Antibodies Flashcards
How are antibodies produced ?
By B lymphocytes
How are lymphocytes produced ?
Lymphocytes arise from stem cells in bone marrow and differentiate into B cells in bone marrow and T cells in the thymus.
Describe naive B cells
These are B cells that have not met antigen, and circulate from the blood into peripheral lymphoid tissues.
Function of Peripheral lymphoid tissues
Main site of antigen encounter
Function of lymphatics
Drain tissues of fluid, through the lymph nodes and into the thoracic duct.
Recirculating B cells enter back into the bloodstream by the thoracic duct.
State the main sites of B cells in the body
Spleen
Lymph nodes
Lymph node organisation
Material draining from the site of infection passes through some regions of B/T cells and varieties of antigen presenting cells.
Germinal centre
Accumulation of clonal B cells, which are expanding rapidly in response to an infection.
Describe the spleen
Site of B cells
Has :
- Red pulp
- White pulp
Red pulp
Site of RBC destruction
White pulp
Lymphoid
Spleen organisation
Where is antigen coming from ?
Antigen is coming through the bloodstream, not the lymphatics (like the lymph nodes)
Describe Secondary response
Secondary (memory) response is :
- faster
- can produce more antibody
- does not prevent you from making a response to another antigen.
(multiple antiegns - vaccination)
Function of B cells
Form part of the ADAPTIVE immune response, the key features of which are antigen specificity, and memory.
Describe some basic features of antibodies
How can they be expressed ?
They can be expressed as membrane bound (B cell receptor)
OR
secreted forms
Describe a key feature of B cell antibodies
B cells express a single Ab specificity only
State the functions of antibodies (Ab)
- Bind to the pathogen that elicited its production
- To recruit other cells and molecules that will lead to clearance or destruction of the pathogen.
Describe the structure of antibodies
4 polypeptide chains :
- 2 identical heavy chains
- 2 identical light chains
Describe the heavy chains of antibodies
Disulphide bonded to each other
Each H chain is also disulphide bonded to an L chain
Describe the light chains of antibodies
2 Light chains exist as lambda and kappa
(either lambda or kappa, never a mix)
In humans ratio is 2:1 in favour of kappa
Function of the 2 identical heavy and light chains
Results in 2 identical binding sites
Function of the constant region of antibodies
Activates the complement pathway
OR
Can assist with processes like phagocytosis
Fab region of antibodies
Contains the binding site for the antigen
Function of Fab and F(ab)2 fragments
Very useful tools in the lab, ie.e can be used to label cells without inducing the effects of the Fc region.
How are the Fab and F(ab)2 fragments removed
Fab - by papaln
F(ab)2 - by pepsin
Describe how antigens have specificity
3 hyper-variable loops determine antigen specificity by forming a surface complimentary to the antigens.
Final specificity is determined by a combination of loops from H and L chains, not either alone.
Germline Theory
Suggested that a separate gene existed for each Ab, which was not really the case.
Somatic Diversification Theory
Proposed that repertoire is generated from a limited number of V region genes that undergo alteration.
Essentially correct.
Chromosomal Rearrangement
The sequence of a V region is generated by the somatic recombination of separate gene segments
What are V region genes constructed from ?
Constructed from multiple gene segments.
Junctional Diversity
Errors in DNA replication
Completely random insertion of bits of DNA/nucleotides to make up a fresh DNA.
New loop at the front of antibody
CREATES EXTRA VARIABILITY
Name the main methods by which you generate antibody diversity
EXAM Q
- Rearranging multiple gene segments
- Junctional diversity
- Different combinations of H and L chains
- Somatic Hypermutation
When do methods to generate antibody diversity occur ?
During B cell development
(happens in bone marrow)
Somatic Hypermutation
Occurs after B cells have become antigen activated in the lymph node.
Accumulation of random mutations
State the 5 classes of antibodies and what they are defined by
Defined by the heavy chain
IgG
IgM
IgD
IgA
IgE
IgE
Sticks on mast cells and causes the allergic responses.
Sequestered away on mast cells.
IgA
Present in secretions, tears and saliva
Good at being transported across epithelium to get into saliva and tears.
IgD
The first B cells that come out of the bone marrow tend to always have IgD
IgG
The most common antibody and most prevalent in the bloodstream.
Describe IgG subclasses
IgG1 is the body common with up to 10mg per ml in blood.
Note : If IgG is increased –> infection, IgG decreased –> deficiency in immune response
Why is IgE concentration low in the blood ?
IgE which is very low, because as soon as you make it, it gets sucked out of the bloodstream and sits on muscle cells where its going to be doing its jobs.
IgM
All B cells initially express a membrane form of IgM (also some IgD).
Describe Antibody multimers
IgA - dimer in secretion
IgM - pentamer in secretion
What antibodies are dimers ?
IgA
What antibodies are pentamers ?
IgM
(can also be a monomer)
Function of dimeric form of IgA
Enables it to get across an epithelial cell and secreted via a transport mechanism.
Where is IgE found ?
Mostly near epithelial surfaces, especially gut, lungs and skin.
Where are IgG and IgM found ?
Predominate in plasma
Where are IgG and monomeric IgA found ?
MAin isotypes in extracellular fluid
Where is dimeric IgA found ?
Secretions across epithelia, including breastmilk.
Found in intestinal tract and respiratory tract.
Brain
Normally free from antibodies, due to blood brain barrier
Function of antibodies
Blocking binding to virus receptor
Opsonisation
Enhances phagocytosis into cells for degradation
What is high in autoimmune diseases ?
High levels of Antibody-Antigen complexes
Ab-Ag complexes
Major cause of glomerulonephritis
Function of Ab-Ag complexes
Important mechanisms for clearing soluble antigens.
Taken up by phagocytes.
Monoclonal Antibodies
A powerful tool for research, diagnosis and maybe treatment.
Antibodies of just one specificity.
Grown in LAB.
New Biologicals
Infliximab
Herceptin
Tocilizumab
Infliximab
Anti-tumour necrosis factor
(inflammatory mediators)
Used in rheumatoid arthritis
Psoriasis
Ankylosing Spondylitis
Inflammatory Bowel disease
Herecptin
Anti HER2
Can block growth and lead to destruction of breast tumour cells that express high levels of HER2.
Tocilizumab
Anti-interleukin 6
Used in Inflammatory conditions
Covid-19
