Asian/Black/Hispanic - 30-40 - will always occur with cytopenias and lymphadenopathy - 4-11 criteria for SLE diagnosis - anti-nuclear Abs non specific, but highly sensitive

- Dry eyes and mouth (Autoimmune destruction of the salivary and lacrimal glands) - women 40-70 - May involve extra glandular fibrosis, Peripheral neuropathy/synovitis or Tubulointerstitial disease of the kidneys - LIP BIOPSY

Progressive perivascular fibrosis - Limited involves skin of fingers hands, forearms and face; Late visceral involvement - diffuse: Widespread skin involvement; Early Visceral involvement. Anti-SCL 70 associated with this form.

Calcinosis, Raynaud's, esophageal dysmotility, Sclerodactyly, talengectasia - similar to SLE -> deposits in BVs - Nodules often seen on extremities: Dystrophic calcification

Autoimmune Diseases Flashcards by Jordan Jacobsen

Central versus peripheral tolerance

Central is based on negative selection, peripheral is based on clonal anergy, but both are designed to remove self antigen T cells from the body.

central: AIRE
peripheral: lack of costimulatory signals CD80/CD86

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AIRE

Autoimmune regulator gene: mutation -> autoimmune polyendocriopathy

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IPEX

Mutated FOXp3

- FOXp3 induced by CD25 (basilixumab) txn factor

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Sequestered Abs

In immunopreviliged sites, may be expressed during trauma and manifest autoimmune diseases

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Susceptibility genes: 4 with assoc conditions

HLA sites
PTPN-22: RA T1DM
NOD-1: crohns
IL-2/7: MS

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CCL19/21

Lymphocyte endothelial migration signal that binds CCR7

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TH1,2 and 17: signaling; cytokines

Macs->IL-12->TH1-> IFNg->macs (intracellular bacteria)
TH2->IL4/5/6/13->Eosinophils
TH17->IL17->macs/neutrophils (extracellular killing)

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SLE: susceptibility

Asian/Black/Hispanic

30-40
will always occur with cytopenias and lymphadenopathy
4-11 criteria for SLE diagnosis
anti-nuclear Abs non specific, but highly sensitive

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Rewires Tcells in SLE

CD3g -> FcRg

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Antiphospholipid Antibody syndrome

Often accompanies SLE, and give false positive for syphilis

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SLE classes

I - III: mild clinically, renal glomeruli not involved in disease process
IV: involves renal glomeruli, hyper cellular
V: mysangial/GBM thickening

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Cardio SLE manifestations

Arrythmias/heart blocks

- Vegetations on both sides of valve leaflets (lineman sacks lesions)

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Chronic discord lupus

Same as Normal SLE except no anti-nuclear antibodies

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Sjorgrens syndrome

Dry eyes and mouth (Autoimmune destruction of the salivary and lacrimal glands)
women 40-70
May involve extra glandular fibrosis, Peripheral neuropathy/synovitis or Tubulointerstitial disease of the kidneys
LIP BIOPSY

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Cellular mechanism of SLE et al.

Tolerance fails and T cells with self antigen recognition Get into circulation. On Destruction of cells self antigens are released And anti-self antibodies are then processed and made Precipitating the autoimmune cascade.

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SSA/SSB

Their presence supports diagnosis of Sjorgrens syndrome,

- SSA assoc. with longer duration

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Scleroderma

Progressive perivascular fibrosis

Limited involves skin of fingers hands, forearms and face; Late visceral involvement
diffuse: Widespread skin involvement; Early Visceral involvement. Anti-SCL 70 associated with this form.

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Crest syndrome

Calcinosis, Raynaud’s, esophageal dysmotility, Sclerodactyly, talengectasia

similar to SLE -> deposits in BVs
Nodules often seen on extremities: Dystrophic calcification

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Anti-SCL 70 antibodies

Associated with diffuse scleroderma

- Anti-DNA topoisomerase 1

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Mixed connective tissue disease

Not clinically valuable diagnosis but may progress to SLE

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Direct versus indirect transplant rejection

Direct: CD4/CD8 initiate direct cellular attack
Indirect: CD4’s initiate cell and antibody mediated injury

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Hyperacute graft Rejection

Resultant from preformed antibodies

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Acute graft rejection

Happens over 1 to 3 months
CD8 and CD4: Cell mediated injury
CD4: Humoral mediated injury

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Chronic graft rejection

Most common and most clinically difficult to manage, Many drugs meant to avoid acute graft rejection enable chronic graft rejection
- Injury mediated by fibrosis causing scarring and ischemia

Clinical suspicion of autoimmune condition

Repeated, opportunistic, not easily cleared, age of onset (eg 3 mo = something Ig related) X-linked in males

Complement deficiency

C-5 through C-9: Increased susceptibility to Neisseria species Meningococcal sepsis: Purpera with defused ecchymosis

Chronic granulomatous disease

Decreased oxidative burst. Resultant caseous necrosis of the liver often causes mortality. Neutrophils and bugs with the ring of macrophages surrounding trying to wall Infection off in a fibrous capsule.

Nitroblue tetrazolium test

Colorless dye is added to cellular sample, Oxidized dye turns blue. Thus partial oxidation reveals heterozygous mutant for chronic granulomatous disease, Lack of oxidation reveals homozygous mutant.

Most common CGD mutations

gp91phox: 75% < Poorer prognosis gp47phox: 25%

XLA

Deficient Bruton's tyrosine kinase. BT K precipitates the progression from pro to pre-B cell. - Decreased IgG,IgM and A - Susceptible to encapsulated bacteria and extracellular bugs : Staph aureus, strep pneumo, H. influenzae, Echo, polio, Cox, Giardia - Never give live attenuated virus Vaccine

DiGeorges syndrome

Catch-22: 22q11.2 Microdeletion Results in failure of migration of the third and fourth pharyngeal arches, Resulting in abnormal facies and thymic aplasia as well as parathyroid agenesis.

SCID

Gamma chain most common, (50 to 60%) ADA deficiency (40%) | Survival requires BMT

Secondary immunodeficiencies

``` Malnutrition: # 1 Burn: #2 Diabetes Milletus Uremia Glucocorticoids Pregnancy AIDS ```

Amyloid

Excessive deposition of miss folded proteins (Cross beta-pleated fibrils) Cells accumulate miss folded proteins and die

Amyloidosis diagnosis

Congo red stain appears Applegreen Under polarized light In the presence of ammo

Familial amyloidosis

Transthyretin: mutated protein | Never threaten the family

Hemodynamically associated amyloidosis

AB2 Microglobulin: Chronic renal failure | Globulin - blood

Alzheimer's disease associated amyloidosis

AB Amyloid precursor protein: Sporadic or familial

Immune dyscrasias

AL Ig light chains: Monoclonal B cell proliferation | Immune: bence jones protein, light chain dimers

Reactive systemic or secondary amyloidosis

Alpha amyloid Serum amyloid protein: Chronic inflammation | Do an AASA to determine systemic or secondary

Features of systemic amyloidosis

Amyloid deposits in various Visceral tissues - microglossia: Amyloid deposits in tongue - Carpel tunnel: Amyloid deposits in joints

Lip biopsy

Gold standard for diagnosing Sjorgrens

CD80/CD86

Costimulatory signals resulting in positive selection

Echo, cox, giardia, polio

Extracellular viruses That individuals with XLA are susceptible to

gp91Phox/gp47Phox

Most common CGD mutations - 91: 75% ~ poor prognosis - 47: 25%

XL - Hyper IgM: etiology, labs

``` Increased or normal IgM with all other Igs decreased - cd40 ligand deficiency (no class switching) ```

Type I HSN: BEEM

IL4: B cell stimulation IL5: eosinophil recruitment IL13: IgE class switching/mucus production

Anticentromere antibodies

Specific to limited type scleroderma

Anti SM, antihistone antibodies

Specific for SLE

Scl 70 antibodies

Specific marker for Diffuse scleroderma

AIRE/CTLA-4

Central vs. peripheral tolerance mechanisms

Leukotrienes C/D

SpasmoDiC | - vasoconstriction, bronchospasm

Perivascular cuffing

Associated with the type 4 hypersensitivity

CD 25

Treg ligand

Type IV vs. type V SLE glomerulonephritis

Type IV is a capsular hypercellular state | Type V is a capsular hyperproliferation of membranes

HLA-DR3

is associated with susceptibility for SLE subcutaneous

Normal - increased IgM, decreased IgG,A and E without lymphocytopenia

CVID

Normal IgG/M; decreased IgE/A

Wieskott-Aldrietch syndrome - defective WASP protein - migration and transduction - BMT is only treatment