B&L Unit 3 Flashcards
What is a primary immunodeficiency?
Mutations in genes required for normal development of parts of the immune system
What is secondary immunodeficiency?
It has an underlying cause
What is the defect in SCID-X1? (3)
Defect in gene for gamma chain that forms receptors for IL-2 and other cytokines necessary for lymphoid development or their signalling pathways
Can also result from adenosine deaminase deficiency, MHC class II deficiency
What happens in X-linked (Bruton) agammaglobulinemia?
Protein tyrosine kinase is defective -> no mature B cells
What types of infections to people with Bruton agammaglobulinema have?
Bacterial infections -> pneumonia, chronic diarrhea
Enteroviruses
What happens in X-linked hyper IgM syndrome?
Defect in IgM to IgG switch
CD40 (B cells) or CD40 ligand (T cells)
What happens in common variable immunodeficiency?
B cells are difficult to activate
What happens in DiGeorge syndrome?
Absent 3rd and 4th pharyngeal pouches -> no thymus (or parathyroid)
What type of pathogens are T cell deficiencies associated with? B cell deficiencies?
Intracellular pathogens, especially candida and pneumocystis jirovecii
Extracellular, pyogenic (high-grade) bacteria like staph, haemophilus, strep
What comorbidity is common in selective IgA deficiency?
Celiac disease
What happens in ataxia telegiectasia?
T and B cell deficiency (not absolute)
IgA depression
Sinus infections, pneumonia, ataxia, telangiectasia (dilated abnormal blood vessels), tumors
What happens in Wiskott-Aldrich syndrome?
Platelet and B cell deficiency
Eczema
Bacterial infections
X-linked
What is a lymphoma called that presents at a site that is not a lymph node?
Extranodal
What is the most common chromosomal abnormality in hematologic malignancies?
Balanced translocations
What are 3 viruses that can cause hematologic malignancies?
Epstein-Barr -> various B cell lymphomas
Human T cell leukemia virus-1 (HTLV-1) adult T cell leukemia/lymphoma
Kaposi sarcoma herpesvirus/Human herpesvirus 8 primary effusion lymphoma
What 5 parameters does the WHO use to classify heme malignancies?
Microscopic appearance
Histologic growth patterns
Presence or absence of specific cytogenic/molecular findings
Relative amounts of cells in marrow and blood
Presence or absence of cell surface, cytoplasmic, and/or nuclear markers
What is myelodysplastic syndrome?
The marrow is overtaken by a neoplastic blood cell clone incapable of making normal blood cells
What is a myeloproliferative neoplasm?
The marrow is overtaken by a neoplastic blood cell clone that makes normal functioning myeloid cells
What is a non-hodgkin lymphoma?
Lymphomas of mature-appearing lymphocytes (that aren’t Hodgkin lymphoma or plasma cells)
CD________ marks B cells
20
CD________ marks T cells
3
What lymphocyte levels are found in CLL/SLL? (chronic lymphocytic leukemia/small lymphocytic lymphoma)
> =5 E9/L
What is the most common genetic alteration in follicular lymphoma?
Translocations of chromosomes 4 and 18, which places the BCL2 gene on chromosome 18 under influence of the IGH promoter on chromosome 14
What is mantle cell lymphoma?
A B-cell neoplasm. Characterized by BCL1 gene rearrangement overexpression of cyclin D1
3 mechanisms of tissue damage in autoimmunity?
Neutrilization
Complement-mediated damage
Stimulatory hypersensitivity (autoantibodies can act as agonists)
Myasthenia gravis involves autoantibodies against __________
Acetylcholine receptor
Goodpasture syndrome involves autoantibodies against ____________
Lung and kidney basement membranes
Dressler syndrome involves autoantibodies against ____________
Heart
What is hybrid antigen formation n autoimmune disease?
B cell binds self + a foreign epitope
Foreign epitopes is presented to Th2 on class II MHC
B cell is activated and secretes antibody to self
Mnemonic for stuff that happens in DiGeorge syndrome
CATCH-22
Calcium – lack of parathyroids -> can’t regulate calcium. Presents first usually as neonatal convulsions
Appearance – wide set eyes, low-set ears, fish mouth
Thymus - missing
Clefts (palate)
Heart – many big defects in development of big veins
Chromosome 22 defect as a de novo mutation
What is IVIg used for besides immunodeficiency?
Anti-inflammatory
Why do we give irradiated RBCs to people with SCID?
RBCs have high adenosine deaminase
Irradiation kills lymphocytes
What is the innocent bystander process of loss of self-tolerance?
An antigen gets attached to normal tissue and then gets fucked up by the immune system
What is an indirect vs. a direct immunofluorescence test?
Direct - look for antibody attached to its target
Indirect - look for antibody in serum
What cell type is in the mantle zone of the lymph node?
B cells
What cell type is predominantly in the light zone of a germinal center? Dark zone?
Centrocytes
Centroblasts
These are both B cells
Cancer of the immature B cell
B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma
B-ALL/LBL
Cancer of the mantle cell
Mantle cell lymphoma
3 cancers of the germinal center B cell
Follicular lymphoma
Burkitt lymphoma
Hodgkin lymphoma
Pre or post-germinal center B cell cancer
Chronic lymphocytic leukemia/small lymphocytic lymphoma
CLL/SLL
Plasma cell cancer
Plasma cell myeloma (multiple myeloma)
5 risk factors for acute leukemia
Previous chemotherapy Tobacco smoke Ionizing radiation Benzene exposure Genetic stuff like Down syndrome, Bloom syndrome, Fanconi anemia, ataxia-telangiectasia
What age group does acute lymphoblastic leukemia occur in?
Usually in children under 6 yo
What 2 things do we look for to identify lymphoblasts?
CD34 TdT expression (not expressed by myeloblasts or mature lymphocytes)
What 3 things do B-lymphoblasts express? What do they not express?
CD19, 22, and/or 79a
CD20
Which subgroup of B-acute lymphoblastic leukemia has the worst prognosis?
Ph+ ALL
The Philadelphia chromosome: t(9;22) -> BCR-ABL fusion protein
Which subgroup of B-acute lymphoblastic leukemia has the best prognosis?
t(12;21)(p13;q22) ETV6-RUNX1
Does T-ALL often come with a component of lymphoblastic lymphoma?
Yes. It often manifests as a large mediastinal mass.
What CDs do T-lymphoblasts express?
CD2-8
CD99
CD1a
How does number of chromosomes affect ALL prognosis?
Hiperdiploidy - good
Hypodiploidy - bad
What distinguishes a myeloblast morphologically?
Auer rods
What CDs indicate monocytic differentiation of myeloblasts?
CD64
CD14
What CDs indicate megakaryocytic differentiation of myeloblasts?
CD41
CD61
What does RUNX1 do?
Encodes the alpha unit of core binding factor
This is a transcription factor needed for differentiation
What does CBFB do?
Encodes the beta unit of core binding factor
This is a transcription factor needed for differentiation
What is the translocation for acute promyelocytic leukemia?
t(15;17)
What leukemia can cause DIC?
Acute promyelocytic leukemia
How can you treat a subset of acute promyelocytic leukemia?
Retinoic acid receptor-alpha becomes a fusion gene that works less well
Can give high doses of retinoic acid
What are 3 causes of neutropenia?
Kostmann syndrome
Schwann-Diamond syndrome
Cyclic neutropenia
What is sjogren syndrome?
An autoimmune reaction against exocrine glands, especially those that secrete tears and saliva
What is a visible sign of vasculitis?
Palpable purpura
What 2 things characterize myelodysplastic syndrome?
Ineffective hematopoiesis
Increased risk of transformation to acute myeloid leukemia
What is the difference between low and high grade myelodysplastic syndrome classification?
Low - myeloblasts are
What is the main genetic change in chronic myeloid leukemia (CML)?
Fusion of BCR-ABL1 From t(9;22) This is the philadelphia chromosome
What is the drug we use for CML (chronic myeloid leukemia)
imatinib (Gleevec)
It is a protein tyrosine kinase inhibitor
What is the main genetic change in polycythemia vera?
Mutation of JAK2
What is the ultimate result of polycythemia vera and primary myelofibrosis?
Fibrosis of the bone marrow so more blood cells cannot be produced
What are the 2 leukemias with BCR-ABL fusions?
CML
B-ALL
Which lymphoma makes a starry sky histological pattern?
Burkitt lymphoma
What is the immunophenotype of Burkitt lymphoma?
5 positive
2 negative
B Cell markers: CD19, CD20
Germinal center B cell markers: CD10, BCL6
Myc
Negative: CD5, CD23
What is the translocation for Burkitt lymphoma?
t(8;14)
Fuses the MYC gene, overexpression MYC, which is a transcription factor
What is the most common type of non-Hodgkin’s lymphoma?
Diffuse large B-cell lymphoma
Which hematologic malignancy results in lytic bone lesions?
Plasma cell myeloma (multiple myeloma)
Where do tumor cells usually hang out in plasma cell myeloma?
In the bone marrow
What is the most common monoclonal gammopathy (too many immunoglobulins)
MGUS - monoclonal gammopathy of undertermied significance
What is a solitary plasmacytoma of bone?
An individual tumor of plasma cell myeloma. There is no evidence of other bone lesions.
So I think it’s when you have plasma cell myeloma and only have 1 bone tumor
What is the immunophenotype of classic hodgkin’s lymphoma? 2 positive, 1 neative
CD30, CD15
No CD45, a common leukocyte antigen
What are the 4 hodgkin’s lymphoma subtypes?
Nodular sclerosis
Mixed cellularity variant
Lymphocyte rich variant
Lymphocyte depleted variant
In order of frequency!
What complement coponents attract neutrophils?
C3a
C5a
Which antibody is helpful for helminth defense? Where are these antibodies?
IgE, which binds to FcER1 receptors on the surface of mast cells
What things attract eosinophils?
Prostaglanding
Leukotrienes
What do eosinophils release that kills helminths?
Major basic protein
What signals the mast cell to degranulate?
IgEs on bound to the FcER1 receptors that are cross-linked by antigen
Why don’t oral antigens affect the rest of the gut?
Because they are destroyed by stomach acid. They can cross the mucus membranes though and encounter mast cells in the oral cavity
What are the two components of asthma?
Bronchoconstriction inflammation
When an activated Th2 cell goes out into the body and locates a helmint, what 2 cells does it attract?
Eosinophils
M2 macrophages
What is atopy?
A tendency to be “hyperallergic”. So they are more likely to have eczema, allergic rhinitis, or asthma.
It gets worse
What are 2 common myeloid markers that are usually not on lymphoblasts?
CD117
Myeloperoxidase
What is t-AML?
AML arising secondary to DNA damage from a prior therapy
Bad prognosis
Myelodysplastic syndrome is a precursor to _____
AML
What is dyshematopoiesis?
> 10% of cells in a lineage are dysplastic?
IL-4 is chemotactic for _______ and _______
Eosinophils
M2 macrophages
What does IL-5 do to eosinophils?
Upregulates production and release of eosinophils from bone marrow
What 3 things are released in the late phase of an allergic reaction?
Prostaglandins
Leukotrienes
ECF-A
What are the 3 phases of CML?
Chronic
Accellerated
BLast
What is the translocation for Burkitt lymphoma?
MYC
t(8;14)
What condition are auer rods in?
AML
What are 4 myeloproliferative neoplasms?
CHronic myelogenous leukemia
Polycythemia vera
Primary myelofibrosis
Essential thrombocythemia
What are the 2 stages of polycythemia vera?
Polycythemic phase
Spent phase / post-PV myelofibrosis
What kills you in polycythemia vera?
Thrombosis
Why does primary myelofibrosis cause hepatosplenomegaly?
Extramedullary hematopoiesis
How does primary myelofibrosis differ from polycythemia vera?
No increased erythrocytes, though megakaryocytes and granulocytes are increased
What mutation is common in essential thrombocythemia?
Jak2
