Exam Questions Flashcards
What are combined immunodeficiencies
Result from an absence of T cells, or impaired T cell function, combined with some disruption of antibody response
Write a note on X-Linked Agammaglobulinemia
(6)
Originally called Bruton’s agammaglobulinemia
Patients have extremely low Ab levels
Babies born with this have virtually no B cells in peripheral blood
Suffer from recurrent bacterial infections
It is caused by a defect in the gene coding for the enzyme Bruton’s tyrosine kinase (Btk) which is involved in B cell development
Developing cells in the basal membrane are arrested at the pre-BCR stage
Write a note on leucocyte adhesion deficiency
(4)
LADI is caused by a mutation in the CD18 gene
CD18 is the B chain of B2 integrins that include CR3. CR4 and LFA-1, all vital for the adhesion cascade
As CR3 and CR4 also function in the complement system phagocytes are unable to engulf microbes opsonised by C3b and C4b
Patients display omphalitis, gingivitis and recurrent infections
What is the role of the clinical immunology laboratory in the diagnosis of primary immunodeficiency
(6)
Detection of autoantibodies -> ELISA, immunofluorescence (direct and indirect)
Measurement of antibody levels - nephelometry
Measurement of specific antibody responses -> vaccination and allergy
Monitoring of serum proteins e.g. monoclonal gammopathy via serum protein electrophoresis
Measurement of complement levels/function - nephelometry, CH50, CH100 and AP50 assays
Leukocyte number/functions - flow cytometry
What are the principles of nephelometry
(3)
Add anti-sera for protein of interest (e.g. antibodies, C3, C4 and C1 inhibitor)
Where immune complexes form they will scatter light which can be detected
Standards can be used to calculate the concentration
What is the principle of serum protein electrophoresis?
(3)
Electrophoresis is a method of separating proteins based on their physical properties
Serum is placed on a specific medium, and a charge is applied
The net charge (positive or negative) and the size and shape of the protein are used to separate and differentiate the various serum proteins
What is the principle of flow cytometry?
Flow cytometry is a technique for counting, examining and sorting microscopic particles suspended in a stream of fluid
Physical characteristics, size and granularity of particles are measured while fluorescently labelled antibodies can be used to examine protein expression
A laser beam is directed at a hydro-dynamically focused stream of fluid containing the cells in single cell suspension
A number of detectors measure properties such as forward scatter(size), side scatter (granularity) and fluorescence (specific protein expression) at different wavelengths
List the order of cells involved in inflammation
(6)
Mast cell -> Gatekeeper
Neutrophil
Monocyte -> macrophage
Dendritic Cells
T cells
Helper T cells
Write a note on macrophages
(4)
Big Eater
Phagocytose
Release chemokines (CXCL-8)
Release pro-inflammatory cytokines
Write a note on the functions of mast cells
(4)
releases histamine and cytokines e.g. IL-8
o Vasodilation in response to histamine -> more blood -> more wbcs
o Increased vascular permeability
o Increased expression of adhesion molecules -> allow for adhesion cascade
How are mast cells activated
(4)
By allergens through cross linking with immunoglobulin E receptors (e.g., FcεRI),
By Physical injury through pattern recognition receptors for damage-associated molecular patterns (DAMPs)
By microbial pathogens through pattern recognition receptors for pathogen-associated molecular patterns (PAMPs),
Complement proteins can activate membrane receptors on mast cells to exert various functions as well
What do anaphylotoxins do?
Activate basophils and mast cells to degranulate resulting in increased vascular permeability and contraction of smooth muscle cells
List the anaphylatoxins
C5a
C4a
C3a
What are the functions of anaphylatoxins
(4)
Degranulation of mast cells
Smooth muscle contraction
Increased vascular permeability
C5a causes chemotaxis of leukocytes
What is the CH50 assay used for?
It demonstrates the ability of serum complement to lyse sheep RBCs coated with antibody
How does the Mannose binding lectin pathway work?
(4)
MBL attaches to mannose/frucose containing polysaccharides on bacteria
MBL is then bound by MASP-1 and MASP-2
MBL associated serine proteases
MASP cleaves C2 and C4
How is the classical pathway activated
(3)
Complement fixation
Activated by IgM and IgG
Complement binds to the CH2 domain of these
How do complement proteins act as opsins
(3)
Complement proteins bind to pathogens and mark them for phagocytosis
The phagocytes express receptors such as CR1 which allows the cell to recognise complement attached to a pathogen
When the receptor meets the complement there is a conformational change and the pathogen is phagocytosed
How does complement activate the inflammatory response?
If complement binds to the receptors found on granulocytes it causes these cells to degranulate e.g. mast cells/gatekeeper cells releasing histamine causing inflammation and vasodilation
How do complement proteins clear immune complexes
Complement marks antibody-antigen complexes for phagocytosis in the liver and spleen
What are the four main functions of complement
Formation of MAC
Opsonisation
Disposal of immune complexes and apoptotic cells
Activation of immune responses e.g. vascular permeability, chemotaxis for phagocytes and degranulation
Define the complement system
The complement system is a biological cascade made up of multiple serum proteins that is part of the innate immune system
