Week 1 Flashcards
What are mature leukocytes divided into
-Precursor cells
- function
-Site of maturation
-Morphology done by Automated Cell Counters & PBS Morphology
-Cell surface markers -Ags identified by Flow Cytometry
how do surface markers identify cell types
-they act as receptors or signal transducers and are able to ID cell types by
Species
-Lineage: CD3 = T lymphs, NK & B cells dont have CD3
-Maturation Stage: Immature T thymocytes = CD4- AND CD8- . Then mature into “+” and are only one or the other
-State of activation: B cells = CD20+, Plasma cells = CD20-, Activated T cell = CD56 (intercellular adhesion molecule)
What is part of WBC development
Colony forming units = progenitor cells
Hematopoietic Stem Cells -HSC
-Pluripontential. They can divide, differentiate or die. Can be a progenitor cell (myeloid/lymphoid)
Progenitor Cells. Either a myeloid or lymphoid
What controls hematopoiesis
Cytokines
Colony Stimulating Factors
Interleukins
How do cytokines control hematopoiesis
they are low molecular weight proteins that help to stimulate or inhibit differentiation, movement, growth and leukocyte production
How do CSF - colony stimulating factors help control hematopoiesis
-promote division and differentiation of progenitor cells
-it is a cytokine
how do Interleukins help to control hematophoiesis
-biological activities, and targets
-it is a cytokine
How do neutrophils develop and mature?
-3 different pools in bone marrow
-share progenitor with monocytes (granulocyte-monocyte-progenitor - GMP)
-production is stimulated by cytokine G-CSF
-released into PB when mature and travel by PB until they are required in tissue. If not needed they die by apoptosis (removed by macrophages) and if needed their lives are prolonged by cytokines
What are the 3 pools of developing neutrophils in bone marrow
Stem Cell pool - HSC - self renewal
Proliferating pool BM = myeloblast, promyloblast, myelocyte . Division in 6 days with 5 division. Committed cells CFU GEM,
Maturation and Storage pool BM- Metamyelocyte, band, segmented neut . Maturation in 6 days. No longer divide. Maturation only . Reserve for release. Stimulated by G-CSF into…
Marginal and Circulating Pool (BLOOD)= neutrophils . Released into blood after stimulated by G-CSF with 7 hour half life and then leave the blood to go into tissues half life depends on if they are acting on infection
What is part of the peripheral blood pool
Circulating pool / Marginating pool (in walls of capillaries and tissues) (total blood granulocyte pool)
-Mobile when mature
-cells can move between the two pools
-no difference in function
-MGP - larger portion
What is neutrophil mobility like in MP and CP
MP
-adhering to vessel endothelium
-go into tissue in response to chemotaxis
-when extra granulocytes are needed like in infection theyll be first.
-through diapedesis
CP
-circulate until they enter tissues randomly
What is a myeloblast
-least amount found
-dividing neutrophil stage
-high N:C 8:1/4:1
-very little cytoplasm
-cytoplasm is basophilic
-2-4 nucleoli
-no visible granules or few 1ary azurophilic granules
-expresses CD13, CD33, CD34 on surface
What is a promyelocyte
-dividing neutrophil stage
-lots of azurophilic 1ary granules
-bigger than myeloblast
-round central nucleus
-1-3 nucleoli
-chromatin starts to clump
-hoff perinuclear halo but not seen in leukemias
What is a myelocyte
Early vs late
has 1ary and 2nadry granules
-cytoplasm starts to get a little pink
-CAN DIVIDE
Early
-just like a promyelocyte but 2ndary pink granules start to be seen at golgi apparatus (dawn of neutrophilia)
-2ndary granules spread until the cytoplasm is lavendar
-with each division of cells there is a decrease of 1ary granules
Late
-smaller than promyelocytes
-clumped nucleus
-cant see nucleoli with a microscope
What are metamyelocytes
-NO DIVISION
-2dary granules
-pink cytoplasm
-clumped chromatin
-kidney bean or peanut like nucleaus - AWAIST
-no nucleoli
-bigger than myelocyte
-cytoplasm has very little RNA so no basophilia
What is the band neutrophil stage
-NO DIVISION
-no RNA
-highly clumped nucleus
-indent is more than half of the nucleus (U on the side)
-no segmentation
What is the function of neutrophils
-major is phagocytosis; destroy foreign orgs, bacteria, fungi and yeast
-part of innate immune system
-complement receptors
Seeking:
-Chemotaxis - recruitment to inflammatory sites - attracted by chemokines
-Migration/Motility - peri or trans cellular (between or through)
-Diapedesis - Anaphylatoxin helps to increase vascular permeability helping diapedesis
Use all this to move toward they chemokines. Then start destroying when they reach the site of infection
Destroy
phagocytosis - engulf
digestion
How does phagocytosis from neutrophils work
Recognition and Attachment - using receptors to bind foreign molecules and opsonin’s
Ingestion - by pseudopodia encloses foreign particle in a phagosome. Grabs and pulls using actin and myosin
Killing and Digestion
Oxygen dependent - needs NADPH, h2O2
Oxygen Independant - pH goes from alkaline to neutral allowing the digestive enzymes to work . Lysosomes bind to phagosome
Formation of neutrophil extracellular traps
Dissolving of nuclear membranes and cytoplasmic enzymes attach to DNA ; they both rupture and bacteria eats the DNA
Where do eosinophils released from and circulate in
-Common myeloid progenitor
-mature in BM pools
-released into PB
-circulate and travel into tissues
-some travel into thymus
-18 hour half life but prolonged in eosinophilia in blood , 2-5 days in tissues
-cytokines, chemokines , lipid bodies
What is the function of an eosinphile
Immune regulation
-release preformed cytokine by acting as AG presenting cells promoting T cell proliferation
Allergic reactions
-more eos the worse the reaction
-Chrons
Parasitic Infection (helminths)
-parasites are destroyed with secretions of Major Basci Protein, Cationic protein and Reactive Oxygen Species -h2o2
-prevent reinfection
-hallmark of allergic reaction
how do eosinophils degranulate
Classical (fuse with PM) and Compound (fuse with each other THEN PM) Exocytosis - granules merge with plasma membrane
Piecemeal degranulation - removal of proteins from granules by vesicles then fuse to PM to empty proteins in extracellular space
cytolysis - deposit intact granules to tissue through cell death
What are the granules in eosinophils
Major Basic Protein
Eosinophil cationic protein
Peroxidase
Lysozyme
Catalase
GM-CSF
Interleukins (cytokines)
Where are basophils produced and found in
<1%
-True luekocytes because they mature in the BM and circulate in the PB have granules
-develop and mature in BM
-released in PB for a short time and move into tissues
-found in blood, spleen, or site of tissue inflammation
-production linked to Mast cell (tissue cells NOT the same cells)
What is the function of a basophil
-found in hypersensitivity reactions
-production based on activation signals
-contain histamine, IL-4, -13, endothelial growth factors
-release cytokines
-regulate Th cells
-induce B cell IgE synthesis
-initiate allergic reaction by releasing preformed cytokines
-part of innate and adaptative immunity
have 2ndary granules
-produce heparin sulfate
What are mast cells
- NOT a leukocyte because the use the blood as a transit system to access the tissues to mature
-tissue effector and not inflammatory reactors
-progenitor start in BM and spleen but when released they head into the tissues (gut and lung) to mature
-effector cell in allergic reaction by releasing lipid mediators , crosslinking IgE on surface
-APR
-enhance and suppress immune system
-gatekeep mucosal surfaces
-mediate innate and adaptive immune system
Mononuclear cells
Mono production and function
-develop in BM
-NO STORAGE POOL IN BM
-released into immediately PB when matured
-pool of immature monos in spleen responding to tissue injury like MI
-circulating and marginal (bigger) pool in blood
-seen in blood before neutrophils when BM recovers from marrow failure = monocytosis
-3 days in marginal pool
why is monocyte development similar to neuts
What helps with mono growth and differentiation
What the are morphological mono stages
-both neuts and monos come from a GMP
-M CSF is the cytokine that is responsible for growth and differentiation
-stages are monoblast, promonocytes, and monocytes
What are the functions of monocytes
Innate immunity
Adaptive immunity
Housekeeping
Monos have different chemokine receptors on them and target tissue depends on pattern of chemokine receptors
What is monocyte/macrophage function in innate immunity
-recognize bacterial pathogens
-stimulate inflammatory cytokine production and phagocytosis
-Macros alone make NO which is cytotoxic to viruses, helminths, tumor cells
-both have Fc receptors and complement receptors which help to break down organisms coated with AB
What is the adaptive immunity function of Monos/Macros
- Marcos are APC
-activate T and B lymphs to start adaptive immune system
-eat foreign material and displays the peptide on the membrane to show T lymphs
What is the housekeeping function of monos/macros
-remove dead cells from site of infection
-destroy senescent RBC
-maintain storage pool of iron for erythropoiesis
-make coag factors, complement components, IL, GF and enzymes
What are the three large groups that lymphs are divided into
T Cells = adaptive immunity
CD4 helper T- activates macros adn B cells by cytokine secretion
CD8 cytotoxic T - Releases chemicals to kill infected cells, tumor cells
B Cells = adaptive immunity
Produces AB , blocks infections
NK Cells = innate immunity , small amount of lymphs
Releases chemicals to kill infected cells, tumor cells
What are two subdivisons of lymps
ones that participate in
Humoral Immunity
-AB producing B Lymphs or B cells
-B cells develop in BM
Cellular Immunity
Attack cells directly
T cell -develop in thymus
NK cells - both BM and thymus
What is lymphopoiesis
-all 3 originate in BM
-for B and T cells there are AG independent and AG dependent stages
-B cells develop in BM to naive B cells that move into lymphoid tissue
T cell lymphoid progenitors go from BM and develop in thymus
NK cells develop in either location
AG Independent development in BM and thymus - primary organs
AG dependent - spleen, tonsil, peyers patches - 2andary
What is the function of lymphocyte and how are they different from other leukocytes
-not end cells; resting cells when they are stimulated they divide into memory and effector cell
-recirculate from blood to tissues and back to blood
-B and T lymps can rearrange AG receptors
-early lymp progenitor originate in BM,
T and NK lymphs develop and mature outside the BM
What are the three stages of B lymp development
-start in BM and go through 3 stages Pro-B, Pre B, Immature B cell (AG naive B cells)
-each stage a unique IgG AG receptor is produced
-immature Naive B that havent been exposed to AG leave BM and move to 2ndary lymph organs (lymph nodes)
pre b - B Lympblast - B cell - plasma cell
cant tell the difference between resting B and resting T cells
What happens when B cell come in contact with AG in 2ndary lymphactic organs
-cell division
-production of memory cells and effector cells
-Naive b cell go through mitosis repeatly to form immature B cell clone lymph node cortex
-when exposed to AG the cells transform, proliferate and migrate into medulla
-activated B cells become memory cells or plasma cells
What is the function of B cells
-Activated T cells are needed to expose the B cells to AG in lymph organs
-B cells turn into plasma cells to produce Ig or AB or memory cells
-plasma cells are not found in PB ,
-Ig is produce in tissues
-APC to T cells
What does a plasma cell look like
Eccentric nucleus
nuclear halo
very basophilic cytoplasm
Plasmacytoid lymph like a plasma cell but with higher N:C ratio
Where do t lymphs develop
what are their stage and what do they produce
-develop in thymus
-lymp progenitor cells moe from BM to thymic cortex
-3 stages: Pro T, Pre T and Immature T
-each phase T cells produce unique T cell receptors
-T cells with receptors that react with self AG are allowed to undergo apoptosis
What are the two subdivisions of T cells
PRESENCE OR ABSENCE OF CD4/CD8
-immature t cell move to medulla in thymus where apoptosis of self reactive T cell happens
-remaining immature T cells or AG naive T cells leave thymus and move to 2ndary lymp organs
-if they come in contact with AG in 2ndary spaces there will be production of memory, effector or both T cells
-T cell make up most of circulating lymphs 51-88%
What causes the formation those large lymphs that we see
-transformation from resting lymp to activated , they also have more cytoplasm but only make up 10% of lymphs
t cells have longer life span
What is T cell function
Secretes compounds that act directly - poison to kill cells attached to sensitized T cells
Secretes compounds that act indirectly
Attracts macrophages to cells
Activates macros for quick phagocytosis
What are CD4+ t cells
Helper T cells
HTC 1 = immune response against INTRAcellular pathogen
HTC2- defense against EXTRAcellular parasites and helminths
HTC2- important in asthma and allergic reactions
HTC17- immune responses against extracellular bacteria and fungi
Treg (CD4+ CD25+) regulatory
-regulate immune response
-maintain self tolerance
-suppress T/B cells activity with chemical release
-stop immune response to prevent uncontrolled activity aka suppressor cell
What are CD8 + cells
Cytotoxic cells
-kill target cells by releasing granules containing granzyme and perforin
-kill by apoptotic pathway activation
Cytotoxic T lymphs
What are NK lymphs
-part of innate immunity
-kills tumor or viral cells without sensitization
-recognize that there is no self AG on intruders surface
-kill by releasing perforins
-modulate function of macros and T cell
SEEN IN PB AS LARGE GRANULAR LYMPH
