autoimmune juju Flashcards
What specific autoimmune disease can affect the brain?
MS, Guillian Barre Syndrome, Autism
What specific autoimmune disease can affect the blood?
Leukemia, Lupus erythematous, Hemolytic Dysglycemia
What specific autoimmune disease can affect the GI tract?
Celiac Disease Crohns Disease Ulcerative Colitis DM Type 1
What specific autoimmune disease can affect the skin?
Vitiligo Eczema Scleroderma Psoriasis
What specific autoimmune disease can affect the muscles?
Muscular Dystrophy Fibromyalgia
What specific autoimmune disease can affect the bones?
Rheumatoid Arthritis Polymyalgia Rheumatica Amylosing Spondylosis
Receptors on __________ of the immune system are antigen specific with diversity derived from ____________
T & B cells gene recombination
Autoimmune Diseases = immune responses to _________.
Immune response to self antigens occur in the context of a genetic predisposition resulting in disease expression. Can be organ or system
Primary Immunodefiency
A direct consequence of structural or functional derangement in the immune network.
Secondary immunodeficiency
A consequence of an alteration in the immune system resulting from a ds process (HIV, CMV, cancer, myelomas)
What is Systemic Lupus Erythematosus?
Multisystem autoimmune disease, associated with the production of antibodies to a variety of nuclear and cytoplasmic antigens
What do pts with systemic lupus erythematous have antibodies to?
antibodies to: Double stranded DNA
-causes inflammation to skin, joints, kidney, cardiovascular system, nervous system, lung and hemopoietic cells.
What are diagnostic signs of systemic lupus erythematous?
Butterfly rash on cheeks + forehead
- arthritis
- oral ulcers
- proteinuria
- cytopenia
What are the labs for systemic lupus erythematous?
- Positive anti-ds DNA
- Positive antiphospholipid antibody
- Positive anti-Sm antibody
- false positive test for syphilis
- abnormal/”speckled ANA”
With systemic lupus erythematous what false positive test?
False positive syphillis test
Sjogren Syndrome description
- Systemic connective tissue disorder
- more common in women
- an autoimmune exocrinopathy: lacrimal glands, salivary glands and less often the pancreas (moisture producing glands)
What are symptoms of sjogren syndrome?
Inflammation contributes to sicca syndrome, dry eyes and mouth
-glandular swelling
- Dry mouth, skin, throat, eyes , dry nose, dry vagina
- Joint /muscle pain
- recurrent bronchitis
- abnormal liver function
- digestive problems
What are the labs for Sjogren Syndrome
Positive ANA Positive SS-A Positive SS-B Positive rheumatoid factor
What diagnostic tests are performed for Sjogren Syndrome
- Test for sicca.
- Dry eye Schirmer test. (tissue paper
- should have a certain mm of tears)
- Bx of salivary gland
What can 2.5% of individuals with sjrogen syndrome develop?
Non hodgkins lymphoma
What is Scleroderma and 3 main characterisitics
- Excessive and widespread deposition of collagen in many organ systems of the body
- common in old ppl, age 70+ characteristics:
- tissue fibrosis
- Proliferative and occlusive vasculopathy of the small blood vessels
- Specific autoimmune response w distinctive autoantibody profile
Scleroderma sx
CREST Calcinosis: calcium deposits in skin Raynaud’s Phenomenum: spasm of blood vessels in response to cold/stress Esophageal Motility Dysfunction: acid reflux,decreased motility Sclerodactyly: thickening +tightening of skin on fingers/hands Telangiectasias: dilation of capilarries-red marks on skin
What are the labs for scleroderma
Positive ANA Antibody Scl-70
What is involved in scleroderma
- Skin
- GI tract
- kidney(renal ischemia)
- lung
- muscles
What are the 3 types of inflammatory muscle disease
Dermatomyositis. (derm signs) Polymyositis. (t cell mediated muscle injury) Inclusion body myositis. (older pts) (10% have pulmonary interstitial fibrosis)
What is dermatomyositis
Heliotrope rash shawl sign: redness where a shawl is Gottron papules. Complement vasculopathy
What are the labs for inflammatory muscle disease
positive Anti Jo Positive ANA “not your average jo, he has (inflamed) muscles”
What are the criteria for inflammatory muscle disease? How much of criteria must be met?
3/5 criteria:
- Proximal muscle weakness
- Muscle pain and tenderness on palpation
- EMG abnormal
- Elevated serum/plasma concentrations of muscle enzymes
- Muscle bx with cellular inflammation
Mixed Connective Tissue Disease involves combined features of
- SLE
- sclerosis,
- polymyositis (t cell mediated muscle injury)
What symptoms of mixed connective tissue disease?
- Arthralgias/myalgias
- fatigue
- Raynaud phenomenon
- Interstitial pneumonitis
- Pulmonary HTN
- Interstitial Fibrosis
- diaphragm & esophagus disfunction
What are labs for mixed connective tissue disease? how do you dx?
Positive ANA Anti-U1 RNP Dx: by clinical features + positive ANA, positive anti-U1 RNP
Rheumatoid Arthritis definition
Systemic autoimmune connective tissue disorder
- primarily affects the synovial joints often starting as a synovitis
- MC: young women
- stiffness in the morning-> as the joints lubricate during the day it improves
- >
You must meet ______ criteria for Rheumatoid Arthritis
3/7 criteria with morning stiffness
Rheumatoid arthritis is most common in
young women
What are the labs for Rheumatoid Arthritis
- Increased serum Rheumatoid Factor
- Anti- CCP
What is Amyloidosis?
- Extracellular deposition of low-molecular-weight fibrils giving a waxy appearance to the infiltrated organs
- multiorgan involvement
- factor x coagulopathy
- MC: males (2:1); 40s onset
Who is amyloidosis most common in? Typical Onset
Male 2:1, onset 40’s
What are symptoms of amyloidosis
sx due to bone marrow disorder: misfolded proteins can accumulate in the body tissues, nerves and organs:
- Fatigue
- SOB
- Proteinuria
- Stiff Heart
- Diarrhea/Consipation
- Kidney Failure
- BP Changes
- Dizzy
- Weight Loss abdominal fat pad
What testing for amyloidosis?
+ Congo red stain on microscopy abdominal fat pad “amy loves congo red lipstick”
In amyloidosis , _____involvement Factor _____
Multiorgan involvement Factor X coagulopathy
Cryoglobulinemia: immunoglobulins in the serum precipitate at a temp…
immunoglobulins in the serum precipitate at a temp… Below 37C, resolves on warming Immune complex vascultitis, arthritis, neuropathy, renal involvement
How to diagnose cryoglobulinemia?
Wintrobe tube collects cyroglubulin reported as a cryocrit
What is X-linked agammaglobulinemia?
Absence of B lymphocyte in males
-causes recurrent Infections
What is common variable immunodeficency and its characteristics
- Affects both male and female adults
- B cells dysfunction characteristics:
-Recurrent infections - Neutropenic
- Immune Hemolytic Anemia
- Pernicious anemia
- B cell Lymphoma
What are frequent symptoms of common variable immunodeficency?
- chronic cough
- swollen lymph nodes
- breathing troubles
- ear pain
- n/v/d
- wt loss
What is hyper-IgM syndrome?
Normal to High IgM with:
- Low IgG + IgA
- normal B cells: but can’t undergo antibody class switching
- cant make antibodies
What is the most common primary immunodeficency syndrome?
Selective IgA deficency
What is the IgA for selective IgA deficency
IgA <5 MG.DL with normal IgG and IgM
Selective IgA deficiency characteristics
- Asymptomatic to Allergies
- Autoimmune disorders
- GI disease
- Pulm Ds
- Recurrent infections
What is DiGeorge syndrome?
Chromosome 22 deletion
- T + B cell abnormalities
- Abnormal parathyroid CATCH 22
- Cardiac abnormality
- Abnormal facies
- Thymic hypoplasia
- Cleft Palate
- Hypocalcemia
What is severe combined immunodeficiency (SCID)?
Cellular and humoral immunity defects
-> bubble babies
severe combined immunodeficiency (SCID) screen/dx and tx
Dx: Neonate heel prick test tx: Bone marrow transplant
-Bubble babies
What does complement protect against
- Pathogens and non self antigens
- cytokine release
- stimulation of phagocytes
- inflammation
-cell killing attack deficiencies = susceptible to infections and predisposes to autoimmune ds
What would a deficency in complement result in
- Susceptibility for infections
- predispose to autoimmune disease
What test is performed for deficencies in complement?
CH50 test
-Uses hemolyze antibody coated sheep red cells complement deficient or congenitally deficienct:
- low
What is AH50 test?
screening test for complement abnormalities in the alternative pathway:
- Addition of complement restore hemolytic activity
What is organ rejection primarily a consequence of ?
The interactions between the immune system of the transplant recipient and the histocompatibility antigens present on the transplanted cells.
Histocompatibility antigens are encoded by a complex of closely linked genes called
Major Histocompatibility Complex (MHC)
- found on the short arm of chromosome 6
- Encodes for the human leukocyte antigen system (HLA )
HLA Class I genes include what 3 types?
HLA-A HLA-B HLA-C
HLA Class 2 genes include what 3 types?
HLA-DP HLA-DQ HLA-DR
What do Class I genes interact with
- T lymphocytes (cytotoxic t cells, t suprressor cells) and CD8 cells
- Found on surface of all cells w nucleus
-> NOT RBCs - Antigen of infection binds to class I HLA surface antigen and triggers immune reaction
What do Class 2 genes interact with
- T lymphocytes, (T helper cells) and CD4 cells
- Found on surface of B lymphocytes, macrophages dendritic cells and t cells
- Help immune cells communicate with each other through IL-1 and IL-2
—— When a macrophage attacks an organism the antigen binds from the pathogen which releases interleukin 1, calls helper t cells which release interleukin 2, which calls b cells-antibodies and t cells- cytotoxic
What do HLA Class 3 include
Cytokines Complement Proteins (prone to hemachromatosis)
What are HLA-A 3 prone to
Hemachromatosis A3
-> Fe3+ overload
What are HLA-B 8 prone to**
Graves disease, Addisons disease, Myasthenia gravis GAM = B8
What are the HLA-B27-associated disorders?***
Psoriasis Ankylosing spondylitis IBS Reiter syndrome PAIR = B27***
-> pair by 27 yrs old
What are HLA-D R2 associated disorders?
MS SLE
What are HLA-D R3 +R4 associated disorder?
DM type 1
What are HLA-D R5 associated disorder?
Hashimoto
___ chance of two siblings being identical, ____ of sharing one haplotype
25%,50% currently, 17,500 HLA alleles= bone marrow match difficult needs to be identical
What are HLA-D Q2 associated disorder?
Celiac Disease
Matching HLA with Siblings
Each person has two sets of HLA genes, called haplotypes—one inherited from each parent
- currently 17,500 HLA alleles
- HLA match between siblings or no match at all is 25%
- 50% chance of siblings sharing one haplotype
Histocompatibility Testing Assays include
HLA Typing HLA Antibody Screening Crossmatching
What is HLA typing?
Uses microlymphocytotoxicity assay: T lymphocytes and B lymphocytes are used to detect Class I (t) and Class II (b) HLA antigens,
- Antibodies in the serum bind to these antigens, causing cell lysis, which is observed to check for matches. Uses DNA polymerase chain reaction: for specific antigens
What is HLA antibody screening
- Serum screened for antibodies from prior exposure
- Percent panel reactive antibody (PRA)
- High PRA: indicates a high risk of rejection, necessitating waiting for a donor with a 0% PRA (no detected HLA antibodies)
—— Percent Panel Reactive Antibody (PRA): Indicates the percentage of antibodies against a panel of known HLA types
What is crossmatching?
Ensure that the recipient’s serum does not contain antibodies that react against the donor’s lymphocytes, which would predict transplant rejection For Renal, heart, lung transplants
If recipient has HLA antibodies against donor antigens
No transpant match! The cells will be lysed
Organ Transplant Requirements: kidney, liver, pancreas, heart, lungs, cornea
Kidney and Pancreas:
- ABO compatible
- crossmatch lymphocytes Lungs and Heart:
- ABO compatible
- additional virtual crossmatch needed if high HLA antibodies are present in the recipient Liver:
- ABO compatible
- Donor specific HLA antibodies not a contraindication Cornea:
- no HLA matching
- No ABO matching
Histocompatibility: Solid Organ Transplants Kidney +Pancreas
- ABO compatible
- crossmatch lymphocytes
Histocompatibility: Solid Organ Transplants Liver
- ABO blood group compatibility
- Donor specific HLA antibodies are NOT contraindication.
Histocompatibility: Solid Organ Transplants Heart+ Lung
- ABO compatible
- additional virtual crossmatch needed if high HLA antibodies are present in the recipient
Histocompatibility: Solid Organ Transplants Cornea
MC tissue transplant doesnt need any match NO HLA or ABO matching
Normal hematopoietic cell transplantation
- Hematopoietic transplantation is a therapeutic option for patients undergoing cytotoxic therapy for malignancy
- Harvested from the bone marrow or from the peripheral blood after giving the donor growth factors
——- Hematopoietic transplantation involves the infusion of hematopoietic stem cells to restore bone marrow function in patients whose marrow has been destroyed
Even with perfect HLA matching, what can occur
2% graft failure
HLA typing can be used to help identify increased risk of a drug hypersensitivity to
Hypersensitivity to :
- Carbamazepine
- allopurinol
- abacavir seizure med, anti virals
