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Year 2 - Musculoskeletal (DP) > Immunology > Flashcards

Flashcards in Immunology Deck (47):
1

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.

IPEX Syndrome:
- Immune dysregulation
- Polyendocrinopathy
- Enteropathy
- X-Linked -> Fatal

2

What causes IPEX syndrome and what does it stand for?

Immune dysregulation
Polyendocrinopathy
Enteropathy
X-Linked -> Fatal
Cause:
- FOXP3 gene defect -> Reduced regulator T cells

3

What cells is HLA Class i found on?

All nucleated cells

4

What is the function of HLA Class i?

Present intracellular peptides:
- Infected cells display virus

5

What types of HLA Class i are there?

HLA-A
HLA-B
HLA-C

6

What cells is HLA Class ii found on?

Antigen-presenting cells

7

What is the function of HLA Class ii?

Present extracellular peptides

8

What types of HLA Class ii are there?

HLA-DR
HLA-DQ
HLA-DP

9

How many variants of each HLA does every person have?

Two

10

What does HLA diversity allow?

Maximises peptide binding since only a few peptides bind to each HLA

11

What are the susceptibility response genes associated with each of the following:
1. Ankylosing spondylitis
2. Goodpasture's Syndrome
3. Grave's Disease
4. SLE
5. T1DM
6. RA

1. HLA-B27
2. HLA-DR2
3. HLA-DR3
4. HLA-DR3
5. HLA-DR3/4
6. HLA-DR4

12

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

13

What type of H/S is SLE?

Type iii

14

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.

SLE

15

What do Anti-Nuclear Antibodies do?

Bind nuclear proteins

16

True or false; Any titre of ANA is indicative of autoimmune disease?

False
A titre of

17

What are speckled autoantibodies associated with?

ENA Abs:
- Anti-Ro
- Anti-La
SLE and Sjogren's

18

What dose Anti-Centromere Antibody do?

Binds to chromosomes (Kinetochore)

19

What is nucleolar ANA associated with?

Proteins associated with nuclear RNA:
- Fibrillarin
- U1RNP
Scleroderma (Diffuse)

20

What conditions is Anti-Jo-1 associated with?

Polymyositis
Dermatomyositis
(ILD in both of these)

21

What is Anti-La associated with?

Sjogren's
SLE

22

What is Anti-Ribonucleoprotein (RNP) associated with?

MCTD
SLE

23

What is Anti-Ro associated with?

SLE
Sjogren's

24

What autoimmune features does Anti-Ro positive SLE tend to present?

Photosensitivity
Thrombocytopaenia
Cutaneous LE

25

What is Anti-Smith associated with?

SLE

26

What is Anti-Topoisomerase I (Scl-70) associated with?

Diffuse scleroderma

27

What do high titres of Anti-DNA binding Ab suggest?

SLE with:
- Renal features
- CNS features

28

What dose the formation of immune complexes activate?

Classical complement pathway:
- C1, C4 + C2 -> C3 -> MAC
Tissue inflammation where complexes deposit

29

When we measure C3 and C4 are we measuring the activated or unactivated levels? What will the result we get indicate disease activity?

Unactivated
Low levels suggest lots of complement activation:
- Very active disease

30

What biopsy features will be present in Type iii H/S?

Immune complexes
Macrophage + Neutrophil infiltrate
Products of complement activation

31

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

32

What will be seen on immunofluorescence of a kidney biopsy in Goodpasture's-related glomerulonephritis?

IgG deposition:
- Linear pattern
- Along glomerular basement membrane
- Suggests Type ii H/S

33

What H/S Type is RA?

iv

34

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
- Cytokines

1. Initial CD4+ T cells infiltrate synovium
2. Cytokines
3. Phagocyte and B cell recruitment
4. Secondary B cell and antibody response
5. Synovial fibroblasts activate
6. Synovial proliferation

35

What joints are initially affected in RA?

MCP
PIP + DIP:
- Swan neck deformity -> PIP hyperextension, DIP hyperflexion
- Boutonnière deformity -> PIP flexion, DIP hyperextension

36

What are some long-term orthopaedic complications of RA?

Osteoporosis
Cartilage destruction
Bone resorption
Ankylosis

37

What are some long-term systemic complications of RA?

Pleuritis
Pericarditis
Vasculitis

38

What does the intimal synovial layer look like on histology?

Hyperplastic

39

What does the sublining of the synovium look like on histology?

Accumulation of mononuclear cells:
- CD4+ T cells
- Macrophages
- B cells

40

How is cartilage and bone destroyed in RA?

Matrix metalloproteinases (MMPs)

41

What cytokines are in high concentrations in the synovium of a RA patient?

TNFalpha
IL-1

42

What do these synovial cytokines do in RA?

Potent stimulation of:
- Fibroblasts
- Osteoclasts
- Chondrocytes
Stimulate MMP release

43

How do Infliximab and Adalimumab work in RA?

They are monoclonal Abs against TNFalpha:
- Block cytokine attaching to receptor

44

What is rheumatoid factor?

Antibody against Fc region of human IgG

45

What rheumatoid factor is most commonly tested for?

IgM anti-IgG antibody

46

What do Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies bind to?

Peptides where arginine has been converted to citrulline by peptidylargine deiminase

47

What does a positive Anti-CCP indicate in RA?

Severity