2 - Anat & Physio Flashcards
what do hematopoietic stem cells have the ability to do
ability to differentiate into many types of blood cells (production of all blood cells)
what do all red and white blood cells develop from during hematopoiesis
pluripotent HSC
where does hematopoiesis occur in adult vertebrates
in the bone marrow
where does hematopoiesis occur in the fetus
in fetal liver
within the bone marrow, HSCs are constantly ______ and directed to differentiate into major types of _______ ________
within the bone marrow, HSCs are constantly renewed and directed to differentiate into major types of progenitor cells
3 major types of progenitor cells
common myeloid progenitor cells (myeloid leukocytes)
common lymphoid progenitor cells
common erythroid progenitor cells
what cells do common myeloid progenitor cells differentiate into
neutrophils, eosinophils, basophils, monocytes, mast cells
what cells do common lymphoid progenitor cells differentiate into?
B and T lymphocytes
Natural Killer (NK) cells
what cells do common erythroid progenitor cells differentiate into
erythrocytes, platelets
what process allows myeloid progenitor cells to differentiate into neutrophils, eosinophils and basophils
granulopoiesis
what process allows myeloid cells to differentiate into monocytes and macrophages
monocytopoiesis
what process allows myeloid progenitor cells to differentiate into erythrocytes
erythropoiesis
what process allows myeloid progenitor cells to differentiate into megakaryocytes and platelets
thrombopoiesis
what process allows lymphoid progenitor cells to differentiate into lymphocytes and plasma cells
Lymphopoiesis
granulopoiesis allows myeloid progenitor cells to differentiate into….
neutrophils, eosinophils and basophils
monocytopoiesis allows myeloid progenitor cells to differentiate into…
monocytes and macrophages
erythropoiesis allows myeloid progenitor cells to differentiate into…
erythrocytes
thrombopoiesis allows myloid progenitor cells to differentiate into…
megakaryocytes and platelets
lymphopoiesis allows lymphoid progenitor cells to differentiate into
lymophocytes and plasma cells
4 main groups of hematopoietic growth factors
- colony stimulating factors (CSF)
- erythropoietin
- il-7, il-15
- inflammatory mediators
what is the function of colony stimulating factors (CSF)
induce myeloid lineage
what is the function of erythropoietin
regulates the production of erythrocytes
what is the function of IL-7 and IL-15
induce lymphoid lineage
what is the function of inflammatory mediators
favour neutrophil production
the function of microenvironment
meshwork of stromal cells support hematopoietic cell growth and differentiation
what types of cells are contained within the microenvironment
fibroblasts, adipocytes (fat cells), endothelial cells, macrophages
what is the microenvironment
cellular matrix with membrane bound diffusible growth factor
what are neutrophils also called
polymorphonucleocytes (PMNs) - multilobulated nucleus
what are neutrophils called in birds and reptiles
heterophils
classification of neutrophils
granulocyte, phagocyte
lineage of neutrophils
myeloid
appearance of neutrophils
segmented, granular
location in health of neutrophils
blood (mostly)
neutrophils lifespan in health
48-72 hours
primary function of neutrophils
antimicrobial effectors (particularly in acute infection)
mechanism of action of neutrophils
phagocytosis/degranulation of antimicrobial peptides and toxic metabolites (azurophilic and specific granules)/ NET formation
describe the appearance of neutrophils
multinucleate and granules
what forms pus
dead neutrophils and bacteria
eosinophil classification
granulocyte
eosinophil lineage
myeloid
appearance of eosinophils
Bi-lobed nucleus, eosinophilic cytoplasmic granules (staining red with eosin)
Location of eosinophils in health
blood and tissue lining gastrointestinal tract and airways
eosinophil lifespan in health
days- weeks
primary function of eosinophils
anti-parasitic effectors particularly in helminthic infection
eosinophil mechanism of action
degranulation/ limited phagocytosis
role of eosinophils
defense against helminths, allergic response (amplify Th-2 response)
what do activated eosinophils release
preformed and stored toxic molecules (major basic protein(MBP), eosinophilic cationic protein, eosinophil-derived neurotoxin –> all cause severe tissue damage
what do eosinophils synthesize
prostaglandins, leukotrienes and cytokines (amplify reactions but have collateral damage and positive feedback resulting in death of cells
describe the physical interaction of eosinophils
ability to attach and produce pores and nematodes
classification of basophils
granulocyte
basophil lineage
myeloid
appearance of basophils
bi-lobed nucleus, purple-blue cytoplasmic granules
location in health of basophils
blood (0.5)
lifespan of basophils
days
primary function of basophils
mediator of inflammation
basophil mechanism of action
degranulation/synthesis and release of pro inflammatory mediators
basophil roles
non-phagocytic cells, anti-helminthic defense, allergic reactions
what cells do basophils often act in concert with
mast cells and eosinophils
what do basophils contain
granule mediators similar to those in mast cells
why are neutrophils tissue damaging and antimicrobial
release proteases, antimicrobials and histamine(pro-inflammatory)
function and examples of proteases
elastase and collagenase: tissue remodelling
examples of antimicrobials
defensins and lysozymes
classification of monocytes
mononuclear phagocyte
monocyte lineage
myeloid
monocyte appearance
large, indented nucleus, diffuse pale blue-grey staining cytoplasm
monocyte location in health
blood (2-10%)
lifespan of monocytes
days (in circulation)
primary function of monocytes
precursors of macrophages and dendritic cells (perpetually replenish tissue with these two cells)
monocyte mechanism of action
limited antimicrobial function in blood
where are monocytes rapidly recruited
inflamed tissues
macrophage classification
mononuclear phagocyte/ sentinel cell/ antigen presenting cell
macrophage lineage
myeloid
macrophage appearance
round nucleus, clear-vacuolated cytoplasm, irregular cell shape
macrophage location in health
peripheral tissue
lifespan of macrophages
months
primary function of monocytes
immune surveillance, moderate antimicrobial capacity, LIMITED antigen presentation, tissue remodelling ** critical in healing (clean up crew)mo
macrophage mechanism of action
detection of threats and release of inflammatory mediators/phagocytosis/enddocytosis
compare macrophage phagocytosis vs antigen presenting capabilities
BEST at phagocytosis, LIMITED antigen presentation
macrophages in connective tissue
histocytes
macrophages in liver
kupffer cells
macrophages in spleen
splenic macrophages
macrophage equivalents in the CNS
microglial cells
macrophages in airways
alveolar macrophages
macrophages in peritoneal cavity
peritoneal macrophage
macrophages in bone
osteoblasts
macrophage roles
immune surveillance, immune activation and immune effector function
describe macrophages role in immune activation
release cytokines and chemokines after activation; acute phase response
describe macrophage role in immune effector function
- phagocyte - engulf and destroy pathogens
- trapping of pathogens in granulomas
- remove dead/damaged cells
classification of dendritic cells
sentinel cell/ antigen presenting cell
dendritic cell lineage
myeloid
dendritic cell appearance
round nucleus, clear cytoplasm, irregular shape with long branched projections (dendrites)
dendritic cell location in health
tissue
dendritic cell lifespan
months (long lived!)
dendritic cell primary function
immune surveillance, antigen presentation (innate and adaptive bridge)
dendritic cell mechanism of action
threat detection and release of inflammatory mediators/ endocytosis (phagocytosis)
what are APCs, which cells are considered these
Potent antigen presenting cells: after capturing antigen by phagocytosis, migrate to lymphoid organs where they present antigens to T-lymphocytes, express many pattern recognition receptors (PRRs)
Dendritic cells! - these are the best at antigen presenting!!
Langerhans cells are..
dendritic cells in skin: epidermis and mucous membrane
interstitial dendritic cells reside in…
organs: ex. heart, lung, liver, kidney, GI
interdigitating dendritic cells are
T-cell areas of secondary lymphoid tissue and thymus
Mast cell lineage
myeloid
mast cell appearance
round nucleus, cytoplasm is densely packed with granules (purple)
mast cell location in health
tissue, particularly connective tissue surrounding vasculature and nerves + lamina propria of the mucosa
lifespan of mast cells
weeks- months
primary function of mast cells
immune surveillance, mediator of inflammation and allergy
mast cell mechanism of action
detection of threats and release of inflammatory mediators (vasoactive amines) via degranulation or synthesis of lipid mediators and cytokines
describe degranulation of mast cells
short time to release granules (can produce inflammation within seconds to minutes) because granules are preformed
describe the purple cytoplasmic granules of mast cells
- potent inflammatory mediators rapidly released
-histamine: vascular dilation and permeability (inflammation) - proteases: cause tissue dmg
What molecules are produced and SLOWLY released by mast cells
- arachadonic acid metabolites: leukotrienes, prostaglandins, platelet- activation factor
- cytokines: TNF-alpha, IL-6,IL4,IL5,IL13
mast cells have a surface expression receptor for…
IgE: allergens binding to IgE trigger degranulation and allergic response
Natural killer cells are also known as…
Null lymphocytes, large granular lymphocytes
Natural killer cells are classified as
lymphocyte
natural killer cell lineage
lymphoid
natural killer cell appearance
large lymphoid cell, round nucleus, azurophilic cytoplasmic granules (granzyme, perforins)
nautral killer cell location in health
blood, spleen
lifespan of natural killer cells
weeks-months
primary function of natural killer cells
destruction of virally infected or abnormal (tumor) host cells
natural killer cell mechanism of action
recognition of virally infected or abnormal host cells and targeted release of cytotoxic granules
NK cell roles
- kill tumor and virus infected cells
- monitors expression of MHC 1 (self marker) (kills cells with low MHC 1/ altered MHC 1 expression
- induced apoptosis
releases enzymes that punch holes in cell membrane (granzyme/ perforins)
T/F: NK cells lack immunologic specificity and memory
true!
where do NK cells mature
secondary lymphoid tissues
location of lymphocytes
blood (20-40& of WBCs), lymph (99% of WBCs)
- lymph nodes, spleen, mucosal lymphoid tissue
lymphocyte 3 main subtypes
T-cells (T-lymphocytes)
B cells (B-lymphocytes)
Null cells (NK cells)(innate)
where do B-cells originate and differentiate
originate in bone marrow, differentiate in Bone Marrow
where do T cells originate and differentiate
originate: bone marrow
differentiate: thymus
when are lymphocytes naive up until
naive until they encounter specific antigens in peripheral lymploid organs (educated but need to find antigen to mature)
what do T lymphocytes (T cells) differentiate into
CD4+ or CD8+ T cells
where do CD4 and CD8+ cells reside
paracortex of lymphnodes and periarteriolar sheath in spleen
60-70% of circulating lymphocytes are…
T-cells!
Helper T-cell function q
(Th-cells)(CD4+) activate B cells and macrophages
cytotoxic T-cell function
(Tc-cells)(CD8+) kill virus infected cells, cancer cells
membrane T-cell receptors (TCR) function
only recognize one antigen bound to an MHC 1/II molecule
regulatory T-cells (Teg-cells) (typically CH4+)
dampen (immune?) responce
memory T cell function
(CH4+ and CD8+) important for vaccines, live for years
B cells/ B lymphocytes are named after…
bird B cells that mature in the bursa of Fabricius
where do B cells mature in mammals
Bone marrow
where do B cells reside
follicles in cortex of lymph node, white pulp of spleen, tonsils and GI tract
what percentage of circulating lymphocytes are B-cells
10-20%
where are B cell receptors found, what do they interact with
B cell receptors are membrane bound antibodies, they interact with antigens and T cells to become activated
activated B cells mature into…
Plasma cells and memory B cells
function of plasma cells
produce antibodies
examples of antibodies that plasma cells produce
IgM, IgA, IgG, IgE
where do plasma cells reside
tissues or lymphoid organs: medulla of lymph nodes, bone marrow, mucosal associated lymphoid tissue
which arm of the immune system are plasma cells responsible for
humoral arm of the adaptive immune system
what percentage of total leukocytes do neutrophils account for
50-70%
what percentage do monocytes account for in total leukocytes
10%
normal or not normal: lack of neutrophils in a blood smear
not normal, will become prone to infection
cyclic neutropenia is caused by a mutation in which gene
gene encoding the protein AP3beta1: interrupts trafficking of certain proteins needed during some stages of hematopoiesis (particular myeloid)
what happens in cyclic neutropenia in gray collies
cycles of neutrophil depletion that coincide with increased susceptibility to many types of infections, especially bacterial infections
describe primary lymphoid organs
sites for lymphocyte development and maturation (lymphocytes become immuno-competent)
name 2 sites of primary lymphoid organs in mammals and one in birds
Thymus
Bone Marrow
Bursa of Fabricius (Birds)
describe secondary lymphoid organs
peripheral: site for trap antigen and mature lymphocytes interact to mount the immune response
name 3 secondary lymphoid organs
lymph nodes, spleen, mucosa-associated lymphoid tissue (MALT)
where does hematopoiesis begin in embryos
yolk sac and aorta-gonad-mesoneprhos
where can mature HSC in fetus’ be isolated from
yolk sac, placenta and liver
are HSCs found in the bone marrow early or late in fetal development
late
when do HSCs populate the bone marrow
post natally
in the bone marrow, where can hematopoietic precurssor cells be found
enmeshed in a fine stromal network with small pockets of concentrated growth factors
where do B lymphocytes develop and mature?
in bone marrow stromal cells
what is the significance of stromal cells
facilitate hematopoietic stem cells proliferation, direct migration and differentiation
where does b cell maturation also occur for cattle and sheep mostly
ileal peyer;s patches
describe the location of development and maturation of T cells
develop initially in bone marrow then migrate to thymus to achieve full maturity
compare development of thymocytes in the thymic cortex vs medulla
cortex of thymus: matures and selects for immunocompetent T cells
medulla of thymus: involved in secondary T cell selection
immunological significance of the Bursa of Fabricius in birds
confirms B cell immunocompetence
significance of secondary lymphoid organs
where the immune response is initiated: lymphocytes encounter antigens, become activated, undergo clonal expansion and differentiate into effector cells
where do lymphatics drain to
thoracic duct, subclavian vein and heart
in lymphnodes, what is the B cell zone
follicle along the CORTEX
in lymphocytes, what is the T cell zone
PARACORTEX
where are macophages and dendritic cells located in lymphnodes
in the inner most medulla
