Immunology Diseases

Question 1

Graves disease

Answer 1

Type II response
Antibodies against TSH-R -» causes continuos stimulation of thyroid hormones bc neg feedback loop interrupted; thyroid hyperplasia causes immune invasion
Clin symptoms: goiter, tachycardia, pop eyes, weight and hair loss, sweating

Question 2

Graves disease therapy

Answer 2

Antithyroidal drugs, radiotherapy

Usually not immunosuppressive

Question 3

Hashimoto thyreoiditis

Answer 3

Type II reaction (little type IV)
Antibodies against thyreoperoxidase -» immune destrusction of thyroid
Clinical simptoms: fatigue, bradycardia, weight increase, skin hair nailchanges
Sometimes caused as consequence of alemtuzumab or checkpoint inhibitor therapy, which kill T cells and allow strongly proliferative autoreactive ones to emerge bc less competition and Treg there

Question 4

Hashimoto thyreoiditis therapy

Answer 4

NSAIDs,
Glucocorticoids
Hormone replacement therapy

Question 5

Pemphigus vulgaris

Answer 5

Type II reaction
IgG4 antibodies against desmogelin 3 in dermis -» activation of serine proteases and destabilisation of epithelial barrier, susceptibility to microbial invasion
Clinical signs: cutaneous blistering to ulcerated lesions forming, encapsulated bacterial infection (risk of sepsis)

Question 6

Pemphigus vulgaris treatment

Answer 6

Immunosuppressive drugs (glucocorticoids)
Rituximab with IVIG

Question 7

Systemic lupus erythromatosus

Answer 7

Type III reaction
AntiB against nucleic acid/proteins left around from impaired cell debris clearing -» small complexes found and deposited in capillaries in body -» neutrophil and mast cell recruitment via C3 chemoattraction
Exasperated by sun exposure (UV damage)
Clinical picture: butterfly rash on cheeks, stiffness of joints, vasculitits, glomerulonephritis, athritis, AIHA and ITP

Question 8

Lupus treatment

Answer 8

Chloroquin
NSAIDs
Glucocorticuids and other immunosuppressive therapy
Plasmapheresis

Question 9

Multiple Sclerosis

Answer 9

Type IV and II reaction
Priming of immune cells in periphery by myelin protein look alike (accidental autoreactivity) then release into CNS -» demyleination and recruitment of Th1, CTL, B cells and macrophages
Clinical signs: white matter lesions: effect depends on location in brain, ataxiam paralysis, blindness, muscle weakness

Question 10

Multiple sclerosis treatment

Answer 10

Glucocorticoids
IFNß
Monoclonal antibodies: Alemtuzumab, Natalizumab, Rituximab)
DMF
Plasmapheresis

Question 11

Rheumatoid athritis

Answer 11

Type IV (and III) reaction
T cells primed by unknown self-antigens and reactivated in joints, several antiB targets known: IgG, type II collagen, citrunllinated proteins (antib not NEC or SUFF for immune invasion) -» joint distruction
Clinical signs: stiffness and sweilling of joints, chronic pain, loss of function of joints

Question 12

Rheumatoid athritis treatment

Answer 12

NSAIDs
Glucocorticoids and other immunosuppressive drugs
Biologicals: Adalizumab (TNFa) Anakinra (IL1ß) Toclizumab (IL6)
Rituximab (CD20) Abdacept (CD80/86 blocks costim of Tcell activation)

Question 13

X linked SCID

Answer 13

IL-2RG cahin missing -» no IL2/4/7/15/21 receptor
Impacts T cell devo -» no thymus formed, NO T cells at all (IL2 msising)
Normal number of NK cells -» no further prolif upon activation bc IL15 R missing
Normal number of B cells, but no class switch bc T cells missing
Clinical signs:
Recurrent severe infections, susceptibility to viruses (no NK prolif) and encapsulated bacteria (no IgG opsinisation) and fungi (no Th1 macrophage recruitment)

Question 14

X SCID treatment

Answer 14

Reduce infection load: antibiosys, aseptic isolation
Compensation for lack of IgG
Gene therapy
HSCT therapy

Question 15

X SCID gene therapy

Answer 15

Insertion of corrected y chain into CD34+ HSC -» normal IL R produced with no further intervention
Successful in 4/5 cases: thymus redevod and B cells able to class switch
Associated with development of Acute T lymphoblastic leukemia bc vector used to insert y chain integrating into proto oncogene LMO2-» switched from retroviral to CRISPR/Cas (other events also needed for cancfer devo though)

Question 16

X linked Hyper IgM syndrome

Answer 16

Mutation in CD40L gene -» loss of costimulation for B cell and macrophage activation
No class switch possible, only IgM in large amounts, absence of IgA/G from blood
Clinical signs: recurrent severe infections
With capsulated bacteria (no IgA) and fungi (no Th1 activation of macrophages) and parasites (no IgA)

Question 17

X Hyper IgM syndrome treatment

Answer 17

Antibiosis
IVIG
HSCT

Question 18

Wiskitt-Aldrich Syndrome

Answer 18

Mutation in gene responsible for leukocyte actin reorganisation -» no actin dependent secretion, podia formation
No imunological synapse to increase contact surface for T cell during devo and activation -» decreased number and function
No NK cell cytotoxin secretion
Absence of marginal zone in spleen (reduced IgM levels)
Reduced macrophage motility and phagocytosis
Clinical signs: increased susceptibility ot infections
Capsulated bacteria (no T cell/activation), viruses (no NK cytotoxicity and B cell antibody release)
Autoimmunity (poor immunological synapses, survival of autoreactive T cells more likely)

Question 19

Wiskott Aldrich Syndrome treatment

Answer 19

Antibiosis
HSCT
Symptomatic treatment

Question 20

MHC I Deficiency

Answer 20

Mut to TAP ER translocation protein impairs transport of MHC to cell surface -» with no MHC T cells don’t make it past positive selection (apoptose), very few found in periphery
Clinical signs:
Recurrent resp tract infections (not cleared well from mucosa in gut and resp), intracellular bacteria (no MHC presentation possible) -» chronic damage to resp epithelium

Question 21

MHC deficiency treatment

Answer 21

Antibiosis focusing on encapsulated bacteria

Question 22

Digeorge syndrome

Answer 22

Monoallelic deletion causing deletion of pharyngeal pouch -» no thymus, parathyroid gland and parts of the heart
No T cells, unless a little bit of thymus left
Clinical signs: recurring encapsulated bact and viral infections, opportunistic fungal too
immunodeficiency and congenital heart defects, hypocalcaemia (bc parathyroid)

Question 23

Digeorge syndrome therapy

Answer 23

Antibiosis
Thymus transplantation of thymus completely missing (self vs non self problems and rejection possible)
Symptomatic treatment

Question 24

Bruton’s disease / X linked Agammaglobilnaemia

Answer 24

Mutation to BTK gene (bruton tyrosine kinase) prevents maturation from pro to pre B cell -» no mature B cells, extremely low Igs
Clinical signs: recurring infections
Encapsulated bacteria (no antibody tag) eg H.I, Strep penumo, Staph aureus

Question 25

Bruton’s disease treatment

Answer 25

Antibiosis, IVIG

Question 26

Selective IgA deficiency

Answer 26

Unknown mutation causing undetectable levels of IgA, other ig types unaffected (some can be carriers unknowingly)
Clinical signs: resp and gastro infection with sped up sever course, associated with development of autoimmune diseases RA, SLE or ITP, allergy and asthma

Question 27

Selective IgA deficiency treatment

Answer 27

Antibiosis, symptomatic treatment
IV IgA not possible since it needs to be secreted from basal lamina to make it to skin and mucosa, might cause anyphylaptic shock otherwise