Immunology Diseases Flashcards
Graves disease
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
Graves disease therapy
Antithyroidal drugs, radiotherapy
Usually not immunosuppressive
Hashimoto thyreoiditis
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
Hashimoto thyreoiditis therapy
NSAIDs,
Glucocorticoids
Hormone replacement therapy
Pemphigus vulgaris
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)
Pemphigus vulgaris treatment
Immunosuppressive drugs (glucocorticoids) Rituximab with IVIG
Systemic lupus erythromatosus
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
Lupus treatment
Chloroquin
NSAIDs
Glucocorticuids and other immunosuppressive therapy
Plasmapheresis
Multiple Sclerosis
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
Multiple sclerosis treatment
Glucocorticoids IFNß Monoclonal antibodies: Alemtuzumab, Natalizumab, Rituximab) DMF Plasmapheresis
Rheumatoid athritis
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
Rheumatoid athritis treatment
NSAIDs
Glucocorticoids and other immunosuppressive drugs
Biologicals: Adalizumab (TNFa) Anakinra (IL1ß) Toclizumab (IL6)
Rituximab (CD20) Abdacept (CD80/86 blocks costim of Tcell activation)
X linked SCID
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)
X SCID treatment
Reduce infection load: antibiosys, aseptic isolation
Compensation for lack of IgG
Gene therapy
HSCT therapy
X SCID gene therapy
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)
X linked Hyper IgM syndrome
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)
X Hyper IgM syndrome treatment
Antibiosis
IVIG
HSCT
Wiskitt-Aldrich Syndrome
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)
Wiskott Aldrich Syndrome treatment
Antibiosis
HSCT
Symptomatic treatment
MHC I Deficiency
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
MHC deficiency treatment
Antibiosis focusing on encapsulated bacteria
Digeorge syndrome
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)
Digeorge syndrome therapy
Antibiosis
Thymus transplantation of thymus completely missing (self vs non self problems and rejection possible)
Symptomatic treatment
Bruton’s disease / X linked Agammaglobilnaemia
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
Bruton’s disease treatment
Antibiosis, IVIG
Selective IgA deficiency
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
Selective IgA deficiency treatment
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
