White Blood Cells and WBC Disorders Flashcards

1
Q

Erythrocytes

A
  • Red blood cells
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2
Q

Leukocytes

A
  • White blood cells
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3
Q

Thrombocytes

A
  • Platelets
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4
Q

What percentage of body weight is blood?

A
  • approx 7-8%
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5
Q

Blood cells

A
  • heavier cells: bottom of tube
  • haematocrit (packed cell volume) represents % to total blood volume occupied by RBCs
  • normal haematocrit for men is 45%, women 42%
  • WBCs and platelets found in buffy coat
  • serum is clotted plasma
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6
Q

Types of white blood cells

A
  • Monocyte
  • Lymphocyte
  • Eosinophil
  • Basophil
  • Neutrophil
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7
Q

Phagocytosis

A
  • proteins on pathogen interacts with phagocyte receptors
  • phagocyte envelops pathogen
  • pathogen is digested
  • pathogen breaks down into proteins and other molecules
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8
Q

Key features of Dendritic cells and macrophages

A
  • phagocytic
  • express receptors for apoptotic cells, DAMPs and PAMPs
  • localize to tissues and T-cell zone of lymph nodes (DCs)
  • express high levels of MHC class II molecules and antigen processing machinery
  • express co-stimulatory molecules following activation
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9
Q

Key features of B cells

A
  • internalize antigens via BCRs
  • express MHC class II molecules and antigen processing machinery
  • express co-stimulatory molecules following activation
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10
Q

Antigen recognition and effector functions of B cells

A
  • antigen recognition: antigen on pathogens/soluble antigen

- effector functions: production of antibodies, neutralisation of pathogens, phagocytosis, complement activation

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11
Q

Antigen recognition and effector functions of helper T cell

A
  • antigen recognition: antigen presented by professional APC

- effector functions: secretion of cytokines, macrophage activation, T cell and B cell activation, inflammation

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12
Q

Antigen recognition and effector functions of cytotoxic T cell

A
  • antigen recognition: antigen presented by infected/malignant cells
  • effector functions: elimination of infected/malignant cells
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13
Q

Antigen recognition and effector functions of regulatory T cell

A
  • no antigen recognition function

- effector functions: regulate and/or suppress immune response

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14
Q

Antigen recognition and effector functions of natural killer cell

A
  • antigen recognition: self-antigen/foreign antigen on host cells
  • effector functions: elimination of infected/malignant cells
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15
Q

Innate immunity

A
  • Non specific
  • Requires no sensitising exposure
  • No memory response
  • Immediate/rapid response to threat
  • First line of defense
  • Includes physical barriers, chemical barriers, muco-ciliary escalator, phagocytes (neutrophils, monocytes and macrophages), NK cells, eosinophils, complement.
  • Inflammation and fever responses
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16
Q

Adaptive immunity

A
  • Involves lymphocytes (B&T cells)
  • Humoral and Cell Mediated Immunity
  • Specific.
  • Exhibits memory (enhanced response on subsequent exposures from primary to secondary)
  • Requires initial exposure to antigen, the sensitisation or priming step
  • Cells have multiple copies of a single antigen specific receptor (SmIg or TCR).
  • Antigens trigger clonal expansion of lymphocytes bearing appropriate receptor.
  • ‘Selective’ rather than ‘Instructive’.
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17
Q

Immune cell origin

A
  • Cells of the immune system are generated from haematopoietic stem cells in the bone marrow
  • cells pass through different lineages of development and give rise to the different cells of the immune system
  • All immune system cells are generated in bone marrow but T cells mature in the thymus
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18
Q

Bone marrow

A
  • Inner spongy tissue of certain bones
  • highly organized / regulated organ
  • Site of haematopoiesis and fat deposition
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19
Q

Immune responses involving WBCs

A
  • Defend against infection by viral, bacterial and parasitic pathogens.
  • Identify and destroy cancer cells
  • Remove injured, dead or dying cells and debris – essential for normal would healing and tissue repair.
  • But can be involved in inflammatory or autoimmune diseases
20
Q

Leukocytes

A
  • WBC arise in bone marrow from single pluripotent stem cell.
  • Various chemicals (colony stimulating factors) determine which specific cell type matures.
  • Mature WBC circulate in peripheral blood so they can be transported to site of damage and/or invasion.
21
Q

Leucocytosis (Leukophilia)

A
  • high levels

- Due to infections, allergies, inflammatory diseases, cancer (blood cancers)

22
Q

Leukopaenia

A
  • low levels
  • Due to bone marrow conditions (primary or secondary), certain drugs or treatments, certain infections (HIV), malnutrition, certain autoimmunity (Lupus/SLE)
23
Q

Cells in innate immunity

A
  • When protective barrier surrounding tissues is penetrated, a fast cellular response is needed to protect tissue from infection
  • Do not recognise specific proteins/peptides related to one microorganism
  • pattern recognition receptors (PRRs)
  • recognise molecular patterns common to many invaders or self molecules which are seen when cells are damaged
24
Q

Monocyte/macrophage

A
  • Cytoplasm is agranular
  • Largest WBC.
  • Abundant light blue cytoplasm.
  • U or kidney bean shaped nucleus – stains dark blue/purple
  • arise from pluripotential stem cells within marrow
  • After release from the marrow into circulation they form between 1-5% of circulating white cells
  • After 24 hrs they migrate into the tissue and transform (differentiate) into tissue macrophages.
  • Monocytes form blood borne phase of macrophages
25
Macrophages
- much more effective phagocytes than monocytes - play key role in antigen processing and presentation to T cells. - also secrete a wide range of crucial cytokines which regulate and control inflammation and adaptive immunity
26
Monocyte/Macrophage function
- antigen presentation - antimicrobial actions - antigen/antibody uptake - wound healing - phagocytosis - bone resorption
27
Location and types of macrophages
- alveolar macrophages (lungs) - Kupffer cells (liver) - microglia (neural tissue) - histiocytes (connective tissue) - osteoclast (bone)
28
M1 macrophages
- pro-inflammatory - microbicidal - anti-tumoral
29
M2 macrophages
- anti-inflammatory - wound healing - pro-tumoral
30
Hepatic macrophages in liver disease/injury
- presentation of MAA adducts - microbicidal activity - phagocytosis - anti-inflammatory function (IL-1Ra, IL-10, TGF-beta) - tissue repair/regeneration growth factors (MMPs, TIMPs) - liver fibrosis - inflammatory function (IL-1, IL-12, IL-23, TNFalpha, chemokines - cytotoxicity tissue injury
31
Neutrophils
- very short half life, 6–8 h, produced at a rate of 5×10^10–10×10^10 cells/day. - Multi lobed nucleus - Most common WBC in peripheral blood - cytoplasm has granules that contains various types of enzymes that can digest microbes - granules are cytotoxic and create Reactive Oxygen Species to kill invading organisms - Interleukin-8 (Chemokine) brings them to sites of damage/injury - inability to make these cells can result in overwhelming infection
32
Chronic Granulomatous disease
- genetic hereditary disease in which neutrophils are dysfunctional mutation in NADPH Oxidase that produces less of this protein - NADPH Oxidase is critical in creating ROS necessary to kill the phagocytosed bacteria - neutrophil due to defected ROS production cannot kill the bacteria it has ingested, leads to granuloma formation in tissues - Common symptoms include recurrent infections, pneumonia and abscess of the skin, tissues and organs
33
Eosinophils
- 2-5% of all blood cells - very important in allergic reactions - Parasites can be bound by a complement protein that can activate eosinophils - can kill parasites e.g. helminths that are too large for phagocytosis - have granules containing many enzymes capable of damaging parasite - on activation produce ROS by respiratory burst - have granule proteins which can create a hole in the parasite membrane - Activated by Interleukin-5
34
Basophils
- Cytoplasmic granules so large often obscure nucleus - stain deep blue/purple. - Uncommon WBC in peripheral blood - <0.2%. - Do not phagocytose - When activated release a variety of mediators - Associated with allergic response - Mostly found in the blood stream (unlike mast cells) - IgE surface receptor
35
Lymphocytes
- Smallest WBC, only slightly larger than RBC (10mM) - Cytoplasm contains few granules, stains pale blue. - Nucleus (dark blue) proportionally large, almost filling cell - 3 main types: NK cells, T cells, B cells - NK cells: innate immune system - T cells and B: adaptive immune system
36
Natural killer cell
- visually similar to B + T cells - part of the innate immune system - 10% of blood lymphocytes - Recognise and destroy cancer cells and virus infected cells - may lose effectiveness as we age, leading to increase in cancer - recently been found to be associated with obesity
37
NK cell signalling
- Target doesn't display critical peptide that signals “I am self.” - NK cell is instructed to kill: If critical "self" peptide isn't present, killing is not suspended; if peptide is present, killing is suspended
38
Mode of cytotoxic killing
- Secretion from cytoplasmic granules of Perforin and Granzyme B. - Granzyme B gains access to the cytoplasm of infected cell, via the Perforin pores. - GrB can activate proteases of Caspase family, leading to apoptosis - also seen in CD8+ cytotoxic T cell killing of infected cells - BUT NK cells do not require any “priming” to perform this, hence NATURAL killer cells
39
Causes of lymphocytosis
- diseases of lymphatic system - during menstruation - hepatitis - rheumatic diseases - tuberculosis - acute infectious diseases e.g. chicken pox - viral infection e.g. flu - after hard physical work
40
WBC disorders symptoms
- fever - fatigue - malaise - unexplained weight loss - mouth ulcers - skin abscesses - pneumonia - frequent infections
41
B-cell deficiencies
- Bruton's agammaglobulinemia: defect in B-cell development - common variable hypogammaglobulinemia: defect in plasma cell differentiation - hyper-IgM syndrome: defect in class switching
42
T-cell deficiencies
- Bare lymphocyte syndrome: lack of class II MHC - Omenn's syndrome: defect in TCR gene arrangement - DiGeorge syndrome: thymic aplasia
43
Phagocytic cell deficiencies
- Chronic granulomatous disease: lack of respiratory burst - Leukocyte adhesion deficiency: lack of PMN extravasation into tissue - Chediak-Higashi syndrome: defect in neutrophil microtubule function and related phagosome/lysosome fusion
44
Complement deficiencies
- C1, C2, or C4 deficiency: defects in clearing immunocomplexes - C3 or C5 deficiency: block in alternative and classical pathways - C6, C7, C8 or C9 deficiency: defect in MAC assembly and function
45
Infectious mononucleosis
- presents with fever, pharyngitis and lymphadenopathy - linked with significant fatigue - Particularly frequent in young adults - caused by the Epstein Barr Virus (EBV) - spread by saliva - Incubation period of 4-8 weeks
46
What happens in infectious mononucleosis?
- virus first infects epithelial cells in the pharynx which causes the pharyngitis the infects the B cells - virus infects the B cells through CD21 - Once inside the B cells it replicates and the B cells become proliferative - A T cell response to the B cells is initiated - increase in lymphocytes: Lymphocytosis
47
Treatments for leukocyte disorders
- Antibiotics - Intra-venous IgG - Colony-stimulating factors - Stem cell transplantation - Dietary supplements (e.g. Vit B)