Physiology of normal WBCs

Question 1

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

Answer 1

The myeloid lineage and the lymphoid lineage.

Question 2

What types of cells are derived from the myeloid lineage?

Answer 2

Granulocytes, antigen-presenting cells, red blood cells, and platelets.

Question 3

Name the three types of granulocytes.

Answer 3

Neutrophils, eosinophils, and basophils.

Question 4

What is the primary function of granulocytes in the immune response?

Answer 4

They are first responders in the immune response, specifically in innate immunity.

Question 5

What do granulocytes contain that are essential for the immune response?

Answer 5

Cytoplasmic granules that carry proteins and other molecules.

Question 6

Name three types of phagocytes/antigen-presenting cells.

Answer 6

Monocytes, macrophages, and dendritic cells.

Question 7

Which type of immunity do lymphoid cells contribute to?

Answer 7

Adaptive immunity.

Question 8

What stain is typically used to visualize granulocyte granules?

Answer 8

The standard haematoxylin/eosin stain.

Question 9

Which type of granulocyte granules stain primarily with eosin?

Answer 9

Eosinophilic granules.

Question 10

Which type of granulocyte granules stain primarily with haematoxylin?

Answer 10

Basophilic granules.

Question 11

What are azurophilic granules, and in which type of white blood cell are they abundant?

Answer 11

Azurophilic granules are granules that do not stain well with the standard haematoxylin/eosin stain. They are abundant in neutrophils.

Question 12

What are the ligands for Pattern Recognition Receptors (PRRs) found in white blood cells?

Answer 12

Pathogen Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Patterns (DAMPs).

Question 13

Name some examples of Pattern Recognition Receptors (PRRs).

Answer 13

Toll-like Receptors (TLRs), C-type Lectin Receptors (CLRs), and many others.

Question 14

Besides myeloid white blood cells, where else are Pattern Recognition Receptors (PRRs) found?

Answer 14

They are also present in skin cells, epithelial and mucosal cells, vascular endothelial cells, and fibroblasts.

Question 15

What is the function of Pattern Recognition Receptors (PRRs)?

Answer 15

They are essential for recognizing a variety of microorganisms and pathogens by myeloid white blood cells and initiating the immune response.

Question 16

What percentage of white blood cells do monocytes typically make up?

Answer 16

Monocytes make up 2% - 12% of white blood cells.

Question 17

Describe the migration and differentiation of monocytes into macrophages.

Answer 17

Monocytes can migrate to tissues and differentiate into macrophages in response to infection.

Question 18

What are the functions of macrophages?

Answer 18

Macrophages are efficient phagocytes that can degrade both pathogens and damaged host cells. They can also initiate signaling to attract other immune cells. Additionally, macrophages serve as tissue-resident phagocytes.

Question 19

Provide examples of tissue-resident macrophages.

Answer 19

Examples of tissue-resident macrophages include alveolar macrophages (lung), Kupffer cells (liver), microglia (central nervous system), splenic macrophages (spleen), myocardial macrophages (heart), dermal macrophages (skin), and intestinal macrophages (lamina propria).

Question 20

What is the role of macrophages as professional Antigen Presenting Cells (APCs)?

Answer 20

Macrophages serve as a bridge between innate and adaptive immunity by presenting antigens to T cells through Major Histocompatibility Complex Class II (MHC-II) molecules on their membrane.

Question 21

How do macrophages enhance antigen recognition through opsonization?

Answer 21

Macrophage receptors (Fc receptors) can recognize antigen/antibody complexes, which leads to opsonization. Opsonization enhances antigen recognition and significantly increases the rate of phagocytosis.

Question 22

Compare the lifespan of monocytes and tissue macrophages.

Answer 22

Monocytes have a short half-life, while tissue macrophages are self-replicating and have a much longer lifespan, ranging from months to years.

Question 23

What is the role of Toll-like receptors (TLRs) in macrophages?

Answer 23

Toll-like receptors interact with the MyD88 protein, initiating a signaling cascade that leads to the production of inflammatory cytokines and inflammation.

Question 24

Describe the TLR signaling pathway in macrophages.

Answer 24

TLR signaling pathways involve the cytoplasmic Toll/Interleukin-1 receptor (TIR) domain. The TIR domain-containing adaptor, MyD88, associates with TLRs and recruits IRAK. IRAK then activates TRAF6, leading to the activation of the IκB kinase (IKK) complex. The IKK complex phosphorylates IκB, resulting in the nuclear translocation of NF-κB, which induces the expression of inflammatory cytokines.

Question 25

What is the role of TIRAP and TRIF in TLR signaling pathways?

Answer 25

TIRAP is involved in the MyD88-dependent signaling pathway through TLR2 and TLR4. TRIF is essential for the MyD88-independent pathway. TRIF mediates activation of IRF-3 and induction of IFN-β. TRAM is specific to the TLR4-mediated MyD88-independent/TRIF-dependent pathway.

Question 26

What are the roles of macrophage receptors?

Answer 26

Macrophage receptors mediate various functions, including cytokine production, inflammation, microbe elimination through reactive oxygen species, nitric oxide, and lysosomal enzymes, tissue repair/angiogenesis through growth factors and angiogenic factors, and phagocytosis of microbes and apoptotic cells.

Question 27

What are some of the functions of macrophages in inflammation?

Answer 27

Macrophages play a role in inflammation by phagocytosing and destroying microbes and dead tissues. They can also potentiate inflammatory reactions. Additionally, alternatively activated macrophages induced by certain cytokines are involved in tissue repair and resolution of inflammation.

Question 28

What are the stimuli that activate monocytes/macrophages into functionally distinct populations?

Answer 28

In classical macrophage activation, monocytes/macrophages are induced by microbial products and cytokines. In alternative macrophage activation, they are induced by other cytokines.

Question 29

What are the characteristics and functions of classically activated macrophages?

Answer 29

Classically activated macrophages phagocytose and destroy microbes and dead tissues. They can potentiate inflammatory reactions. They are induced by microbial products and cytokines.

Question 30

What are the characteristics and functions of alternatively activated macrophages?

Answer 30

Alternatively activated macrophages are induced by certain cytokines. They are important in tissue repair and resolution of inflammation.

Question 31

What are the abbreviations NO, ROS, TGF-β, and TLR in the context of macrophages?

Answer 31

NO stands for nitric oxide, ROS stands for reactive oxygen species, TGF-β stands for transforming growth factor-β, and TLR stands for Toll-like receptor.

Question 32

What percentage of leukocytes in circulation do neutrophils make up?

Answer 32

Neutrophils make up 50% - 70% of leukocytes in circulation.

Question 33

What are the main functions of neutrophils in infection?

Answer 33

Neutrophils release signaling molecules, phagocytose infectious pathogens, and are involved in tissue remodeling. They contain proteases and antimicrobials in their granules.

Question 34

How do neutrophils contribute to wound healing and repair?

Answer 34

Neutrophils are involved in tissue remodeling by remodeling elastin and collagen fibers, which aids in wound healing and repair.

Question 35

What are some characteristics and functions of eosinophils?

Answer 35

Eosinophils have characteristic granules that appear dark pink/red when stained. They are involved in defense against parasitic worms, contribute to allergy and asthma through IgE receptors, and release signaling molecules that can influence the adaptive immune response.

Question 36

What is the role of basophils in the immune response?

Answer 36

Basophils contain histamine granules, which are released in response to binding antibody/antigen complexes. Histamine increases blood vessel permeability, allowing immune cells to enter infection sites. Basophils also release signaling molecules and recruit eosinophils and lymphocytes to infection sites. In the absence of infection, basophil release of histamine is linked to allergy symptoms.

Question 37

What is the composition of pus in infections?

Answer 37

Pus is composed of dead neutrophils, bacteria, and extracellular fluid.

Question 38

How are pathogens destroyed inside phagocytes?

Answer 38

Pathogens are destroyed inside phagocytes through the fusion of phagosomes with lysosomes, where low pH, lysosomal enzymes, reactive oxygen species (ROS) in neutrophils, or nitric oxide (NO) in macrophages contribute to the destruction of pathogens.

Question 39

Where are mast cells primarily found and what do they contain?

Answer 39

Mast cells can be found in the skin, connective tissue, and mucosal epithelial tissues of the respiratory and digestive tracts. They contain granules with histamine and contribute to the allergic response.

Question 40

What is the function of dendritic cells?

Answer 40

Dendritic cells capture antigens through phagocytosis and receptor-mediated endocytosis. They then present these antigens to other immune cells, such as T cells, thereby linking innate and adaptive immunity. Upon antigen capture, dendritic cells can migrate to lymphoid organs.

Question 41

What is the role of B cells in the immune response?

Answer 41

B cells are lymphoid antigen-presenting cells (APCs) that can present antigens to T cells. They can also mature into antibody-producing plasma cells.

Question 42

What are the specific surface membrane proteins and receptors of T cells and B cells?

Answer 42

T cells have the T cell receptor (TCR), while B cells have the B cell receptor (BCR). These receptors enable T and B cells to recognize specific antigens.

Question 43

What are the two main types of T cells and their functions?

Answer 43

T cells can be classified as T helper cells and T cytotoxic cells. T helper cells interact with antigen-presenting cells (APCs) and B cells, playing a role in immune activation and regulation. T cytotoxic cells are responsible for recognizing and killing infected or abnormal cells, such as those in transplant rejections.

Question 44

What distinguishes natural killer (NK) cells and what are their functions?

Answer 44

NK cells contain various antigen recognition receptors and cytotoxic granules. They can recognize and kill target cells, such as infected or cancerous cells, through their cytotoxic activity.

Question 45

What are cytokines and their role in inflammation?

Answer 45

Cytokines are signaling molecules released by immune cells that play a crucial role in inflammation. They regulate various aspects of the immune response, including cell communication, recruitment of immune cells, and inflammation initiation and resolution.

Question 46

What are the mechanisms of inflammation mediated by mast cells and basophils?

Answer 46

Mast cells and basophils are histamine-producing cells that contribute to inflammation. They release histamine, which leads to vasodilation, increased blood flow, increased permeability of blood vessels, and the characteristic symptoms of inflammation such as redness, swelling, heat, and pain.

Question 47

How do tissue resident dendritic cells and macrophages contribute to inflammation?

Answer 47

Tissue resident dendritic cells and macrophages have pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This recognition triggers the release of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α, as well as the chemokine IL-8, which promotes neutrophil recruitment.

Question 48

How does leukocyte recruitment and tissue migration occur during inflammation?

Answer 48

Circulating leukocytes adhere to the vascular endothelium through cell adhesion molecules (CAMs), which allows their recruitment and migration to the inflamed tissue. This process is essential for the immune response and the resolution of inflammation.

Question 49

What are the risks associated with excessive inflammation?

Answer 49

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 progress to septic shock, causing severe complications.

Question 50

How is inflammation regulated to prevent excessive immune response?

Answer 50

Regulation of inflammation involves the production of anti-inflammatory cytokines, such as IL-10, by macrophages. Negative feedback loops through proteins in the pattern recognition receptor (PRR) signaling pathways, as well as the use of soluble receptors to sequester excess inflammatory cytokines like TNF-α and IL-1β, also help to regulate inflammation.

Question 51

What are the differences between acute and chronic inflammation?

Answer 51

Acute inflammation is caused by infection and is characterized by short-term effects followed by healing. Chronic inflammation, on the other hand, persists over a long period and remains unresolved. It can be caused by unresolved infection, gut microbes, autoimmune responses, allergic responses, and conditions like obesity.

Question 52

What are some diseases and conditions associated with chronic inflammation?

Answer 52

Chronic inflammation is associated with various diseases and conditions, including type 2 diabetes, cardiovascular disease, autoinflammatory diseases, inflammatory bowel disease, and arthritis.

Question 53

What are some of the inflammatory mediators involved in chronic inflammation?

Answer 53

Inflammatory mediators such as IL-6, TNF-α, IL-1β, and others play a role in chronic inflammation and are implicated in the development and progression of associated diseases.

Question 54

What is atherogenesis and what does it lead to?

Answer 54

Atherogenesis is the process that leads to the development of an atherosclerotic plaque and atherosclerosis, which is the hardening of the vascular wall. It is a disease of the endothelium characterized by damage to the endothelium and the release of inflammatory cytokines.

Question 55

What role does the endothelium play in atherogenesis?

Answer 55

Damage to the vascular endothelium initiates the process of atherogenesis and is a crucial step in the development of atherosclerosis. It triggers the release of inflammatory cytokines and can lead to the formation of a blood clot (thrombus) through activation of the coagulation cascade.

Question 56

What is the role of macrophages in atherogenesis?

Answer 56

In atherogenesis, blood circulating monocytes adhere to the damaged endothelium and migrate to the subendothelial tissue. There, they differentiate into macrophages that engulf oxidized low-density lipoprotein (LDL) through scavenger receptors. These macrophages accumulate oxidized LDL, leading to the formation of foam cells. Foam cells can rupture, releasing their contents, including cytokines and chemokines, which recruit more monocytes and amplify the inflammatory response around the endothelial lesion.

Question 57

What are the steps involved in atherogenesis?

Answer 57

The steps in atherogenesis include endothelial dysfunction, monocyte/macrophage adhesion to the damaged endothelium, smooth muscle cell migration, the formation of a fibro/lipid plaque, and inflammation.