Autoimmunity

Question 1

How is autoimmunity defined?

Answer 1

misdirected immune response against the body
breakdown of tolerance
failure of self tolerance

Question 2

In which steps is tolerance induced?

Answer 2

Central (during lymphocyte maturation in thymus and BM)

Peripheral (After maturation in peripheral tissues)

Question 3

Name risk factors for autoimmune disease

Answer 3

Genetic factors (HLA, non-HLA)
Environmental triggers (Infection, microbiome, xenobiota (smoke, heavy metals), microorganisms, nutrition (gluten, Vit D)
Defective regulation (Tregs --> FOXP3 CTLA4, IL2...)

Question 4

Name mechanism of viral infections that could lead to autoimmune reactions

Answer 4

Molecular mimicry (Virus carries antigen similar to self antigen)

Bystander activation (non-specific viral response, self antigens released from damaged tissue –> self ag presentation by APC)

Epitope spreading (persisitent viral infection– > more tissue damage and release of new self antigens –> self ag presented to autoreactive T cells –> reaction is spread to other T cells)

Question 5

Name some reasons for impaired Teff Treg ratio in autoimmunity

Answer 5

reduced susceptibility of Teff to Treg supression signals

Inadequate Treg numbers or defective Treg function or phenotype

Question 6

Define Autoimmune response

Answer 6

The demonstration of auto-ab or T cell-mediated reactivity directed to a self antigen

Question 7

Major phases of autoimmune diseases

Answer 7

Initiation (genetic predisposition, environmental triggers)

Propagation (cytokine, epitope spreading, Teff/Treg disruption)

Question 8

Whats a Type 1 Hypersensitivity reaction?

Answer 8

Immediate HS: IgE mediated response against allergens
IgE receptors (FceR1) on mast cells and basophils
Atopic individuals: elevanted eosinophils and IgE
–> Hay fever and asthma

Question 9

Whats a Type 2 Hypersensitivity reaction?

Answer 9

Antibody-mediated HS: IgM or IgG mediated or cytotoxic
Ab against surface or matrix proteins
Induce cell lysis through complement or ADCC
–> Pemphigus, autoimmune haemolytic anaemia, Goodpasture syndrome

Question 10

Whats a Type 3 Hypersensitivity reaction?

Answer 10

Immune-complex mediated HS: IgG mediated
Soluble immune complexes–> activation of complement (classical path) –> elevation of neutrophils-> cytotoxic molecules
–> RA, SLE

Question 11

Whats a Type 4 Hypersensitivity reaction?

Answer 11

Delayed type HS: T cell mediated
Sensitation phase
Effector phase: release of proinflammatory cyto- and chemokines, Th1 induced activation of CTL
–> Hypersensitivity pneumonitis, contact dermatitis

Question 12

Possible therapies for autoimmune diseases

Answer 12

Immunosupression, Monoclonal Ab, Removal of thymus, Plasmapheresis, modified peptides, T cell vaccination