First-Aid: Immunology Flashcards
Palivizumab
Target: RSV F protein
Use: RSV prophylaxis for infants
vizu virus
Omalizumab
Target: IgE
Use: Allergic asthma, prevents IgE binding to FceRI
Digoxin immune Fab
Target: Digoxin
Use: Antidote for digoxin toxicity
Denosumab
Target: RANKL
Use: Osteoporosis, inhibits osteoclast maturation (mimics osteoprotegrin)
OS osteoclasts
Abciximab
Target: Glycoprotein IIb/IIIa
Use: Anti-platelet, prevents ischemia in coronary intervention
IIb x IIIa = “cix”
Infliximab and adalimumab
Target: TNF-a
Use: IBD, rhematoid arthritis, ankylosing spondylitis, psoriasis
RA “inflix” pain in “da lim”bs
Natalizumab
Target: a4-integrin
Use: MS, Chron disease
Risk: PML in patients with JC virus
(a4-integrin facilitates leukocyte adhesion)
Trastuzumab
Target: HER2/neu
Use: Breast cancer, gastric cancer
HER2 – “2”
Rituximab
Target: CD20
Use: B-cell NH’s lymphoma, rheumatoid arthritis (with MTX), ITP
Cetuximab
Target: EGFR
Use: Stage IV colorectal cancer, head and neck cancer
Bevacizumab
Target: VEGF
Use: Colorectal cancer, renal cell carcinoma
Alemtuzumab
Target: CD52
Use: CLL
“lem” for lymph
IFN-y
Use: chronic granulomatous disease
IFN-B
Use: Multiple sclerosis
IFN-a (x8)
Use: Chronic Hep B and Hep C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
Aldesleukin (interleukin-2)
Use: Renal cell carcinoma, metastatic melanoma
Sargramostim (granulocyte-macrophage colony stimulating factor)
Use: recovery of bone marrow
Filgrastim (granulocyte colony-stimulating factor)
Use: recovery of bone marrow
Oprelvekin (interleukin-1)
Use: Thrombocytopenia
Thrombopoietin
Use: Thrombocytopenia
Epoetin alfa (erythropoietin)
Use: anemias (especially in renal failure)
Glucocorticoids
Target: NF-kB, decrease transcription, suppress B/T cells
Use: Transplant rejection prophylaxis , many autoimmune disorders, inflammation
Tox: Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, peptic ulcers
Note: Can cause iatrogenic Cushing syndrome
Azathioprine
Mech: antimetabolite precursor of 6-mercaptopurine, blocks nucleotide synthesis and inhibits lymphocyte proliferation
Use: Transplant rejection prophylaxis, RA, Chron, glomerulonephritis, other autoimmune
Tox: Leukopenia, anemia, thrombocytopenia
Note: toxicity increased by allopurinol, since 6-MP is degraded by xanthine oxidase
“purine” “prine”
Basiliximab
Mech: monoclonal Ab to IL-2R
Use: Kidney transplant rejection prophylaxis
Tox: Edema, HTN, tremor
Sirolimus (Rapamycin)
Mech: mTOR inhibitor, binds FKBP. Prevents IL-2 signal transduction, thereby blocking T-cell activation and B cell differentiation.
Use: Kidney transplant rejection prophylaxis
Tox: Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia. NOT nephrotoxic.
Note: Kidney “sir-vives” Synergistic with cyclosporine. Used in drug eluting stents.
Tacrolimus
Mech: Calcineurin inhibitor, binds FK506 binding protein (FKBP), blocks T-cell activation by preventing IL-2 transcription.
Use: transplant rejection prophylaxis
Tox: Diabetes and nephrotoxicity, similar to cyclosporine but without gingival hyperplasia or hirsutism
Note: “-limus” drugs bind FKBP
Cyclosporine
Mech: Calcineurin inhibitor, binds cyclophilin, blcoks T-cell activation by preventing IL-2 transcription.
Use: transplant rejection prophylaxis, psoriasis, RA
Tox: Nephrotoxicity, HTN, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia
Hyperacute rejection
Onset: minutes
Mech: Recipient antibodies, Type II reaction, activation of complement
Path: Widespread thrombosis –> ischemia and necrosis
Treat: graft must be removed
Acute rejection
Onset: Weeks to months
Mech: Cellular or humoral. Cytotoxic T-cell react to donor MHCs, or host antibodies develop after transplant, leading to a syndrome similar to that seen in hyperacute
Path: Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
Treat: prevent/reverse with immunosuppression
Chronic rejection
Onset: months to years
Mech: Recipient MHC percieve donor MHC as recipient and react against donor antigens presented. has both cellular and humoral components.
Path: Heart - atherosclerosis, Lungs - bronchiolitis, Liver - vanishing bile ducts, Kidney - vascular fibrosis and glomerulopathy
Irreversible damage.
Graft-vs-host disease
Onset: variable
Mech: Graft T-cells proliferate in immunocompromised host and attack host cells
Path: Sever organ dysfunction. Maculopapular rash, jaundice, diarrhea, HSM.
Notes: Often found in bone marrow and liver transplants (rich in lymphocytes). Can be beneficial in leukemia (graft-vs-tumor effect)
Chronic granulomatous disease
Immune def: phagocyte decreased ROS. NADPH oxidase defect, absent respiratory burst in neutrophils, X-linked recessive.
Presents: Increased sus. to catalase + organisms (PLACESS)
Findings: Abnormal flow cytometry dihydrohodamine test. Negative tetrazolium dye reduction test (out of favor).
Catalase + organisms (PLACESS)
Pseudomonas, listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia
Chediak-Higashi syndrome
Immune def: phagocyte microtubule dysfunction in phagosome-lysosome fusion. Defective LYST gene, autosomal recessive.
Presents: Recurrent pyogenic infections by staph and strep. Partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.
Findings: giant granules in neutrophils and platelets. Pancytopenia, mild coag defects.
Leukocyte adhesion deficiency (Type 1)
Immune def: phagocyte impaired migration and chemotaxis, impaired LFA-1 integrin (CD18) on lymphocytes, autosomal recessive.
Presents: Recurrent bacterial skin/mucosal infections. Absent pus formation, impaired healing. Delayed separation of umbilical cord (>30 days).
Find: Increased neutrophils, but absence of neurtophils at infection sites
Wiskott-Aldrich syndrome
Immune def: T-cells unable to recognize actin cytoskeleton. WAS gene, X-linked recessive.
Presents: (WATER) Thrombocytopenia, eczema, recurrent infections. Increased risk of autoimmunity and malignancy.
Find: Elevate IgE and IgA, low-normal IgM and IgG. Fewer and smaller platelets.
Hyper-IgM syndrome
Immune def: Th cells, class switching defect, defective CD40L. x-linked recessive.
Presents: Sever pyogenic infections in early life. Opportunistic Pneumocystis, Cryptosporidium, and CMV.
Find: Elevated IgM, Massively decreased IgG, IgA and IgE
Ataxia-telangiectasia
Immune def: T-cell cell cycle arrest. Defect in ATM gene, so DNa double strand breaks cause arrest.
Presents: (AAA-triad) cerebellar defects, spider angiomas, and IgA deficiency.
Find: Increased AFP, decreased IgA, IgG, IgA. Lymphopenia, cerebellar atrophy.
Severe Combined Immunodeficiency (SCID)
Immune def: T-cell disorder, several types.
1) IL-2R gamma chain defect, X-linked
2) adenosine deaminase deficiency (autosomal recessive)
Presents: Failure to thrive, chronic diarrhea, thrush, recurrent infections of all sorts. Treat with bone marrow transplant. There won’t be any rejection, so that’s cool.
find: Decreased T-cell receptor excision circles. Absent thymic shadow on CXR, absent germinal centers on lymph node biopsy, and absent T-cells on flow.
Chronic mucocutaneous candidiasis
Immune def: T-cell dysfunction, many causes
Presents: Candida infections on skin and mucous
Find: No T-cell proliferation or cutaneous reaction in response to Candida.
Autosomal dominant hyper IgE syndrome (Job syndrome)
Immune def: Th17 cell deficiency due to STAT3 mutation -> impaired recruitment of neutrophils
Presents: (FATED) coarse facies, cold staph abscesses, retained primary teeth, increase in IgE, Dermatologic problems (eczema).
Find: Increased IgE, decreased IFN-y
IL-12 receptor deficiency
Immune def: decreased Th1 response, autosomal recessive.
Presents: Disseminated fungal and mycobacterial infections, sometimes after admin of BCG vaccine.
Find: Decreased IFN-y
Thymic aplasia (DiGeorge syndrome)
Immune def: failure of 3rd and 4th pharyngeal pouches with absent thymus and parathyroids, 22q11 deletion
Presents: Tetany (hypocalcemia), recurrent viral/fungal infectons (T-cell mediated), other conotruncal abnormalitites (ToF, truncus arteriosis)
Find: decreased T-cells, decreased PTH, decreased calcium. Absent thymic shadow on CXR. Detect 22q11 mutation on FISH.
Common variable immunodeficiency
Immune def: B-cell differentiation defect. Many causes.
Presents: can be acquired mid-life, increased risk of autoimmune, bronchiectasis, lymphoma, sinopulmonary infections
Find: decreased plasma cells, decreased immunoglobulins
Selective IgA deficiency
Immune def: Unknown mechansim. Decreased IgA (
X-linked (Bruton) agammaglobulinemia
Immune def: No B-cell maturation. Defect in BTK gene (a tyrosine kinase), X-linked recessive
Presents: Recurrent bacterial and enteroviral infections after 6 months post-birth.
Find: Normal CD19 B-cell count, but decreased pro-B, Ig of all classes, and scanty lymph nodes and tonsils.
Lack of B-cells makes patient vulnerable to…?
Encapsulated organisms (SHiNE SKiS)
Strep pneum, Haemophilus influenza B, Neisseria mening, E coli, Salmonella, Klebsiella pneum, group B Strep
AND
Enteroviral encephalitis, poliovirus (DO NOT GIVE LIVE VACCINE)
AND
GI giardiasus, since no IgA. Bacterial infections predominate
Lack of T-cells makes patient vulnerable to…?
Sepsis AND
CMV, JCV, EBV, VZV, and chronic respiratory/GI viruses AND
Candida, PCP
Lack of granulocytes makes patient vulnerable to…?
Staph, Burkholderia cepacia, Serratia, Nocardia, AND Candida, Aspergillus
Lack of complement makes patient vulnerable to…?
Neisseria (since no membrane attack complex)
Anti-ACh receptor Abs
Myasthenia gravis
Anti-basement membrane Abs
Goodpasture syndrome
Anti-cardiolipin Abs, lupus anticoagulant
SLE, antiphospholipid syndrome
Anticentromere Abs
Limited scleroderma (CREST syndrome)
Anti-desmoglein Abs
Pemphigus vulgaris
Anti-dsDNA ab, anti-smith Abs
SLE (these are both subtypes of ANAs)
Anti-glutamate decarboxylase Abs
Type 1 DM
Anti-hemidesmosome Abs
Bullous pemphigoid
Antihistone Abs
Drug-induced lupus
Anti-Jo-1, anti-SRP, anti-Mi-2 Abs
Polymyositis, dermatomyositis
Antimicrosomal, antithyroglobulin Abs
Hashimoto thyroiditis
Antimitochondrial Abs
1* biliary cirrhosis
Antinuclear Abs
SLE, nonspecific
Anti-Scl-70 (anti-DNA topoisomerasa 1) Abs
Scleroderma (diffuse)
Anti-smooth muscle
Autoimmune hepatitis
Anti-SSA, anti-SSB (anti-Ro, anti-La) Abs
Sjogren syndrome (no tears or saliva or lubrication)
Anti-TSH receptor Abs
Graves disease
Anti-U1 RNP (ribonucleoprotein) Abs
Mixed connective tissue disease
c-ANCA (PR3-ANCA)
Granulomatosis with polyangiitis (Wegener)
IgA antiendomysial, IgA anti-tissue translgutaminase
Celiac disease
p-ANCA (MPO-ANCA)
Microscopic polyangiitis, Churg-Strauss syndrome
Rhematoid factor (antibody, most often IgM, specific to IgG Fc region, anti-CCP
Rhuematoid arthritis
