Flashcards in Immunology Deck (47):
A 2 year old patient presents as the mother is concerned about his growth. The mother is also concerned about the scratch marks on her son's ankles and wrists. He looks tired and is very quiet. On urine dipstick glucose is +++ and ketones are +. You examine the excoriated areas and diagnose them as eczema. The mother explains that he has a number of food allergies and has suffered regularly from URTIs.
- Immune dysregulation
- X-Linked -> Fatal
What causes IPEX syndrome and what does it stand for?
X-Linked -> Fatal
- FOXP3 gene defect -> Reduced regulator T cells
What cells is HLA Class i found on?
All nucleated cells
What is the function of HLA Class i?
Present intracellular peptides:
- Infected cells display virus
What types of HLA Class i are there?
What cells is HLA Class ii found on?
What is the function of HLA Class ii?
Present extracellular peptides
What types of HLA Class ii are there?
How many variants of each HLA does every person have?
What does HLA diversity allow?
Maximises peptide binding since only a few peptides bind to each HLA
What are the susceptibility response genes associated with each of the following:
1. Ankylosing spondylitis
2. Goodpasture's Syndrome
3. Grave's Disease
How does Type iii H/S arise?
1. AutoAB + Circulating Ag = Immune complex
2. Complexes deposit in small vessels
- eg. Bowman's capsule
3. Complement activation
What type of H/S is SLE?
A 19 year old female is referred with arthralgia. She has a 4 months history of fatigue. The arthralgia is in her hands and she has some mouth ulcers. On examination you note a rash on her face sparing the nasolabial folds, there are no joint swellings. She has vasculitis present on her fingers and soft heart sounds. Her ANA titre is > 1:640, and she has positive Anti-Ro and Anti-La antibodies.
What do Anti-Nuclear Antibodies do?
Bind nuclear proteins
True or false; Any titre of ANA is indicative of autoimmune disease?
A titre of
What are speckled autoantibodies associated with?
SLE and Sjogren's
What dose Anti-Centromere Antibody do?
Binds to chromosomes (Kinetochore)
What is nucleolar ANA associated with?
Proteins associated with nuclear RNA:
What conditions is Anti-Jo-1 associated with?
(ILD in both of these)
What is Anti-La associated with?
What is Anti-Ribonucleoprotein (RNP) associated with?
What is Anti-Ro associated with?
What autoimmune features does Anti-Ro positive SLE tend to present?
What is Anti-Smith associated with?
What is Anti-Topoisomerase I (Scl-70) associated with?
What do high titres of Anti-DNA binding Ab suggest?
- Renal features
- CNS features
What dose the formation of immune complexes activate?
Classical complement pathway:
- C1, C4 + C2 -> C3 -> MAC
Tissue inflammation where complexes deposit
When we measure C3 and C4 are we measuring the activated or unactivated levels? What will the result we get indicate disease activity?
Low levels suggest lots of complement activation:
- Very active disease
What biopsy features will be present in Type iii H/S?
Macrophage + Neutrophil infiltrate
Products of complement activation
What will be seen on immunofluorescence of a kidney biopsy in SLE-related glomerulonephritis?
IgG and C3 deposition:
- Granular, 'lumpy-bumpy' pattern
- Suggests Type iii H/S
What will be seen on immunofluorescence of a kidney biopsy in Goodpasture's-related glomerulonephritis?
- Linear pattern
- Along glomerular basement membrane
- Suggests Type ii H/S
What H/S Type is RA?
Put the following events in the immunopathogenesis of RA in order:
- Secondary B cell and Ab response
- Initial CD4+ T cells infiltrate synovium
- Phagocyte and B cell recruitment
- Synovial proliferation
- Synovial fibroblasts activate
1. Initial CD4+ T cells infiltrate synovium
3. Phagocyte and B cell recruitment
4. Secondary B cell and antibody response
5. Synovial fibroblasts activate
6. Synovial proliferation
What joints are initially affected in RA?
PIP + DIP:
- Swan neck deformity -> PIP hyperextension, DIP hyperflexion
- Boutonnière deformity -> PIP flexion, DIP hyperextension
What are some long-term orthopaedic complications of RA?
What are some long-term systemic complications of RA?
What does the intimal synovial layer look like on histology?
What does the sublining of the synovium look like on histology?
Accumulation of mononuclear cells:
- CD4+ T cells
- B cells
How is cartilage and bone destroyed in RA?
Matrix metalloproteinases (MMPs)
What cytokines are in high concentrations in the synovium of a RA patient?
What do these synovial cytokines do in RA?
Potent stimulation of:
Stimulate MMP release
How do Infliximab and Adalimumab work in RA?
They are monoclonal Abs against TNFalpha:
- Block cytokine attaching to receptor
What is rheumatoid factor?
Antibody against Fc region of human IgG
What rheumatoid factor is most commonly tested for?
IgM anti-IgG antibody
What do Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies bind to?
Peptides where arginine has been converted to citrulline by peptidylargine deiminase