Immunology (conditions and immune system)

Question 1

IPEX syndrome

• what is it
• symptoms
• treatment

Answer 1

Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance syndrome (IPEX)

> Rare genetic disorder of immune dysregulation

• presents early childhood
• characterised by overhwhelming systemic autoimmunity

> Symptoms include:

• • Severe infections
• • Intractable diarrhoea
• • Eczema
• • Very early onset insulin dependent diabetes mellitus
• • Autoimmune manifestations

> Treatment

• Cure: hematopoietic stem cell transplantation (HSCT)
• Supportive care: immunosuppressive drugs
• plus total parental nutrition

Question 2

Pathogenesis of IPEX

Answer 2

> Pathogenesis

• mutation in ONE gene.
• the FOXP3 gene (essential for development of regulatory T cells)
• X linked
• “monogenic”

Question 3

IPEX is due to?

Answer 3

A failure of peripheral tolerance due to defective regulatory T cells (Tregs)

Specific tolerance mechanisms are required:

1. Removal of self-reactiven lymphocytes in primary lymphoid tissues (central tolerance)
2. Inactivation of self-reactive lymphocytes that escape central tolerance (peripheral tolerance)

Question 4

Tolerance mechanisms of the immune system

Answer 4

1. Removal of self reactive lymphocytes in primary lymphoid tissues (central tolerance)
2. Inactivation of self reactive lymphocytes that escape central tolerance (peripheral tolerance)

Question 5

Peripheral tolerance induction is mediated by?

Answer 5

Regulatory T cells

Maintenance of peripheral tolerance

Question 6

Mutations in the FOXP3 gene leads to…

Answer 6

Loss of function of regulatory T cells

Loss of peripheral tolerance

Question 7

What do all nucleated cells express?

Answer 7

Class 1 HLA (HLA-A, B & C) on the cell surface.

Each individual possesses 2 variants of each HLA molecule

Question 8

Specialised antigen presenting cells also express?

Answer 8

Class II HLA

HLA DRM DQ & DP

Question 9

An individual possesses how many variants of each HLA molecule?

Answer 9

2 varitans

there are 15 different HLA molecules

So 30 variants in total

Question 10

How many HLA genes does an individual express?

Answer 10

30

15 on maternal and 15 on paternal

Question 11

HLA/MHC molecules are involved in many…

Answer 11

autoimmune diseases.

Question 12

Acute rheumatic fever after Streptococcal infection

Answer 12

Streptococcoal cell wall stimulates antibody response
(contains Strep M5 protein)

A similar protein is found in cardiac tissue. (Molecular mimicry)

Some antibodies cross react with heart tissue, causing rheumatic fever.

Question 13

Super antigens

Answer 13

Protein involved in toxic shock syndrome for example.

Proteins that can bind outside protein groove on a T cell

Can activate any T cell (including any autoreactive T cells)

Question 14

What type of hypersensitivity reaction is SLE driven by?

Answer 14

Type III hypersensitivity

(immune complex mediated)

Can activate classical pathway of complex activation.

Complexes are difficult to dispose of and end up in vasculature and joints –> symptoms

Question 15

SLE diagnostic criteria

Answer 15

SOAP BRAIN MD

Serositis (pleuritis, pericarditis)
Oral ulcers
Arthritis
Photosensitivity

Blood (all are low – anaemia, leukopenia, thrombocytopenia)

Renal (protein)
ANA
Immunologic (DS DNA)
Neurologic (psych, seizures)

Malar rash
Discoid rash

Question 16

Anti nuclear antibodies

Answer 16

Group of antibodies that bind to nuclear proteins

Non pathogenic

Very common

SLE, systemic sclerosis, SJÖGRENS

Question 17

Type III hypersensitivity management

Answer 17

Limit sun exposure 
Analgesia
Hydroxychloroquinine
Decrease inflammation:
-- Corticosteroids – prednisolone

Decrease production of auto-antibodies:

– Immunosuppressive agents (anti-proliferative agents)
Azathioprine
Mycophenolate
Cyclosphosphamide

– Inhibit B cell proliferation
Belimumab

Question 18

Which cytokines play a large role in RA?

Answer 18

TNFα & IL-1

High synovial concentrations

Question 19

Serological tests for RA

Answer 19

1. Rheumatoid factor - auto antibody directed against the common (Fc) region of human IgG

Only 70% of patients with RA are +ve for RF at the time of diagnosis

Absence of RF is insufficiently sensitive to rule out the diagnosis of RA

2. Anti-citrullinated peptide antibodies (ACPA)
   - bind to peptides in which arginine has been converted to citrulline
   - approx 70% of RA cases are ACPA+ve
   - highly specific for RA, occurring in many patients before clinical onset of the disease