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Heart, Lungs and Blood > Physiology of normal WBCs > Flashcards

Physiology of normal WBCs Flashcards

1
Q

What is haematopoiesis?

A

Haematopoiesis is the process of blood cell production in the body.

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2
Q

What is a hematopoietic stem cell (HSC)?

A

A hematopoietic stem cell (HSC) is a self-renewing cell that has the potential to differentiate into different blood cell lineages.

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3
Q

What are the two lineages that a HSC can differentiate into?

A

A HSC can differentiate into the myeloid lineage and the lymphoid lineage.

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4
Q

What cells are produced in the myeloid lineage?

A

The myeloid lineage produces granulocytes, antigen presenting cells, red blood cells, and platelets.

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5
Q

What cells are produced in the lymphoid lineage?

A

The lymphoid lineage produces T cells and B cells.

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6
Q

What is the function of granulocytes?

A

Granulocytes are a type of white blood cell that helps fight infection by engulfing and destroying foreign particles.

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7
Q

What is the function of red blood cells?

A

Red blood cells transport oxygen from the lungs to the body tissues and remove carbon dioxide from the body tissues to the lungs.

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8
Q

What is the function of platelets?

A

Platelets are involved in the formation of blood clots to stop bleeding.

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9
Q

What is the function of T cells?

A

T cells play a role in the immune response by recognizing and attacking foreign invaders.

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10
Q

What is the function of B cells?

A

B cells produce antibodies that recognize and neutralize foreign invaders.

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11
Q

What are the two lineages that the hematopoietic stem cell (HSC) can differentiate into?

A

The myeloid lineage and the lymphoid lineage.

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12
Q

What are the different types of granulocytes?

A

The different types of granulocytes are neutrophils, eosinophils, basophils, and mast cells.

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13
Q

What is the function of granulocytes?

A

Granulocytes are first responders in the immune response, and they contain cytoplasmic granules that carry proteins and other molecules essential for the immune response to infection.

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14
Q

What are phagocytes/antigen-presenting cells?

A

Phagocytes/antigen-presenting cells include monocytes, macrophages, and dendritic cells.

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15
Q

What is the function of lymphoid cells?

A

Lymphoid cells are involved in adaptive immunity.

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16
Q

How do granulocyte granules appear when stained with haematoxylin/eosin?

A

Granules that appear dark pink or red stain primarily with eosin and are called eosinophilic granules. Granules that appear dark purple or blue stain primarily with haematoxylin and are called basophilic granules.

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17
Q

What are azurophilic granules?

A

Azurophilic granules are abundant in neutrophils, and they do not stain well with the standard haematoxylin/eosin stain.

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18
Q

What is the function of neutrophils?

A

Neutrophils are involved in the immune response to infection, and they are phagocytes that engulf and destroy invading microorganisms.

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19
Q

What is the function of eosinophils?

A

Eosinophils are involved in the immune response to parasitic infections and allergies.

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20
Q

What is the function of basophils?

A

Basophils are involved in the immune response to allergies and parasitic infections, and they release histamine and other inflammatory mediators.

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21
Q

what cell is this

A

neutrophil

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22
Q

what cell is this

A

monocyte

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23
Q

what cell is this

A

eosinophils

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24
Q

what cell is this

A

basophils

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25
Q

what cell is this

A

lymphocyte

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26
Q

What are Pattern Recognition Receptors (PRRs)?

A

PRRs are receptors present in myeloid white blood cells and other cells that recognize Pathogen Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Patterns (DAMPs).

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27
Q

What are some examples of PRRs?

A

Toll-like Receptors (TLRs) and C-type Lectin Receptors (CLRs) are two examples of PRRs.

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28
Q

What is the function of PRRs?

A

PRRs are essential for recognizing microorganisms and pathogens and initiating the immune response.

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29
Q

Are PRRs only found in white blood cells?

A

No, PRRs are also present in skin cells, epithelial and mucosal cells, vascular endothelial cells, fibroblasts, and other cells.

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30
Q

What are PAMPs and DAMPs?

A

PAMPs (Pathogen Associated Molecular Patterns) are molecules found on microorganisms that are recognized by PRRs, while DAMPs (Damage Associated Molecular Patterns) are released by damaged cells and tissues and can also be recognized by PRRs.

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31
Q

Why are PRRs important for the immune response?

A

PRRs allow white blood cells to recognize and respond to a wide variety of microorganisms and pathogens, even those they have not encountered before.

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32
Q

How do TLRs and CLRs differ?

A

TLRs are membrane-bound receptors that recognize a variety of PAMPs, while CLRs are primarily involved in recognizing fungi and other specific types of pathogens.

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33
Q

Can PRRs cause an immune response without the presence of a pathogen?

A

Yes, in some cases PRRs can recognize DAMPs released by damaged cells and tissues, which can trigger an immune response.

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34
Q

Are PRRs specific to particular types of microorganisms or pathogens?

A

Some PRRs are specific to certain types of pathogens (such as CLRs and fungi), while others can recognize a wide variety of PAMPs from different microorganisms (such as TLRs).

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35
Q

How do PRRs help white blood cells distinguish between self and non-self?

A

PRRs are able to distinguish between self and non-self by recognizing PAMPs and DAMPs that are not present on normal, healthy cells.

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36
Q

What are monocytes?

A

Monocytes are a type of white blood cell that make up 2% - 12% of white blood cells.

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37
Q

What happens to monocytes in response to infection?

A

Monocytes can migrate to tissues (inflammatory monocytes) and differentiate into macrophages in response to infection.

38
Q

What are macrophages?

A

Macrophages are efficient phagocytes that can degrade both pathogens and damaged host cells. They can initiate signalling that attracts other immune cells.

39
Q

Where can tissue resident macrophages be found?

A

Tissue resident macrophages can be found in various organs and tissues, such as alveolar macrophages (lung), Kupffer cells (liver), microglia (central nervous system), splenic macrophages (spleen), myocardial macrophages (heart), dermal macrophages (skin), intestinal macrophages (lamina propria).

40
Q

What is the function of tissue resident macrophages?

A

Tissue resident macrophages act as phagocytes and help to maintain tissue homeostasis by removing dead cells, pathogens, and debris. They also play a role in immune surveillance and can initiate immune responses when necessary.

41
Q

How do macrophages contribute to the immune response?

A

Macrophages can initiate signalling that attracts other immune cells and phagocytose pathogens and damaged host cells. They also act as antigen-presenting cells and activate other immune cells such as T cells.

42
Q

What is the difference between patrolling and inflammatory monocytes?

A

Patrolling monocytes circulate in the blood and can survey for signs of infection or tissue damage. Inflammatory monocytes migrate to tissues in response to infection and differentiate into macrophages.

43
Q

What is the role of macrophages in antigen presentation?

A

Macrophages are professional Antigen Presenting Cells (APCs), and can present antigen to T cells via Major Histocompatibility Complex Class II (MHC-II) molecules on their cell membrane.

44
Q

What is opsonisation and how does it enhance antigen recognition?

A

Opsonisation is the process by which antigen/antibody complexes enhance antigen recognition via antibody binding. This leads to a significant increase in the rate of phagocytosis by macrophages, as they can more effectively recognise and bind to the antigen.

45
Q

What is the difference between patrolling monocytes and inflammatory monocytes?

A

Patrolling monocytes circulate in the blood and survey tissues for infection, while inflammatory monocytes migrate to tissues in response to infection and differentiate into macrophages.

46
Q

What are tissue resident macrophages?

A

Tissue resident macrophages are a type of macrophage that reside in specific tissues, such as alveolar macrophages in the lungs, Kupffer cells in the liver, and microglia in the central nervous system. They play a role in maintaining tissue homeostasis and responding to infection.

47
Q

What are Toll-like receptors (TLRs)?

A

Toll-like receptors (TLRs) are a type of pattern recognition receptor (PRR) present in myeloid white blood cells, as well as other cells such as skin cells and epithelial cells. TLRs recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response.

48
Q

What is the function of MyD88 in the TLR signaling pathway?

A

MyD88 is a TIR domain-containing adaptor protein that associates with the cytoplasmic TIR domain of TLRs and recruits IRAK to the receptor upon ligand binding. This initiates a signaling cascade that leads to the production of inflammatory cytokines and inflammation.

49
Q

What is the role of IRAK in the TLR signaling pathway?

A

IRAK (Interleukin-1 receptor-associated kinase) is recruited to the TLR receptor by MyD88 and is responsible for activating TRAF6, which in turn leads to the activation of the IKK complex. The IKK complex then phosphorylates IκB, resulting in nuclear translocation of NF-κB and induction of inflammatory cytokines.

50
Q

What is the role of TRIF in the TLR signaling pathway?

A

TRIF (TIR-domain-containing adaptor protein inducing interferon-β) is a TIR domain-containing adaptor protein that is essential for the MyD88-independent pathway in TLR signaling. TRIF mediates activation of IRF-3 and induction of IFN-β downstream of TLR3 and TLR4.

51
Q

What is the difference between MyD88-dependent and MyD88-independent pathways in TLR signaling?

A

MyD88-dependent pathway leads to the activation of NF-κB and production of inflammatory cytokines, while the MyD88-independent pathway leads to the activation of IRF-3 and induction of IFN-β. TLR2 and TLR4 can activate both MyD88-dependent and -independent pathways, while TLR3 and TLR4 are specific for the MyD88-independent pathway.

52
Q

What is opsonisation?

A

Opsonisation is a process by which pathogens are marked for destruction by phagocytes. This is achieved through the binding of antibodies to the pathogen, which enhances recognition by macrophage receptors (Fc receptors) and increases the rate of phagocytosis.

53
Q

What is the role of tissue-resident macrophages?

A

Tissue-resident macrophages are self-replicating and have a much longer lifespan compared to monocytes. They are present in various tissues such as the lung, liver, central nervous system, spleen, heart, skin and lamina propria of the intestine. Tissue-resident macrophages are efficient phagocytes that can degrade pathogens and damaged host cells. They also initiate signalling that attracts other immune cells.

54
Q

What is the function of the major histocompatibility complex (MHC)-II molecules on macrophages?

A

MHC-II molecules on macrophages are responsible for antigen presentation, which is essential for the activation of T cells in the adaptive immune response. After a macrophage has come in contact with a pathogen, antigen presentation is achieved through the MHC-II molecules on the macrophage membrane.

55
Q

What is the role of Fc receptors on macrophages?

A

Fc receptors on macrophages recognise antigen/antibody complexes, which is an example of opsonisation. This leads to the enhancement of antigen recognition through antibody binding and a significant increase in the rate of phagocytosis.

56
Q

What are some of the factors involved in microbe elimination during inflammation?

A

Reactive oxygen species, nitric oxide, and lysosomal enzymes.

57
Q

What are some of the factors involved in tissue repair and angiogenesis during inflammation?

A

Growth factors and angiogenic factors.

58
Q

What are some of the processes involved in the phagocytosis of microbes during inflammation?

A

Microbe phagocytosis.

59
Q

Microbe phagocytosis.

A

Apoptotic cell phagocytosis.

60
Q

What is the difference between classically activated and alternatively activated macrophages?

A

Classically activated macrophages are induced by microbial products and cytokines and are important for phagocytosing and destroying microbes and dead tissues, as well as potentiating inflammatory reactions. Alternatively activated macrophages are induced by other cytokines and are important in tissue repair and resolution of inflammation.

61
Q

What are the functions of reactive oxygen species, nitric oxide, and lysosomal enzymes in microbe elimination?

A

Reactive oxygen species, nitric oxide, and lysosomal enzymes are all involved in microbe elimination by macrophages.

62
Q

What are the functions of growth factors and angiogenic factors in tissue repair and angiogenesis?

A

Growth factors and angiogenic factors are important for tissue repair and angiogenesis.

63
Q

What is phagocytosis, and what are the types of phagocytosis performed by macrophages?

A

Phagocytosis is the process by which cells engulf and digest other cells or particles. Macrophages perform microbe phagocytosis and apoptotic cell phagocytosis.

64
Q

What is the function of neutrophils?

A

Neutrophils are a type of white blood cell that phagocytose infectious pathogens, release signalling molecules, and are involved in tissue remodelling and wound healing. They quickly migrate to the site of infection and are essential for resolving fungal infections.

65
Q

What is the lifespan of neutrophils?

A

Neutrophils have a short lifespan of only a few hours.

66
Q

How are neutrophils produced?

A

Neutrophils emerge in the bone marrow in response to cytokine activity and circulate in the blood, then migrate to tissues. In infection, they release signalling molecules that reach the bone marrow and initiate the production of more neutrophils.

67
Q

What are the contents of neutrophil granules?

A

Neutrophil granules contain proteases and antimicrobials that help kill microbes inside phagosomes with reactive oxygen species (ROS) and hydrolytic enzymes.

68
Q

What is the clinical indication of infection?

A

Increased neutrophil numbers are used as a clinical indication of infection.

69
Q

What is pus?

A

Pus is the accumulation of dead neutrophils, bacteria, and extracellular fluid in infection, and neutrophils are the main component of pus.

70
Q

How are pathogens destroyed inside phagocytes?

A

Pathogens are destroyed inside phagocytes in the phagosome/lysosome fusion due to low pH, the activity of lysosomal enzymes, reactive oxygen species (ROS) (neutrophils) or nitric oxide (NO) (macrophages).

71
Q

: What is the function of eosinophils?

A

Eosinophils are involved in the defence against parasitic worms. They also contribute to allergy and asthma, and release signalling molecules that influence the adaptive immune response.

72
Q

What is the function of basophils?

A

Basophils contain histamine granules that increase blood vessel permeability, allowing immune cells to enter a site of infection. They also release cytokines and recruit eosinophils and lymphocytes to infection sites. In the absence of infection, basophil release of histamine is linked to allergy symptoms.

73
Q

What is the function of dendritic cells?

A

They capture antigens and present them to other immune cells, acting as a link between innate and adaptive immunity.

74
Q

What are the subtypes of dendritic cells?

A

Dendritic cells are a heterogenous cell type with different subtypes based on common cell surface markers, developmental lineage, tissue localisation, and functions.

75
Q

What are T cells and B cells?

A

T cells and B cells are lymphocytes that can be distinguished by their specific surface membrane proteins and each have specific membrane receptors (T cell receptor for T cells and B cell receptor for B cells).

76
Q

What is the function of B cells?

A

B cells are lymphoid pAPCs and present antigens to T cells. They can also mature into antibody-producing plasma cells.

77
Q

What is the function of T helper cells?

A

T helper cells interact with pAPCs and B cells.

78
Q

What are NK cells?

A

NK (Natural Killer) cells contain a variety of antigen recognition receptors as well as cytotoxic granules that kill target cells.

79
Q

What are the functions of IL-1, IL-6, and TNF-α cytokines?

A

IL-1, IL-6, and TNF-α are cytokines involved in inflammation. IL-1 enhances neutrophil production, increases vascular permeability, and can cause fever. IL-6 regulates neutrophil production, increases vascular permeability, and can cause fever. TNF-α increases vascular permeability and can cause fever.

80
Q

What cells produce IL-12 and IL-18 cytokines, and what are their functions?

A

Monocytes, macrophages, and dendritic cells produce IL-12 and IL-18 cytokines. These cytokines act on T-cells and NK-cells, which are important in bridging innate and adaptive immunity.

81
Q

What is the function of GM-CSF cytokine, and what cells produce it?

A

GM-CSF is a cytokine produced by macrophages and endothelial cells. It stimulates haematopoiesis, which is the production of blood cells.

82
Q

Which cells are responsible for histamine release during inflammation?

A

Mast cells and basophils are responsible for histamine release during inflammation.

83
Q

What are some of the effects of vasodilation during inflammation?

A

Vasodilation during inflammation leads to increased blood flow, redness/heat of inflamed tissue, and increased permeability of the blood vessels.

84
Q

What cells release pro-inflammatory cytokines during inflammation?

A

Tissue resident dendritic cells and macrophages release pro-inflammatory cytokines IL-1, IL-6 and TNF-α, as well as the chemokine IL-8.

85
Q

How do leukocytes migrate to the site of inflammation?

A

Leukocytes migrate to the site of inflammation through adhesion to the vascular endothelium, which is achieved through Cell Adhesion Molecules (CAMs).

86
Q

What are the consequences of excessive inflammation?

A

Excessive inflammation can lead to sepsis which is characterized by fever, increased heartbeat, increased rate of breathing, low blood pressure, circulatory problems and compromised organ function. Sepsis can further lead to septic shock which is caused by blood infection involving gram-negative and gram-positive bacteria. During sepsis, the inflammatory response is amplified and phagocyte activity destroys vascular endothelial cells, leading fluid loss to tissues and lowering of blood pressure.

87
Q

How is inflammation regulated?

A

Inflammation is regulated through negative feedback loops involving proteins that act in the PRR signaling pathways, inhibitors for the inflammatory cytokines TNF-α and IL-1β in the form of soluble receptors that can sequestrate excess cytokines, and the production of anti-inflammatory cytokines such as IL-10 which inhibits inflammatory cytokines and promotes wound healing.

88
Q

What are the differences between acute and chronic inflammation?

A

Acute inflammation is caused by infection and is characterised by short-term effects followed by healing, while chronic inflammation is long-term and unresolved. Chronic inflammation can be caused by unresolved infection, gut microbes, autoimmune response, allergic response, and obesity. Chronic inflammation is associated with various diseases such as type 2 diabetes, cardiovascular disease, autoinflammatory disease, inflammatory bowel disease, and arthritis. The inflammatory mediators IL-6, TNF-α, IL-1β, and others are involved in both acute and chronic inflammation.

89
Q

What is atherogenesis?

A

Atherogenesis is the process that leads to the development of an atherosclerotic plaque and atherosclerosis, which is the hardening of the vascular wall.

90
Q

What is the role of the endothelium in atherogenesis?

A

Atherogenesis is caused by damage to the endothelium that leads to the release of inflammatory cytokines.

91
Q

What is the link between arterial thrombosis and atherosclerosis?

A

Arterial thrombosis is linked to atherosclerosis of the vessel wall.

92
Q

How do macrophages contribute to atherogenesis?

A

Blood circulating monocytes can ingest oxidised LDL through scavenger receptors. These monocytes migrate to subendothelial tissue and differentiate into macrophages that accumulate oxidised LDL becoming foam cells. Foam cells can rupture releasing their molecular content, including cytokines and chemokines, recruiting more monocytes and amplifying the inflammatory response around the endothelial lesion.

Heart, Lungs and Blood (51 decks)

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