autoimm

Question 1

what is pnh

Answer 1

Recurrent hemoglobinura secondary to intravascular hemolysis, due to lack of GPI anchored protein
Can get thrombis and aplastic anemia first
Caused by PIGA or PIGM somatic mutation - needed for GPI anchored proteins protecting cells from complement mediated lysis (esp CD59) - diagnose with flow to CD59 and DAF (CD55)
Eculizumab blocks c5 so prevent INTRAVASCULAR hemolysis via MAC, but not the EXTRAvascular one
BW: CBCd, retic, DAT, smear, flwo for CD59 and CD55

Question 2

what does eculizumab target

Answer 2

treats HUS and PNH
must give men b vaccine

Blocks C5 in complement preveing recruitment of inflammatory cells
Used for PNH and HUS

Question 3

name earyl and complement diffenciency effects

Answer 3

Early
C1,4,2,3 - SLE and bacterial infections (enscapsulated, h flu strep mening) and arthersclerosis
Terminal
C5-9, neisserial disease, vacciante q3 years
Regularory
Factor D, I, H properidine — neissieria or HUS
Activationof complement on endothelium leading to HUS, can treat with eco (anti c5) but then give MEN B vaccine → TMA is characteristic
C1 esterase inh
Secondary complement def: cirrhosis, maluntrion HAE
Immune complex diseas: SLE, glomerulopneprisis, qendocarditis, cryo, HUVS
MOST COMMON is poorly handled specimen

Question 4

give an example of T cell mediated autoimm and B cell mediatd automm

with b cell it sgould target receptor

Answer 4

Myesthenia gravis (B cell mediated)
IgG autoantibodies to ACH receptor, fixing complement and attack the receptor over time
AChR antibodies block Ach binding, and also cross linch AchR and activating complement mediated ACh R destruction
Another example is TRAB (thyrotropin receptor antibodies to thyroid receptor- causing graves)
Insulin dependant diabetes (T cell mediated)
Autoimm destruction of insulin producing beta cells in islet of langerhan
Thought to be T cell dependant (along with MS myelin proteins, RA)

Question 5

Discuss the phenomenon of antibody production in various disease states under those

circumstances where you feel that the autoantibodies produced.

a) Are the primary cause of the disease state observed
b) Are associated with immunopathological tissue damage in a secondary fashion.
c) Are laboratory curiosities, or epiphenomena, without direct pathogenetic bearing on the disease processes

Answer 5

a. Myesthenia Gravis and Anti GBM (antibody against basement membrane collagen)
b. WM leading to AIHA (APS and AIHA)
c. Anti CCP in RA, Anti ds DNA in SLE

Question 6

70 yo M with
Present with fatigue, wieght loss, oozing blood from nose and gum and peripheral neurpathy
Can get hyperviscosity sx

Answer 6

Waldernstorms macroglobenemia
Cancer of B cell, can come after MGUS, with monogamopathy hyper IgM
Presents in 70th year of life, sausage appearing retinal veins
Ddx:
MGUS, multiple myeloma, CLL
Present with fatigue, wieght loss, oozing blood from nose and gum and peripheral neurpathy
Can get hyperviscosity sx
Clonal prolif of B cell (can be with myd88 or cxcr4) -
High SPEP and IgM on immunofixation, BMA show hgih B cell
Diagnosic criteria
SPEP and high IgM on immunofixation
BMA >10% infirltarion with plasma cell differnetation (intertrabecular pattern)
Can have myd88
Treatment
Can be smouldering where you follow q4-6months
Any sx of hypervis, LAD, splenomeg, neuropathy, cro, cold agglutinun hemolytic anemia, AIHA or low plt, neirpathy, amyloidiosis, low hbg or plt
Ritux and can give chemo if high burden
If high - bendamustine or dex and cyclphoasmaide
Aif hypervisocisty - oronasal beleding, headache blurred vision, hemm, papiledema or coma → PLASMAPHARESIS emergently

Question 7

steroid MOA

desstabilize mRNA via TTYP
prevent DNA unwinding by activation histone deacytlase

Answer 7

transactivation
upregulate anti inflammatnory pathway IL10
causes bad side effect

Transrepression
inhibito NFKB AP1 and NFAT
inibit pro inflammatory cytokine chemokine and adhesion molecules

Question 8

HLA disease associatuions

Answer 8

• SLE: DR2, DR3
• Rheumatoid arthritis associated with DR4
• Diabetes: DR3, DR4, DQ2, DQ8
• Celiac; DQ2, DQ8
• Ankylosing spondylitis / juvenile spondyloarthropathy associated with HLA-B27.
• Behcet’s disease associated with HLA-B51.
• Psoriatic Arthritis associated with B13, B17, and B57.

From genome-wide association studies

B) from UTD: how do HLA antigens confer disease susceptibility?

●Shaping the T-cell repertoire during development

●Shaping the peripheral T-cell repertoire

●Determining which antigenic peptides are bound and therefore presented to the immune system for recognition [31]

●Generating molecular mimicry between self-antigens and either the HLA molecule itself or peptides that it recognizes

●Affecting HLA protein presentation of either foreign or self-antigenic peptides to autoreactive T cells [1]

●Influencing how infection, exogenous agents, or “molecular mimicry” may reactivate silenced T cells in autoimmune diseases [1]

●Affecting immune suppression and cancer development in important ways through the loss of HLA gene expression because of viral infection, somatic mutations, or other causes [1]

●Influencing antigen processing and presentation

Question 9

What are the antinuclear antibodies that can be found in the following conditions: **Paria

a) SLE:
b) Mixed connective tissue disease:
c) Scleroderma:
d) Dermatomyositis

Answer 9

ANA associated with
SLE: anti dsDNA, anti sm,, anti histaone anti ro and la
MTD: anti RNP
Scleroderma: anti scl 70 and anti cetremore
Dermatomyositis : anto jo and anti Pm1