Lecture 12: Autoimmunity

Question 1

What is Koch’s postulates?

Answer 1

1. Isolate the pathogen (Virus, microbe,etc) from sick creature 2. Grow the pathogen in the laboratory and obtain a pure culture 3. Inoculate a healthy creature with a sample from pure culture. The pathogen should cause the same disease symptoms that were seen in first creature 4. Re-isolate the same pathogen from second sick animal

Question 2

Autoimmune disease

Answer 2

Clinical manifestation directly linked to immune cell activation Evidence of T and or B cell autoimmunity Disease is transferred in animal models by adoptive transfer of T cells or autoantibodies or immunisation with self-Antigens Exclusion of an infective cause Often familiarity or “clustering” of AD Genetic predisposition and environmental trigger

Question 3

What type are related to autoimmune diseases?

Answer 3

Type II, III, IV diseases

Question 4

What is type I hypersensitivity reactions related to?

Answer 4

Allergy

Question 5

What is type 1 classification ?

Answer 5

Binding of Ig to Fc receptor which activated mast cell and basophils There is a burst of granules and this gives you fever/ asthma attack

Question 6

What is type 2 classification?

Answer 6

Conduction of Antibodies which are directly pathogenic Binds to either receptor or particular cell type Cause damage by: ADDC or complement activation

Question 7

What is type 3 classification?

Answer 7

Stimulated by antibodies Immune complexes Once the complexes are deposited in the kidney of glomerulus - activate complement that attract cells of immune system

Question 8

What is type 4 classification?

Answer 8

Delayed hypersensitivity reactions Involved in organic specific chronic inflammatory diseases Involved in intracellular pathogens

Question 9

Give examples of Type I reactions

Answer 9

Churg-Strauss Vasculitis Eosinophilic diseases

Question 10

Give examples of type II Hypersensitivity reactions

Answer 10

Hemolytic anemia, Myasthenia Agra is, Graves’ disease, SLE

Question 11

Give examples of type III hypersensitivity reactions

Answer 11

SLE, Panarteritis Nodosa, RA

Question 12

Give examples of IV hypersensitivity reactions

Answer 12

Crohn’s disease, Rheumatoid arthritis

Question 13

What are the FC Gamma receptors?

Answer 13

2B1 and 2B2 are non-inhibitory Fc receptors

Question 14

What does Fc Gamma III do?

Answer 14

Kill tumour cells

Question 15

What are the cell types of FcyR1?

Answer 15

Macrophages, neutrophils, Eosinophils, Dendritic cells

Question 16

What is the effect of ligation for FcyRI?

Answer 16

Uptake, respiratory burst

Question 17

What is the cell type got FcyRIIA?

Answer 17

Macrophages, neutrophils, eosinophils, platelets, Langerhan cells

Question 18

What is the effect of ligation for FcyRIIA?

Answer 18

Uptake, granule release

Question 19

What is the cell type for FcyRIIB1?

Answer 19

B cells, mast cells

Question 20

What is the effect of ligation for FcyRIIB1?

Answer 20

No uptake, inhibition of stimulation

Question 21

What is the cell type got FcyRIIB2?

Answer 21

Macrophages, Neutrophils, Eosinophils

Question 22

What is the effect of ligation for FcyRIIB2?

Answer 22

Uptake, inhibition of stimulation

Question 23

What is the cell type of FcyRIII?

Answer 23

NK cells, Eosinophils, macrophages, neutrophils, mast cells

Question 24

What is the process of ADDC?

Answer 24

Antibodies bind antigens on the surface of target cells NK Cell CD16 Fc receptors recognise cell- bound antibodies Cross-linking of CD16 triggers degranulation into lytic synapse Target Cell die by apoptosis

Question 25

What is goodpasture glomerulonephritis?

Answer 25

Rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys - bleeding from lungs and kidney failure

Question 26

What is SLE glomerulonephritis?

Answer 26

Inflammation of kidneys caused by systemic lupus erythematosus Auto-Immune disease - glomeruli become inflamed

Question 27

What is Rheumatoid Arthritis?

Answer 27

Chronic inflammatory destructive arthropathy

Question 28

What is the pathogenesis of Rheumatoid Arthritis ?

Answer 28

Inflamed of synovial membrane

Question 29

What is the evidence of RA as autoimmune disease?

Answer 29

B cell compartment: Autoantibodies. Rheumatoid factor (IgM anti-IgG) Anti-citrullinated proteins (ACPA). Collagen, BiP, RA33. T cell compartment: HLA-DRQ (shared epitope)

Question 30

What is the Role of M1?

Answer 30

TH1, tumour Resistance, Killing of intracellular parasites, tissue destruction

Question 31

What is the role of M2s?

Answer 31

Parasite encapsulation, immunoregulation, Angiogenesis, tissue remodelling, tumour promotion time

Question 32

What is M1 activated by?

Answer 32

Classical activation: IFNgamma, LPS, TNFalpha

Question 33

What is activated by M2?

Answer 33

Alternative activation: Il-4, IL-13, IL-10, TGF beta

Question 34

What does M1 cause?

Answer 34

Cytotoxicity tissue injury

Question 35

What does M2 lead to?

Answer 35

Immune suppression: tissue repair

Question 36

TNF- alpha

Answer 36

Proinflammatory cytokine release: IL-1, IL-6, IL-23 and GM-CSF

Question 37

TNF alpha

Answer 37

Hepcidin induction: acute-phase response PGE2 Production Osteoblasts Activation (bone resorption) Chondrocyte Activation (metalloproteinaise production, cartilage destruction) Angiogenesis Leukocyte accumulation ( induction/ maintenance of HLA class II Expression) Endothelial Cell Activation (upregulation of E-selectin and VCAm-1, leukocyte accumulation) Chemokines release (RANTES, MCP-1, IL-8 and SDF-1) - leukocyte accumulation

Question 38

IL-2, IFN-Gamma, TNF-alpha

Answer 38

Cell mediated immunity Intracellular pathogens Immunopathology Organ-specific autoimmunity

Question 39

IL-17

Answer 39

Gut bacteria | Immunopathology Arthritis

Question 40

TH2: IL4, IL5, IL10, IL-13

Answer 40

Helminths humoral immunity Immunopathology Allergy Atopyy