2 Microanatomy of Blood

Under what conditions are *eosinophils* elevated?

*N*eoplasia *A*sthma *A*llergic processes *C*onnective tissue diseases *P*arasites (invasive) *NAACP*

What is the makeup of the white blood cell population in the blood, from highest percentage present in circulation to lowest?

*N*eutrophil (54-62%) *L*ymphocytes (25-33%) *M*onocytes (3-7%) *E*osinophils (1-3%) *B*asophils (0-0.75%) *N*ever *L*et *M*onkeys *E*at *B*ananas

What are the two types of white blood cells/leukocytes?

-Granulocytes -Agranulocytes

Sickle cell mutations in the hemoglobin genome are found at the (3rd/4th/5th/6th/7th/8th/9th) amino acid residue.

6th

Neutrophils constitute ___% of the leukocytes in circulation.

70%

Lymphocytes and monocytes are examples of (granular/agranular) leukocytes.

Agranular

(T/B/NK) cells are part of the *humoral* immune response and arise from stem cells and mature in the *bone marrow*. Upon encountering an antigen, these cells differentiate into *antibody-producing plasma cells* or *antigen-memorizing memory cells*. They may also serve as *antigen-presenting cells (APCs)*, processing and presenting exogenous antigens to *Th cells* via *MHC II*.

B cells

Spectrin is a protein within erythrocytes that forms a hexagonal latticework that is anchored to the plasma membrane by ____________, ____________, and _____________.

Band 4.2 Band 3 Ankyrin

(Neutrophil/Eosinophil/Basophil) granules appear dark blue to black on a Giemsa or Wright stain.

Basophil

(Neutrophils/Eosinophils/Basophils) mediate *allergic reactions*. They contain *densely basophilic granules* (stain blue) that are packed with *heparin* (anticoagulant), *histamine* (vasodilator), *prostaglandins*, *chemotactic factors* for the *attraction of eosinophils and neutrophils*, *platelet-activating factor*, and *leukotrienes* that are used to cause *bronchoconstriction*, *increased mucus production*, and *increased vascular permeability*. Often these granules are so densely packed that the nucleus is *not visible* on microscopic inspection. They typically survive for the *longest amount of time* out of the granular leukocytes, but are particularly *rare*.

Basophils

(Helper/Cytotoxic) T cells originate from bone marrow, but mature in the *thymus*. These cells are part of the *cellular* immune response and are responsible for the *destruction of cells* bearing *endogenous antigens*. They express *CD3* and *CD8* on their surface and recognize class I of the major histocompatibility complex (*MHC I*).

Cytotoxic *MHC I x CD8 = 8* MHC II x CD4 = 8

(Macrophages/Mast cells/Dendritic cells/Plasma cells) are *highly phagocytic* APCs that function as a *link* between *innate and adaptive immunity*. These cells express *MHC II* and Fc receptors on their surface. They are referred to as *Langerhans cells* when present in the epidermis.

Dendritic cells

(Neutrophil/Eosinophil/Basophil) granules appear red to orange on a Giemsa or Wright stain.

Eosinophil

(Neutrophils/Eosinophils/Basophils) possess a *bilobate nucleus* and are packed with large *eosinophilic granules* containing a crystalline core of *major basic protein*, giving them a *pink* appearance on stains. They are highly *phagocytic for antigen-antibody complexes*, and are typically the first line defenders against *helminthic infections (worm-like)*. They are also sources of *histaminase* and arylsulfatase, enzymes that help to *limit reaction* following mast cell degranulation. They typically survive for 8-12 days.

Eosinophils

(Erythrocytes/Thrombocytes/Leukocytes) refer to anucleate, biconcave cells. These cells possess large surface area-to-volume ratio for rapid gas exchange and have a life expectancy of *120 days*. Their primary energy source is *glucose*, and they serve to *transport oxygen* to tissues and *CO2* from the periphery to the lungs *for elimination*.

Erythrocytes (Red blood cells)

(T/F) Basophils possess phagocytic activity.

False. Basophils have *no phagocytic activity*.

(T/F) Platelets have nuclei.

False. Platelets have *no nuclei*.

Sickle cell anemia results from a substitution mutation in which ____________ is exchanged for a ___________ residue, resulting in abnormal hemoglobin. This results in erythrocytes that are no longer malleable or able to bend, causing the collecting of erythrocytes and occlusion and blockage of vessels.

Glutamate exchanged for Valine

Neutrophils, eosinophils, and basophils are examples of (granular/agranular) leukocytes.

Granular

Neutrophils use the free radical _______ to destroy phagocytosed bacteria.

H2O2

(Helper/Cytotoxic) T cells originate from bone marrow, but mature in the *thymus*. These cells are part of the *cellular* immune response and are responsible for the *secretion of cytokines* that *regulate the intensity* and *duration of immune responses*. They express *CD3* and *CD4* on their surface and recognize class II of the major histocompatibility complex (*MHC II*).

Helper (Th) MHC I x CD8 = 8 *MHC II x CD4 = 8*

(Iron deficiency anemia/Pernicious anemia/Sickle cell anemia/Hereditary spherocytosis/β-thalassemia) is characterized by mutations in spectrin, causing defects in the erythrocyte cell membrane. This condition is autosomal dominant.

Hereditary spherocytosis

What are the two types of agranular leukocyte?

I. Lymphocyte II. Monocyte

What are the three types of granular leukocyte?

I. Neutrophil (Polymorphonuclear leukocytes or PMNs) II. Eosinophil III. Basophil

(Iron deficiency anemia/Pernicious anemia/Sickle cell anemia/Hereditary spherocytosis/β-thalassemia) is characterized by impaired hemoglobin (Hb) production resulting from low iron intake, chronic blood loss, or increased demand for iron (e.g., in pregnancy).

Iron deficiency anemia

(Erythrocytes/Thrombocytes/Leukocytes) are responsible for *defense against infections*. There are typically *4,000-10,000* cells/mm^3 in the blood. This cell group is composed of *granulocyte* and *agranulocyte* divisions.

Leukocytes (White blood cells)

(Lymphocytes/Monocytes) are further divided into *B cells*, *T cells*, and *NK cells*. This group of cells is a mediator of adaptive immunity and part of the innate immune response. They are characterized by round, *densely staining* nuclei with a *small amount of pale cytoplasm* at the periphery.

Lymphocytes

(Macrophages/Mast cells/Dendritic cells/Plasma cells) are the main cells responsible for the *phagocytosis of bacteria, cellular debris, and senescent red blood cells*. They are *differentiated from monocytes* and have a very *long life* in tissues. These cells become activated in the presence of *γ-interferon* and can serve as *APCs via MHC II*. The primary cell surface marker for this cell type is *CD14*.

Macrophages

(Macrophages/Mast cells/Dendritic cells/Plasma cells) *mediate allergic reactions* in local tissue. These cells *resemble basophils* structurally and functionally but are not the same cell type. This type of cell *binds the Fc portion of IgE to its membrane*. Upon cross-linking of IgE, *degranulation results*, causing a massive release of *histamine*, *heparin*, and *eosinophil chemotactic* factors. These cells are the culprits involved in *type I hypersensitivity reactions*.

Mast cells

(Lymphocytes/Monocytes) differentiate into macrophages once inside tissues. They possess large, *kidney-shaped nuclei* and an extensive *"frosted glass" cytoplasm*. They typically only survive for a few months.

Monocytes

(T/B/NK) cells are the only lymphocyte member of the *innate* immune response. They utilize *perforin* and *granzymes* in order to *induce nonspecific apoptosis* of *virally infected* cells and *tumor* cells. These cells are activated by the *absence of MHC I* on target cell surfaces, or by *CD16* on the target cell which binds to the Fc region of a bound immunoglobulin, triggering the cell's cytotoxic response.

NK (Natural Killer) cells

(Neutrophil/Eosinophil/Basophil) granules appear dusty rose-colored on a Giemsa or Wright stain.

Neutrophil

(Eosinophils/Basophils/Neutrophils) are the *acute inflammatory response* cells of the body. They are markedly *increased in bacterial infections* and carry out immune functions via *phagocytosis*. They possess a *multilobed nucleus* and contain numerous, small granules filled with ALP, collagenase, lysozyme, and lactoferrin. They also possess larger, less numerous *azurophilic granules (lysosomes)* that contain proteinases, acid phosphatase, myeloperoxidase, and β-glucuronidase. They typically survive for *hours to days*.

Neutrophils

(Neutrophils/Eosinophils/Basophils) possess the largest amount of azurophilic granules within their cytoplasm.

Neutrophils

(Iron deficiency anemia/Pernicious anemia/Sickle cell anemia/Hereditary spherocytosis/β-thalassemia) is characterized by the impaired production of red blood cells resulting from vitamin B12 deficiency, usually due to inadequate synthesis of intrinsic factor.

Pernicious anemia

(Macrophages/Mast cells/Dendritic cells/Plasma cells) produce large amounts of *antibody* specific to a particular antigen. They possess an *eccentric nucleus*, *clock-face* chromatin distribution, *abundant RER*, and a *well-developed Golgi apparatus*.

Plasma cells

(Iron deficiency anemia/Pernicious anemia/Sickle cell anemia/Hereditary spherocytosis/β-thalassemia) is characterized by production of abnormal hemogloblin (HbS) resulting from a substitution mutation that exchanges glutamate for valine. This condition is autosomal recessive (heterozygotes are usually asymptomatic).

Sickle cell anemia

_____________ is a protein within erythrocytes that forms a hexagonal latticework that is anchored to the plasma membrane by band 4.2, band 3, and ankyrin.

Spectrin

(Erythrocytes/Thrombocytes/Leukocytes) refer to small cytoplasmic fragments derived from megakaryocytes. They typically have a lifespan of *7-12 days*. Upon endothelial injury, they become activated, *aggregate* with other cells of their kind, and *interact with fibrinogen* to form plugs and clots. They possess dense granules that contain ADP and calcium, along with α granules that contain *von Willebrand factor* and fibrinogen. δ granules and λ granules (lysosomes) are present as well. Approximately *1/3rd* of this cell population is found in the *spleen*.

Thrombocytes (Platelets)

(T/F) Anemia may also result from mutations in the latticework protein, Spectrin.

True.

(Iron deficiency anemia/Pernicious anemia/Sickle cell anemia/Hereditary spherocytosis/β-thalassemia) is characterized by various mutations in the hemoglobin β-chain, causing decreased globulin production, dysfunctional erythrocyte morphology, and short-lived red blood cells. This condition is autosomal recessive (heterozygotes are asymptomatic or show mild disease).

β-thalassemia