Week 9 Autoimmune Flashcards
Etiology factors for autoimmune diseases:
Genetic predisposition
Environmental triggers
Loss of self-tolerance
T-cell activation/differentiation
Autoantibodies
Activation of autoimmune response
General process of autoimmune reaction:
Genetic predisposition + environmental factors > antigen presentation of self-antigen + faliure of self tolerance > generation of autoantibodies and self-reactive T cells > inflammation and destruction of self tissues
T cells in autoimmune:
Th1: cell mediated with TFN and IFN-gamma
Th2: antibody mediated with interleukins
Common genetics in autoimmune disorders:
HLA variants encoding for MHC proteins altering immune regulation, allowing for self targeting
Environmental triggers for autoimmunity:
Disruption to normal immune regulation > creation/activation of autoreaction
Infections, chemicals/toxins, hormone changes, physical/psych. Stress, compounded with genetic predisposition
Loss of self tolerance in autoimmune:
Faliure to recognise self-antigens > damage from autoantibodies and autoreactive T-cells
Autoantibodies in autoimmune:
Self reactive B cells > antibodies against self-antigens > Immune complex deposited in tissue > immune reaction
Common autoantibodies: rhematoid factor (RA), anti-nuclear antibodies in lupus
Adaptive immune process in autoimmune:
Antigen presenting cells (dendritic/macro.) endocytose FB > process into peptide antigens > presented to naive CD4+ T cell via MHC on APC surface > Differentiate to T helper cell (Th1/2) > mediate inflammation via cytokines
Activation of autoimmune response:
Molecular mimicry/self-presenting dendritic cell autoantigen exposure > autoimmune response > inflammatory cascades > cytokine release/macrophage recruitment > tissue damage
Graves’ disease patho:
Unknown trigger > production of IgG antibodies against thyroid stimulating hormone receptor
Activation of TSHRs > ^thyroid hormone production > hyperthyroidism
Thyroid ophthalmopathy occurs seccondary to Graves’
Graves’ disease symptoms
^metabolism > weight loss, sweating, heat intolerance
Hyperactive sympathetic NS > nervousness, irritability, heart palpatiations
Negative feedback mechanism > high TH, low thyrotropin-releasing hormone
Fatigue, enlarged thyroid gland (neck), alopecia
Thyroid eye disease risks:
Thyroid ophthalmopathy from 25-50% grave’s Px.
^with smoking, immunotherapy, radioactive iodine therapy (graves’ treatment)
TED patho:
IgG against TSHRs cross-react with similar antigens in orbit soft tissue fibroblasts/adipocytes (TSHR mRNA)
Cross-reactivity > autoreactive T cells infiltration to orbit fat/muscle (initiation) > T-cells release cytokines stimulating fibroblast proliferation and GAG production > GAG water retention/cellular infiltration > orbit fat/adipocyte/EOM swelling
TED process:
Inflammatory phase (1.5-3y) > Fibrotic (quiescent) stage
Superior and inferior lid retraction in TED:
Inflammation > fibrosis > lid retraction > clinical signs:
Dalrymple sign: retraction in primary gaze
Kocher sign: staring/attentive fixation
Von Graefe sign: abnormal descent of upper lid on downgaze
Soft tissue involvement in TED:
Superior limbic keratoconjuntivitis: secondary to mech. Friction on blink from proptosis
Soft tissue expansion > periorbital swelling
DED from lid retraction/lagopthalmos secondary to proptosis
TED PC:
Burning, pain, blur, diplopia, strained eye motion
TED clinical symptoms:
Proptosis: forwarding globe > incomplete lid closure
EOM dysfuntion: inflammation restriction > fibroblast fibrosis of muscle
Sup./inf. Lid retraction: fibrosis of muscle
Soft tissue involvement: Sup. Lim. Keratoc.
Optic neuropathy: ON compression
Classifications of TED:
[NO SPECS > increasing severity]
No symptoms
Only signs (lid retraction)
Soft tissue involved
Proptosis
EOM involvement
Corneal involvement
Sight loss
Management of TED:
Active TED self-limiting 1-3 weeks
Requires Graves’ addressment
Lubricant/anti-inflammatory(SLK/DED)
Nocturnal lid taping
Systemic glucorticoids(60mg/day) or orbit decompression
Lid/EOM correction post inflammation
Graves’ disease management:
Thioamine (Carbimazole) > inhibit iodide oxidation to iodine > low TH formation
B-blockers > reduced heart palp.
Radioactive iodine > uptake to thyroid > low TH formation
Quantifying proptosis:
Exophthalmometer measures ent. Protrusion from orbit
Ruler placed on lateral orbit margin
21-23mm mild, 24-27 moderate, >28 severe
Proptosis DDX:
Infection: orbital cellulitis
Inflammatory: TED
Vasculitis: Wegener granulomatosis
Neoplasic: Lymphoma/leukemia
Orbital vascular disease: arteriovenous malformation
Trauma: orbit fracture
Pseudoptosis: Contralateral blepharoptosis
Sjogrens management:
Manage symptoms
Lubricant gels/ointment, punctal plugs
Therapeutic ciclosporin/liftegrast/steroids
Immunosuppressive therapy
Giant cell arteritis patho:
Systemic vasculitis, usually >50yo women
Autoimmune against adventitial layer of large BV walls > thickening > narrowing of lumen > artery occlusion > infiltration of mononuclear cells in wall > giant cell formation
Sjogrens syndrome:
Genetic/environment > autoantibody (anti-Ro/SSA, anti-La/SSB) production > Immune-mediated destruction of targeted exocrine glands > ADDE/Xerostomia (dry mouth)/peripheral neuropathy/joint pain
Associated with RA/Lupus (secondary)
GCA symptoms and management:
Persistent headache near temples w/scalp tenderness
Jaw pain on chew/talk
Fatigue/malaise/weight loss/ night sweats
Ophthalmic artery affected > Arteritic ischemic optic neuropathy (AAION) > painless sudden vision loss, RAPD
Requires high dose cortico.
Myasthenia gravis patho/symptoms:
Autoantibodies against AChR of striated muscle > immune mediated destruction > poor Ach uptake
Muscle fatigue, low facial expression, ptosis/diplopia, poor speaking, poor breathing
Worsens throughout day
MG testing and management:
Unable to upgaze for 1min > EOM/LPS loss
Ptosis improves after 2min icepack (acetylcholinesterase inhibition)
Requires ophthal as is life threatening
MS symptoms and management:
Optic neuritis: VF loss/pain
Diplopia: EOM loss
Nystagmus: eye coordination loss
Internuclear ophthalmoplegia: medial longitudinal fasciculus loss (MR loss)
Uveitis: inflammation secondary to macula oedema
Requires optic neuritis/uveitis treatment and prism lenses
Multiple sclerosis patho:
Autoimmune against myelin > inflammation/demylination/secondary axonal damage > disrupted conduction
Affects ON, brain, spinal cord
T1DM patho:
Autoimmune against pancreatic beta cells > insulin loss > uncontrolled blood sugar
T1DM clinical presentation:
Polyuria: ^unregulated glucose > ^urine filtration > osmotic diuresis (^urination)
Polydipsia: osmotic diuresis > dehydration > ^thirst
Polyphagia: cells unable to intake glucose > cellular starvation > ^hunger
Weight loss: poor cellular glucose metabolism > fat/protein breakdown for energy
Fatigue: poor metabolism > low energy
Blur: ^glucose > osmotic changes in lens > refraction change
T1DM management:
Education, lifestyle modification
Glucose monitor
Insulin
Regular screening (blood/kidney)
T1DM vascular complications:
^ glucose > BV endothelial damage
Macrovascular: coronary artery/cerebrovascular disease
Microvascular: (endo. Is sole component)
D retinopathy, D neuropathy, D nerphropathy
Diabetes related ocular diseases:
DR: endo. Loss of small BV
Cataract: lens protein glycation
DED: nerve damage > poor tear reflex/neurotrophic GF
CN palsy: secondary D.neuropathy
CR(A/V)O/BR(AV)O or NAION: endo loss
