autoimmune Flashcards

1
Q

examples of autoimmune disease

A

-brain- multiple sclerosis, guillaun-barre syndrome, autism
-thyroid- thyroiditis, hashimoto’s disease, graves disease
-bones- rheumatoid arthritis, ankylosing spondylitis, polymyalgia rheumatica
-muscles- muscular dystrophy, fibromyalgia
-skin- psoriasis, vitiligo, eczema, scleroderma
-nerves- peripheral neuropathy, diabetic neuropathy
-GI tract- celiacs, crohns, ulceratic colitis, diabetes type 1
-blood- leukemia, lupus erythematosus, hemolytic dysglycemia

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2
Q

autoimmune

A

-Receptors on T & B cells of the immune system are antigen specific with diversity derived from gene recombination
-Cells have memory and on a subsequent engagement with an antigen the cells exhibit more rapid and robust responses
-Immune response to self-antigens as in autoimmune & failure to recognize pathogens and eliminate
-Autoimmune Diseases: immune response to self antigens occur in the context of a genetic predisposition resulting in disease expression. Can be organ or system.

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3
Q

Immunodeficiency: primary vs secondary

A

Primary are a direct consequence of structural or functional derangement in the immune network.

Secondary are a consequence of an alteration in the immune status resulting in manifestation of infectious disease.

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4
Q

systemic autoimmune diseases: connective tissue: systemic Lupus Erythematosus

A

-Multisystem autoimmune disease, associated with the production of antibodies to a variety of nuclear and cytoplasmic antigens
-Antibodies to ds DNA, causes inflammation to skin, joints, kidney, cardiovascular system, ervous system,lung and hemopoietic cells.
-Diagnosis with criteria of signs (rash, arthritis, oral ulcers, etc) proteinuria, cytopenia
-+ anti-ds DNA
-+ antiphospholipid antibody
-+ anti-Sm antibody
-false positive syphilis (boards q)
-abnormal (speckled) ANA -> usually first test
-butterfly rash
-arthritis, raynauds, lupus nephritis, heart problems, pleural effusions

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5
Q

systemic autoimmune diseases: connective tissue: sjogren syndrome

A

-Systemic connective tissue disorder
-MC in women than is men
-an autoimmune exocrinopathy involving the lacrimal GLANDS, salivary glands and less often the pancreas
-Inflammation contributes to sicca syndrome, dry eyes and mouth.
-Positive ANA, positive SS-A, positive SS-B, positive rheumatoid factor
-Can be primary or associated with another autoimmune disorder.
-Test for sicca
-Dry eye Schirmer test- tissue paper put up to eye to measure how far down the wet travels
-Biopsy of salivary gland
-2.5% develop non-Hodgkin Lymphoma
-joint pain, abnormal liver, digestive problems, muscle pain, vaginal dryness, neurological problems, recurrent bronchitis
-fertility problems due to lack of fluid

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6
Q

systemic autoimmune diseases: connective tissue: scleroderma

A

-Excessive and widespread deposition of COLLAGEN in many organ systems of the body

skin, GI tract, kidney(renal ischemia), lung and muscles:
- tissue fibrosis,
- proliferative and occlusive vasculopathy of the small blood vessels
- specific autoimmune response associated with distinctive autoantibody profile

-Subtypes including CREST (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly and Telangiectasia)
-pulmonary HTN -> CHF, lung problems -> can die
-Positive ANA, antibody Scl-70
-Calcinosis- calcium deposits in skin
-Raynauds phenomenon
-Esophageal dysfunction- acid reflex and decrease motility
-Sclerodactyly- thickening and tightening of skin on fingers and hands
-Telangiectasis- dilation of capillaries causing red marks on surface of skin

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7
Q

systemic autoimmune diseases: connective tissue: inflammatory muscle diseases

A

-3 types:
-1. dermatomyositis. Heliotrope rash, shawl sign, Gottron papules. Complement vasculopathy.
-2. Polymyositis. T-cell medicated muscle injury
-3. Inclusion body myositis. Older
-Pulmonary interstitial fibrosis in 10%,
-3/5 criteria present -> proximal muscle weakness, muscle pain and tenderness on palpation, EMG abnormal, elevated serum/plasma concentrations of muscle enzymes, muscle bx with cellular inflammation
-Positive ANA, anti-Jo
-calcification in skin, joint pain, arthritis, arrhythmias, myocarditis, pericarditis, gastroesophageal reflex disease, dysphagia, aspiration pneumonia
-progressive muscle wasting
-fever, fatigue, weight loss

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8
Q

systemic autoimmune diseases: connective tissue: mixed connective tissue disease

A

Combined features of SLE, sclerosis, and polymyositis
- combo of scleroderma, rheumatoid arthritis, lupus, sjogrens

Sx:
-Arthralgias, myalgias, fatigue & Raynaud phenomenon.
-Pulmonary (interstitial pneumonitis, Pulmonary HTN, Intersitital Fibrosis, diaphragm & esophagus disfucntion)

Dx
- by clinical features: must have synovitis or myositis
- positive ANA, anti-U1 RNP

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9
Q

systemic autoimmune diseases: connective tissues: rheumatoid arthritis

A

-primarily affects the synovial joints often starting as a synovitis.
-Young women.
-3/7 criteria with morning stiffness.
-Increased serum Rheumatoid Factor, anti- CCP

wasnt on slide:
→ 3/7 criteria w/ morning stiffness 6+ weeks
● Arthritis in 3+ small joints
● Morning stiffness >30 mins
● Arthritis of small joints in hands
● Rheumatoid nodules
● Symmetrical arthritis, often w/ synovitis
● Positive test for RF
● Radiographic changes affected joints

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10
Q

systemic autoimmune diseases: connective tissue: amylodosis

A

-Extracellular deposition of low-molecular-weight fibrils from a soluble circulating precursor giving a waxy appearance to the infiltrated organs.
-Congo red stain on microscopy, abdominal fat pad,
-Multiorgan involvement Factor X coagulopathy
-Male 2:1, onset 40’s
-fatigue
-SOB
-protein in urine
-BP changes
-dizzy
-pain
-kidney issues
-stiff heart
-diarrhea/constipation
-weight loss

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11
Q

systemic autoimmune diseases: connective tissue: cryoglobulinemia

A

-Immunoglobulins in the serum that precipitate at a temp below 37C, resolves on warming.

Sx:
-Immune complex vascultitis, arthritis, neuropathy, renal involvement
-red blotchy rash**
-occurs at cold temp and resolves with warm

Dx:
-Wintrobe tube collects cyroglubulin reported as a cryocrit.

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12
Q

positive ANA flow chart

A

-order the whole panel at once
-anti-jo differentiation is based on symptoms
-

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13
Q

diseases of immune system: X-linked agammaglobulinemia

A

-Absence of b lymphocytes in males
-Recurrent infections

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14
Q

disease of immune system: common variable immunodeficiency

A

-Male & females in adult
-B cells are dysfunctional
-Recurrent infections, immune hemolytic anemia, neutropenia, pernicious anemia, B cell Lymphoma
-chronic cough
-swollen lymph nodes
-breathing trouble
-pain in ear
-nausea, vomiting, and diarrhea, weight loss

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15
Q

disease of immune system: hyper IgM syndrome

A

-low IgG and IgA with normal IgM OR high IgM, normal B cells

inability to switch antibody production from IgM to other types of antibodies (IgG, IgA, and IgE). This leads to an excess of IgM antibodies and a deficiency of other types

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16
Q

disease of immune system: selective IgA deficiency

A

-MC primary immunodeficiency syndrome
-asymptomatic to increased risk for allergies, autoimmune disorders, recurrent infections, GI diseases
-IgA < 5 with normal IgG and IgM

17
Q

diseases of immune system: DiGeorge Syndrome

A

-Chromosome 22 deletion
-Catch 22 (Cardiac abnormality, abnormal facies, thymic hypoplasia, cleft palate & hypocalcemia) -> board question
-T cell abnormalities and B Cell dysfunction, parathyroid abnormal

18
Q

diseases of the immune system: severe combined immunodeficiency syndrome

A

-Cellular and humoral immunity defects
-Bubble babies
-Bone marrow transplant
-Neonate heel prick test.

19
Q

deficiencies in complement

A

-Complement protects against pathogens and non-self antigens. Cytokine release, stimulation of phagocytes, inflammation, cell killing attack.
-Deficiencies result in susceptibility for infections and predispose to autoimmune diseases.

CH50 test:
- Hemolyze antibody coated sheep red cells.
-Low result: if depleted of complement or congenitally deficient.

AH50: screens for complement abnormalites in the alternative pathway
- addition of complement restores hemolytic activity

———————

The complement system defends against pathogens and foreign antigens through cytokine release, stimulation of phagocytes, inflammation, and direct cell killing.
Deficiencies in this system can increase susceptibility to infections and predispose individuals to autoimmune diseases.
The CH50 test evaluates the overall activity of the classical complement pathway by measuring the ability to lyse antibody-coated sheep red blood cells.
A low CH50 result can indicate depletion of complement components or a congenital deficiency.
The AH50 test measures the activity of the alternative complement pathway, where adding complement can restore the ability to lyse red blood cells.

If the red blood cells are effectively lysed, it indicates that the alternative pathway is functioning well. Conversely, little to no lysis suggests a deficiency or dysfunction in the alternative pathway components.

20
Q

perform CH50 chart

A

she barely went over this…

21
Q

HLA genes and gene products

A

-Organ rejection is 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 the major histocompatibility complex (MHC). Found on the short arm of chromosome 6 and encodes for the human leukocyte antigen (HLA) system

22
Q

HLA class 1, 2, and 3 (the surface antigen)

A

-CLASS 1 GENES HLA-A, HLA-B, HLA-C
-Interacts with t-lymphocytes, (cytotoxic T-cells, T suppressor cells) CD 8
-Found on surface of all cells with nucleus (not RBC)
-Healthy cell verses infected cell
-Antigen of infection binds to the Class I HLA surface antigen and triggers an immune reaction
-CLASS 2 GENES HLA-DP, HLA,DQ, HLA-DR
-Interacts with t-lymphocytes (T helper cells) CD4
-Found on surface of B-lymphocytes, macrophages, dendritic cells and some T cells
-Help immune cells communicate with each other!
-When a macrophage attacks an organism the antigen binds from the pathogen which releases interlukin 1 calls the helper T cells which release interlukin 2 which calls B cells (antibodies) an T cells (cytotoxic)
-CLASS 3
-cyotkines
-complement proteins

23
Q

positive antigen findings**

A

-HLA-A 3 : hemochromatosis
-HLA-B 8 : graves, addisons, myasthenia gravis
-HLA-B 27: PAIRS (psoriasis, ankylosing sponylitis, IBS, reiter’s syndrome)
-HLA-D R2: MS, SLE
-HLA-D R3 & HLA-D R4: DM type 1
-HLA-D R5: hashimoto
-HLA-D Q2: celiac disease

24
Q

matching HLA with siblings

A

-Each person gets one halotype from each parent. The two haplotypes represent the HLA genotype
-Four genotypes are possible in the offspring
-25% chance of tow siblings being identical
-50% of sharing one haplotype
-Currently 17,500 HLA alleles

25
Q

histocompatibility testing assays: HLA typing

A

microlymphocytotoxicity assay.
-T lymphocytes for class I antigens
-B lymphocytes for class II antigens
-Antibody in the serum binds to antigen causing cell lysis

DNA Polymerase chain reaction -Used for specific antigen

26
Q

histocompatibility testing assays: HLA antibody screening

A

-Serum screened for antibodies from prior exposure
-Percent panel reactive antibody
-High PRA must wait for a donor 0% PRA
-These patients have a higher risk of rejection

27
Q

Histocompatibility Testing Assays: crossmatching

A

-Lymphocyte cross match
-Renal, heart, lung transplants
-If recipient has HLA antibodies against donor antigens the cells will be lysed… then no transplant match.

28
Q

histocompatibility: solid organ transplants

A

-kidney- ABO blood group compatibility, cross match donor lymphocytes with recipient serum
-liver- ABO blood group compatibility, donor specific HLA antibodies are not a contraindication
-heart- ABO blood group compatibility, if HLA high antibodies in recipient, then virtual crossmatch
-lung- ABO blood group compatibility, if HLA high antibodies in recipient, then virtual crossmatch
-pancreas- ABO blood group compatibility, cross match donor lymphocytes with recipient serum
-cornea- no HLA or ABO matching

29
Q

histocompatibility: cell transplants

A

-Normal hematopoietic cell transplantation is a therapeutic option in which normal hematopoietic stem or progenitor cells are used to replace abnormal hematopoietic cells or to reconstitute the bone marrow of patients undergoing high-dose cytotoxic therapy for malignancy.
-Harvested from the bone marrow or from the peripheral blood after giving the donor growth factors.
-HLA matching, 2%graft failure even with match

——————-

Hematopoietic cell transplantation is a treatment option that involves using normal hematopoietic stem or progenitor cells to replace abnormal cells or to reconstitute the bone marrow of patients who have received high-dose cytotoxic therapy for cancer.
These cells are typically harvested from the bone marrow or from the peripheral blood, following administration of growth factors to the donor, which stimulate the release of these cells into the bloodstream.
The process includes human leukocyte antigen (HLA) matching to minimize the risk of graft rejection; however, even with a match, there is about a 2% risk of graft failure.

30
Q

HLA typing and non-transplantation related applications

A

-Clinically HLA typing can be used to help identify increased risk of a drug hypersensitivity.
-Hypersensitivity to : Carbamazepine ( Tegretol), allopurinol, abacavir (Ziagen)