Immuno Flashcards
Hypersensitivity reactions
I: IgE-mediated. allergic asthma or anaphylaxis
II: cytotoxic, ab-dependent. Autoimmune hemolytic anemia, immune thrombocytopenia
III: Ag-Ab complex. Serum-sickness like syndrome of acute Hep B
IV: delayed rxn, T-cell mediated. Dermatitis, PPD test
Immune thrombocytopenia (ITP)
acquired thrombocytopenia
AutoAb-mediated destruction of PLTs
Tx:
- PLTs >=30K, asxs, minor mucocutaneous bleeding: observe
- PLT <30K, asxs, minor mucocutaneous bleeding: corticosteroids
- Urgent mgmt bleeding or prior to urgent procedure: IVIG
High risk of postop complications in pts w/ IBD
pts on steroid therapy within 4 weeks before surgery
Greater incidence of infection-related complications (abscess)
5-ASA acts on bowel lining, different from aspirin, don’t need to be stopped before surgery
Anti-TNF in 3 months prior to surgery has not been shown to affect wound healing
Preop hypoalbuminemia is strong predictor of postop morbidity and mortality
Thiopurines (azathioprine) within 6 weeks of surgery have increased risk of postop morbidity, anastomotic leak/sepsis
Management of ITP
1st line: steroids
2nd line: IVIg
3rd line: Rituximab, romiplostim (after splenectomy failure); splenectomy if med mgmt fails
Factors associated with Radiation Resistance
Hypoxia Smoking status Inherent tumor cell characteristics Repopulation Tumor location Tumor grade
Management of Periop Steroids in pts at risk for HPA Axis suppression (20mg/day pred for >3 weeks)
Minor/ambulatory surgery (local anesthetic, hernia): Take normal AM dose of PO steroid day of surgery, no supplemental steroids
Mod stress (leg revascularization): Take normal AM dose of PO steroid day of surgery. Before induction: hydrocortisone 50mg IV. POD 0-2: hydrocortisone 25mg q8h x 24h, POD 2: PO outpt dose
Major stress (cardiac, abd, thoracic): Take normal AM PO dose day of surgery. Before induction: hydrocortisone 100mg IV, POD 0-2: hydrocortison 50mg q8h x24h, POD 2: hydrocortisone 25mg q8h, POD 3-4: outpt dose
Management of periop steroids in pts at intermediate risk for HPA axis suppression (5-20mg/d pred for >=3 weeks)
Eval of HPA axis suppression periop to determine need for additional stress dose steroids
Cortisol levels, ACTH stimulation test
Graft-versus-host disease (GVHD)
T-cell-mediated disease
3 steps:
1) damage to recipient tissue as part of conditioning process for stem cell transplant (circulating immune cells are destroyed) -> translocation of microbes and activation of innate immune system
2) Differentiation of donor T-cells into Th2 and Th17. Recognize host as foreign, activate JAK1/2, TLR, cause release of proinflammatory CKs (IL-6, IFG), cause host tissue destruction (donor NK cells targeting MHC-1 cells)
3) Tissue dysregulation from CKs -> host tissue failure (skin, gut), fail to regenerate after being destroyed
Transfusion-related acute lung injury (TRALI)
Recipient cells target donor cells
Chronic GVHD
Dysregulation of donor T regulatory cells, resultant fibrosis
Phases of wound healing
Inflammatory (1-3 days)
Proliferative (4 days - 3 weeks)
Remodeling (3 - 8 weeks)
MPs in wound healing
Arrive at wound w/in 3-5 days after injury.
Release growth factors, proliferation of immune cells, initiate angiogenesis
Phagocytize tissue/bacteria/other phagocytes
Participate in regeneration and are essential for found healing
First cells in wound
NPs
Hodgkin Lymphoma staging
Stage I: Dz located in single lymphatic site
Stage II: Dz in 2+ sites either above or below diaphragm
Stage III: Dz located above & below diaphragm
Stage IV: Disseminated dz. Involves non-lymph tissue
add “b” designation if patient also has B sxs: night sweats, weight loss, pruritus
Delayed immune hemolytic reaction
ABO-compatible RBCs containing a specific antigen, RhD Duffy or Kell, transfused in pts with preformed alloantibodies.
Development of new Ab from previous blood transfusions
Abs are to minor Age - Rh, Duffy, Kell
Prevent by retyping & screening pt’s blood to ID new Abs
Can occur up to 30 days after transfusion
Sxs appear in 3-10 days - fever, malaise, unconjugated hyperbilirubinemia, declining Hg/Hct
Dx: Direct Coombs test + peripheral smear
Tumor lysis syndrome
hematuria, leukocytosis, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, AKI
Phosphate binds calcium. CaPhos crystals precipitate in kidneys –> AKI
Pt w/ Crohn’s disease, on azathioprine, noted with TI mass, received treatment (chemo) then noted with hyperkalemia, AKI, hyperphosphatemia, hematuria
tumor lysis syndrome from aggressive lymphoma (non-Hodgkin B cell lymphoma)
Howell-Jolly bodies
nuclear remnants in RBCs
usually cleared by spleen
Seen on peripheral smear after splenectomy
Heinz bodies
aggregates of denatured Hg
Found in G6PD deficiency pts
Pappenheimer bodies
Iron-containing blue granules in RBCs
Seen in pts w/ siderblastic anemia
DIC
Acquired coagulopathy. Excessive thrombin, diffuse microthrombi generation. consumptive thrombocytopenia, depletion of coagulation factors.
Prolonged PT and PTT. High fibrin split products, Low fibrinogen.
Thoracic duct
Originates at cisterna chyli at midline L1-L2
Course superiorly through aortic hiatus at T10-12 (to right of aorta)
Runs along right of midline, crosses R -> L at T4-6
Empties into junction of L subclavian and L IJ vein
Carries chylomicrons and LCFA.
Renal transplant rejection types
Hyperacute: min - hrs. preformed Abs, complement activation. endothelial damage, inflammation, thrombosis. Prevent by pre-transplant crossmatch, ABO type match
AcuTe: weeks - months. T cell-mediated, acquired Ab response. Lymphocytic infiltration, complement deposition, parenchymal necrosis. Prevent by initial immunosuppressive T cell depletion following by tapered T-cell inactivation
Chronic: months - years. T & B cells, donor-specific Ab. parenchymal replacement with fibrous tissue, intimal smooth muscle proliferation leading to vessel occlusion. prevent acute rejection episodes, limit ischemia/reperfusion at transplant
Neutropenic enterocolitis
CT: thick colon, no evidence of bowel perf
Diarrheal dz in HIV patients
MCC AIDS-related diarrhea = CMV 2/2 reactivation of latent infection RFs: CMV viremia, advanced immunosuppression (CD4 <50) Stool studies: viral inclusion bodies Endoscopy: ulcers, erosions
Tx: noon NPO/IVFs, Abx, Antiretroviral, +ganciclovir or valganciclovir (if CD4<50).
hemolytic vs nonhemolytic transfusion reactions
febrile non hemolytic: host ab against donor leukocytes. CKs from donor. stop transfusion. tx sxs
hemolytic: ABO incompatibility - host Ab against donor RBCs. tx stop transfusion, IVFs
Source and Effects of IL-1
MPs, monocytes
T-cell & APC stimulation, B-cell growth, Ab production
Induces fever through activity on hypothalamus
Source and Effects of IL-2
Activated T-cells
T-cell growth & proliferation (CD4 cell)
Source and Effects of IL-4
T-cells, mast cells
B-cell proliferation
IgE production
Involved in asthma exacerbation
Source and Effect of IL-5
T-cells, mast cells
Eosinophil growth and modulation
Involved in asthma exacerbation
Source and Effect of IL-6
Activated T-cells
Induces inflammation
Lymphocyte differentiation
Source and Effects of IL-8
MPs
NP stimulation/recruitment, demargination, degranulation
Inhibition of endothelial adhesion
Implicated in obesity, cystic fibrosis
Source and Effects of IL-10
Activated T-cells, B-cells, monocytes
Type 1 T-helper cell suppression
Down-regulates MHC II Ags
Source and Effects of IL-12
MPs, B-cells
NK cell stimulation
Enhances IFN-gamma expression of B-cells
Source and Effects of IL-13
Type 2 T-helper cells
IgE production
Assoc w/ asthma and allergy exacerbation
Cells that stain CD3+ and recognize HLA-1 molecules
CD8+ cytotoxic T-cell
Causes release of lysosomal granules containing perforin, holes in cell membranes, granzymes responsible for cell lysis, promote apoptosis through CD95 (Fas) rec
Primary lymphoid organs
Generate lymphocytes from immature cells
Liver
Bone
Thymus
Secondary lymphoid organs
Maintain current lymphocytes and initiate adaptive immune response
LNs Spleen Peyers patches Tonsils Adenoids
Mechanisms of apoptosis
Extrinsic: binding death rec -> recruitment of Fas associated death domain protein -> activation of caspase 3
intrinsic: protein mediators (Bcl-2) -> increased mitochondrial membrane permeability -> release of mitochondrial cytochrome C -> activates caspase 3
Caspase
mediates organized breakdown of nuclear DNA –> apoptosis
Ipilimumab (Yervoy)
CTLA-4 inhibitor, upregulates CD4
Nivolumab (Opdivo)
PD1 inhibitor, up regulates CD4
Pembrolizumab
Tx of metastatic melanoma
PD1 inhibitor
