Week 9 Autoimmune Flashcards by Dyllan Nye

Etiology factors for autoimmune diseases:

Genetic predisposition
Environmental triggers
Loss of self-tolerance
T-cell activation/differentiation
Autoantibodies
Activation of autoimmune response

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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

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T cells in autoimmune:

Th1: cell mediated with TFN and IFN-gamma
Th2: antibody mediated with interleukins

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Common genetics in autoimmune disorders:

HLA variants encoding for MHC proteins altering immune regulation, allowing for self targeting

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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

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Loss of self tolerance in autoimmune:

Faliure to recognise self-antigens > damage from autoantibodies and autoreactive T-cells

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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

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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

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Activation of autoimmune response:

Molecular mimicry/self-presenting dendritic cell autoantigen exposure > autoimmune response > inflammatory cascades > cytokine release/macrophage recruitment > tissue damage

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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’

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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

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Thyroid eye disease risks:

Thyroid ophthalmopathy from 25-50% grave’s Px.
^with smoking, immunotherapy, radioactive iodine therapy (graves’ treatment)

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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

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TED process:

Inflammatory phase (1.5-3y) > Fibrotic (quiescent) stage

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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

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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