Week 3 Flashcards
MHC genetics
- 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
atopy
predisposition to develop allergies
• Immediate reaction:
o Late-phase reaction:
• 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
• Goodpasture syndrome
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
type three monitoring
levels of C3 can be used to monitor disease activity
type 4
• 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
Caseating vs non- granulomas
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)
FAS, FAS ligand
FAS on target cell, FASL on CTL tells target to die
aka CD95
T cell mutations
somatic hypermutation does not happen
somatic mutation due to TdT
• HLA-B27 →
- 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
HLA-DR2 →
HLA-DR2 → 130x more likely to develop narcolepsy – also linked to MS, hay fever, and SLE.
HLA-A3/B14 →
HLA-A3/B14 → 90x more likely to develop hemochromatosis (too much iron adsorption → organ damage)
• HLA-DQ2/GQ8 →
• HLA-DQ2/GQ8 → Celiac disease (thanks mom and dad ☹)
• HLA-DR3 →
• HLA-DR3 → DM type I, Grave’s disease; HLA-DR4 → RA and DM type 1
• HLA-B53
- HLA-B53 is associated with protection against childhood malaria!!!!!
- Specific global distribution pattern: gene frequency in Ghana = 40%; in China & South Africa = 1-2%
Auer Rods
=AML
o M0 – acute myeloblastic leukemia, minimally differentiated
- ↑↑↑ 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)
o M1 – acute myeloblastic leukemia without maturation
• ↑↑↑ myeloblasts, no maturation (all blasts), Auer rods (only difference from M0), MPO positive
o M2 – acute myeloblastic leukemia with maturation
• ↑ myeloblasts, maturing neutrophils, t(8;21) in some cases (better prognosis)
o M3 – acute promyelocytic leukemia**
- ↑↑↑ 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
o M4 – acute myelomonocytic leukemia
- ↑↑ 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
o M5 – acute monocytic leukemia
- ↑↑ 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
o M6 – acute erythroblastic leukemia
• ↑↑ erythroblasts + ↑↑ myeloblasts – dyserythropoiesis (RBC are not going properly + look funny)
o M7 – acute megakaryoblastic leukemia
- ↑↑ 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
