Antibodies

Question 1

What are antibodies produced by?

Answer 1

B lymphocytes (plasma cells)

Question 2

Which stem cells produce all of the blood cells?

Answer 2

Haematopoietic cells

Question 3

Where do B cells come from?

Answer 3

• Stem cells in bone marrow

* Differentiate in the central organs

Question 4

Where do T cells come from?

Answer 4

The thymus

Question 5

Where are B cells that haven’t met their antigen located?

Answer 5

• From blood to peripheral lymphoid tissues

Question 6

Where is the main site of antigen encounter?

Answer 6

Peripheral lymphoid tissues

Question 7

How do recirculating B cells enter back into the blood stream?

Answer 7

Thoracic duct

Question 8

Describe the structure of a lymph node

Answer 8

• Cortex:
- Outer section of B cells organised into follicles
- Paracortical area of T cells and dendritic cells
• Medulla:
- Macrophages
- Antibody secreting cells= plasma cells

Question 9

What forms during an immune response?

Answer 9

Germinal centres of B cell proliferation in the cortex

Question 10

Where do lymph enter the lymph nodes?

Answer 10

Afferent lymphatic vessel

Question 11

Where do B cells enter the lymph node?

Answer 11

Artery

Question 12

What causes swelling in the lymph nodes?

Answer 12

The growing germinal centres of B cell proliferation

Question 13

What makes up the red pulp in the spleen?

Answer 13

Site of RBC destruction

Question 14

What is white pulp in the spleen?

Answer 14

Lymphoid

Question 15

How do antigen enter the spleen?

Answer 15

From the blood stream

Question 16

What are the basic features of antibodies?

Answer 16

• Expressed as membrane bound (B cell receptor) or secreted forms
• B cells express a single Ab specificity only
• Ab have 2 separate functions

Question 17

What are the 2 functions of Ab cells

Answer 17

• Firstly to bind to the pathogen that elicited its production
• Secondly to recruit other cells and molecules that will lead to clearance or destruction of the pathogen

Question 18

Describe the structure of an antibody

Answer 18

• 2 identical heavy chains that are disulfide bonded to each other
• 2 light chains
• Each H chain is also disuldfide bonded to an L chain

Question 19

What are the types of L chain

Answer 19

• Lamba or kappa

* Ab either has one or the other

Question 20

Which is the more common L chain?

Answer 20

Kappa

Question 21

What are the 2 ways to cleave an antibody?

Answer 21

• Proteolytic by papain: 2 FAB regions

* Proteolytic by pepsin: F(‘ab)2

Question 22

Where is the binding site for the antigen?

Answer 22

In the FAB region

Question 23

What is the Fc region?

Answer 23

• Interact with receptors

Question 24

Describe the hypervariability of antibodies

Answer 24

• 3 hypervariable loops

* Determine antigen specificity by forming a surface complimentary to the antigen

Question 25

What determines the final specificity of the antibody?

Answer 25

Combination of loops from H and L chains

Question 26

What limits the number of antibody specificities?

Answer 26

The number of B cells present

Question 27

Germline theory

Answer 27

Separate gene exists for each Ab - not correct

Question 28

Somatic Diversification theory

Answer 28

Repertoire is generated from a limited number of V region genes that undergo alteration

Question 29

Chromosomal rearrangement

Answer 29

The sequence of a V region is generated by the somatic recombination of separate gene segments

Question 30

Regions in Heavy chains

Answer 30

* Variable * Dregion * J regions * Constant

Question 31

What happens in chromosomal rearrangement

Answer 31

* Somatic mutation, VDJ come together (light and heavy chain) * Multiple V regionsand junction and D regions and multiple constant regions * Splicing to each giving potential for diversity

Question 32

What accounts for the variation?

Answer 32

* Chromosomal rearrangement * junctional diversity * Different combinations of light and heavy chains * Somatic Hypermutation

Question 33

Junctional Diversity

Answer 33

Gap left in cleavage which allows for an enzyme to come in and insert random DNA

Question 34

Somatic hypermutation

Answer 34

Mutations occur in the V regions of the H and L chains | • Some will bind antigen better and these are selected for to expand and secrete antibodies

Question 35

What are the 5 classes of antibodies?

Answer 35

``` • IgG • IgM • IgD • IgA • IgE Defined by the heavy chain ```

Question 36

Which class of antibody do we have most of

Answer 36

IgG

Question 37

What drives allergic response?

Answer 37

IgE- sucked out of the blood stream and absorbed by mast cells

Question 38

Which classes can exist as a multimeric form?

Answer 38

IgM - pentamers | IgA - dimeric

Question 39

What is special about the dimeric form of IgA

Answer 39

Taken up by endothelial cells and moved across

Question 40

Antibodies predominating the plasma

Answer 40

IgG and IgM

Question 41

Antibodies in extracellular fluid

Answer 41

IgG and monomeric IgA

Question 42

Antibodies in secretions

Answer 42

Dimeric IgA

Question 43

Which antibody does the foetus receive by transplacental transfer?

Answer 43

IgG

Question 44

Which antibody is mostly near to the epithelial surfaces?

Answer 44

IgE - especially gut, lungs and skin

Question 45

Which area of the body is free from Ab?

Answer 45

The brain

Question 46

How does an antibody protect against a virus?

Answer 46

Blocks binding of the cell to the virus receptor

Question 47

How do antibodies protect against toxins?

Answer 47

* Neutralising antibodies blocks the binding of the toxin | * e.g. tetanus toxoid

Question 48

How do antibodies protect against bacteria?

Answer 48

* Coats bacteria * Increases phagocytosis * Acts as an opsonin

Question 49

What is a clinical issue of antibody-antigen complexes?

Answer 49

Accumulate and can activate the complement pathway | Glomerulonephritis autoimmune diesases

Question 50

Monoclonal antibodies

Answer 50

* Mouse produced B cells immunised with antigen and myeloma (cancer) cell * Fuse the cells * Grow in a drug containing medium * Select for antigen-specific hybridoma * Clone selected hybridoma cells

Question 51

What is the problem with monoclonal antibodies? How are they overcome?

Answer 51

Mouse so body reacts to them | • humanise them

Question 52

Infliximab

Answer 52

* Anti tumour necrosis Factor * Rheumatoid arthritis * Ankylosing spondylitis * Psoriasis * Inflammatory bowel disease

Question 53

Herceptin

Answer 53

* Anti HER2 | * Can blck growth and lead to the destruction of breast tumour cells that express high levels of HER2

Question 54

Gleevac

Answer 54

Anti-tyrosine kinase | • Effective against chronic myeloid leukaemia