Immunology Exam 4 (Hypersensitivies and Autoimmune disorders) Flashcards
1
Q
Hypersensitivity Type I notable diseases
A
Anaphylaxis
2
Q
Hypersensitivity Type II notable diseases
A
HDFN, transfusion reactions
3
Q
Hypersensitivity Type III notable diseases
A
SLE, serum sickness, RA, cellular drug reactions
4
Q
Hypersensitivity Type IV notable diseases
A
Contact dermatitis (poison ivy), PPD
5
Q
What antibodies are involved in Type IV hypersensitivies?
A
None
6
Q
What antibodies are involved in Type III hypersensitivies?
A
IgM and IgG
7
Q
What antibodies are involved in Type II hypersensitivities?
A
IgM and IgG
8
Q
What antibodies are involved in Type I hypersensitivities?
A
IgE
9
Q
What cells are involved in Type IV hypersensitivities? What is the “reaction”?
A
Reaction = T cell dependent (Cell-mediated/delayed type)
Cells = Stimulated T helper cells, Macrophages, CD8 T cells
Complement is NOT involved
10
Q
What cells are involved in Type III hypersensitivities? What is the “reaction”?
A
Reaction = Immune complex mediated
Cells = Macrophages, PMNs, Mast cells
Complement is involved
11
Q
What cells are involved in Type II hypersensitivities? What is the “reaction”?
Is complement involved?
A
Reaction = Antibody-mediated cytotoxic
Cells = macrophages and neutrophils
Complement is involved
12
Q
What cells are involved in Type I hypersensitivities? What is the “reaction”? Is complement involved?
A
Reaction = Anaphylaxis
Cells = Mast cells, basophils, APCs
Complement is NOT involved
13
Q
What is the mechanism of injury for Type I hypersensitivities? Are cytokines involved?
A
Allergic/anapylactic reactions
Cytokines are involved (histamine)
14
Q
What is the mechanism of injury for Type II hypersensitivities? Are cytokines involved?
A
Targeted cell lysis, cell mediated cytotoxicity
Cytokines are NOT involved
15
Q
What is the mechanism of injury for Type III hypersensitivities? Are cytokines involved?
A
Immune complexes (Ab/Ag)
Cytokines are involved
16
Q
What is the mechanism of injury for Type IV hypersensitivities? Are cytokines involved?
A
Immune complexes (Ab/Ag)
Cytokines are involved
17
Q
Hypersensitivity
A
Exaggerated, but normal, immune response to an antigen that produces inflammation
18
Q
Allergy
A
Atopy; any altered reaction to external substances mediated by IgE antibodies
19
Q
Anaphylaxis
A
Type 1 hypersensitivity reaction resulting in systemic immune reactions affecting respiratory, cardiovascular, GI, and integumentary systems
20
Q
What are the FOUR categories of hypersensitivities?
A
Type 1 - anaphylactic
Type 2 - cytotoxic antibody
Type 3 - immune complex formation
Type 4 - T cell dependent
21
Q
What are the immediate reaction hypersensitivities? What are the delayed reaction hypersensitivities?
A
Immediate - Type 1,2,3
Delayed - Type 4
22
Q
What cells are involved in Type IV hypersensitivies?
A
Stimulated T helper cells
Macrophages
CD8 T cells
23
Q
What cells are involved in Type III hypersensitivies?
A
Macrophages
PMNs
Mast cells
24
Q
What cells are involved in Type II hypersensitivies?
A
Macrophages
Neutrophils
25
What cells are involved in Type I hypersensitivies?
Mast cells
Basophils
APCs (B cells, macrophages)
26
Which hypersensitivities involve complement?
II and III
27
Auto-immune disorders are more common in ________ (males/females).
Females
28
Auto-immune disorders are more common in __________ (dizygotic/monozygotic twins).
Monozygotic twins
29
Autoimmune disorders are the result of loss of ______________.
Self tolerance
30
Where does Central Tolerance occur?
Primary lymphoid organs (bone marrow and thymus)
31
Where does Peripheral Tolerance occur?
Secondary lymphoid organs (spleen, lymph nodes)
32
Anergy
Absence of normal immune response to a particular antigen
33
Explain the genetic and environmental factors in the development of autoimmunity.
Certain environmental/endogenous triggers raise the risk of autoimmune disorders such as female hormones, tissue injury, microbial infections, or epigenetic factors. A genetically susceptible individual possesses a certain HLA or gene and can lose immunologic tolerance that leads to an autoimmune disease.
34
Influential factors for developing auto-immune disorders
- Genetics (more common in females, certain HLA proteins correlate with AI disorders)
- Age (peak age is 60-70, risk increases w/ age)
- Exogenous factors (UV light exposure, drugs, viruses, chronic infectious diseases)
35
How can microbial infections be an endogenous factor to an autoimmune disorder?
Molecular mimicry
- Antigens of pathogens are structurally similar to host proteins and creates cross-reactivity of antibody response against the pathogen (Ex. S. pyogenes and Rheumatic Fever)
36
What is the bystander effect?
Presence of pathogens in tissue create inflammatory responses that recruit WBCs/APCs for T cell activation and accidental antigens are processed for allo-recognition
(Wrong place, wrong time)
37
Superantigens
Proteins produced by microbes that bind to MHC class II and TCRs regardless of MHC restriction/binding sites (Ex. Staphylococcal enterotoxins and toxic shock syndrome)
38
What are ANAs?
Anti-Nuclear Antibodies
Heterogenous group of circulating antibodies that can either be IgG, IgM, or IgA
True auto-antibodies that are classified by:
- Antibodies to DNA (native dsDNA or denatured ssDNA) histones, non-histones, or nucleolar antigens
39
How are ANAs detected?
Via IFA
40
ANA screening with IIF titers
1:80 and 1:160 dilutions performed because low titer positives may occur in healthy people, positive samples may be further diluted to determine titer
41
Homogenous ANA pattern
- Interphase and metaphase positive
- Uniform staining of entire nucleus
- Associated with SLE, drug-induced lupus, AI hepatitis, and JIA
**Presents as solid, green circles!**
42
Speckled ANA pattern
- Interphase positive, metaphase negative
- Associated with anti-ENAs in SLE, Sjogrens, SSc, and SARDs
**Presents as speckled cells with metaphase cells having a greyed out area/line down the middle!**
43
Centromere ANA pattern
- Interphase and metaphase positive
- Associated with CREST syndrome
**Presents as speckled cells with metaphase cells having a bright green fluorescence down the middle!**
44
Nucleolar ANA pattern
- Interphase positive, metaphase negative
- ONLY nucleoli fluoresce
- Associated with anti-RNA in patients w/ SSc or SARDs
**Presents as large fluorescing circles inside the cell representing the nucleoli**
45
What are the "other" ANA detection methods?
Oucherlongy double diffusion
Solid phase immunoassays (ELISA)
Immunoassays using Crithidia luciliae
46
Peripheral/rim ANA pattern
Outer rim of nucleus will fluoresce green
47
Anti-dsDNA is an autoantibody associated with which disease and immunofluorescent pattern?
SLE; homogenous
48
Anti-ssDNA is an autoantibody associated with which disease and immunofluorescent pattern?
SLE, not detected on routine screen
49
Anti-Sm is an autoantibody associated with which disease and immunofluorescent pattern?
Diagnostic for SLE, Coarse speckled pattern
50
Anti-SS A (Ro) is an autoantibody associated with which disease and immunofluorescent pattern?
SLE, Sjogren's syndrome
Fine Speckled
51
Anti-SS B (La) is an autoantibody associated with which disease and immunofluorescent pattern?
SLE, Sjogren's syndrome
Fine speckled
52
Anti-Scl-70 is an autoantibody associated with which disease and immunofluorescent pattern?
Systemic sclerosis, scleroderma
Compound pattern with speckling
53
Anti-centromere is an autoantibody associated with which disease and immunofluorescent pattern?
CREST syndrome
Discrete speckled
54
Anti-RNP is an autoantibody associated with which disease and immunofluorescent pattern?
SLE
Speckled
55
Examples of SARDs (Systemic autoimmune rheumatic diseases)
RA
SLE
Scleroderma
Osteoporosis
Gout
Systemic sclerosis
Sjogrens syndrome
56
Scleroderma
SARD associated with anti-SSc, anti-Scl70
Centromere ANA pattern
Excessive fibrosis of skin, abnormal vasculature, & internal organ damage by 30 y/o
Raynaud's phenomenon is common
57
What does CREST syndrome stand for and what AI disorder is it aligned with?
C = calcinosis
R = Raynaud's phenomenon
E = eosophageal dysmotility
S = sclerodactyly
T = telangiectasia
Associated w/ Scleroderma
58
Sjogren's Syndrome (what is it, signs and symptoms)
Chronic inflammation of exocrine glands (predominantly lacrimal and salivary glands)
S&S: dry eyes and mouth AKA "sicca syndrome", hoarse voice, dry vagina, failure to produce acidic urine
59
Lab diagnosis of Sjogren's Syndrome and associated ANA patterns
Hypergammaglobulinemia
Anti-SSA and Anti-SSB, sometimes Anti-Sm
Fine speckled or homogenous pattern
60
What is SLE?
Chronic inflammatory disorder involving joints, connective tissue, collagen during disease progression
61
Variants of lupus?
Can be discoid, systemic, drug-induced, and neonatal
62
Which AI disorder involved anti-phospholipid antibodies that bind T cells?
SLE
63
Treatment for SLE
Hydroxychloroquine, systemic glucocorticoids, and steroids, newer therapies include monoclonal antibodies Belimumab and Ritiximab
64
SLE is considered to be a hypersensitivity type _____ reaction.
III
65
Clinical symptoms of SLE
Multi-joint involvement
Bilateral rash on nasal bridge
Renal involvement (Nephritis = major death cause)
Neurological symptoms
Anemia/leukopenia/thrombocytopenia
66
What are some lab tests to assist in the diagnosis of SLE?
CBC (anemia, leukopenia)
Urinalysis (Renal disease)
CRP/ESR (elevated during flare ups)
Complement deficiencies
ANAs - anti-dsDNA, anti-Sm, anti-SSA/SSB
67
Lupus anticoagulants are anti-phospholipids associated with _________ activation, meaning:
prothrombin activation; meaning patient is more likely to form a clot instead of bleed
68
What is immunofluorescence using Crithidia luciliae?
IIF using a non-pathogenic trypanosome as the substrate to detect anti-dsDNA in Lupus patients
Positive result = stained kinetoplast
69
Rheumatoid arthritis lab values
Increased uric acid levels
Increased CRP
Disruption of synovial fluid - exudative/transudative
Increased ESR
ANA reactivity
70
Lab diagnosis for RA
Low serum iron
Low TIBC
Elevated ESR and CRP
Elevated complement
Elevated a2-macroglobulins and gamma globulins
Immune complexes
RF and anti-CCP
71
What is a specific marker for RA?
anti-CCP
72
Treatment for RA
NSAIDs
Methotrexate - reduces pyrimidine and nucleotide synthesis and pro-inflammatory cytokines like TNF-alpha
73
What is Wegener's granulomatosis?
Rare AI disease involving inflammation of small to medium sized blood vessels and respiratory tract showing reoccurring rhinitis, sinusitis, and otitis media
74
What disease is associated with ANCA (anti neutrophil cytoplasmic antibody) ?
Wegener's granulomatosis
75
Lab ID of Wegener's granulomatosis
Normocytic, normochromic anemia
Leukocytosis, eosinophilia
Elevated ESR
Decreased albumin
Severe renal insufficiency (Decreased GFR)
Elevated CRP
Positive ANCA
76
What is ANCA?
Anti neutrophil cytoplasmic antibodies
Produced against proteins in neutrophil granules
Two fluorescent patterns: Cytoplasmic (Anti-PR3) and perinuclear (Anti-MPO)
77
C-ANCA is associated with anti- ______ ?
PR3
78
P-ANCA is associated with anti- ______ ?
MPO
79
Standout features of Warm AIHA
Most common
Antibodies react at 37C, IgG, complement involvement
Pan-agglutination in blood bank
80
Standout features of Cold AIHA
Cold agglutinin disease due to cold ab
Complement involvement
IgM
Associated w/ mycoplasma pneumoniae or lymphoma
Raynaud's phenomenon may occur
81
Standout features of PCH
Associated with viral infections in children
Autoantibody to IgG that reacts at colder temps of the body that binds complement
Associated with anti-p specificity
Donath-landsteiner antibody
82
Drug induced hemolytic anemia: Drug adsorption
Drug binds to a membranous protein forming a RBC/hapten complex that stimulates antiibody production
Extravascular
83
Drug induced hemolytic anemia: Immune complexing
Drugs in the serum are viewed as foreign and antibodies bind to them forming immune complexes in serum
Intravascular hemolysis
84
ITP
Autoimmune disorder characterized by petechiae, bruising, and menorrhagia
Marked thrombocytopenia
Commonly seen in children
85
Addison's disease: Target cells/tissues and associated autoantibodies
Adrenal glands
Antibody to adrenal cells
86
Celiac disease: Target cells/tissues and associated autoantibodies
Small intestine and others
Anti-transglutaminase (tTG)
Anti-DGPs
Endomysial antibodies
87
Goodpasture's syndrome: Target cells/tissues and associated autoantibodies
Kidneys/lungs
Antibody to an antigen in the renal and pulmonary basement membranes
88
Grave's disease: Target cells/tissues and associated autoantibodies
Thyroid gland
TRAbs, anti-thyroglobulin, anti-TPO
89
Hashimoto's thyroiditis: target cells/tissues and associated autoantibodies
thyroid gland
Anti-thyroglobulin
anti-TPO
90
Multiple sclerosis: target cells/tissues and associated autoantibodies
Myelin sheath of nerves
Antibodies to myelin basic protein
91
Myasthenia gravis: target cells/tissues and associated autoantibodies
Nerve-muscle synapses
Antibodies to AChR, MuSK, LRP4
92
Pernicious anemia: target cells/tissues and associated autoantibodies
Stomach
Intrinsic factor antibody
93
Type 1 diabetes mellitus: target cells/tissues and associated autoantibodies
Pancreas
Anti-insulin
Islet cell antibodies
Anti-GAD
94
Hashimoto's vs Grave's
Hashimotos: hypothyroidism, cold intolerance, brittle hair, goiter, Anti-Tg/Anti-TPO
Grave's: hyperthyroidism, heat intolerance, TRAbs antibodies
95
Celiac disease
Affects small intestine triggered by gluten ingestion
96
Autoimmune hepatitis liver diseases
Anti-mitochondrial Abs (AMAs)
Elevated liver enzymes, jaundice, etc
Must be differentiated from hepatitis viruses
97
Goodpasture's syndrome
Autoantibodies against basement membranes that line renal glomeruli and lung alveoli
Antibodies to GBM
Renal failure, respiratory problems such as shortness of breath and hemoptysis
98
Pernicious anemia
Megaloblastic anemia (MCV >100), def. in vitamin B12
Autoimmune response against parietal cells in stomach degrade intrinsic factor
Associated with D. latum infections
99
Multiple sclerosis
Inflammation/destruction of CNS
Plaques form in white matter of brain and spinal cord (destruction of myelin sheath)
Pins and needles, weakness, vision loss
100
Lab diagnosis of MS
Electrophoresis will show Tau protein (carbohydrate deficient transferrin protein)
101
Myasthenia gravis
Affecets neuromuscular junctions resulting in weak/easily fatigued skeletal muscle (dropping of eyelids, double vision)
Autoantibodies against acetylcholine receptors used for muscle contraction
