White Blood Cells

physiology + pathophysiology + pathology

What type of leukocytes are made in the bone marrow

granulocytes monocytes lymphocytes

macrophages, bly and dendritic cells are

apcs

Terminal phase of a chronic leukemia

blastic crisis

They have CD19 and CD20 as phenotypic markers on their surface

bly

t cells respond to

protein on the surface of host cells

What type of leukocytes are made in the lymph tissue

lymphocytes and plasma cells

Two major lineages of WBCs

(1) Myeloid

-granulocytes, monocytes -> Macrophages

(2) Lymphoid

-lymphocytes -> T cells, B cells, Natural killer cells

In times of serious tissue infection, this total life span is often ____________ because ______________

shortened, the granulocytes proceed even more rapidly to the infected area, perform their functions and are themselves destroyed

Monocytes transit in blood, then swell in tissues and become

macrophages

location of life of granulocytes

bone marrow - blood - tissues

continual circulation cycle of lymphocytes

lymph tissue - circ system - tissue - reenter lymph to blood

integrins and selectins

adhesion molecules that allow neutrophils to enter tissues from blood (diapedesis)

neutrophils that don't migrate into tissue undergo

apoptosis

primary (azurophilic) granules

neutrophil granules that are formed during promyelocyte stage and are last to be released

secondary (specific) granules

neutrophil granules that are formed during myelocyte and metamyelocyte stages, third to be released

Tertiary granules

neutrophil granules formed during metamyelocyte and band stages, second to be released

Secretory granules (secretory vesicles)

neutrophil granules formed during band and segmented neutrophil stages, first to be released

myeloperoxidase, cathepsins and defensins are what

primary (azurophilic) neutrophil granules

collagenase, gelatinase and lactoferrin are what

secondary (specific) granules

collagenase, gelatinase and lysozyme are what

tertiary neutrophil granules

integrins, alkaline phosphatase and complement receptor are what

secretory (secretory vesicle) neutrophil granules

Neutrophil recruitment to an inflammatory site begins when

chemotactic agents bind to neutrophil receptors

first neutrophil response

roll along endothelial cells of the blood vessels using stronger adhesive molecules;

what is endothelial cell rolling in diapedesis

transient adhesive contacts between neutrophil selectins and adhesive molecules on the surface of endothelial cells

During diapedesis, at the same time as endothelial cells roll,

secretory granules containing additional adhesive molecules are fused to the neutrophil's plasma membrane.

Role of integrins from secretory granules in diapedesis

binding bw neutrophils and endothelial cells

diapedesis

passage of blood cells through intact walls of the capillaries (transmigration of neutrophils bw endothelial cells)

Tertiary granules containing gelatinase and collagenase are released by _______

transmigrating neutrophils

Role of gelatinase during diapedesis

degrades denatured collagen as well as types IV and V collagen and activates chemokines

chemotaxis

neutrophils and macrophages to move toward the source of the chemical

What products can cause chemotaxis

- pathogenic toxins

- degenerative products of inflamed tissues

- rxn products of complement complex + plasma clotting

Whether phagocytosis will occur depends on:

- smooth surfaces (if rough, higher risk phagocytosis)

- protective protein coats (absent in dead tissue + foreign)

- opsonization

steps of phagocytosis

- neutrophil attach + project pseudopodia

- fuse, phagosome forms inside cytoplasm

role of C3

anitbody molecule product of complement cascade, initiates phagocytosis

enzymes + bactericidal agents into vesicle and digests particle

the lysosomes of macrophages contain __ which _________

lipases, digest thick lipid membranes of some bacteria

The mechanisms by which phagocytes kill the organisms they ingest are traditionally divided into oxidative and non-oxidative depending on:

depending on whether the cell consumes o2 in the phagocytosis process

most of the killing effect results from oxidizing agents formed by ___________ which contain _______-

peroxisome

superoxide, h202 and OH-

myeloperoxidase

lysosomal enzyme involved in phagocytosis that forms hypochlorite (bactericidal)

non-oxidative killing by phagocytes involves use of

the phagocyte's cytotoxic granules

reticuloendothelial system

total combo of monocytes, mobile and fixed macrophages and endothelial cells in bone marrow, spleen and lymph nodes

Where are macrophages in the spleen and bone marrow in response to invading organism

macrophages entrapped by reticular meshwork

macrophages of spleen

trabeculae of red pulp and venous sinuses lined with macrophages (blood flows instead of lymph in spleen)

macrophages of lungs

in alveolar walls, either digest them or if large, form giant cell capsule and dissolve it

Macrophages/Kupffer cells in liver

bacteria from ingested food passes thru GI mucosa into portal blood - liver sinusoids lined w/ kupffer cells (filter)

eosinophils

weak phagocytes, often produced in parasitic infections

How do eosinophils kill parasites?

release of hydrolytic enzymes + reactive forms of O2 + major basic proteins from their granules

Mast cells and basophils in allergic rxns release

eosinophilic chemotactic factors, causes eosinophils to migrated to target

role of eosinophils in allergic rxns

- detoxify inflammation-inducing substances of mast cells and basophils

- destroy allergen-antibody complexes

Basophils

A circulating leukocyte that produces histamine

Mast cells (+basophils) release _______ during inflammation

bradykinin, histamine, serotonin

Mast cell

granulocyte from myeloid stem cell w/ granules rich in histamine + heparin

Role of mast cell

in allergy, wound healing, angiogenesis, immunity, vascular permeability in brain tumours

When IgE binds to antigen, what happens to mast cells or basophils?

rupture and release histamine, bradykinin, serotonin, heparin, leukotrienes and lysosomal enzymes (create allergic rxn)

Lymphocytes

makes antibodies, responsible for acquired immunity

T lymphocytes

T and B lymphocytes are derived from ________- that form ___________

pluripotent hematopoietic stem cells that form common lymphoid progenitor cells

T lymphocytes are where and are responsible for what

thymus, cell-mediated immunity

B lymphocytes are where and are responsible for what

form antibodies, processed in liver then marrow

The only t lymphocytes that are released from thymus are those that are

nonreactive against body's own antigens

Thymus-derived T lymphocyte

develop into effector cells of cell immunity, help B cells produce antibodies

Thymus-derived T lymphocytes sense only

peptide fragments of proteins displayed by molecules of MHC

Major Histocompatibility Complex (MHC)

system of molecules with antigenic role (specific )

actions of T lymphocytes

- kill virus-infected cells

- activate phagocytes

- activate b lymphocytes that have ingested antigens

MHC molecules - actions

transport peptides to surface of infected cell and presented to T cell (t cell recognizes MHC and peptide)

each chain of an MHC molecule has

- variable region that participates in peptide antigen binding

- constant region that interacts w/ signaling molecules

T helper lymphocytes

regulator of all immune fxns, forming lymphokines that act on immune cells

WHat do T helper lymphocytes do

- help B cells produce antibodies

- help activate killer T cells

- help activate macrophages

Th1

type of T helper lymphocyte

- activates bactericidal activities of macrophages + induces B-cells to make opsonizing antibodies (cell mediated immunity)

Th2

type of T helper lymphocyte

- releases interleukin 4, which activated B cells to make neutralizing antibodies (humoral immunity)

Th1 responses are more effective against ___________while Th2 responses are more effective against ___________

intracellular pathogens

extracellular pathogens

Killer (cytotoxic) T cells (CD8)

attach to a cell bcus they've seen it before, inject enzymes thru holes in membrane or bind to cell death receptors on membrane

Suppressor (regulatory) T cells

produce substances that help end immune response

Natural killer T cells (NKT)

Shares properties with T cells and NK cells

role of NK cells

destroy tumor or viral infected cell (innate immunity)

nk cells are formed by

common progenitor cells

B lymphocytes are found in

BM and lymphoid follicles in lymph tissue

BCD (B cell receptor)

receptor on b lymphocyte that recognizes diff chem structures

Differences of b vs t lymphocytes

- actively secrete antibodies that are reactive agents (instead of T cell that activates whole cell reactivity)

- B cell has greater diversity

B lymphocytes are transformed into ______ that make _______

plasmocytes

immunoglobins (antibodies)