lecture 10 - autoimmunity

Question 1

Describe type 3 hypersensitivity

Answer 1

Mediated by immune complexes - high conc. of antigen and antibody

Question 2

What are the pathological conditions that result in type 3

Answer 2

vasculitis (vessels)
Glomerulonephritis (kidney)
Arthritis (joints)

Question 3

Describe Arthus reaction

Answer 3

High antigen and antibody concentrations
Induces complement activation
Frustrated phagocytosis

Question 4

What is frustrated phagocytosis (type 3)

Answer 4

Polymorphs unable to ingest immune complexes stuck to basement membrane - damage - complement-mediated inflammation

Question 5

Describe phase 1 of type 3 hypersensitivity

Answer 5

Antibody and antigen bind to each other - complex formation

Question 6

Describe phase 2 of type 3

Answer 6

Influx of neutrophils - bind antibody via Fc receptor
Complement activation

Question 7

Describe phase 3 of type 3

Answer 7

Frustrated phagocytosis - damage due to complement-mediated inflammation
(neutrophil lysosomal enzymes)

Question 8

Describe Systemic Lupus Erythematosus (SLE)

Answer 8

Common - nephritis, skin lesions, arthritis
Major autoantibodies directed at nuclear antigens (ANAs)
Remitting and relapsing

Question 9

How do you diagnose SLEs

Answer 9

Symptoms - rash, arthritis, ulcers, renal, neurologic, haematologic and immunologic disorders
Anti-nuclear antibody (ANA) - alot of people have anyway

Question 10

Describe SLE in the skin

Answer 10

Liquefactive degeneration of basal layer
Oedema at dermal-epidermal junction
IgG deposits along dermal-epidermal junction (drives chronic inflammation)

Question 11

Describe systemic sclerosis (scleroderma)

Answer 11

Rare (type 3 & 4)
Abnormal accumulation of fibrous tissue
Cause unknown but CD4 T cells involved
Combination of immune response and vascular damage - local accumulation of growth factors (fibroblasts -> collagen production)

Question 12

Describe type 4 hypersensitivity and mechanisms

Answer 12

Cell medicated response
- Delayed type - cytokine mediated inflammation
- Direct cell cytotoxicity - CD8-mediated

Question 13

Describe the Mantoux test

Answer 13

Mainly Th - recruit macrophages
- Cytokines mediate
- Diagnostic for T cell immunodeficiency

Question 14

Describe Crohn’s disease

Answer 14

‘Skip’ lesions along gastro-intestinal tract
HLA-DR1 association (27%)
Inflammasome involvement proposed (innate immunity) (disruption - leaky -> drive auto-inflammatory disease)
CD4 T cell activation and granuloma formation

Question 15

Describe Multiple sclerosis

Answer 15

Demyelinating disorder - CD4 T cells specific for antigens from myelin sheath - Th1 cells activate macrophages
Relapsing-remitting disease

Question 16

Describe type 1 diabetes

Answer 16

Beta-islet cells attacked by CD8 T cells - also CD4 T cells
pancreas no longer make insulin - associated with infection (antigen unknown)
Linked to HLA (susceptibility)

Question 17

Describe Hashimoto’s thyroiditis

Answer 17

Hypothyroidism - gradual thyroid failure (autoimmunity)
- Autoantibody and ADCC (antibody dependent cytotoxicity cells)
Dense lymphocytic infiltrate with germinal centres (in thyroid)