heme exam 2

What is the normal WBC reference range?

4.5–11.5 × 10³/µL

Which leukocytes are classified as Granulocytes?

Neutrophils, eosinophils, basophils

Which leukocytes are classified as Mononuclear cells?

Monocytes and Lymphocytes

What is the difference between innate and adaptive immunity?

Innate Immunity/Nonspecific: Immediate response

EX. Phagocytosis by neutrophils

Adaptive Immunity/specific: Immune memory and produces antibodies

EX. Mediated by Lymphocytes and plasma cells

What factors affect WBC count?

Physiologic events: pregnancy, time of day, activity level

Pathologic events: infections, immune regulated responses

ALWAYS CONSIDER: Patients age

where and how do the leukocytes mature? (starting from bone marrow)

1) Leukocytes originate and is released from bone marrow

2) they circulate briefly in blood (finish maturing in blood)

3) Move to tissue in response to stimulation (diapedesis)

4) perform most of the defenses in tissues

what is the maturation pathway for Neutrophils called?

The Granulocyte-Monocyte Pathway (GMP)

What are on leukocyte surface antigens?

Cell surface marks

what do the cell surface markers help identify for leukocytes?

Cell lineage and subsets within the lineage

Stage of maturation

State of cell activation

NOTE: Antibodies with similar characteristics are assigned a cluster of differentiation (CD) number.

What reactions identify leukocyte cell surface markers?

reactions with specific Monoclonal Antibodies

what is the Granulocyte-Monocyte Pathway (GMP) sequence for neutrophils, basophils, and eosinophils?

Hematopoietic stem cell → CMP → GMP → Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band → Segmented neutrophil

Neutrophil development: Which stage has high N:C ratio?

Myeloblast

What neutrophil stage is this describing: High N:C ratio, 1-5 nucleoli, Scanty, blue, agranular cytoplasm

Myeloblast

Neutrophil development: At which stage do Azurophilic (primary) Granules first appear?

Promyelocyte

What neutrophil stage is this describing: Larger size azurophilic primary granules appear, Nucleoli disappear and Chromatin begins to condense

Promyelocyte

Neutrophil development: At which stage do secondary granules first appear?

Myelocyte

What neutrophil stage is this describing: Smaller size Secondary granules appear, Round/oval nucleus and No nucleoli, LAST STAGE CAPABLE OF MITOSIS

Myelocyte

Neutrophil development: when does an indented kidney-shaped nucleus appear?

Metamyelocyte

What neutrophil stage is this describing: Kidney-shaped (indented) nucleus, Clumped chromatin, More specific granules

Metamyelocyte

Neutrophil development: When does a Horse shoe/cheeto puff shaped nucleus start forming?

Band

What neutrophil stage is this describing: Horse Shoe nucleus, no distinct segmented lobes, No nucleoli and Mature granules

Band

Neutrophil development: when does 2-5 lobes start to appear?

Segmented neutrophil

What neutrophil stage is this describing: 2-5 lobes, Clumped chromatin, Pale pink to lavender granular cytoplasm, Fully mature and functional

Segmented neutrophil

Neutrophil development: what happens to the nucleus and nucleoli?

Nucleoli disappear, chromatin condenses, round nuclear mass indents and segments

primary/nonspecific azurophilic granules: when is it produced and what does it contain?

During promyelocyte stage

Contain myeloperoxidase. defensins, lysozyme, acid hydrolases

secondary specific granules: when is it produced and what does it contain?

Produced at myelocyte stage (and continues to metamyelocyte stage)

Contain lactoferrin, collagenase, lysozyme

secretory tertiary granules: when is it produced and what does it contain?

produced at Metamyelocyte stage

Contain alkaline phosphatase, membrane receptors

Tertiary vesicles granules: when is it produced and what does it contain?

Produced in mature segmented neutrophils

Contain gelatinase and other enzymes

Neutrophil development: which stage is the last stage capable of mitosis?

Myelocyte

what are the three pools of Neutrophils maturation called? And where do they mature?

In Bone Marrow

1) stem cell pool

2) proliferation (mitotic) pool

3) Maturation (storage) pool

Three pools of developing neutrophils: What is happening and what cells are in the stem cell pool?

hematopoietic stem cells (HSC)

self-renewal & differentiation

Three pools of developing neutrophils: What is happening and what cells are in the Proliferation (mitotic) pool?

(Common myeloid progenitors (CMPs)) aka CFU-GEMM: colony-forming units-granulocyte, erythrocyte, monocyte, & megakaryocyte

Myeloblasts, promyelocytes, & myelocytes

Consists of cells that are dividing

Three pools of developing neutrophils: What is happening and what cells are in the maturation (storage) pool / mature neutrophil reserve?

Metamyelocytes, band neutrophils, & segmented neutrophils

Consists of non-dividing cells undergoing nuclear maturation that form the marrow reserve & are available for release

The largest section/compartment

Which cells are found in the proliferation pool?

Myeloblasts, promyelocytes, myelocytes, CFU-GEMM

Which cells are found in the maturation pool?

Metamyelocytes, band neutrophils, and segmented neutrophil

What is the function of the maturation pool?

It stores maturing and mature neutrophils for release when needed.

(reserve/storage)

What is the function of the circulating pool (CNP)?

Neutrophils circulating freely

About the same size as MNP

What is the function of the Marginating pool (MNP)?

neutrophils are loosely localized to the walls of capillaries in tissues such as the liver spleen, & lung

About the same size as CNP

What is the difference between the circulating and marginating neutrophil pools?

Circulating neutrophils move freely in blood. Marginating neutrophils are temporarily associated with capillary walls.

What is the approximate neutrophil half-life in peripheral blood?

7 hours

What is diapedesis (extravasation)?

Neutrophils marginate as well as exit the blood and enter the tissues, by integrins & selectins

What is the steps of diapedesis (extravasation)?

1) Margination

2) Rolling

3) Firm Adhesion

4) Transmigration (Diapedesis/extravasation)

what helps Diapedesis happen?

1) Chemotactic agents bind to neutrophil receptors

• Chemotatic agents are made by microorganisms, damaged cells, or by other leukocytes.

2) Selectins help activate the rolling

3) Intergrins binding to a neutrophil surface activates an out-side-in signal pathway which helps firm adhesion and movement from blood to tissue

Neutrophils always go to where area of greatest concentration of chemotactic agents.

Which molecules are associated with rolling and firm adhesion?

Selectins mediate rolling; integrins mediate firm adhesion

What is chemotaxis?

Directed movement of leukocytes toward chemical signals.

Neutrophil function: what immune system is it apart of?

Innate immune system

Neutrophil function: How does it kill bacteria?

Phagocytosis

Neutrophil function: How does it digest bacteria?

respiratory burst

Oxygen dependent: respiratory burst (NADPH oxidase) → H₂O₂

Oxygen independent: fusion with lysosomes and release hydrolytic enzymes

Neutrophil function: What does Neutrophil extracellular traps (NETs) do?

trap and help kill microorganisms in the extracellular environment

NETosis: process of NET formation.

Leukocyte terms: what is Granulocytopenia?

decrease in all granulocytes (neutrophils, basophils and eosinophils)

Leukocyte terms: what is neutropenia?

decrease in all neutrophils

Leukocyte terms: what is Agranulocytosis?

Absence of granulocytes (neutrophils, basophils and eosinophils)

NOTE: High risk of developing an infection

Leukocyte terms: what is Granulocytosis?

Increase in all granulocytes (neutrophils, basophils and eosinophils)

Leukocyte terms: what is Neutrophilia?

Increase in all neutrophils

NOTE: Reactive response to bacterial infection, metabolic intoxication, drug intoxication, tissue necrosis

What is the progenitor cell of eosinophils, basophils, and neutrophils?

CMP - common myeloid progenitor

What is the characteristic morphology of an eosinophil?

bilobed nucleus with large reddish-orange granules

Which cytokine(s) is especially important for eosinophil development?

IL-3 , IL-5 (induced by IL-33), GM-CSF

Eosinophil maturation: what is the first recognizable stage?

Eosinophilic Myelocyte

Eosinophil granules: What are the primary granules (during promyelocyte stage)?

Charcot-Leyden crystal protein

Eosinophil granules: What are the secondary granules?

Formed throughout remaining maturation

Major basic protein (core)

Eosinophil granules: What are the three sub granules?

small lysosomal granules, lipid bodies, and storage vesicles

Eosinophils: what are the functions?

Degranulation: Releases cytokines, chemokines, growth factors and cationic proteins

Immune regulation: Modulates inflammatory and immune responses

Allergic response: Hallmark of allergic disorders

NOTE: also in parasitic infections

What cytokines promote basophil growth and differentiation?

IL_3 and TSLP (Thymic stromal lymphoprotein)

What is the special aspect of the granules of basophils?

Water soluable

Basophils: what are the functions?

Role in innate and adaptive immunity

Mast cells: what is the progenitor cell?

MCP - Mast cell progenitor

What is the function of a mast cell?

MAINLY IN TISSUE

Antigen presenting cell

Allergic reaction effector cells

Inflammatory reactions

Immediate hypersensitivity reactions

kinda a look out

What is the half life for… eosinophils?

18 hrs

What is the order of WBC from most common to least common in blood?

Neutrophils → Lymphocytes → Monocytes → Eosinophils → Basophils

What percentage of peripheral blood WBCs are neutrophils?

50–70%

What percentage of peripheral blood WBCs are lymphocytes?

20–40%

What percentage of peripheral blood WBCs are monocytes?

2–8%

What percentage of peripheral blood WBCs are eosinophils?

1–4%

What percentage of peripheral blood WBCs are basophils?

0–1%

What is the normal total WBC count?

4.5–11.5 × 10³/µL

What is the monocyte developmental sequence?

Monoblast (very low concentration in BM) → Promonocyte → Monocyte → Macrophage

what is the progenitor of Monocytes?

GMP- Granulocyte- monocyte progenitor

Which cytokine promotes monocyte growth and differentiation?

M-CSF

Monocyte morphology

Round, oval, or kidney shaped More often deeply indented (horseshoe shaped) or folded

Blue-gray or ground-glass appearance

Promonocyte: features

At least one nucleoli is present

Slightly indented or folded

Blue & contains scattered azure granules

What is the major function of macrophages/monocytes in innate immunity?

Recognize a wide range of bacterial pathogens which stimulate inflammatory production & phagocytosis

Synthesize nitric oxide →toxic to viruses, bacteria, fungi, protozoa, helminths, & tumor cells

Fc receptors & complement receptors →phagocytize foreign org. or materials coated with ABS or complement components

What is the major function of macrophages/monocytes in adaptive immunity?

antigen presenting cells

Interact w T & B lymphs to initiate adaptive response

Dendritic cells are the most efficient & potent of the antigen-presenting cells.

What is the major function of macrophages/monocytes in house keeping?

Removal of debris and dead cells

maintenance of storage pool of iron for erythropoiesis

synthesis of wide variety of proteins, including coagulation factors, complement components, interleukins, growth factors, and enzymes

Does monocytes have a storage pool?

No storage pool and released immediately into circulation

How many monocytes comes from one promonocyte?

1 promonocyte → 4 monocytes (2 mitotic divisions)

what are the destinations of monocytes?

In areas of inflammation or infection (inflammatory macrophages) or as "resident" macrophages in a variety of organs

macrophages reside in?

Tissues

What do dendritic cells do?

antigen presenting cells

Monocytes can differentiate in osteoclasts, what do osteoclasts do?

Bone resorption

what is the life cycle of resident macrophages?

~21 days

What are the lymphocyte groups?

T, B, and NK cells

What is the function of B cells?

Antibody production

Antigen presentation to T cells

Optimal CD4+ activation

Cytokines

Where do B cells develop in?

Bone marrow

What is the function of T cells?

Cellular immunity participation

CD4+ T cells (helper)

CD8+ T cells (cytotoxic)

Where do T cells develop in?

Thymus

Where do NK cells develop in?

BM and Thymus

What are the functions of NK Lymphocytes?

“Natural Killers” just directly phagocytosis the cell directly kills it

What is the migration of T cells?

bone marrow → thymus → undergoes self tolerance process → migrates to secondary lymphatic zones

what is the maturation series of B lymph?

pro b cell → pre b cell → immature b cell → exits as naive B cells

How do NK cells destroy abnormal or infected cells?

Through perforin and granzymes