Describe the role of IgE as an antibody

A

Binds to Fc receptors on basophils and mast cells to cause the inflammatory response.
Involved in allergic reactions.
Binds to the mast cell before it comes into contact with the allergen.

52
Q

Describe the role of IgD as an antibody

A

Expressed on B cells when they leave the bone marrow and move to secondary lymphoid tissue.
It is lost from B cells once the cell has matured.
With IgM on B cell surface.

53
Q

How does antibody avidity and affinity change from the primary and secondary immune response?

A

In the first immune response the antibodies released are mostly IgM, with a high avidity for the antigen (pentamer).
In the secondary response IgG antibodies are released which have a greater affinity for the antigen so IgM is no longer required.
If an antibody has a high avidity and affinity it can form immune complexes that may add to inflammation and block pathways.

54
Q

List the 4 main effects of antibodies

A

1) Neutralisation of toxins
2) Neutralisation of viruses
3) Direct opsonisation for phagocytosis
4) Activating complement

55
Q

How does antibody neutralise toxins?

A

The antibody binds to the toxin so that the toxin cannot bind to the cell receptor and cause pathology.

56
Q

How does antibody neutralise viruses?

A

Antibody binds to the virus so the virus cannot bind to a cell receptor and cause disease.

57
Q

How does antibody cause opsonisation?

A

The antibody can coat bacteria.
The Fc receptor on phagocytes is specific for the antibody, so the bacteria can be taken up by phagocytosis.
Bacteria with capsules will be resistant to this.

58
Q

Which Fc receptor is specific for IgG antibodies?

A

Fc gamma receptors

59
Q

Which major component of complement causes its activation when split with enzymes?

A

C3 -> It is split into C3a and C3b

60
Q

What is the function of C3b?

A

It marks out bacteria for opsonisation of phagocytes.

61
Q

Which complement component does C3a combine with to have an effect?

A

It combines with C5a

62
Q

What is the effect of C3a?

A

1) Promotes inflammation by activating mast cells. Increases local vascular permeability so more neutrophils, monocytes and antibodies flow to tissues.
2) Causes degranulation of mast cells, and combines with C5b, C6, C7, C8 and C9 to form the membrane attack complex. This creates pores in the cell membrane which leads to cell lysis or apoptosis.

63
Q

Which 3 places are complement receptors found?

A

1) Phagocytes
2) Erythrocytes
3) B lymphocytes

64
Q

Name the 3 pathways to activate complement

A

1) Alternative pathway - microbial cell walls
2) Classical Pathway - Antibody binds to the microbe
3) Lectin pathway - microbial sugars

65
Q

What is released by Th cells to induce class switching of antibodies?

A

Cytokines (IL 4 and TGF beta)

66
Q

List some uses of monoclonal antibodies

A

1) Measuring
2) Monitoring
3) Detection of substances
4) Treatment of disease

67
Q

Outline the process of flow cytometery

A

1) B cells are passed through a small nozzle and a laser is shined on them.
2) Each antibody with fluoresce a different colour.

3) Computer can then count how many antibody are bound to each cell, how many different populations of cell are present depending on how much fluorescence they give.
Further along the axis = stronger fluorescence.

Infections and Defence (8 decks)

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