White Blood Cells and WBC Disorders Flashcards
1
Q
Erythrocytes
A
- Red blood cells
2
Q
Leukocytes
A
- White blood cells
3
Q
Thrombocytes
A
- Platelets
4
Q
What percentage of body weight is blood?
A
- approx 7-8%
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
6
Q
Types of white blood cells
A
- Monocyte
- Lymphocyte
- Eosinophil
- Basophil
- Neutrophil
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
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
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
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
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
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
13
Q
Antigen recognition and effector functions of regulatory T cell
A
- no antigen recognition function
- effector functions: regulate and/or suppress immune response
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
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
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’.
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
18
Q
Bone marrow
A
- Inner spongy tissue of certain bones
- highly organized / regulated organ
- Site of haematopoiesis and fat deposition
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)
