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AP0509 Component 2 Exam > White Blood Cells and WBC Disorders > Flashcards

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
Q

Macrophages

A
  • 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
Q

Monocyte/Macrophage function

A
  • antigen presentation
  • antimicrobial actions
  • antigen/antibody uptake
  • wound healing
  • phagocytosis
  • bone resorption
27
Q

Location and types of macrophages

A
  • alveolar macrophages (lungs)
  • Kupffer cells (liver)
  • microglia (neural tissue)
  • histiocytes (connective tissue)
  • osteoclast (bone)
28
Q

M1 macrophages

A
  • pro-inflammatory
  • microbicidal
  • anti-tumoral
29
Q

M2 macrophages

A
  • anti-inflammatory
  • wound healing
  • pro-tumoral
30
Q

Hepatic macrophages in liver disease/injury

A
  • 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
Q

Neutrophils

A
  • 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
Q

Chronic Granulomatous disease

A
  • 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
Q

Eosinophils

A
  • 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
Q

Basophils

A
  • 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
Q

Lymphocytes

A
  • 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
Q

Natural killer cell

A
  • 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
Q

NK cell signalling

A
  • 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
Q

Mode of cytotoxic killing

A
  • 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
Q

Causes of lymphocytosis

A
  • 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
Q

WBC disorders symptoms

A
  • fever
  • fatigue
  • malaise
  • unexplained weight loss
  • mouth ulcers
  • skin abscesses
  • pneumonia
  • frequent infections
41
Q

B-cell deficiencies

A
  • Bruton’s agammaglobulinemia: defect in B-cell development
  • common variable hypogammaglobulinemia: defect in plasma cell differentiation
  • hyper-IgM syndrome: defect in class switching
42
Q

T-cell deficiencies

A
  • Bare lymphocyte syndrome: lack of class II MHC
  • Omenn’s syndrome: defect in TCR gene arrangement
  • DiGeorge syndrome: thymic aplasia
43
Q

Phagocytic cell deficiencies

A
  • 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
Q

Complement deficiencies

A
  • 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
Q

Infectious mononucleosis

A
  • 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
Q

What happens in infectious mononucleosis?

A
  • 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
Q

Treatments for leukocyte disorders

A
  • Antibiotics
  • Intra-venous IgG
  • Colony-stimulating factors
  • Stem cell transplantation
  • Dietary supplements (e.g. Vit B)

AP0509 Component 2 Exam (21 decks)

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