Ambruso lectures unit II Flashcards Preview

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Flashcards in Ambruso lectures unit II Deck (56)
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1
Q

Describe the developmental time course of a monocyte/macrophage.

A

~7 days in the marrow, released immediately , 3-5 days in intravascular compartment, then moves to tissues for days-months.

2
Q

What is the function of a monocyte/macrophage?

A

1.) move to sites of infection and inflammation 2.) filter function 3.) process and present antigens 4.) clear apoptotic cells and debris

3
Q

T or F: Monocytes are stored in the bone marrow before release?

A

FALSE

4
Q

Describe the developmental time course of a neutrophil.

A

Produced in marrow and stored for defense for 10-14 days, released from peripheral blood ~6 hrs then move to tissues. 1-2 day turnover

5
Q

What is the function of a neutrophil?

A

Non-specific defense against microbes, important in acute tissue injury

6
Q

Describe the developmental time course of a eosinophil.

A

Produced in bone marrow under IL-5 stimulation. Are stored in bone marrow before release. Released in peripheral blood, move to external surfaces, and survive for weeks.

7
Q

What is the function of an eosinophil?

A

Phagocytes, role in allergies, parasite infection, response to tumors. May be immuno-enhancing or immuno-suppressive.

8
Q

Describe the developmental time course of a basophil.

A

Produced in bone marrow under IL-3 and GM-CSF stimulation, released in peripheral blood, move to tissues. Ambruso did not give specifics on time.

9
Q

What is the function of a basophil?

A

Receptors for IgE, involved in inflammation, pathophys of hypersensitivity reactions.

10
Q

Which WBCs are stored in bone marrow before release?

A

Neutrophils, eosinophils

11
Q

What is in the neutrophil bone marrow storage compartment?

A

Band and seg neutrophils, metamyelocytes

12
Q

What is a normal adult neutrophil count?

A

2500-6000/uL

13
Q

At what value of ANC are you considered at increased serious risk for infections?

A

500/uL

14
Q

How do you evaluate for neutropenia?

A

History, physical, labs. Should ask about duration and periodicity, toxin or drug exposure, family history. LOOK AT MOUTH, lymph nodes, liver, spleen, wound sites. Labs can include CBC, marrow aspirate, blood chemistries, anti-neutrophil antibodies, among others.

15
Q

What is the most common cause of neutropenia?

A

Infection

16
Q

T or F: Infection-related neutropenia is usually chronic?

A

False. Usually acute, resolves in days to months.

17
Q

What are the mechanisms of infection-related neutropenia?

A

Increased utilization, complement mediated margination, marrow suppression/failure, cytokine and chemokine induced margination, anti-neutrophil antibody production

18
Q

Name some viruses associated with neutropenia.

A

EBV, CMV, influenza, RSV, HIV, hepatitis, parvovirus, roseola

19
Q

Name some bacteria associated with neutropenia.

A

Gram negative sepsis, brucellosis, tularemia, TB, typhoid

20
Q

What cells are in the neutrophil mitotic pool?

A

Myeloblast, promyelocyte, and myelocyte

21
Q

T or F: The mitotic compartment is the largest bone marrow neutrophil compartment (in terms of cell number).

A

False. The maturation-storage compartment is the largest.

22
Q

What is alloimmune neutropenia?

A

Mother makes antibodies to her baby?s neutrophils. Usually seen 2-4 weeks after birth, but can last for months. Marrow shows increase in mitotic pool but decrease in storage pool. To determine alloimmune neutropenia from neutropenia due to sepsis, test mom for antibodies.

23
Q

What is autoimmune neutropenia?

A

Autoantibodies, often due to HIV infection, lupus, or other autoimmune diseases. Shows normal marrow cellularity and arrest of late maturation pool.

24
Q

What is the most common cause of autoimmune neutropenia?

A

HIV

25
Q

How can you treat autoimmune neutropenia?

A

Treat underlying disorder and hematologic antibodies. G-CSF may be helpful if marrow storage is depleted.

26
Q

How can you treat alloimmune neutropenia?

A

Antibiotics and supportive care, IVIG infusion sometimes, consider G-CSF for severe infections.

27
Q

What is Kostmann?s syndrome?

A

Apoptosis of myeloid procurers associated with elastase or HAX-1 genes. Severe neutropenia at birth, will see monocytosis and eosinophilia, risk for AML and myelodysplasia

28
Q

How can you treat Kostmann?s syndrome?

A

Treat infections, give G-CSF, consider bone marrow transplant

29
Q

What is cyclic neutropenia?

A

Apoptosis of precursors, mutations in ELA-2. Typically AD and S inheritance. Recurrent infections, cycles ~21 days for most, ANC <200 for 3-5 days. Bone marrow shows hypoplasia, arrest at myelocyte stage. May see cycles of platelet and retic count as well

30
Q

How do you treat cyclic neutropenia?

A

Aggressive antibiotics, supportive care, G-CSF daily during neutropenia

31
Q

What is Shwachman-Diamond syndrome?

A

Apoptosis of marrow precursors, stromal defect, recessive inheritance, also have pancreatic insufficiency, chondrodysplasia and bone related disease

32
Q

How can you treat Shwachman-Diamond syndrome

A

Pancreatic enzyme replacement, G-CSF, antibiotics, bone marrow transplant eventually

33
Q

What is neutrophilia?

A

Increase in neutrophils over 7500/uL for anyone except neonates. May be caused by increased release, increased production, decreased egress from circulation, reduced margination

34
Q

What is eosinophilia?

A

Increase in eosinophils over 3500/uL. Can be caused by allergic disorders, parasites, drug reactions

35
Q

What is the normal neutrophil range for neonates?

A

7-13000/uL

36
Q

What is monocytosis?

A

Increase in monocytes over 500/uL for adults, over 1000/uL for newborns. Can be caused by hematologic malignancies, collagen vascular diseases, granulomatous disease, infections, and carcinoma.

37
Q

What are the 4 basic neutrophil functions?

A

Rollings/adherence, chemotaxis, ingestion, degranulation/killing

38
Q

What is required for rolling/adherence?

A

Plasma membrane, stored cytoplasmic granules that contain receptors, cytoskeletal proteins

39
Q

What is required for chemotaxis?

A

Plasma membrane, stored cytoplasmic granules, cytoskeletal proteins, energy source ATP

40
Q

What is required for ingestion?

A

Plasma membrane, cytoskeletal proteins, energy source - glycolysis

41
Q

What is required for degranulation/killing?

A

Plasma membrane, stored cytoplasmic azurophilic granules, cytoskeletal proteins, energy source - glycoslysis

42
Q

What is inside a phagolysosome?

A

Reactive oxygen species (made my O2 anions)

43
Q

Where does the extra electron come from to make an oxygen anion?

A

NADPH

44
Q

How can you test neutrophil function?

A

Bactericidal activity, chemotaxis, expression of adhesion molecules or test adherence to inert substance/endothelial cells, look at ability to oxidize and look at granules

45
Q

What is leukocyte adhesion deficiency I?

A

Recurrent infections, NEUTROPHILIA, decreased adherence to endothelial surface leading to defect in movement to infected site. Deficiency in CD18, resulting in lack of CD11b/CD18. Autosomal recessive.

46
Q

What protein is often defective in neutrophil chemotaxis disorders?

A

Actin (may occur with or without actin binding protein mutations). Ingestion also affected along with chemotaxis. Tends to be an autosomal recessive condition.

47
Q

What happens if a person has an Fc receptor disorder?

A

Impairment in neutrophil phagocytosis, autosomal recessive

48
Q

What is Chediak-Higashi syndrome?

A

Causes oculocutaneous albinism, nystagmus photophobia, recurrent infections of skin and mucous membranes, hepatosplenomegaly, neurodegeneration. Neutrophils have giant granules, abnormal degranulation, and microbicidal activity. Alterations in membrane fusion with formation of giant leaky granules.Other metabolic abnormalities lead to altered microtubule assembly. Autosomal recessive (CHS1 gene)

49
Q

What is myeloperoxidase deficiency?

A

Generally healthy but have an increase in fungal infections with diabetes. Mild defect in killing candida. Caused by a post-translational modification defect. Autosomal recessive.

50
Q

What is chronic granulomatous disease (CGD)?

A

Recurrent infections with catalase + bacteria and fungi involving skin and mucous membranes. Deep infections of liver, spleen, lymph nodes, bones. Neutrophilia. No toxic oxygen metabolites produced. Cannot kill coagulase + bacteria and fungi. Autosomal recessive, or in one case, X-linked recessive.

51
Q

What are some indications of a phagocyte disorder?

A

Recurrent bacterial and fungal infections, periodontal disease, infections at interface areas (deep infections as well), infections with atypical pathogens, for CGD an inability to kill catalase + organisms

52
Q

What complement protein deficiency results in recurrent bacterial infections?

A

C3

53
Q

What complement protein deficiency results in recurrent neisseria infections?

A

C5-9

54
Q

How do you manage innate immune defects?

A

Aggressive treatment of infection with broad spectrum antibiotics, surgery, may give G-CSF, may need to give prophylactic antibiotics. For some disorders, stem cell transplant can be done

55
Q

How is CGD treated?

A

CGD patients are treated with INFgamma. Experimental gene therapy has been tried.

56
Q

What complement protein deficiency deficiencies are associated with autoimmune disorders?

A

C1q, C2, C4