Antibodies and Immune Complexes

Frage	Antworten
Which chain determines the class of antibody?	The heavy chain (IgM - mu, IgA - alpha, IgE - epsilon, IgD - delta, IgG - gamma).
Kappa and lambda chains are found in combinations in antibodies. What are the combinations found in each antibody class?	Trick question: Any antibody will have a random mixture of kappa and lambda chains.
What chemical would you apply to antibodies to separate the heavy and light chains?	Detergent e.g. sodium dodecyl sulphate.
What length in kilodaltons are light chains? And heavy chains?	L: 21-22 kDa. H: 52-64 kDa.
What type of bonds hold the chains in an antibody monomer together?	Disulphide bonds.
Antibodies consist of Fab variable regions and Fc constant regions. How many constant domains do each of the different antibody classes have?	IgA, IgD, and IgG have three constant domains, and each has a flexible hinge region too, while IgM and IgE have four constant domains and no flexibility for binding around the Fc region.
Which region determines the function of the antibody?	The Fc region, as this is able to have intracellular effects, or to bind to receptors on different cell types to bring about immune responses.
What holds both IgA dimers and IgM pentamers together?	J chains
What is the secretory component of IgA?	A remainder of the polymeric Ig receptor (pIgR) which allows dimeric IgA to be secreted across mucous membranes, and is cleaved by an enzyme in IgA release, leaving a short peptide chain attached to the IgA dimer - the secretory component.
List some secretions produced by mucous membranes that IgA is secreted in.	Break milk, saliva, tears.
How many antigens can IgM bind at once? How many does it tend to bind at once?	It can bind 10, but tends to bind 8.
What is the isotype of an antibody?	Its class and light chains e.g. IgA-k.
What is the allotype of an antibody?	Subtle differences in constant regions between individuals which can lead to complications in immunotherapy and transplant.
What is the idiotype of an antibody?	It's antigen specificity - what the variable regions bind to.
What is an antigen?	Any protein that is immunogenic to an individual.
How many antibodies bind to an antigen?	Antigens contain different antigenic epitopes (surface structures), each of which is recognised by a different antibody, so the number of antibodies that can bind to the antigen will depend on how many different antigenic epitopes it has.
What region of an antibody becomes active when it binds to antigen?	The Fc region.
Which antibodies, once they've bound antigenic epitopes, can activate the complement cascade in order to produce membrane attack complexes, anaphylatoxins for inflammation, and opsonins for further immune activation?	IgG and IgM
Which antibody isotype is the best opsonin (which activates phagocytes to increase their phagocytic activity)?	IgG
Which antibody isotype activates mast cells to release histamine and kill worms or cause hypersensitivity (e.g. hayfever)?	IgE
Which antibody isotype activates natural killer cells to release granules and kill infected/cancer cells (via antibody-dependent cellular cytotoxicity, ADCC)?	IgG
How does antibody neutralise mucosal infections?	It binds to antigenic epitopes and prevents the antigen/organism from binding to mucosal cells and entering the body. The antigen is then trapped in mucous and carried away by cilia e.g. to be swallowed and hydrolysed by gastric acid.
What is the main role of IgD?	It acts as the B cell receptor - it recognises antigen with its Fab fragments, which activates its Fc region to have intracellular effects, namely the recombination of VDJ genes and RNA splicing to produce specific antibody (B plasma cells).
Which is the only antibody isotype to protect a baby/foetus?	IgG
Where is most IgE found (clue: not the serum)?	On the surface of mast cells acting as mast cell receptors - when antigen binds to IgE, such as that from helminths or allergens, it stimulates the mast cell to release histamine to aid an inflammatory response.
Which is the only antibody to be part of the innate immune response?	IgM - it agglutinates antigen to take it out of solution and is constitutively present in the serum.
What is the different between avidity and affinity?	Avidity refers to being able to bind multiple antigens with low specificity, whereas affinity refers to having high specificity for an antigen and thus only being able to bind that one antigen or those highly similar to it.
Which laboratory technique can be used to detect antibody/antigen? How is it quantitative?	ELISA - When looking for antigen, one is looking for presence of an organism. A plate is coated with antibody for the antigen being sought. However, just because antigen is found, doesn't mean the organism isn't dead. When looking for antibody, one is looking for an immune response to an organism. It takes time to seroconvert, so you'll tend to see IgM in an acute or early infection and IgG in later or chronic infection. Use of diluted standards mean that the technique can be quantitative as long as you have a known volume of serum.
What are immune complexes? How do they form?	Immune complexes are long chains or lattices of antibody-antigen interactions - they may be small or large depending on how much antibody/antigen is present. In order for them to form, there must be persistent antibody or antigen such as in an autoimmune disease or a chronic infection.
How are immune complexes made soluble?	When immune complexes bind to C1q in the complement cascade, they activate the classical complement pathway. When C3b, the opsonin, is formed, it binds to the immune complexes and solubilises them.
How are immune complexes transported and cleared in health?	The immune complexes bind to erythrocytes and leukocytes via CR1 receptors and the C3b that has opsonised and solubilised them, they are able to be transported to the liver and spleen for clearance. Once they reach these organs, Kupffer cells in the liver and macrophages in the spleen have 100x higher concentrations of CR1 receptors than the erythrocytes/leukocytes and thus pull the immune complexes off them, engulf and digest the immune complexes in phagolysosomes, and the erythrocytes/leukocytes can then re-circulate.
When might immune complexes be deposited in tissues (leading to pathology) rather than cleared by the liver and spleen macrophages?	When they are produced in excess.
Which inflammatory condition is caused when immune complexes are deposited in small blood vessels?	Vasculitis
Which inflammatory condition is caused when immune complexes are deposited in sinovial joints?	Arthritis
Which inflammatory condition is caused when immune complexes are deposited in the glomerular basement membrane of the kidney?	Glomerulonephritis
What signs are seen in tissues where immune complexes are deposited and cause inflammation?	Cardinal signs - rubor, dolor, calor, tumor, functio laesa.
Which type of response are all of the pathologies caused by immune complex deposition?	Type III hypersensitivity response.
How does the process of deposition (immune complexes going from blood to tissues) occur?	The Fc region of activated antibody is recognised by endothelial cells of blood vessels, resulting in the release of highly inflammatory cytokines: IL-6, TNF-α, 1L1-β, and IL-8. This results in vasodilation such that the immune complexes are able to extravasate and are deposited in the tissues below the capillary endothelial cells.
What is frustrated phagocytosis and how does it cause tissue damage in type III hypersensitivity reactions?	The activated Fc region of antibody bound to antigen and deposited in tissues is able to activate the classical complement cascade, resulting in the production of the opsonin C3b. C3b coats our tissues and also activates C3a and C5a which cause inflammation and recruit phagocytes. These anaphylatoxins also activate C5b-C9, which forms membrane attack complex in bodily cells, causing them to lyse. Phagocytes are 'attracted' to the opsonised tissue, but bodily cells are too large for them to engulf. Instead, they release lytic enzymes and reactive oxygen species onto the tissue to break it down, causing damage and further inflammation (frustrated phagocytosis).
How can the Mancini technique (radial immunodiffusion) be used to demonstrate autoimmune disease in an individual?	Patient serum is mixed with agar before allowing it to set and cutting wells out. Tissue antigens are placed into the wells and diffuse throughout the agar. If complementary antigen and antibody are present, they will form a ring of immune complexes which precipitate out of solution and are visible if there are excessive amounts of both - demonstrating autoimmune disease.
What is nephelometry?	Nephelometry looks at the density of immune complexes (or protein antigen or immunoglobulin alone) present in a given sample based on how much light is reflected by it. The severity of the disease is proportional to the concentration of immune complexes present.
Why would lack of the first four complement proteins in the classical complement cascade (C1, C2, C3, C4) be an important diagnostic marker in immune complex mediated disease?	Lack of these can suggest that individuals with excessive immune complex mediated disease have exhausted their early complement proteins.
Name three persistent infectious agents which may result in the formation of immune complexes?	Streptococcus spp., meningococcus spp., and hepatitis spp.
Name three autoimmune diseases which may result in the formation of immune complexes.	Systemic lupus erythromatosis, rheumatoid arthritis, and multiple sclerosis.
What type of antibodies are tested for presence of in Mancini (radial immunodiffusion) assays?	Autoantibodies.

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