Physiology of Normal White Blood Cells Flashcards
Leukopoiesis
form of haemotopoiesis that forms WBCs
Haematopoiesis
Myeloid cells are innate immunity.
True or False?
True
Granulocytes:
- names of cells
- nuclei features
- function
- contain
- neutrophils, eosinophils, basophils,
mast cells - nuclei have many lobes
- innate immunity
- contain cytoplasmic granules that
carry proteins and other molecules
essential for the immune response
to infection
pAPCs are
- professional antigen presenting
cells - monocytes, macrophages, dendritic
cells
Lymphoid cells are adaptive immunity.
True or False?
True
Haematopoiesis
White blood cells numbers table (the pictures are more important)
White Blood Cell Receptors are called
- Pattern Recognition Receptors
(PRRs)
PRRs
- pattern recognition receptors
- present on all myeloid white blood
cells - their ligands are Pathogen
Associated Molecular Patterns
(PAMPs) - and Damage Associated Molecular
Patterns (DAMPs) - also present in skin cells, epithelial,
mucosal, vascular endothelial,
fibroblasts - eg Toll like receptors
- essential for the recognition of a
variety of microorganisms and
pathogens by the myeloid WBC and
initiation of the immune response
What % of WBCs do monocytes make up?
2-12%
Monocytes
- enter circulation as monocytes
(patrolling monocytes) - can migrate to tissues
(inflammatory monocytes) - and differentiate into macrophages
in response to infection
Tissue Resident Phagocytes:
- can be macrophages
- do not circulate but carry specific
phagocytic functions and continue
to act as pAPC - eg: Kupffer cells (liver), microglia
(nervous system)
Macrophages
- bridge between adaptive and
innate - pAPCs
- antigen presentation after a
macrophage has come in contact
with a pathogen, is achieved
through the MHC II molecules - Fc receptors on macrophages:
opsonisation, the enhancement of
antigen recognition through
antibody binding, significantly
increases rate of phagocytosis
Monocytes have a short half life, tissue macrophages are ———
self-replicating and have a much longer life span (months or years)
Toll Like Receptors interact with
MyD88 protein
activates a signalling cascade leading to inflammatory cytokines and inflammation
Macrophage receptors
LPS receptors:
- stands for
- found on
- recognises
- liposaccharide receptor
- on macrophage
- recognises bacterial cell wall
liposaccharides
Scavenger Receptors:
Neutrophils:
- short life span (hours)
- in infection neutrophils:
- release signalling molecules
that will reach the bone
marrow and initiate the
production of more
neutrophils
- phagocytose infect patho
- tissue remodelling (elastin and
collagen fibres) leading to
wound healing and repair
Which cytokine causes migration of neutrophils? Which cells produce this cytokine?
Interleukin 8
macrophages, dendritic cells, endothelial cells
Neutrophils are essential for resolving —— infections. They kill microbes ———————-.
- fungal
- inside phagosomes with ROS
(reactive oxygen species) and
hydrolytic enzymes
What is the main component of pus?
Neutrophils
Phagocytosis
pathogens are killed inside phagosome due to low pH, activity of lysosomal enzymes, ROS (neutrophils) and NO (macrophages)
Eosinophils
- characteristic granules
- defence against parasites
- circulate in the blood and migrate
to tissues - abundant in the small intestine
- IgE (FcepsilonR) contribute to
allergy and asthma - release signalling molecules which
influence the adaptive immune
response
Basophils
- contain histamine granules
- histamine is released in response
to basophils binding to
antibody/antigen complexes - histamine increases blood vessel
permeability and allows immune
cell in circulation to enter the site of
infection - release signalling molecules
- in abscence of infection, release of
histamine is linked to allergy
symptoms
Mast cells
- immature mast cells leave the bone
marrow and circulate in the blood - released to tissues, where they
mature - mast cells can be found in the skin,
connective tissue, mucosal
epithelial tracts, and resp and GI
tract - contain granules with histamine
and are contributors to the allergy
response
Dendritic Cells
- resemble dendrites
- capture antigens by phagocytosis
and internalise those through r
eceptor mediated endocytosis,
followed by subsequent
presnetation fo the antigen to other
immune cells (T cells) - links innate and adaptive
- antigen presenting function can
cuase their migration to lymphoid
organs once an antigen has been
captured
Lymphocytes (T, B, Natural Killer)
- T cells have T cell receptors
- T cells are either cytotoxic or
helpers - B cells are lymphoid pAPCs and
present to T cells - B cells can mature to antibody
producing plasma cells - both interact with pAPCs
- natural killer cells contain a varierty
of antigen recognition receptors as
well as cytotoxic granules that kill
target cells
Inflammation overview
Mechanisms of Inflammation
- basophil receptors recognise
PAMPs and DAMPs and release
histamine as a response - PRRs on tissue resident dendritic
cells and macrophages initiate the
signalling cascade to release pro-
inflammatory cytokines for
neutrophil recruitment - circulating leukocyte adhesion to the vascular endothelium is essential in their recruitment and tissue migration
- achieved through cell adhesion
molecules CAMS: selectin, integrin
Excessive inflammation can lead to
sepsis, which is can lead to septic shock
- blood infection involving gram negative and gram positive bacteria
- activation of TLR4 receptor and
other PRRs causes an increaded
production of cytokines and
increased vasodilation
Regulation of inflammation (3):
- IL-10: anti-inflammatory cytokine
produced by macrophages, inhibits
inflamm cytokines and promotes
wound healing - negative feedback loops involving proteins that act in the PRR signalling pathways (MyD88)
- inhibitors of inflammtory cytokines TNF alpha and IL-1 beta in the form of soluble receptors can sequestrate excess cyotkines
Acute vs Chronic inflammation
Artherogenesis Steps:
- endothelial dysfunction
- macrophage adhesion
- smooth muscle migration
- fibro/lipid plaque
- inflammation
Macrophages in atherogenesis
- blood circulating monocytes can ingest oxidised LDL through SCAVENGER RECEPTROS
- these monocytes can migrate to subendothelial tissue and differentiate into macrophages that accumulate oxidised LDL becmoing FOAM CELLS
- foam cells cna rupture releasing their molecular content, incluuding chemokines, recuiting more monocytes, ampkifying the inflammation process around the endothelilal lesion
Atherosclerosis Risks
