Immunology Flashcards
1
Q
HLA A3
A
hemochromatosis
2
Q
HLA B27
A
PAIR
- psoriatic arthritis, ank spon, IBD, reactive arthritis
3
Q
HLA DQ2/DQ8
A
celiac disease
4
Q
HLA DR2
A
MS, hay fever, SLE, goodpasture, syndrome
5
Q
HLA DR3
A
DM 1, SLE, Graves Disease
6
Q
HLA DR4
A
RA, DM 1
7
Q
HLA DR5
A
pernicious anemia, Hashimoto thyroiditis
8
Q
IL-1
A
secreted by macrophages. endogenous pyrogen, also called osteoclast activating factor. causes fever, acute inflammation. activates endothelium to express adhesion molecules, induces cytokine secretion to recruit leukocytes
- “Hot T-bone stEAK”
- stimulates hot (fever), T cells, bone marrow, IgE, IgA, aKute phase reactants production
9
Q
IL-2
A
secreted by all T cells, stimulates growth of helper, cytotoxic and regulatory T cels
- can be used for tumor regression in RCC and metastatic melanoma
10
Q
IL-3
A
secreted by all T cells
- support the growth and differentiation of BM stem cells. functions like GM-CSF
11
Q
IL-4
A
secreted by TH2 cells
- induces differentiation into TH2 cells, promotes growth of B cells
- enhances class switching to IgG and IgE
12
Q
IL-5
A
secreted by TH2 cells
- promotes differentiation of B cells, enhances class switching to IgA
- stimulates the growth and differentiation of eosinophils
13
Q
IL-6
A
secreted by macrophages and TH2 cells
- an endogenous pyrogen
- fever and stimulates production of acute phase proteins
14
Q
IL-8
A
secreted my macrophages
- major chemotactic factor for neutrophils
15
Q
IL-10
A
secreted by TH2 cells and Treg
- modulates inflammatory response, inhibits actions of activated T cells and Th1
- enhances IL4 and 5 secretion from TH2
16
Q
IL-12
A
secreted by macrophages and B cells
- induces differentiation of T cells into Th1 cells
- activates NK cells
17
Q
TNF-alpha
A
secreted by macrophages
- mediates septic shock, activates endothelium, causes leukocyte recruitment and vascular leak
- mediates cachexia
18
Q
IFN gamma
A
secreted by Th1 cells
- has antiviral and antitumor properties
- activates NK cells
- increases MHC expression and antigen presentation in all cells
- used therapeutically in CGD
19
Q
INF alpha and beta
A
- interferes with viral replication by halting protein synthesis in virally infected cells
- essentially results in apoptosis
- alpha used therapeutically in Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC and malignant melanoma
- beta used therapeutically in MS
20
Q
T cell surface receptors
A
- TCR, CD3, CD28 (binds to B7 in APC)
- Helper T cells have CD4 and CD40 ligand
- Cytotoxic T cells have CD8
21
Q
B cell surface receptors
A
- CD19, CD20, CD21 (EBV entry), CD40
- MHC II, B7
22
Q
macrophage cell surface receptors
A
- CD 14, CD 40
- MHC II, B7
- Fc and C3b receptors
23
Q
NK cell surface receptors
A
- CD 16 (binds Fc of IgG)
- CD 56 (unique marker for NK)
24
Q
Type I HS reaction
A
- anaphylactic and atopic - free antigen cross links with IgE (aggregation of IgE-Fc receptors triggers degranulation) on mast cells/basophils triggering immediate release of histamine and tryptase (sensitive for mast cell activation)
- delayed response due to leukotrienes
- test: skin test for IgE
25
Type II HS reaction
- cytotoxic "cy-2-toxic" - IgG and IgM bind fixed antigen on enemy cell, leading to cellular destruction
- 3 mech: opsonization (phagocytosis or complement), complement mediated lysis (transfusion reaction), Ab dependent cell mediated tox with NK or macrophage
- test: direct and indirect Coombs
26
Coombs test
- direct tests for antibodies that have adhered to antigen (test Rh + baby with Rh- mom)
- indirect tests for antibodies that can adhere to other RBCs (test Rh - mom for Abs)
27
Type III HS reaction
- immune complex - IgG complexes activate complement, which attracts neutrophils that release lysosomal enzymes
- ex: serum sickness, arthus reaction
- III - 3 things stuck together - antigen-antibody-complement
28
serum sickness
immune complex idsease in which Abs to the foreigh proteins are produced (takes 5 days)
- immune complexes form and are deposited in membranes, where they fix complement --> tisue damage
- assoc with monoclonal Ab drugs
- fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure
- small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration
- hypocomplementemia
29
arthus reaction
- local subacute type III HS reaction
- interdermal injection of antigen induces antibodies, which form complexes in the skin
- edema, necrosis and activation of complement
- test: IF staining
30
Type IV HS reaction
- delated (T cell mediated)
- sensitized T cells encounter antigen and then release lymphokines (leads to macrophage activation, no Ab involved)
- 4 T's - T lymphocytes, Transplant rejections, TB skin tests, Touching (contact derm)
31
What type of reactions characterize each HS reaction?
ACID
- I - Anaphylactic and Atopic
- II - Cytotoxic
- III - Immune complexes
- IV - Delayed (cell mediated)
32
Type I HS disorders
- anaphylaxis
| - allergic and atopic disorders (rhinitis, hay fever, eczema, hives, asthma)
33
Type II HS disorders
- AI hemolytic anemia
- pernicious anemia
- ITP
- erythroblastosis fetalis
- acute hemolytic transfusion reactions
- Rheumatic fever
- Goodpasture syndrome
- Myasthenia gravis
- Bullous Pemphigoid
- Pemphigus Vulgaris
34
Type III HS disorders
- SLE, polyarteritis nodosa, PSGN, serum sickness, arthus reaction (swelling and inflammation following tetanus vaccine)
35
Type IV HS disorder
- MS, GBS, Graft v. Host disease, PPD, contact derm
36
allergic blood transfusion reaction
- Type I HS reaction against plasma proteins in transfused blood
- urticaria, pruritis, wheezing, fever
- treat with antihistamines
37
anaphylactic blood transfusion reaction
- severe allergic reaction
- IgA deficient pts need blood without IgA or this will happen
- dyspnea, bronchospasm, hypotension, respiratory arrest, shock
38
febrile nonhemolytic transfusion reaction
- Type II HS reaction
- host Abs against donor HLA antigens and leukocytes
- fever, headaches, chills, flushing
39
acute hemolytic transfusion reaction
- Type II HS reaction
- intravascular hemolysis due to ABO incompatibility or extravascular hemolysis due to host Ab reaction against foreign antigen on donor RBCs
- complement mediated
- fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia and jaundice
40
Bruton agammaglobulinemia
- X linked recessive defect in BTK - a tyrosine kinase gene - no B cell maturation
- presents with recurrent bacterial, enteroviral and giardia infections after 6 months
- normal CD19+ B cell count, dec pro-B, dec Ig of all classes
- absent/scanty lymph nodes and tonsils with no germinal centers
41
selective IgA deficiency
- most common primary immunodeficiency
- can see airway and GI (mucosal) infections, autoimmune disease (assoc with celiac), atopy, anaphylaxis to IgA containing products
- IgA < 7 mg/dL with normal IgG and IgM levels
42
common variable immunodeficiency
- defect in B cell differentiation due to B cell or helper T cell defect (cant make immunoglobulins)
- can be acquired in 20s-30s, inc risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
- bacterial, enterovirus and giardia infections
- decreased plasma cells, decreased immunoglobulins
43
C1 esterase inhibitor deficiency
- causes hereditary angioedema
| - NO ACE inhibitors
44
C3 deficiency
increases risk of severe, pyogenic sinus and resp tract infections, inc susceptibility to type III HS reactions
45
C5-C9 deficiencies
- increased susceptibility to Neisseria infections, no ability to make MAC
46
DAC (GP1 anchored enzyme) deficiency
- causes complement mediated lysis of RBCs and PNH
47
Thymic aplasia (DiGeorge)
- 22q11 deletion, failure of 3rd and 4th pharyngeal pouches (no thymus or parathyroids)
- presents with hypocalcemia, recurrent viral/fungal infections, conotruncal abnormalities (ToF, truncus arteriosus)
- dec T cells, dec PTH, dec Ca
- no thymic shadow
48
IL-12 receptor deficiency
- decreased Th1 response, AR
- disseminated mycobacterial and fungal infections, may present after administration of BCG vaccine
- decreased IFN gamma
49
AD Hyper-IgE syndrome (Job syndrome)
- deficiency of Th17 cells due to STAT3 mutation --> impaired recruitment of neutrophils to sites of infection
- FATED: coarse Facies, staph Abscesses, retained Primary teeth, inc IgE, Dermatologic problems
50
Chronic mucocutaneous candidiasis
- T cell dysfunction (many causes)
- non invasive candida infections of the skin and mucous membranes
- absent in vitro T cell proliferation or cutaneous reaction in response to candida antigens
51
SCID
- several types, most important is adenosine deaminase deficiency (AR)
- adenosine accumulation is toxic to T and B cells
- FTT, chronic diarrhea, thrush
- recurrent bacterial, fungal, viral and protozoal infections
- no thymic shadow, no germinal centers
- DO NOT GIVE LIVE VACCINES
- treat with BM transplant
52
Ataxia-telangiectasia
- defects in ATM gene -- DNA double strand breaks -- cell cycle arrest
- triad: Ataxia (cerebellar defects), spider Angiomas, IgA deficiency
- inc AFP, dec IgA, IgG, IgE, lymphopenia and cerebellar atrophy
53
Hyper IgM syndrome
- defective CD40L on Th cells --> X linked recessive class switching defect
- severe pyogenic infections early in life, opportunistic infections
- inc IgM with all other lines down
54
Wiskott-Aldrich Syndrome
- WATER
- Wiskott Aldrich: Thrombocytopenic purpura, Eczema, Recurrent infections
- inc risk of autoimmune disease and malignancy
- dec to normal IgM and IgG
- inc IgE and IgA
55
Leukocyte adhesion deficiency
- defect in LFA-1 integrin (CD18) protein on phagocytes, impaired migration and chemotaxis, AR
- recurrent bacterial skin and mucosal infections, no pus formation, impaired wound healing, delayed umbilical cord separation
- inc neutrophils, none at infection site
56
Chediak-Higashi syndrome
- defect in lysosomal trafficking regulator gene (LYST)
- microtubule disfunction in phagosome-lysosome fusion, AR
- recurrent pyogenic infections by staph and strep, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistocytosis
- giant granules in neutrophils and platelets, pancytopenia and mild coag defects
57
Chronic Granulomatous Disease
- defect in NADPH oxidase, no respiratory burst and dec ROS
- X linked recessive
- inc susceptibility to cat + organisms
- abnormal dihydrorhodamine (flow cytometry) test
- nitroblue tetrazolium due reduction test is negative (neutrophils will not turn blue)
58
acute transplant rejection
- CTLs activated against donor MHCs + humoral Abs develop after transplant
- leads to vasculitis of the graft vessels with dense interstitial lymphocytic infiltrate
- prevent/reverse with immunosuppressants (calcineurin inhibitors)
59
chronic transplant rejection
humoral and cellular, recipient T cells react against donor antigens presented on donor MHC
- irreversible damage
- heart - atherosclerosis
- lungs - inflammation/fibrosis of small bronchioles (bronchiolitis obliterans)
- liver - vanishing bile ducts
- kidney - vascular fibrosis, glomerulopathy, loss of glomeruli, atrophy
60
graft v. host disease
graft T cells proliferate in the immunocompromised host and reject host cells with "foreign" proteins --> severe organ dysfunction
- rash, jaundice, diarrhea, HSmegaly
- usually in BM and liver transplants
- potentially beneficial for BM transplant
61
cyclosporine
- calcineurin inhibitor that blocks cyclophilin
- blocks T cell activation by preventing IL-2 trascription
- used for rejection ppx, psoriasis, RA
- tox: nephrotox, HTN, HLD, hyperglycemia, tremor, hirsuitism, gingival hyperplasia
62
tacrolimus
- calcineurin inhibitor, binds FK506 binding protein (FKBP)
- blocks T cell activation by preventing IL-2 transcription
- used for rejection ppx
- tox: similar to cyclosporine, inc risk of diabetes and neurotoxicity, no gingival hyperplasia or hirsuitism
63
sirolimus
aka rapamycin
- mTOR inhibitor, binds FKBP
- blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction
- used in kidney transplant rejection prophylaxis
- tox: anemia, thrombocytopenia, leukopenia, insulin resistance, HLD, non-nephrotoxic
- kidney "sir"vives
64
basiliximab
- monoclonal Ab blocks IL-2R
- kidney transplant rejection ppx
- tox: edema, HTN, tremor
65
azathioprine
- antimetabolite precursor of 6-mercaptopurine
- inhibits lymphocyte proliferation by blocking nucleotide synthesis
- used in rejection ppx, RA, crohns, glomerulonephritis, and other AI conditions
- tox: leukopenia, anemia, thrombocytopenia
- degraded by xanthine oxidase, tox increases with allopurinol
66
glucocorticoids
- inhibits NFkB
- suppress both B and T cell function by dec transcription of many cytokines
- used in rejection ppx, many AI d/o, inflammation
- tox: hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers
67
alemtuzumab
- targets CD52
- used in CLL
- "alymtuzumab" used in chronic Lymphocytic leukemia
68
bevacizumab
- VEGF Ab
| - used in colorectal cancer, RCC
69
cetuximab
- EGFR Ab
| - used in stage IV colorectal cancer, head and neck cancer
70
rituximab
- CD20 Ab
| - used in B cell non-Hodgkin lymphoma, RA and ITP
71
trastuzumab
- HER2/neu Ab
| - used in breast cancer and gastric cancer
72
infliximab, adalimumab
- TNF alpha antibody
| - used in IBD, rheumatoid arthritis, ank spon, psoriasis
73
natalizumab
- alpha 4 integrin Ab
- used in MS and crohns
- alpha 4 is used in leukocyte adhesion
- risk of PML in pts with JC virus
74
abciximab
- glycoprotein IIb/IIIa Ab
| - anti-platelet agent for prevention of ischemic complications in pts undergoing PCI
75
denosumab
RANKL Ab
| - used for osteoporosis, inhibits osteoclast maturation
