Antibodies Flashcards
What are antibodies produced by?
B lymphocytes (plasma cells)
Which stem cells produce all of the blood cells?
Haematopoietic cells
Where do B cells come from?
- Stem cells in bone marrow
* Differentiate in the central organs
Where do T cells come from?
The thymus
Where are B cells that haven’t met their antigen located?
• From blood to peripheral lymphoid tissues
Where is the main site of antigen encounter?
Peripheral lymphoid tissues
How do recirculating B cells enter back into the blood stream?
Thoracic duct
Describe the structure of a lymph node
• Cortex:
- Outer section of B cells organised into follicles
- Paracortical area of T cells and dendritic cells
• Medulla:
- Macrophages
- Antibody secreting cells= plasma cells
What forms during an immune response?
Germinal centres of B cell proliferation in the cortex
Where do lymph enter the lymph nodes?
Afferent lymphatic vessel
Where do B cells enter the lymph node?
Artery
What causes swelling in the lymph nodes?
The growing germinal centres of B cell proliferation
What makes up the red pulp in the spleen?
Site of RBC destruction
What is white pulp in the spleen?
Lymphoid
How do antigen enter the spleen?
From the blood stream
What are the basic features of antibodies?
- Expressed as membrane bound (B cell receptor) or secreted forms
- B cells express a single Ab specificity only
- Ab have 2 separate functions
What are the 2 functions of Ab cells
- 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
Describe the structure of an antibody
- 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
What are the types of L chain
- Lamba or kappa
* Ab either has one or the other
Which is the more common L chain?
Kappa
What are the 2 ways to cleave an antibody?
- Proteolytic by papain: 2 FAB regions
* Proteolytic by pepsin: F(‘ab)2
Where is the binding site for the antigen?
In the FAB region
What is the Fc region?
• Interact with receptors
Describe the hypervariability of antibodies
- 3 hypervariable loops
* Determine antigen specificity by forming a surface complimentary to the antigen
What determines the final specificity of the antibody?
Combination of loops from H and L chains
What limits the number of antibody specificities?
The number of B cells present
Germline theory
Separate gene exists for each Ab - not correct
Somatic Diversification theory
Repertoire is generated from a limited number of V region genes that undergo alteration
Chromosomal rearrangement
The sequence of a V region is generated by the somatic recombination of separate gene segments
Regions in Heavy chains
- Variable
- Dregion
- J regions
- Constant
What happens in chromosomal rearrangement
- 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
What accounts for the variation?
- Chromosomal rearrangement
- junctional diversity
- Different combinations of light and heavy chains
- Somatic Hypermutation
Junctional Diversity
Gap left in cleavage which allows for an enzyme to come in and insert random DNA
Somatic hypermutation
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
What are the 5 classes of antibodies?
• IgG • IgM • IgD • IgA • IgE Defined by the heavy chain
Which class of antibody do we have most of
IgG
What drives allergic response?
IgE- sucked out of the blood stream and absorbed by mast cells
Which classes can exist as a multimeric form?
IgM - pentamers
IgA - dimeric
What is special about the dimeric form of IgA
Taken up by endothelial cells and moved across
Antibodies predominating the plasma
IgG and IgM
Antibodies in extracellular fluid
IgG and monomeric IgA
Antibodies in secretions
Dimeric IgA
Which antibody does the foetus receive by transplacental transfer?
IgG
Which antibody is mostly near to the epithelial surfaces?
IgE - especially gut, lungs and skin
Which area of the body is free from Ab?
The brain
How does an antibody protect against a virus?
Blocks binding of the cell to the virus receptor
How do antibodies protect against toxins?
- Neutralising antibodies blocks the binding of the toxin
* e.g. tetanus toxoid
How do antibodies protect against bacteria?
- Coats bacteria
- Increases phagocytosis
- Acts as an opsonin
What is a clinical issue of antibody-antigen complexes?
Accumulate and can activate the complement pathway
Glomerulonephritis autoimmune diesases
Monoclonal antibodies
- 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
What is the problem with monoclonal antibodies? How are they overcome?
Mouse so body reacts to them
• humanise them
Infliximab
- Anti tumour necrosis Factor
- Rheumatoid arthritis
- Ankylosing spondylitis
- Psoriasis
- Inflammatory bowel disease
Herceptin
- Anti HER2
* Can blck growth and lead to the destruction of breast tumour cells that express high levels of HER2
Gleevac
Anti-tyrosine kinase
• Effective against chronic myeloid leukaemia
