Leukocyte development

Define monophyletic theory

all blood cells are derived from a single pluripotent hematopoietic stem cell

Effect of cytokines and growth factors on stem cells

• modulate the functional activities of other cells

• stimulation or inhibition of replication, differentiation, and/or, trafficking of mature blood cells

• varied effect on stem cells based on stage of development

Colony stimulating factors

• GM-csf = granulocyte macrophage

• Meg-csf = megakaryocyte

• G-csf = granulocyte

• M-csf = monocyte

Define: apoptosis

programmed cell death

Define: necrosis

accidental cell death

Define: erythropoiesis

Formation of RBCs

Define: leukopoiesis

Formation of WBCs

Define: myelopoiesis

Formation of neutrophils

Define: lymphopoiesis

Formation of lymphocytes

Define: megakaryopoiesis

Formation of megakaryocytes and platelets

Define: cellular immunity

Define: innate immunity

Born with it

slow

Define: humoral immunity

the host response to extracellular pathogens mediated by antibodies that enhance phagocytosis, block pathogen interactions with host cells, and activate complement pathways for cell lysis.

Define: chemotaxis

neutrophil recruitment to the inflammatory site caused by chemotaxis agents released from other phagocytes

changes that occur during cell maturation in the nucleus

• loss of nucleoli

• decrease size

• condensing chromatin

• nuclear shape changes

• loss of nucleus

changes that occur during cell maturation in the cytoplasm

• decrease basophilia (blueness)

• increase amount of cytoplasm

• granule production

Proliferation (mitotic) pool

• neutrophil pool in bone marrow

• HSCs → myelocytes

• undergo mitosis division

Maturation (storage) pool

• neutrophil pool in bone marrow

• metamyelocyte → PMNs

• nuclear and cytoplasm maturation

• no mitosis division

Marginated pool

• neutrophil pool

• endothelial lining, spleen, or liver

Circulating pool

• neutrophil pool

• neutrophils split equally b/w marginated and circulating pools

Tissue pool

• neutrophils migrated into tissues in response to infection or inflammation

• WBCs → tissues is irreversible

Leukocyte adhesion cascade: Capture

chemoattractant draws leukocytes to a position closer to endothelium of blood vessels

Leukocyte adhesion cascade: Rolling

P-selectin

• cell adhesion molecule

• required for rolling

• on endothelium cells

Leukocyte adhesion cascade: Slow rolling

requires expression of E-selectin on endothelium cells and CD18 integrin on WBC

Leukocyte adhesion cascade: Firm adhesion

E-selectin and CD18 adhere to each other

Leukocyte adhesion cascade: Transmigration

adhered WBC escapes from interior of blood vessel

Basophil vs. Mast cell

Basophil

• originate and mature in bone marrow

Mast cell

• originate in bone marrow

• matures in tissues

Primary function of: Neutrophils

phagocytosis

Primary function of: eosinophils

• increased in parasitic infections

• allergic disorders such as asthma and food allergies

Primary function of: basophils

• allergic inflammation

• helminth infections (worms)

Primary function of: mast cells

Same as baso but in tissues

Primary function of: monocytes/macrophages

Innate immunity

• phagocytosis

Adaptive immunity

• act as antigen presenting cells to T and B

Housekeeping

• remove debris

• protein production

Primary function of: 3 types of lymphocytes

T cells:

• adaptive immunity

• cellular immunity (attack foreign cells)

B cells:

• adaptive immunity

• humoral immunity (create antibodies)

NK cells:

• innate immunity

• recognize self vs non-self

What happens to monocytes after they enter the tissue

they can mature into macrophages, osteoclasts, or dendritic cells

Maturation and Kinetics of: B Cells

• in the bone marrow

• Ab production, partial role in antigen presentation to T cells

• can become

  • memory B-cells

  • Plasma cells

Maturation and Kinetics of T cells

• origin in BM

• Mature in Thymus

• regulate immune response, killing target cells directly

• Two type:

  • CD4+

    • helper T cells

    • regulate immune responses

    • maintain self-tolerance

  • CD8+

    • cytotoxic T cells

    • kill target cells or activate apoptotic pathway

Maturation and Kinetics of NK cells

• develop in BM and thymus

• kill tumor cells and virus infected cells without prior sensitization