S4: monoclonal antibodies Flashcards
Describe the basic structure of an antibody
FAB – antibody binding fragment containing hypervariable regions that allow for recognition of virtually unlimited array of antigens
FC region – responsible for binding to the immune effector cells to elicit the immune response
Describe monoclonal antibodies
Recognise only one epitope
-monovalent
-produced from a single B-lymphocyte clone which will produce an antibody specific for one antigen
Of use clinically for both treatment and diagnosis
Describe the result of antibodies binding with cell surface receptors
Can activate or inhibit cell signalling resulting in:
1) Cell death induction
2) Antibody dependent cell mediated toxicity activation
3) Complement dependent cytotoxicity
Describe how monoclonal antibodies are used in diagnostics
Use of emission of light (fluorescent tag) OR
An enzymatic reaction (enzymatic tag)
Identify specific cells using immunohistochemistry and flow cytometry
Describe lymphoma
Clonal proliferations of lymphoid cells
B cell lymphoma is the most common type, with diffuse large B cell lymphoma being the most common haematological malignancy in the UK
Describe the diagnosis of lymphoma
Via biopsy and histochemistry
Can be diagnosed via structure and the use of CD20 immunohistochemistry to diagnosis B cell lymphoma
List treatment options for lymphoma
Chemotherapy Radiotherapy Monoclonal antibody therapy Emerging targeted therapy Stem cell transplantation
Why can adverse reactions result from monoclonal antibody treatment?
Due to immune activation
Patients are pre-dosed with paracetamol, antihistamines and steroids to prevent hypersensitivity reaction-infusion reactions
-can cause significant clinical problems and must be treated properly
Describe rheumatoid arthritis
Autoimmune disease associated with autoantibodies to the Fc portion of immunoglobulin G and to citrullinated cyclic peptide
Persistent synovitis, causing chronic symmetrical polyarthritis with systemic inflammation
Cause of rheumatoid arthritis is unknown
Outline the articular manifestations of rheumatoid arthritis
RA typically presents as a progressive, symmetrical, peripheral polyarthritis in patients between 30 and 50 years of age
Synovitis occurs when chemoattractants produced in the joint recruit circulating inflammatory cells
Over-production of TNF-alpha leads to synovitis and joint destruction (interaction of macrophages and T & B lymphocytes drive this over-production)
List non-articular manifestations of rheumatoid arthritis
Pericarditis Anaemia Lymphadenopathy Tendon sheath swelling Carpal tunnel syndrome
Describe the d-dimer test
D-dimer is a fibrin degradation product containing two cross-linked D domains released by the action of plasmin
Blood-based assay that uses antibodies to the d-dimer protein to measure the presence/level of circulating d-dimer
Elevated d-dimer levels can occur in malignancy, pregnancy, recent surgery, infection etc
Negative test is helpful in ruling out a PE or other significant clot
Describe the pathogenesis of systemic lupus erythematous (SLE)
When cells die by apoptosis, the cellular remnants appear on the cell surface as small blebs that carry self antigens
In SLE, removal of these blebs by phagocytes is inefficient, so that they are transferred to lymphoid tissues, where they are taken up by APCs
Self antigens from these blebs can then be presented to T cells, which in turn stimulate B cells to produce autoantibodies directed against these antigens
List clinical features of SLE
Butterfly rash Raynaud’s phenomenon Arthritis in small joints Anaemia Fits, hemiplegia, ataxia
Describe SLE nephritis
Overt renal disease occurs in at least 1/3 SLE patients
Immune deposits in the glomeruli and mesangium are characteristic of SLE
