Autoimmune disease 2 Flashcards
Molecular mimicry
- Description
- Examples
A theory behind the link between infection and autoimmune disease.
There can be homology between pathogenic epitopes and host peptides
- T and B cells recognise host peptides as antigenic post-infection and develop inflammatory responses against them.
This process depends on:
- Host containing the correct MHC to common peptide common to pathogen and host.
- Having the correct T cell to recognise the peptide.
Examples
- Autoimmune haemolysis after mycoplasma. pneuominae
- Rheumatic fever after streptococcal infection
Autoimmune haemolysis after mycoplasma. pneuominae
Infection of M.pneumoniae involves antigen that is homologous to I antigens on rbc.
IgM against m.pneuomniae antigen can respond to I antigens on rbc and cause transient haemolysis.
Rheumatic fever after streptococcal infection
Molecular mimicry
- Anti-Streptococcal antibodies are believed to react to antigens on connective tissue
Causes inflammation of the heart, joints, skin and brain
Evidence for type 1 DM as an AID
Anti-Islet ab are detected months/ years precipitating the clinical onset of diabetes.
- Ab do not cause destruction of pancreas
HLA associations
Pancreatic biopsy: T cell infiltration
- By the time it presents, inflammation is not active.
Genetics and T1 DM
100% concordance in monozygotic twins.
HLA class 2 is major genetic factor (present islet cell antigens to T cells)
- DR3/4 = 6 times more risk
- DR3 + 4= 15 time risk
Coxsackie virus and T1 DM
Some evidence that molecular mimicry could be involved
- Protein 2c of coxsacki virus is homologous to GAD on islet cells
- Stronger immune response to virus conicides with developing DM later in some cases
Can cause pancreatitis in mice and humans
Can precipitate AI DM in mouse models.
Antibodies as diagnostics
Identifying and characterising them is important in determining disease.
Can be directly pathogenic
- I.e T2 hypersensitivity reactions (autoimmune haemolysis_
Can be a bystander of AID diseases
- As seen with coeliac disease (anti tTG ab) and T1 DM (anti-islet Ab)
Indirect immunofluorescence
Method of detecting Ab in the blood.
- Being replaced with specific immunoassay for islet cell antigens (GAD, IA2, insulin)
- Tissue of interest from animal source is placed on glass side.
- Detection Ab(specific to ab bound to tissue antigens) w/ fluorescent marker is added and binds .
- Florescence is looked for under microscope
ELSA
- Using a plastic 96 well plate
- It is coated with tTG antigen then excess Ag is washed off. - Milk powder solution is added to block spare spaces on the plastic.
- XS Milk solution washed after. - Patient sample is added to the well and incubated.
- If containing the anti-tTG antibody, it will bind to immobilised tTG antigen.
- XS ab from patient sample is washed off - Secondary anti-IgA Ab linked with enzyme (horse radish peroxidase) is added
- Binds to IgA Fc region of anti-tTG ab bound to tTG antigen.
- XS secondary Ab is washed away. - Substrate is added to react with horse radish peroxidase bound to secondary Ab
- Colour change occurs
- Amount of colour change can be measured with photocell.
Direct immunofluorescence
- Biopsy of affected tissue with Ab already bound to antigen is taken.
- Detection Ab with fluorescent marker is added
- Fluorescence is looked for under the microscope.
Pemphigoid
Bullous skin disease
Presents:
- Thick wall bullae
- Rarely on mucuos memrbae
Mechanism
- Ab made against antigens at demo-epidermal junction–> linear deposits
- Ab activates complements and produces skin dehiscence and blister
Diagnosis
- Linear deposit of Ab seen in immunofluorescence
Pemphigus
Bullous skin disease
- More detrimental effects Tham pemphigoid
- Ab-mediated disease
Presents
- Thin wall bull on skin + mucus membrane–> affects absorption, loss of water, more prone to infection
- Bullae rupture easily
Diagnosis
- Antigen, desmoglein 3 is found intercellularly in superficial skin layers–> targeted for Ab immunofluorescence
Coeliac disease diagnosis
Early
- Ab binding to endomysium on SM
Now
- Anti-tTG antibodies immunoassay
- HLA typic (DQ2/8)
Pernicious anaemia immunology
Ab are directed against gastric parietal cells= destruction
- Unable to produce intrinsic factor and absorb Vit. B12
No B12 presents as
- Anaemia
- Neurological problems
- Subfertility
Drugs for immunomodulation
More suitable for multi-system autoimmune disease
Include
- Systemic corticosteroids
- Small immunosuppressive drugs (methotrexate, azathioprine, cyclosporin)
- High dose IV immunoglobulin
