Week 3

Question 1

MHC genetics

Answer 1

• Class I MHC: coded by HLA-A, B, & C genes; display antigens that are recognized by CD8+ T-cells and NK cells
• Class II MHC: coded by HLA-DP, DQ, & DR genes; display antigens that are recognized by CD4+ T cells

Question 2

atopy

Answer 2

predisposition to develop allergies

Question 3

• Immediate reaction:

o Late-phase reaction:

Answer 3

• Immediate reaction: characterized by vasodilation, congestion, and edema
o Late-phase reaction: characterized by an inflammatory infiltrate rich in eosinophils, along with neutrophils and T cells

Question 4

• Goodpasture syndrome

Answer 4

type 2
circulating autoAb to Ag intrinsic to glomerular basement membrane results in Ab mediated injury
o Resulting anti-GBM immune complexes can be visualized with IF microscopy as a **linear pattern of deposition

Question 5

type three monitoring

Answer 5

levels of C3 can be used to monitor disease activity

Question 6

type 4

Answer 6

• Inflammation resulting from cytokines produced by CD4+ T cells and cell killing by CD8+ T cells (no Ab involved)
• T cells are sensitized to exogenous/endogenous antigens → resultant T cell immune response results in cell/tissue injury
• Mechanisms of T cell-mediated (Type IV) hypersensitivity rxns:
o CD4+ TH1 cells: secrete cytokines that stimulate inflammation and activate phagocytes
• CD4+ TH17 cells contribute to inflammation by recruiting neutrophils (and monocytes)
• Ex. tuberculin skin test (PPD test), forms of granulomatous inflammation, contact dermatitis, MS, IBD
o CD8+ T cell: directly kill tissue cells – ex. type I diabetes and graft rejection
• CD4+ T cell-mediated inflammation:
o In response to repeat exposure of an antigen, CD4+ T cells secrete cytokines, leading to recruitment and activation of macrophages and neutrophils. This inflammatory response leads to tissue injury.
o Ex. delayed-type hypersensitivity reaction, a tissue reaction to antigens given to immune individuals
• Antigen administered into skin of a previously immunized ind results in a detectable skin reaction within 24-48 hrs
• CD8+ T cell-mediated cytotoxicity: CD8+ cytotoxic T cells kill antigen-expressing target cells

Question 7

Caseating vs non- granulomas

Answer 7

o **Caseating granulomas: granulomas that induce cell mediated immune response with central necrosis
• Usually associated with infections that are difficult to eradicate (ex. mycobacterial, fungal infections)
o **Non-caseating granulomas: granulomas that induce cell mediated immune response without central necrosis (ex. Sarcoidosis, Crohn’s disease)

Question 8

FAS, FAS ligand

Answer 8

FAS on target cell, FASL on CTL tells target to die

aka CD95

Question 9

T cell mutations

Answer 9

somatic hypermutation does not happen

somatic mutation due to TdT

Question 10

• HLA-B27 →

Answer 10

• HLA-B27 → 90x more likely to develop ankylosing spondylitis (destruction of the vertebral cartilage)
• Also linked to psoriasis, inflammatory bowel disease, and Reiter’s syndrome

Question 11

HLA-DR2 →

Answer 11

HLA-DR2 → 130x more likely to develop narcolepsy – also linked to MS, hay fever, and SLE.

Question 12

HLA-A3/B14 →

Answer 12

HLA-A3/B14 → 90x more likely to develop hemochromatosis (too much iron adsorption → organ damage)

Question 13

• HLA-DQ2/GQ8 →

Answer 13

• HLA-DQ2/GQ8 → Celiac disease (thanks mom and dad ☹)

Question 14

• HLA-DR3 →

Answer 14

• HLA-DR3 → DM type I, Grave’s disease; HLA-DR4 → RA and DM type 1

Question 15

• HLA-B53

Answer 15

• HLA-B53 is associated with protection against childhood malaria!!!!!
• Specific global distribution pattern: gene frequency in Ghana = 40%; in China & South Africa = 1-2%

Question 16

Auer Rods

Answer 16

=AML

Question 17

o M0 – acute myeloblastic leukemia, minimally differentiated

Answer 17

• ↑↑↑ myeloblasts (A TON), blasts are bland (hard to tell it’s a myeloblast)
• MPO negative (special stain for myeloid series); need markers (have to do flow cytometry)

Question 18

o M1 – acute myeloblastic leukemia without maturation

Answer 18

• ↑↑↑ myeloblasts, no maturation (all blasts), Auer rods (only difference from M0), MPO positive

Question 19

o M2 – acute myeloblastic leukemia with maturation

Answer 19

• ↑ myeloblasts, maturing neutrophils, t(8;21) in some cases (better prognosis)

Question 20

o M3 – acute promyelocytic leukemia**

Answer 20

• ↑↑↑ promyelocytes (blast equivalents)– not a lot of myeloblasts
• Faggot cells – “bundle of sticks” – cell with lots of Auer rods
• DIC (coagulation) – granules have procoagulants inside, if not treated correctly or if chemo causes lysis
• t(15;17) in all cases → best prognosis (AML with genetic abnormality)
• Funky retinoic acid receptor – Rx with all-trans retinoic acid → cells mature past promyelocyte stage

Question 21

o M4 – acute myelomonocytic leukemia

Answer 21

• ↑↑ myeloblasts (at least 20%) + ↑↑ monocytic cells
• Extramedullary tumor masses – any time there are ↑ monocytes you have to worry about that
• Put some chemo in subarachnoid space (CSF) to kills cells before they get to brain
• Also common to go to gums/mouth
• inv(16) in some cases

Question 22

o M5 – acute monocytic leukemia

Answer 22

• ↑↑ monocytic cells – can be at any stage of maturation
• NSE positive (nonspecific esterase) = stain used to detect monocytes, promonocytes, monoblasts
• Two stages: M5A (monoblasts) and M5B (promonocytes)
• Extramedullary tumor masses

Question 23

o M6 – acute erythroblastic leukemia

Answer 23

• ↑↑ erythroblasts + ↑↑ myeloblasts – dyserythropoiesis (RBC are not going properly + look funny)

Question 24

o M7 – acute megakaryoblastic leukemia

Answer 24

• ↑↑ megakaryoblasts (platelet precursors) + bland blasts
• MPO negative (not of neutrophil series) + also negative for NSE
• Need markers – very little to go on, need to do flow

Question 25

o Good prognosis AML

Answer 25

• t(8;21) – lots of cytoplasm
• inv(16) – deep, dark eosinophils
• t(15;17) – AML-M3, abnormal retinoic acid receptor that stops cell from maturing (Rx: ATRA)

Question 26

o Poor prognosis AML

Answer 26

11q23 – more common in monocytic AML

Question 27

• AML with FLT-3 mutation

Answer 27

o Mutation of FLT-3 (a tyrosine kinase) → allows WBC count to get really high, allows cells to divide really quickly
o Present in 1/3 of cases of AML! – often involves monocytic cells, poor prognosis

Question 28

• AML with multilineage dysplasia

Answer 28

o Previous chemo (2-5 yrs to onset) – alkylating agents (Busulfan) or topoisomerase II inhibitors (Etoposide)
o Chromosomal abnormalities sometimes (5, 7, 11q23)
o Very hard to treat

Question 29

other AML prognosis

Answer 29

o Better: t(8;21), inv(16), t(15;17) [have to treat with ATRA before regular chemo so you don’t kill patient]
o Worse: FLT-3, therapy-related

Question 30

Clinical Myelodysplastic Syndrome findings

Answer 30

o Older patients (>40)
o Asymptomatic or bone marrow failure (abnormal stem cells + failure of cells to get out into the blood)
o Macrocytic anemia

Question 31

Acute Lymphoblastic Leukemia

Answer 31

• Need to know: malignant proliferation of lymphoid blasts in blood/bone marrow
o Classified by immunophenotype (B vs. T)
o More common in children – child with acute leukemia → assume ALL until proven otherwise
o Prognosis often good! (kids do better than adults)
o B cell markers = 19, 20, 21
• MOST COMMON IN CHILDREN – adults that get it do a lot worse
• Prognosis
o Immunophenotype – T is worse
o Age – kids>adults – within kids 1-10 y/o is good
o WBC –

Question 32

T-Lymphoblastic Leukemia

Answer 32

= T-Lymphoblastic Lymphoma → T-Lymphoblastic Leukemia/Lymphoma
• Typical patient: teenage male with mediastinal mass (probably because thymus is there)
• WBC usually ↑↑↑
• Bad prognosis
• Morphology: two kinds of blasts

Question 33

B-Lymphoblastic Leukemia

Answer 33

= B-cell Lymphoblastic Lymphoma
• Several sub- and sub-subtypes
• Rarely, Ph + (Philadelphia chromosome 9;22 translocation) – commonly seen in CML → worsens prognosis
• Better prognosis than TLL

Question 34

stabilizing anaphylaxis

Answer 34

Airway
Breathing
Circulation
Rapid Treatment

Epinephrine 0.01 mg/kg IM (0.01 ml/kg of 1:1000 epinephrine)