Immunology Flashcards
(90 cards)
1
Q
Serum IgG
A
1000 mg/dL
2
Q
Serum IgG
A
200 mg/dL
3
Q
Serum IgM
A
100 mg/dL
4
Q
Plasma 1/2 life of IgG
A
3 weeks
5
Q
Proteins involved in complement Lytic function
A
MAC - C5 –> C6 C7 C8 C9 –> poke holes in membrane
6
Q
Proteins involved in complement opsonizing function
A
C3b binds membranes
Phagocytotic cells (PMN, macrophages) have C3b receptors that give them a better grip
**IgG is also opsonizing (Phagocytotic cells have FcR) but IgM is not.
7
Q
Proteins involved in complement chemotactic function
A
C5a is chemotactic or phagocytes (esp. neutrophils) This explains much of the inflammatory response seen in complement
8
Q
Proteins involved in Anaphylotoxic function of complement
A
C3a, C4a, and C5a release histamine from mast cells and basophils, allowing increased blood flow to area and increased inflammatory response.
9
Q
Th0
A
Undifferentiated Helper T cell precursor
All have CD4 and begin in paracortex of lymph node
When DC arrives w/correct antigen, they divide and differentiate (determined by DC determinants)
10
Q
Th1
A
Circulate through body and secrete Lymphokines
IFNgamma*==> macrophage chemotaxis and M1 activation
IL-2==> CTL activation
11
Q
M1/angry macrophage secretions
A
TNF alpha and IL-1
12
Q
Th17
A
**Secretes Il-17
resistant to bacterial and yeast pathogens
activate M1
13
Q
Chemokines
A
small, short range mediators that primarily cause inflammation
14
Q
Th2
A
secrete* IL-4*, IL-5, IL-13 that attract and activate M2 macrophages!
IL-4 is also chemotactic for eosinophils
15
Q
Tfh
A
Activated helper T’s migrate from paracortex to cortes and help B -cells to differentiate and class switch
16
Q
Treg
A
T cells whose main job is to suppress activation of other Th Cells
- Make Transcription factor Foxp3
- Make TGF beta and IL-10
- Respond to their antigen and suppress all nearby Th cells
17
Q
CTL death signal
A
(1) engage Fas death receptor on target (CTL’s bear death ligand CD95L)
(2) Secrete ‘lytic granules’ which contain granzymes and perforins that lead to apoptosis
18
Q
CTL activation
A
- in lymph nodes, requrie Th1 and IL-2
* *need Il-21 to convert to memory cells**
19
Q
Memory cells
A
- sort of like immune stem cells
- self-replication, rapidly differentiate into helper and killer when re-exposed to antigen
20
Q
T cell markers
A
CD3- all T Cells CD4 - all helpers CD8 - CTL's (these play a role in T cell activation) CD20 - B Cells
21
Q
MHC restriciton
A
CTL’s only see antigen presented to them on the surface of a genetically identical cell.
Antigen-presenting cell must come from individuals who share MHC alleles
22
Q
Antigen presentation extrinsic pathway
A
Something infects locally, breakdown products are phagocytosed by DC and then presented on the cell surface with an MHC.
23
Q
T cell Receptor
A
- Sort of looks like an antibody, but just two chains (alpha and beta)
- Constant and Variable region
- VDJ Variable regions recombine like in B cells in the thymus
24
Q
CD3
A
-Transduces signal from TCR when it binds MHC
25
3 ways Th cells are activated by a good APC
(1) TCR sees the TCR-pMHC cell
(2) Accessory molecular interactions that modify activation
(3) Cytokines from APC
26
MHC class 1
Presented on all cells
27
MHC Class II
On the surface of dendritic and macrophage-type cells, B Cells, etc. (Antigen presenting cells!)
28
Which MHC does an antigen associate with if it's taken up by the DC extrinsic pathway?
MHC II
29
Which T cells recognize peptides on MHC II molecules?
TH1, Th17, Tfh, Treg, Th2
30
Intrinsic pathway
antigen is a protein sampled from within the cell itself, presents on MHC I
31
Which T cells recognize stuff in MHC I?
CTL's!
32
Cross-presentation
DC's are wonderful, and they let peptides from antigens leak over into the "intrinsic pathway" so it presents on MHC I and II
33
What does CD4 bind on Th's
The base of MHC II (CD8 binds base of MHC I
34
causes of increased hydrostatic pressure
- Heart failure
- Fluid overload
- Venous obstruction or compression
- Arteriolar dilation
35
Causes of decreased oncotic pressure
- Protein loss (kidney, GI)
| - Low protein production
36
Causes of lymphatic obstruction
Inflammation, infection, neoplasm
37
Hyperemia
Active increase in blood flow due to arteriolar dilation
| Causes red color (erythema)
38
Congestion
Pathologic accumulation of blood due to impaired venous clearance
39
Virchow Triad
Endothelial Damage, Abnormal blood flow (stasis or turbulence) and hypercoagulability (inherited or acquired (cancer)
40
Common cause of arterial thrombosis
Endothelial injury and turbulent blood flow, often associated with atherosclerosis
Most common in cerebral, coronary, and femoral arteries
41
Thrombus progression
Initial thrombus is attached to the wall and additional layers propagate and eventually become less stable and throw thromboemboli
42
Embolus
A free floating, intravascular mass of a solid, liquid, or gas
43
Venous embolism common target
Lungs
44
Arterial emboli common targets
Legs and Brain
45
Disseminated intravascular coagulation (DIC)
thrombosis and hemorrhage occur concurrently
| Involves a systemic activation of thrombin
46
White (anemic) infarcts
Arterial blockage, single blood supply, dense tissue
| Heart, kidney, spleen
47
Red infarcts
When blood flow is subsequently reestablished, allowing flow into the necrotic area - lungs, liver, intestine
48
Shock
circulating blood volume is not adequate to perfuse body tissues
49
Cardiogenic Shock
failure of heart to pump blood to tissues/ generate adequate blood pressure
coolness and pallor of their skin, tachycardia, and decreased urine output
50
Hypovolemic Shock
Not enough volume, not enough blood gets back to the heart to do its job
coolness and pallor of their skin, tachycardia, and decreased urine output
51
Septic shock
High levels of inflammatory mediators in the blood cause widespread vasodilation, vascular leakage, and venous blood pooling.
52
HLA
the family of genes that are important for histocompatibility in humans
HLA-A, HLA-B, and HLA-D
*HLA-DR is most important for transplant
53
MHC III
HLA Loci that encode components of the complement system and certain cytokines
54
MHC loci gene expression
co-dominant
(You'll have mom's and dad's expressed on the surface of each cell)
HLA-D (MHC II) will only be expressed on antigen presenting cells
55
AIRE gene
causes thymus to express a large variety of extrathymic peptides, helping to prevent autoimmunity against, say, Liver peptides
56
Minor Histocompatibility antigens
H-Y a gene coded on Y-chromosome, the protein pdt is presented by MHC I, but only on male cells! (So female bodies reject male skin grafts, but NOT vice versa)
57
Hyperacute Rejection
A graft is given to a patient who has preexisting antibody against the tissue (from prior graph/transfusion or in a mismatch)
Complement causes vasospasms (via anaphylatoxins and histamine)
Avoid by testing for cytotoxic antibodies before transplanting.
58
Is Class I or Class II MHC match more important?
Class II!
►(1) If the donor and
recipient are identical at Class I but different at Class II, Th1 will be activated; but no CTL will
be activated, because there is no Class I difference for them to see. The graft will still be rejected,
but since only Th1 and not CTL would be involved, rejection may be slower. ►(2) If the donor
and recipient are different at Class I but identical at Class II, there will be no Th1 activated, no
IL-2 will be generated, and so few CTL will be activated.
59
Ankylosing spondylitis
Arthritic condition in which there is inflammation at insertion of tendons into bones
followed by eventual calcification
92% of those people are HLA-B27
60
Neoplasia
Autonomous, progressive cell growth involving clonal cell population
61
Cyclophosphamide
for breast: combine with doxyrubicin, methotrexate and 5-fluorouracil
- Also for lymphomas, childhood tumors, solid tumors
- Must be activated by metabolism to phosphoramide mustard
- Active metabolite is inactivated by Aldehyde dehydrogenase
62
Alkylating agent repair resistance mxns
GSH inactivates alkylating agents
| DNA repair
63
Alkylating toxicity
```
Hematopoietic (dose-limiting)
Intestinal toxicity
Gonadal toxicity
Alopecia
Carcinogenesis (leukemia)
```
64
Cisplatin
- Nephrotoxic
- Crosslinks DNA (CpG)
- Testicular cancer! Also ovarian, head and neck, lung, bladder
65
Resistance to platinum compounds
- Increased efflux/decreased cellular uptake
- GSH inactivation
- Loss of Mismatch Repair (also activates apoptosis)
66
Platinum toxicity
**Nephrotoxicity!* (hydration!)
Nausea, ototoxicity, neurotoxicity
Carboplatin: myelosupression/ platelet toxicity
Oxaliplatin - sensory neuropathy
67
5-fluorouracil
-pyrimidine analog
-Activated by thymidine kinase to FdUMP
FdUMP inhibits thymidilate synthase, inhibitin DNA synthesis
Other metabolites enter DNA/RNA- DNA DAmage--> apoptosis
68
5-FU resistance
Alterations in target enzyme (TS)
| Increase in Levels of TS (Drug leads to inactivation of normal feedback mechanisms to regulate TS levels. )
69
5-FU toxicity
What you'd expect:
Myelosupression, gastro toxicity, alopecia
+ Derm problems
70
Topo I inhibitors
campothesins (topotecan, irinotecan), epipodophyllotoxins
71
Topo II inhibitors
etoposide, anthracyclines, doxorubicin, daunorubicin
72
Topo interacting agent resistance
Increased efflux, topo mutations
73
Topo interacting agent toxicity
Myelosupression (all)
Cardiotoxicity (anthracyclins - improved by Fe chelation)
Secondary malignancy (esp. AML after ALL treatment)
74
Vinca Alkaloids
Vinca alkaloids (vinblastine and vincristine)
- Bind tubulin and cause MT depolymerization
- Ped malignancies, hematopoietic tumors, and some solid tumors
75
Vinca resistance
Increased drug efflux (MDR transporters)
| Tubulin mutations
76
Vinca toxicity
Neurotoxicity (nerve cell damage)
| Myelosupression, neutropenia
77
Taxanes
Docetaxel, paclitaxol
Bind inside of microtubules and prevent mitosis--> apoptosis
Ovarian and breast+ other solid tumors
78
Taxane resistance
Increased Efflux (MDR)
Tubulin mutation
Inhibited apoptosis
79
Taxane toxicity
Myelosupression (neutropenia)
Peripheral neuropathy
Alopecia
80
Hormonal Agents that block receptor activity
Tamoxifen - blocks estrogen receptor
| Bicalutamide and flutamide block androgen receptor
81
Hormonal agents that block hormone synthesis
```
Aromatase inhibitors (Letrozole) block synthesis of estrogen from androgens (major source in post-menopausal people)
GNRH analogue (Leuprolide) inhibit testostrone production
```
82
Resistance to steroid receptor inhibitors
- Alternative activation mechanisms
| - Mutations in receptor (if it's mutated to be activated by chemo, withdrawl can inhibit tumor growth)
83
Hormonal toxicities
- Hormone signalling side effects in women (hot flashes, decreased bone density)
- Gynecomastia in men treated with flutamide/bicalutamide)
84
Rituximab
Anti-CD20 treats B cell tumor
85
Trastuzumab/Herceptin!
Anti-Her2 for breast cancer
86
Bevacizumab/Avastin
Anti-VEGF colon cancer
87
Antibody chemo function
-Inhibits target function (Ex. Avastin blocks VEGF from stimulating receptor to promote angiogenesis
Also, CTL response can occur in response to antibodies
Immunoconjugates can also deliver toxins, chemotherapueutic drugs, radioisotopes to tumor cells
88
Kinase Inhibitors
Targeted
Best ex. Imatinib for CML and GIST
But MOST don't cure cancer on their own and resistance to therapy almost always occurs
89
CML
caused by BCR-abl constituitively active kinase, inhibited by imatinib
90
Dasatinib
A drug that works in CML patients with mutated Bcr-Abl resistant to Imatinib
