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Hematology > Lecture 4 - dont study > Flashcards

Lecture 4 - dont study Flashcards

1
Q

what is the reference range of leukocytes and how many types do we study from the PBS

A

3.6-10.6x10^9/L

we look at 5 basic types in wrights stain

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2
Q

how are leukocytes identified

A

-through antigen typing - they have surface antigens s
-surface antigens are confirmed with antibodies are tagged by a detection system reaction with cell membrane proteins

-by immunophenotyping of blood cells by membrane antigen
-detected using fluorescent dyes or enzymes
-based on CD# or cluster of differentiation
-CD34= stem cell can make CD4 = helper t lymph, CD 8 = cyto toxic tlymph, and cd3 - activated t lymph
-flow cyto - in hem
-immunohistochemistry

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3
Q

where do leukocytes develop from

A

-hemaotopoietic stem cells in the bone marrow
- after differentiation and maturation they are released into peripheral circulation and then into tissues via kinetics

-the number of circulating cell lines varies based on gender, age, ethnicity, and state of leukocytes (stresses)

-their main function is mediating immunity (ADAPTIVE OR INNATE)

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4
Q

how do leukocytes act in innate immunity

A

NON SPECIFIC

-cells that defend against other orgs
-recognize and respond in generic manner
-does NOT provide long lasting immunity

PHAGOCYTOSIS BY NEUTROPHILS, MONOCYTES AND MACROPHAGES

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5
Q

how do leukocytes act in adaptive immunity

A

SPECIFIC

-specialized cells that eliminate pathogens or prevent their growth
-creates immunological memory to specific pathogen
-enhances response to subsequent exposure

PRODUCTION OF ANTIBODIES TO SPECIFIC ANTIGENS BY LYMPHOCYTES AND PLASMA CELLS

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6
Q

neutrophils and monocytes have common progenitor

GMP

G-CSF

M CSF

A

-neutrophils and monocytes have common progenitor - GRANULOCYTE- MONOCYTE PROGENITOR -GMP

G-CSF- granulocyte -colony stimulating factor - major cytokine responsible for stimulating NEUTROPHIL production

M-CSF -major cytokine responsible for stimulating Monocyte production

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7
Q

Eosinophils and Basophils share
a common progenitor

A

Eosinophils and Basophils share
a common progenitor called EOSINOPHIL- BASOPHIL PROGENITOR EBP

Interleukin-3, -5 (IL-3 and IL5) and GM-CSF- cytokines responsible for stimulating eosinophil production

Interleukin-3 (IL-3) and Thymic stromal lymphoprotein (TSLP)– cytokine responsible for stimulation of basophil production

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8
Q

what happens as a granulocyte matures

A
  • the N:C ration decreases

-nuclear chromatin gets coarser a and the nucleoli disappears
-the nucleus starts to change shape
- cytoplasm starts to get less blue
-presence and type of granules - none, primary or 2ndary

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9
Q

how do Promyelocyte look?

A

-high n:c ratio 3:1
-large round oval nucleus
-fine chromatin - small clumps
-more cytoplasm than a blast
-blue/basophilic cytoplasm
-ABUNDANCE OF PRIMARY GRANULES RED OR AZUROPHILIC (non specific with anti bacterial properties)
-1-3 nucleolus
-divides
-HAS PRIMARY OR NON SPECIFIC GRANULES
BIGGER ONE

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9
Q

how do myeloblasts look ?

A

-high n:c ratio 4:1
-large round oval nucleus
-multiple nucleoli
-fine chromatin - no clumps
-little cytoplasm
-blue/basophilic cytoplasm
-absent or 20 primary granules
-2-5 nucleolus
-divides

BIGGER ONE

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10
Q

what does a Myelocyte look like

A

-n:c ratio depends on cell line
-round to OVAL nucleus- can be flat or a weird
-nucleoli not visible -FAINT
-more clumped than pro
-cytoplasm less basophilic -pink lavender
-loss of primary granules
-SECONDARY OR SPECIFIC GRANULES APPEAR IN THE CYTOPLASM (eos, baso, neut)
-gradual transition from pro - myelocyte (there are early and late myelocytes)
-LAST DIVIDING STAGE
-the number of 2ndary granules increases as the cell matures
-if you say myelocyte ALONE then it refers to the neutrophilic cell line
-has a FOCAL PERINULEAR CLEARING

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11
Q

what appears in a neutrophilic myelocyte

A
  • DAWN OF NEUTROPHILIA
    -appearance of secondary granules in Golgi apparatus area
    -2ndary granules give the neut cytoplasm a LAVENDER pink colour
    -these granules increase in number and spread throughout the cytoplasm as the cell matures
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12
Q

what appears in a metamyelocyte

A

n:c ratio depends on the cell line
-indented nucleus in the shape of a kidney bean or peanut
-nucleoli are not visible
-moderately clumped
-cytoplasm only has 2ndary granules with very little basophilia
-FOCAL PERINULEAR CLEARING IS COMMON

NO MORE DIVISION

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13
Q

what do band cells look like

A
  • n:c depends on the line
    -nuclear indentation is greater than 1/2 the width of the nucleus (pinched but not segmented)
    -nucleus is thin sausage shaped S or C - BUBBLE LETTERS
    -chromatin coarse clumped
    -abundant 2ndary granules
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14
Q

What are the stages (pool) of Neu maturation

A

-neuts most numerous in Bone Marrow and Peripheral blood
-Neuts in BM released into the peripheral blood

1) - Stem cell pool - self renewing, pluripotent stem cells - Hematopoietic stem cell
2)Proliferation (MITOTIC) pool - consists of cells that are dividing CMP-GMP-MYELOBLAST- PROMYELOBLAST- MYELOCYTE
3) Maturation (storage) pool - cells that are undergoing maturation make up the BM reserve are ready for release - METAMYELOCYTE TO MATURE NEUTROPHIL

-stages earlier than Band neut are not normally found in the PB earlier form may be seen in severe leukemia (only metamye or myelo)
-infection severity in indicated by increase in band forms - report under LEFT SHIFT

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15
Q

PATH from stem cell pool to myeloblast

A

stem cell pool - cmp with IL3 - to GMP with GM-CSF - to myeloblast with IL3, GM-CSF, G-CSF

16
Q

what is the function on neuts in the PB

A

–innate immunity
-phagocytosis and destruction of foreign material and microorganisms
-half CIRCULATE free in CIRCULATING POOL while the other half adhere to the vessel wall in Marginal (capillary walls of liver, spleen , and lung)
-in PB the half life is 7 hours then they migrate into tissues where their half life can be a few hours or longer if they are fighting infection /inflammation

17
Q

what is the function of neutrophil granules

A

-lysosomes containing many proteins and enzymes
-lysosomes can merge with phagosomes to kill engulfed bacteria

Primary granules in Pro & early Myelocytes
‒ Myeloperoxidase
‒ Defensins
‒Elastase

secondary, tert and scretory granules from late myelo or segmented nuet stage have
‒ Lactoferrin
‒ Alkaline phosphatase
‒ Lysozyme
‒ Gelatinase

18
Q

what is the function of eosinphils

A

-no phagocytosis
–half life of 18 hours
-secrete cytokines to stimulate other cells like antigen presenting cells to promote proliferation of T cells
- initiate type 1 or type 2 immune response

-can be increased in parasitic infections - kills Helminths via secretion of 2ndary granules

-increased allergic reactions (hallmark finding)
-best studied in asthma
-eos can invade and damage through degranulation the respiratory and GI tract mucosa

19
Q

what is the function of eosinophil granules

A

-eos can form 1mary , 2ndry granules, small lysosomal granules, lipid bodies and storage vesicles

-release granule content into extracellular spaces (degranulation -MBP CATIONIC PROTEIN AND GROWTH FACTOR NGF

-2ndry granules have various enzymes and presynthesized proteins like cytokines or chemokines
-MAJOR BASIC PROTEIN, ACID PHOSPHATASE, LYSOZYME, CATALASE, GM-CSF

20
Q

what is the basophil function

A

-poorly understood function - it will enter the tissues via PB with half life of 60 hours

–2ndary granule contents not fully understood but production is changed based on activation signals
-has histamine , IL3, IL4, vascular growth factors , HEPARIN SULFATE
-can release large amounts of cytokines
-regulate T2H cells and indue B cells to produce IGE
-initiates allergic inflammation and in hypersensitivity reactions

Mast cells are similar - tissue effector cells of allergic and inflammatory reactions
they enter a mucosal surface from BM before maturing

21
Q

monocytes in BM, PB and PB TO TISSUE

A
  • in BM there are few monocytes
  • no storage pool and are released in PB right after maturing
    -reservoir of immature mono in spleen

in PB - there is a pool along vessel walls - small circulating pool

PB to Tissue - migrate to lots of tissue sites and turn into MARCOPHAGES
liver, spleen, lungs , skin, intestines BONE MARROW

22
Q

what are the resident macrophages in
Liver
lungs
brain
skin
spleen
intestines
peritoneum
bone
synovial
kidneys
reproductive
lymph nodes

A

Liver - KUPFFER CELLS
lungs - ALVEOLAR MACROS
brain - MICROGLIA
skin -LANGERHANS CELLS
spleen -SPLENIC MACRO
intestines -INTESTINAL MACRO
peritoneum -PERITON MACRO
bone -OSTEOCLASTS
synovial-TYPE A CELL
kidneys - RENAL MACRO
reproductive - REPROD ORG MAC
lymph nodes - DENDRITIC CELLS

23
Q

what does a macrophage look like

A

-bigger than monocyte
-oval eccentric nucleus
-reticulated chromatin
-vacuolated cytoplasm - with debris of phagocytized cells or orgs

24
Q

Monocyte/Macrophage Function in innate immunity, adaptive and housekeeping

A

INNATE Stimulate phagocytosis and release cytotoxins (for
example, nitric oxide) against:
‒ Bacteria, Viruses
‒ Fungi, Parasites
‒ Tumor cells

Adaptive Act as an antigen-presenting cell by exposing Activate B-Lymphs and T-Lymphs to initiate adaptive immune response

Housekeeping
Destruction of senescent RBCs
● Removal of debris or dead cells
● Maintenance of iron storage pool for erythropoiesis
● Synthesis of proteins (such as, coagulation factors, complement components, interleukins, growth factors, and enzymes

25
Q

what are they 3 group divisions of lymphopoiesis

A
  1. B cells (adaptive immunity)
  2. T cells (adaptive immunity) - MOST
  3. Natural Killer (NK) cells (innate immunity)
    ‒ Only a small % of Lymphs are NK
    ● Lymphocytes make up 20- 40% circulating WBCs
26
Q

what are the two FUNCTIONAL CATEGORIES that lymphs can be put into

A
  1. Produce antibodies (Humoral Immunity):
    ‒ B cell Lymphocytes
  2. Attack foreign organisms or cells (Cellular immunity):
    ‒ T cell Lymphocytes
    ‒ NK cells
27
Q

how does B cell maturation take place

A

-lymphoid progenitors develop in the BM (they are not exposed to antigen but have IG antigen receptors)

-these cells then travel into 2ndry lymph orgs like germinal centerss of lymph nodes) where the cells are then exposed to antigens - look like resting lymphs

-after being exposed to antigens they transform into plasma (EFFECTOR ) cells and memory cells

-essential for antibody production and presenting antigens to T cells

28
Q

what is a plasma cells

A
  • final stage of B cell lymph differentiation
    -produces IMMUNOGLOBULIN OR ANTIBODIES against antigens
    -NOT SEEN IN PB unless in disease state
  • on PBS oval cell, round nuc, perinuclear hof (halo), dark blue cytoplasm

-in PBS you can see B cells that have transformed with dark blue cytoplasm called PLASMACYTOID LYMPHOCYTE

29
Q

how does T cell maturation take place

A
  • lymphoid progenitors migrate from BM to thymus
  • cell MATURE in thymus by making t cell receptors or surface markers unique to each T cell
  • t cells then MIGRATE to 2NDARY LYMPH ORGS or pb where they are exposed to antigens causing activation, transformation into memory cells or effector T cells
30
Q

what to T lymphs look like

A

● CD surface antigens develop as T cells mature into specific types in thymus
● Main ‘markers’ are: CD4 and CD8
● CD4+ T cells are often called Helper T cells
● CD8+ T-cells are called Cytotoxic T cells

31
Q

what are reactive lymphs

A
  • Cytotoxic T - Lymphocytes (CD8+)
    -Activation and transformation after antigen exposure seen in disease conditions or viral infections like mononucleosis
    -the cell is very large, lots of spreading, dark blue cyto, big nuc,
    -cell is then capable of division
32
Q

what are Natural Killer Lymphocyte

A

Maturation:
● either the BM or Thymus
● Non-specific immunity – (innate immunity) capable of killing tumor cells or virally infected
cells without prior exposure or sensitization
● Modulate function of Macrophages and T cells

Morphology:
● Large cell with increased cytoplasm
● Cytoplasm contains azurophilic (burgundy) granules
● Similar morph to Cytotoxic T cells

33
Q

Monopoiesis

A

Stages include:
1. Monoblast
2. Promonocyte
3. Monocyte
4. Macrophage

Hematology (12 decks)

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