Immunology Flashcards
Cervical node drainage
Head and neck
Hilar node drainage
Lungs
Mediastinal node drainage
Trachea and esophagus
Axillary node drainage
Upper limb, breast, skin above belly button
Celiac node drainage
Liver, stomach, spleen, pancreas, upper duodenum
Superior mesenteric node drainage
Lower duodenum, jejunum, ileum, colon to splenic flexure
Inferior mesenteric node drainage
colon from splenic flexure to upper rectum
Internal iliac node drainage
Lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), prostate
Para-aortic node drainage
Testes, ovaries, kidneys, uterus
Superficial inguinal node drainage
Anal canal (below pectinate line), skin below belly button (not popliteal territory), scrotum
Popliteal node drainage
Dorsolateral foot, posterior calf.
Right lymphatic duct drainage
Right side of body above diaphragm
Thoracic duct drainage
Everything RLD doesn’t drain. Goes into subclavian and Internal jugular veins
Encapsulated organisms to look out for
1) Strep Pneumo
2) H. flu
3) N. meningitidis
4) E. Coli
5) Salmonella
6) Klebsiella
7) Group B Strep
Part of lymph node underdeveloped in DiGeorge Syndrome
paracortex - houses T cells and provides a route for T and B cells to enter blood.
MHC 1
HLA- A, B, C
Binds to TCR and CD8
Expressed on all nucleated cells. Not on RBCs
Present endogenously made antigens (viral or cytosolic proteins) to CD8+ cytotoxic T cells.
Antigen peptides loaded onto MHC1 in RER after delivery via TAP (a transporter associated with antigen processing)
Associated with B2-microglobulin
MHC 2
HLA- DR, DP, DQ
Binds to TCR and CD4
Expressed on APCs
Presents exogenously made antigens (bacterial proteins) to CD4+ helper T cells.
Antigen loaded following release of invariant chain in an acidified endosome
Associated with Invariant chain (a protein).
HLA A3
Hemochromatosis
HLA B27
Psoriatic Arthritis, Ankylosing spondylitis, IBD, Reactive arthritis (Reiter Syndrome). PAIR.
HLA DQ2/DQ8
Celiac disease
HLA DR2
MS, hay fever, SLE, Goodpasture
HLA DR3
Diabetes mellitus type 1, SLE, Graves, Hashimoto thyroiditis
HLA DR4
Rheumatoid arthritis, diabetes mellitus type 1
HLA DR5
Pernicious anemia leading to vitamin B12 deficiency Hashimoto thyroiditis
Enhances NK cell activity
IL-2, IL-12, IFN alpha, IFN beta
Th1 cells
Secrete IFN-gamma
Activated by IFN-gamma and IL-12 (from Macrophage)
Inhibited by IL-4, IL- 10 (from Th2)
Th2 cells
Secrete IL4, IL-5, IL-10, IL-13
Activated by IL-4
Inhibited by IFN-gamma (from Th1)
Acute phase reactants
released by liver. Their concentrations change in response to inflammation. Chronic made by liver too. Induced by IL-6
CRP, Ferritin, Fibrinogen, Hepcidin, Serum amyloid A, Albumin, Transferrin
C-reactive protein
(Positive) upregulated in immune response.
Opsonin - fixes complement and facilitates phago. Measured clinically as a sign of ongoing inflammation.
Ferritin
(Positive) Upregulated in IR.
Binds and sequesters iron to inhibit microbial iron scavenging
Fibrinogen
(Positive) Upregulated in IR.
Coagulation factor that promotes endothelial repair - correlates with ESR.
Hepcidin
(Positive) Upregulated in IR.
Prevents release of Iron bound by ferritin (anemia of chronic disease)
Serum Amyloid A
(Positive) Upregulated in IR.
Prolonged elevationcan lead to amyloidosis
Albumin
(Negative) Downregulated in IR
Reduction conserves amino acids for positive reactants
Transferrin
(Negative) Downregulated in IR
Internalized by macrophages to sequester iron.
C1 esterase inhibitor deficiency
Causes hereditary angioedema. ACE inhibitors are contraindicated.
C3 deficiency
Increases risk of severe, recurrent pyogenic sinus and respiratory infections. Higher susceptibility to type 3 hypersensitivity rxns
C5-C9 deficiencies
Terminal complement deficiency increases risk to recurrent Neisseria bacteremia
DAF (GPI-anchored enxyme) deficiency
causes complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
cytokines released by macrophages
IL-1, IL-6, IL-8, IL-12, TNF-alpha
cytokines released by ALL T cells
IL-2, IL-3
cytokines released by Th1 cells
IFN-gamma
cytokines released by Th2 cells
IL-4, IL-5, IL-10
IL-1
“osteoclast-activating factor”
causes fever, acute inflammation. Activates endothelium to express adhesion molecules. Induces chemokine secretion to recruit WBCs
IL-6
Causes fever and stimulates production of acute-phase proteins
IL-8
Major chemotactic factor for neutrophils
IL-12
Induces differentiation of T cells into Th1 cells. Activates NK cells.
TNF-alpha
Mediates septic shock. Activates endothelium. Causes WBC recruitment, vascular leak.
IL-2
Stimulates growth of helper, cytotoxic, and regulatory T cells. Also NK cells.
IL-3
Supports growth and differentiation of bone marrow stem cells. Functions like GM-CSF
IFN-gamma
secreted by NK cells in response to IL-12 from macrophages. Stimulates macrophages to kill phagocytosed pathogens.
Also activates NK cells to kill virus-infected cells. Increases MHC expression and antigen presentation by all cells.
IL-4
Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG
IL-5
Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.
IL-10
Modulates inflammatory response. Lowers expression of MHC class II and Th1 cytokines. Inhibits activated macrophages and dendritic cells. Also secreted by Treg.
TGF-Beta and IL-10 aTENuate the immune response.
Chronic granulomatous disease
Patients cannot make superoxide radical and therefore can’t generate ROS.
Can still utilize H2O2 generated by invading organisms to make ROS. However, Cat (+) organisms can neutralize their own H2O2… higher risk of infection from these organisms.
Cell surface proteins on all nucleated cells
MHC1. Not on RBCs (no nucleus)
Cell surface proteins on T cells
TCR (binds antigen-MHC complex)
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
Cell surface proteins on Th cells
CD4, CD40L
Cell surface proteins on Tcytotox
CD8
Cell surface proteins on Treg
CD4, CD25
Cell surface proteins on B cells
Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV), CD40
MHC2, B7
Cell surface proteins on Macrophages
CD14, CD40
MHC2, B7
Fc and C3b receptors (enhanced phagocytosis)
Cell surface proteins on NK cells
CD16 (binds Fc of IgG), CD56 (unique marker for NK)
Cell surface proteins on Hematopoietic stem cells
CD34
Chronic granulomatous disease
Patients cannot make superoxide radical and therefore can’t generate ROS. Deficiency in NADPH oxidase.
Can still utilize H2O2 generated by invading organisms to make ROS. However, Cat (+) organisms can neutralize their own H2O2… higher risk of infection from these organisms.
X-Linked (Bruton) agammaglobulinemia
Defect in BTK (tyrosine kinase gene) leading to no B cell maturation. X-linked recessive and higher in boys.
Presents w/ recurrent bacterial and enteroviral infections after age 6 months (lower maternal IgG at this time)
You’ll find absent B cells in peripheral blood, lower Ig of all classes, and absent/scanty lymph nodes and tonsils.
Selective IgA deficiency
Unknown cause, but most common primary immunodeficiency
P/w: Majority asymptomatic. You can see airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA containing products.
You’ll find lower IgA with normal IgG, IgM levels
Common variable immunodeficiency
Defect in B-cell differentiation from many causes.
p/w: can be acquired in 20s-30s; higher risk of autoimmune diseases, bronchiectasis, lymphoma, sinopulmonary infections.
You’ll find lower plasma cells, lower immunoglobulins.
Thymic aplasia (DiGeorge Syndrome)
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches leadings to absent thymus and parathyroids
P/w: tetany (hypocalcemia), recurrent viral/fungal infections (T Cell deficiency), conotruncal abnormalities (e.g. tetralogy of fallot, truncus arteriosus)
Findings: low T cells, low PTH, low Ca
Absent thymic shadow on CXR. 22q11 deletion detected by FISH
IL-12 receptor deficiency
lower Th1 response. Autosomal recessive
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine
Findings: low IFN-gamma
Autosomal dominant hyper-IgE Syndrome (Job Syndrome)
deficiency of Th17 cells due to STAT3 mutation leads to impaired recruitment of neutrophils to sites of infection.
p/w: FATED - coarse Facies, cold (noninflamed) staphlococcal Abscesses, retained primary Teeth, higher IgEEEE, Derm problems (eczema)
Findings: high IgE, Low IFN-gamma
Chronic mucocutaneous candidiasis
T cell dysfunction from many causes.
p/w: noninvasive candida albicans infections of skin and mucous membranes
Severe Combined Immunodeficiency
Dif types: Defective IL-2R gamma chain (most common, X-linked). Adenosine deaminase deficiency also possible (Auto recess)
p/w: Failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal and protozoal infections. Tx = bone marrow transplant (no rejection concern)
Findings: Low T cell receptor excision circles (TRECS). No Thymic shadow on CXR. No germinal centers (lymph node biopsy), No T cells (flow cytometry)
Ataxia-Telangiectasia
Defects in ATM gene leads to failure to repair DNA ds breaks leading to cell cycle arrest.
Triad: cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA deficiency
Findings: Higher AFP (alpha fetoprotein), Lower IgA, Low IgG, Low IgE
Lymphopenia, cerebellar atrophy
Hyper-IgM Syndrome
Defective CD40L on Th cells leads to class switching defect. X recessive.
p/w: Severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Crypto, CMV
Findings: High IgM. Very low IgG, IgA, IgE
Wiskott-Aldrich Syndrome
Mutation in WAS gene (X recess); T cells unable to reorganize actin cytoskeleton
p/w: Thrombocytopenic purpura, eczema, recurrent infections. Higher risk of autoimmune diseases and malignancy
Findings: Low to normal IgG, IgM. High IgE, IgA, Fewer and smaller platelets
Chronic granulomatous disease
Patients cannot make superoxide radical and therefore can’t generate ROS. Deficiency in NADPH oxidase.
Can still utilize H2O2 generated by invading organisms to make ROS. However, Cat (+) organisms can neutralize their own H2O2… higher risk of infection from these organisms.
Nocardia, Pseudomonas, Listeria, Aspergillis, Candida, E Coli, S aureus, Serratia
Findings: Abnormal dihyrdorhodamine (flow cytometry) test. Nitroblue tetrazolium dye reduction test is negative
Leukocyte adhesion deficiency (type 1)
Defect in LFA-1 integrin (CD18) protein on phagoctyes leads to impaired migration and chemotaxis. Auto recess.
Recurrent bacterial skin and mucosal infection, absent pus formation, impaired wound healing, delayed separation of umbilical cord (>30 days).
Findings: High neutrophils. Absence of neutrophils at infection sites.
Chediak-Higashi Syndrome
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; auto recess
Recurrent pyogenic infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis
Findings: Giant granules in granulocytes and platelets. Pancytopenia. Mild coagulation defects.
Cyclosporine
Inhibits calcineurin. It binds to cyclophilin to do this. Blocks T cell activation by preventing IL-2 transcription.
Use in transplant rejection prophylaxis, psoriasis, RA.
Toxicity: Nephrotoxicity, HTN, hyperlipidemia, neurotox, gingival hyperplasia, hirsutism
Tacrolimus (FK506)
Inhibits calcineurin - binds FK506 binding protein (FKBP). Blocks T cell activation by preventing IL-2 transcription
Use in transplant rejection prophylaxis
Toxicity: Nephro, similar to cyclosporine, increases risk of diabetes and neurotox - no gingival hyperplasia or hirsutism.
Sirolimus (Rapamycin)
mTOR inhibitor, binds FKBP. Blocks T cell activation and B cell differentiation by preventing response to IL-2.
Use in Kidney transplant rejection prophylaxis
Toxicity: Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia, NOT NEPHROTOX
Kidney SIRvives. Works well with cyclosporine. Also used in drug-eluting stents.
Daclizumab, basiliximab
Monoclonal antibodies - block IL-2R
Use in kidney transplant rejection prophylaxis
Toxicity - Edema, HTN, tremor
Azathioprine
Antimetabolite precursor of 6-mercaptopurine (6-MP). Inhibits lymphocyte proliferation by blocking nucleotide synthesis.
Use in transplant rejection prophylaxis, RA, Crohn, glomerulonephritis, other autoimmune disorders
Toxic: Leukopenia, anemia, thrombocytopenia
6-MP degraded by XO so toxicity is increased by allopurinol
Glucocorticoids
Inhibit NF-kB. Suppress both B and T cell function by lowering transcription of many cytokines.
Use in transplant rejection prophylaxis (immunosuppression), many autoimmune disorders, inflammation.
Toxic: Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, avascular necrosis
Can cause iatrogenic Cushing syndrome.
Anti-ACh receptor antibody
Myasthenia gravis
Anti-basement membrane antibody
Goodpasture syndrome
Anticardiolipin, lupus anticoagulant antibodies
SLE, antiphospholipid syndrome
Anticentromere antibody
Limited scleroderma (CREST Syndrome)
Anti-desmosome (anti-desmoglein) antibodies
Pemphigus vulgaris
Anti-dsDNA, ant-Smith antibodies
SLE
Anti-glutamic acid decarboxylase (GAD-65) antibodies
Type 1 diabetes mellitus
Antihemidesmosome antibodies
Bullous pemphigoid
Anti-histone antibodies
Drug-induced lupus
Anti-Jo-1, anti-SRP, anti-Mi-2 antibodies
Polymyositis, dermatomyositis
Antimicrosomal, antithyroglobulin antibodies
Hashimoto thyroiditis
Antimitochondrial antibodies
Primary biliary cirrhosis
Antinuclear antibodies
SLE, nonspecific
Antiparietal cell antibodies
Pernicious anemia
Anti-Scl-70 (anti-DNA topoisomerase I) antibodies
Scleroderma (diffuse)
Anti-smooth muscle antibodies
Autoimmune hepatitis
Anti-SSA, anti-SSB (anti-Ro, anti-La) antibodies
Sjogren Syndrome
Anti-TSH receptor antibodies
Graves disease
Anti-U1 RNP (ribonucleoprotein) antibodies
Mixed connective tissue disease
IgA anti-endomysial, IgA anti-tissue transglutaminase antibodies
Celiac Disease
MPO-ANCA/p-ANCA antibodies
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome)
PR3-ANCA/c-ANCA antibodies
Granulomatosis with polyangiitis (Wegener)
Rheumatoid factor (IgM antibody that targets IgG Fc region), anti-CCP (more specific) antibodies
Rheumatoid Arthritis
