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Week4 Flashcards

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1
Q

TI Hypersensitivity

A

Anaphylactic, Allergic, Asthma
IgE
Early: 2-30mins, mast cells mediators (vasoperm + sm contraction)
Late: 2-8hrs-24-72hrs, cellular infiltrate (eosinophils +)
Systemic: mast cells
Local: tissue (URT/LRT, GI, skin)
Rxns: anaphylaxis, rhinitis, asthma, food allergy
[Ag] < picogram range

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2
Q

TII Hypersensitivity

A

Cytotoxic
Ab (IgM,IgG) —> binds Ag —> complement—> ADCC
Immediate onset w preformed Ab
Cell membrane action
Rxns: transfusion, hemolysis, allograft rejection, drugs, autoimmune

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3
Q

TIII Hypersensitivity

A

Immune-complex
Ag + IgM/IgG —> soluble Ab-Ag complexes —> tissue deposition
Preformed + Ab induction (6-12d)
Rxns: inflammation, vasculitis, serum sickness (complexes in kidney, joints), Arthus, drugs
Non-blanching capillary damage rash
[Ag] - mg range

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4
Q

TIV Hypersensitivity

A

DTH
CD4 Th1 cells
Pre-sensitization: Th1 stimulates by APCs
Delayed 24-72hrs rxn: Th1 re-stimulation —> cytokines (IFNy, TNFB, MCF, MIF) —> macrophage (ROI, lytic enzymes)
Skin & organs
Rxns: contact hypersensitivity, tuberculin, granulomatous

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5
Q

Addisons

A

Primary adrenal insufficiency
Autoimmune/other attack on adrenal cortex
Dec all adrenocorticosteroids
Fatigue, appetite loss, weight loss, dizzy, nausea
Hyperkalemia (via red aldosterone)
Cortisol treatment

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6
Q

Secondary adrenal insufficiency

A

Hypothalamus, pituitary disorders
Prolonged glucocorticoids
—> reduced ACTH —> reduced cortisol/androgens
Regular aldosterone
Fatigue, appetite loss, weight loss, dizzy, nausea
Cortisol treatment

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7
Q

Cushing’s syndrome

A

Adrenal, pituitary (“disease”), ectopic tumor
Increased cortisol
Iatrogenic cause most common (drugs)
Adipose distribution, hypertension, osteoporosis, immunosuppression, diabetes)

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8
Q

Glucocorticoid replacement therapy

A 
Adrenal insufficiency 
Physiological/small doses 
Oral cortisol (Primary &amp; secondary)
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9
Q

Glucocorticoid anti-inflammatory treatment

A 
Suppress inflammation (asthma, RA) 
Pharmacological/ high doses (keep effects local, not systemic) 
Inhaled, topical, depot
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10
Q

Glucocorticoid side effects

A 
Hyperglycaemia/insulin resistance 
Diabetes 
Fast twitch muscle atrophy 
Fat redistribution (central obesity) 
Inhibited Vit D absorption (hyperparathyroidism) 
Osteoporosis
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11
Q

Glucocorticoid antagonist

A

Blocks GR
Treat elevated glucocorticoid levels (ACTH tumor)
Mifepristone: progesterone R antagonist for abortion

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12
Q

Glucocorticoid synthesis inhibitor

A 
Not specific
Mitotane 
Aminoglutethimide 
Ketoconazole 
Metyrapone 
Trilostane
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13
Q

Aldosterone synthesis regulation

A
  1. RAA system (inc Ca2+ inc side chain enzyme)
  2. Inc extracellular K+ (depolarise ZG cells and inc Ca2+)
  3. ACTH (stimulates, but no feedback)
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14
Q

Aldosterone hypofunction

A 
Reduced synthesis (primary) 
Dec in renin (diabetic renal insufficiency) 
Salt wasting, V depletion, hyperkalemia, acidosis
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15
Q

Aldosterone hyperfunction

A 
Inc aldosterone (hyperplasia/adenoma) 
ECV expansion, renin suppression, potassium wasting, hypokalemia, hypertension
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16
Q

Mineralocorticoid agonist

A

Can’t use aldosterone, undergoes 1st pass metabolism

Fludrocortisone

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17
Q

Mineralocorticoid antagonist

A

K+ sparing diuretics
Hyperkalemia
Eplerenone & spironolactone

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18
Q

IGIV

A

Ig from large donor group
Normalising serum
Low doses: humoral deficiency
High doses: asthma, autoimmune, Kawasaki

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19
Q

Rho Ig

A

Human IgG w Ab to Rho(D) RBC Ag
Prevents Rh- mother sensitisation
Given 24-72hrs post birth

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20
Q

Hyperimmune Ig

A

Pools of selected human or animal donors

High titer to particular Ag (CMV, respiratory syncytial virus)

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21
Q

Warburg effect

A

Tumor cells favor lactate production over ox phos

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22
Q

Tumor genetic instability causes

A
  1. Homologous recombination issues (BRCA1/2)
  2. NER defects (UV light damage: XP)
  3. MMR deficiencies (DNA insertion/deletion issues —> inc microsatellite DNA variation: Lynch syndrome/HNPCC)
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23
Q

TAMs

A

Tumor associated macrophages (tumor promoting)

  1. GF secretion (EGG, FGe, IL6, TNF)
  2. Angiogenesis (VEGF, PDGF)
  3. Invasion/metastasis (metalloproteases)
  4. Immune inhibition via cytokines (TGFB?)
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24
Q

Hematogenous spread

A

Venous invasion > arterial

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25
Desmoplastic response
Malignant | Local fibroblast response to tumor —> inc collagen
26
Scirrhous
Malignant tumor | Firm, irregular, gritty texture
27
Benign mesenchymal tumors
``` CT and derrivates: Fibroma Lipoma (fibrous capsule surrounds) Chondroma Lieomyoma ```
28
Benign epithelial tumors
Papilloma Adenoma Cystadenoma
29
Hamartoma
Benign tumor of cells that belong in a tissue but not arranged properly
30
Choristoma
Heterotropic rest | Normal cell nest from a different tissue
31
Teratoma
Cells from diff germ layers
32
Malignant epithelial tumor
Carcinoma Spread to regional lymph nodes, then blood T N M Skin, glands, respiratory, renal, liver, UT, placenta, testicles, melanocytes
33
Malignant mesenchymal tumor
Sarcoma Hematogenous spread —> lungs CT, endothelial (vessels), mesothelium, muscle
34
Malignant cell features
``` Pleomorphism Anisocytosis Dec cell-cell adhesion Polarity loss Mitotic figures Hyperchromatic nuclei Chromatin clumping Large nucleoli Anaplasia Dysplasia ```
35
Epithelial progression towards malignancy
Metaplasia Dysplasia Carcinoma in situ
36
Tumor invasion routes
Direct body cavity seeding Lymphatics (carcinomas) Hematogenous (sarcomas)
37
Cutaneous fungi
Infect keratinised layer of skin, hair, nails
38
Subcutaneous fungi
Infect dermis, subcutaneous tissue, bone, cornea
39
Systemic/endemic fungi
Dimorphic, confined to specific geographic regions | Infect lung & disseminate
40
Opportunistic fungi
``` Human commensals, environmental Affect immunocompromised ppl Not very virulent Conditions: Loss of bacterial flora Iatrogenic immunosuppression Immunodeficiency Diabetes Break in skin Indwelling catheter ```
41
SDA
Standard nutrients medium for fungi Mold growth & spore (conidia) ID Low pH & antibacterial 1-4wks to grow at 25C Yeast can be grown at 37C on special media IDed directly in tissue Cutaneous forms w KOH treatment
42
Definitive host
Species in which parasite undergoes sexual reproduction
43
Intermediate host
Species in which parasite undergoes Asexual reproduction
44
Incidental host
Unnatural host Unusual pathology Dead end host
45
Vectors
Transmit parasite from one host to another
46
Trophozite
Binary fission life cycle
47
Cyst
Dormant life form Non-replicating Resists environmental extremes Frequently transmitted
48
Herd immunity
Insufficient # of non-immune individuals to sustain transmission of an organism
49
Live vaccines
Attenuated: no virulence, can grow & elicit response | Antigenically cross-reactive: not human pathogen, shares similarity to produce response (smallpox)
50
Inactivated / killed vaccine
Whole: structural proteins intact (polio, measles) Subunit: specific subunit w antigenic determinants
51
CYP11A1
Side chain cleavage enzyme Converts cholesterol to pregnenolone + StAR
52
CYP11B1
ZF Cortisol Corticosterone Deficiency: excess aldosterone & androgens
53
CYP11B2
ZG | Aldosterone synthase
54
CYP17
ZF/ZR 17a hydroxylase Androgens & cortisol
55
ACTH absence
Atrophy if ZF, ZR
56
ZG
Angiotensin II & Hugh serum K+ tropic factors
57
Transcortin
Binds cortisol High affinity Low capacity
58
Albumin
Binds cortisol Low affinity High capacity
59
TII GR
Glucocorticoid receptor Cortisol causes GR-hsp90 dissociation Nucleus translocation GRE binding (10% of all genes)
60
Cortisol metabolic effects
Liver (gluconeogenesis) Muscle (aa release) Adispose (HSL activation)
61
Cortisol anti-inflammatory effects
``` Annexin I (inhibits PLA2) MAPK phosphatase I (blocks c-Jun & cytokines) Blocks NFkB (anti-cytokine) ```
62
Fludrocortisone
Mineralocorticoid agonist F at C9 Use instead of aldosterone
63
Prednisolone | Methylprednisolone
Glucocorticoid Dbl bond CH3
64
Dexamethasone
Glucocorticoid > mineralocorticoid | F & CH3
65
Cortisone / Prednisone
``` Absorbed better than cortisol (oral) Inactive topically Carbonyl replaces OH Inactive Prodrug activated by liver (11B-HSD1) Inactive form produced by kidney (11B-HSD2) ```
66
Inhaled corticosteroids
Extensive 1st pass metabolism, don’t go systemic | Fluticasone, beclomethasone, flunisolide, triamcinolone
67
Topical corticosteroids
For psoriasis & dermatitis Can’t use prodrugs Cortisol, methylprednisolone, dexamethasone
68
Depot corticosteroids
Intra-articular RA/gout Methylprednisolone in polyethylene glycol
69
Glucocorticoid tapering
<2wks no taper 2-4wks = 1-2wk taper >4wks = 1-2mo taper High cortisol suppresses CRH/ACTH —> cortical atrophy
70
TI GR
MR (mineralocorticoid receptor) | Nucleus translocation
71
CYP21 deficiency
Most common congenital adrenal hyperplasia | Anti- aldosterone & cortisol
72
Transplant prep
Immunosuppression drugs Daclizumab ATG Anti-CD3
73
Hyperacute & chronic rejection
Can’t be stopped
74
Acute rejection
Calcineurin inhibitor (cyclosporine / tacrolimus) + Cell cycle inhibitor (mycophenolate mofetil / sirolumus) +\- Steroids
75
Goodpastures
``` T II rxn Glomerulonephritis Auto-Ab against basement membrane Alveolar haemorrhage Smooth distribution ```
76
Graves’ disease
Auto-Ab against thyroid acinar cells (LATS) Mimic TSH Inc thyroid hormone production IgG Ab mediated (placental transfer) Anti-TSH receptor Ab T3/T4 overproduction TII hypersensitivity
77
Ag tolerogenic response
``` IV, oral, inhaled Ag Very large doses Prenatal & neonatal periods Persistence in host No adjuvants (gel, salt) Low costimulation ```
78
CD22
On B cells FcyRIIB receptors Cows-linkage inhibits activation Prevents low affinity IgM from being produced if high affinity IgG is already being made
79
Neuroendocrine regulation
Stress —> corticosteroids & endorphins | IL-1/6 —> inc body temp, slow wave sleep, inc ACTH —> dec Th1 /inc TGF-B
80
T cell positive selection
Self MHC reaction Dbl + cells => MHC restriction Others die by apoptosis
81
T cell negative selection
``` AIRE (autoimmune regulator) In thymus medulla Tx peripheral organ specific genes Inhibits autoimmunity High affinity cells deleted Self tolerance ```
82
Treg cells
Auto reactive T cells in periphery FoxP3 (absence = IPEX) Depend on IL-2 Induced by +TGF-B, -IL-6/23 from dendritic cells Produce IL-10/TGF-B (inhibitory cytokines) High CTLA-4
83
Peripheral T cell tolerance
``` Anergy (only Signal #1) CTLA-4 down regulation Persistence of self-Ag AICD (T cells express Fas, via exhaustion) Treg cells ```
84
Central B cell tolerance
Receptor editing: Self-Ag prompt RAG1/2 rearrangement of VJ LC Failure = clinal deletion, anergized
85
Peripheral B cell tolerance
Depends on T cell tolerance | Controls autoreactive B cell proliferation
86
B vs T cell tolerance
Naive B cells shorter lived Ig somatic mutation T cell help from neighbors
87
Immune privilege
Brain Testes Ovary Placenta Eye
88
Infections breaking tolerance
1. Disruption of barrier exposing sequestered self Ag (eye) 2. By-stander effect (inc B7 on self MHC cells) 3. Foreign Ag binds to self —> epitope spread 4. Molecular mimicry —> cross reactive T/B cells —> effector activation 5. Polyclonal activation vs superantigen
89
Autoimmune progression
Predisposition (genes, hormones) Stochastic event (environment, mutation, infection) Propagation (epitope spread)
90
MS
Relapsing-remitting or chronic progression IL-17/Th17 cells Fas on oligodendrocytes
91
TI Diabetes
CTLs Th1 cells Macrophages TIV hypersensitivity
92
Pernicious anemia
Auto-Ab against IF TII hypersensitivity B12 supplement
93
SLE
TIII hypersensitivity Lumpy bumpy glomerulonephritis High ANA (B cell) + nuclear debris Histone H1 reactive Th cells can activate anti-histone/anti-DNA B cells
94
RA
Early: neutrophils, lymphocytes, plasma cells Late: lymphocytes, plasma cells, macrophages, fibroblasts (calcify) RF T cells
95
MG
Anti-Ach Ab IgG (placental transfer) TII hypersensitivity Folding membrane destruction
96
MLR
Mixed lymphocyte reaction T cells and foreign MHC II Donor + recipient: one way (irradiate) Quantitate 3H thymidine in DNA
97
PRA rest
``` Panel reactive Ab Pre-transplant evaluation Recipient serum + pooled WBCs donors Complement + blue dye Inc PRA = inc preformed Ab ```
98
Crossmatch
Once ID donor Recipient serum + donor PBCs Positive is bad
99
Serological Ab lysis
Microcytotoxocity Cells + Ab against specific HLA + complement —> lysis
100
Cr release assay
CTL response test, MHC I Target cells loaded w Cr51 Donor target (HvG) Recipient target (GvH)
101
HSCT HLA match
10 Ag gold standard | HLA A, B, C, DR, DQ
102
Platelet granulomere
Alpha (PDGF, VWF, Va) Delta (Ca2+, ADP, ATP, serotonin) Lambda (lysosomal enzymes)
103
ATIII
``` Antitheombin III Liver Inactivates t & Xa & others Serpin Heparin inc activity ```
104
Protein C-S Complex
Inactivates VIIIa & Va | Thrombin-thrombomodulin complex
105
Factor V Leiden
Thrombophilia / hypercoaguability | Resistant to APC

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