Autoimmunity Flashcards
Effector machanisms of autoimmunity
- autoantibodies
2. autoimmune T cells
autoimmune diseases arise via
the breakdown of the negative selection processes that remove self reactive t cells and b cells from the lymphocyte reservoire
Autoimmune responses are NEVER mediated by
IgE
Therefore there are no Immediate Type I autoimmunties
Caused by ab’s specific for components of cell surfaces pr ECM
Type II autoimmune disease
Autoimmune hemolytic anemia class
Type II
Autoimmune hemolytic anemia
IgG and IgM bind to RBC’s
- ->activate classical compliment pathway
- ->MAC destroys RBCS
- ->C3b deposition also leads to phagocyte clearance in the SPLEEN
- RESULT IS ANEMA
test for autoimmune hemolytic anemia
DIRECT coomb’s
are nucleated cells efficiently cleared through compliment activation
no
Neutropenia autoimmune class
Type II
Nutropenia MOA
WBC’s destroyed via most via phagocytosis
*ab responses directed at WBC surface antigens–> FC receptors recognize Ab’s
Common tx. for neutropenia
splenectomy
Goodpasture’s syndrome is what Autoimmune class
Type II
Goodpasture’s Syndrome MOA
Ab’s specific for ECM autoantigens
- specifically alpha chain of Type Iv collagen (basement membranes)
- ->ab’s deposit on basement membranes of renal glomeruli and tubules eliciting inflammation
- ->kidney failure
tx. for Good pastures
removal of self-reactive ab’s and immunosuppression
255 of all kidney failure are related to
immune system
Acute rheumatic fever class
type II autoimmunity
Acute Rheumatic Fever MOA
(MOLECULAR MEMORY)
Ab’s produced in response to Strep Pyogenes (initially for protecton)–> react with self antigens on human heart (become autoantigens)–> inflammation and damage
Is Rheumastic fever transient or persistent
Transient–> t cells cannot recognize the strep surface antigens, B cells cannot be activate fully–> NO IMMUNOLOGIC MEMORY IS CREATED
AUTOIMMUNE CLASS FOR GRAVE’S DISEASE
Type II
Graves’ disease
Ab’s that bind to TSH receptors and mimic binding of TSH–> chronic overproduction of TH that is independent of regulation
Graves’ disease results in
Hyperthyroidisms–> heat intolerance, nervouseness, irritability, warm moist skin
Can TSH mimicking antibodies cross placenta
yes– baby can be born with Grave’s
TSH mimicking antibody in Graves is of what isoform
IgG–> it can cross placenta
tx. for adult graves
drugs
removal of thyroid
tx for grave’s infants
removal of anti-TSHR ab’s via total exchange of blood plasma
Myasthenia gravis Classification
Type II
Myasthenia gravis MOA
signaling from nerve to muscle is impaired
–> Ab’s bind to self-ACH recptors and cause them to be internalized–> muscle is then LESS responsive to ACH
Tx. of Myasthenia Gravis
Immunosuppressive agents, or PYROSTIGIMINE which inhibits acetylcholinesterase
Guillian Barre Class?
Type II
Autoimmune Deficiencies that classify as MOLECULAR MIMICRY
- GBS
- Acute Rheumatic fever
- Wegener’s Granulomatosis
GBS MOA
mediated by IgG specific for gangliosides–> mediate Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
GBS is most commonly caused by molecular mimickry from which organism
C. jejuni
GBS morphology
Descending–from legs to head (happens very quickly weeks to days)
Miller-Fischer Syndrome
GBS except it progresses from top to bottom
Wegener’s is what type of Autoimmune disease
Type II
Wegener’s is meadiated by which Ab’s
cANCA’s: anti-neutrophil cytoplasmic ab’s
Wegener’s MOA
cross reactive ANCA’s(originally formed to bacterial pathogen response) bind to neutrophils–> actiavted them–> they bind to endothelial cells and cause VASCULITIS
Autoimmune Thrombocytopenic Purpura is in what Class
Type II
ITP cause
IgG mediated inhibition of an enezyme responsible for cleavage of VWF– (ROBBIN;s has this as ADAMSt13
Leads to thrombocytopenia, neurological symptoms and microangiopathic hemolytic anema
Microangiopathic hemolytic anemia
rbc’s get cleaved (schistocytes) as they are pushed through microscopic clots
Scleroderma (Type II) cause
destrcution of vascular endothelium and smooth muscle cells–. replacement with abundant collagen from fibroblasts
Scleroderma is associated with what Ab’s
Anti topo 1 (Diffuse) anti centromere (CREST)
Findings of CREST Systemic Scleroderma
*Milder form calcinosis Raynaud's esophageal dysmotility Sclerodactyly Telangeictasia
Anti centromer Ab’s are specific to
Limited Scleroderma: CREST
Anti Topo 1 ab’s are specific to
diffuse scleroderma
Pemphigus Vulgaris (Type II autoimmunity)
autoimmune condition specific for 2 proteins
Desmoglein 1 and 3
*cohesion of kratinoctyes–> painful and chronic blistering of the skin
tx for pemphisus bulgaris
rituximab
SLE is what type of autoimmune
III
Ab’s present in SLE
ANA’s (non diagnostic)
Anti-histone (non diagnostic)
Anti-SMith–> diagnostic
Anti-dsDNA–> diagnostic
SLE pt.’s usually die from failure of what organs
KIDNEY
BRAIN
Post Strep Glomerulonephritis
immune compex disorder that follows infections with GAS–> Ab-GAS complexes get lodged in the glomeruli resulting in inflammation that hinders kidney fxn
Pt.s with Insulin Dependent TYPE 1 diabetes have what autoimmune process going on
T cell mediated autoimmune response that desstroys beta cells in islets of langerhans
IDDM is what class of Autoimmune disease
TYPE IV–> T CELL MEDIATED
CTL’s in IDDM do what
bind to undefined antigen on Beta cells and kill them over time–> decreased insulin production
CD4 and Ab’s cells in IDDM do what
involved in producing specific for products of B cells (anti-insulin Ab’s and anti-glutamate dehydrogenase)
RA is what type of autoimmunity
Type IV
What is rehumatoid factor
IgM, IgA, IgG AUTOANTIBODIES that are specific to the FC recgions of human IgG molecules–> this si not required for tissue damage, but helps diagnose
Test more specific for RA
anti-CCP : cyclic citrullinated proteins
Cells found in infiltrates of all ppl with RA
CD4 CD8 T cells, B cells, Plasma cells, neutrophils, macrophages
Tx for RA
TNF-Alpha blockers
Multiple Sclerosis is what type
IV
Cause of MS
immune response directed at myelin sheath
*causes sclerotic plaques of demyelinated tissue in white matter of CNS–> loss of coordination and spasticity
Cell type responsible for demyelination in MS
TH1
*produce IFN gamma that activated macrophages in sclerotic plaques–> mac’s release proteases and cytokines–> demyelination
Tpe Iv autoimmune disease that attacks exocrine glands
Sjogren Syndrome
Sjogren’s is usally found
in conjucntion with another Autoimmune condition
Ab’s specific for Sjogren’s
Anti-SS A/RO and Anti SS B/LA
APECED is caused by a defect in…
AIRE gene–> impaired negative selection of t cells in the thymus (therefore b cells are affected too)
PPL that express HLA-DR2 are
16 times more likely to develop goodpasture’s syndrome than those that do NOT express HLA-DR2
Immunologically priveledges dites
Anterior chamber of the eye
uterus
testes
Sympathetic ophthalmia
an alteration on what is believed to be a immune preveledged site
is a bilateral diffuse granulomatous uveitis (a kind of inflammation) of both eyes following trauma to one eye. It can leave the patient completely blind. Symptoms may develop from days to several years after a penetrating eye injury.
