11: Cellular Components of the Cutaneous Immune System

Question 1

What are the components of the skin immune system?

Answer 1

The skin immune system consists of specialized skin-resident immune cells and circulating lymphocytes. Key components include:

• Langerhans cells and resident memory T cells (CD8+) found in the epidermis
• CD4+ and γδ T cells located in the upper dermis
• Innate lymphoid cells (ILC) near the dermal-epidermal junction
• Mast cells near the dermal blood vessels
• Dendritic cells and macrophages found in the dermis

Question 2

What are the dual characteristics of innate and adaptive immune cells?

Answer 2

The dual characteristics include innate lymphoid cells (ILC) and innate-like T cells, which exhibit features of both the rapid, non-specific innate immune response and the slower, specific adaptive immune response.

Question 3

How does the innate immune system recognize pathogens?

Answer 3

The innate immune system recognizes pathogens by identifying proteins, lipids, and nucleotides. This recognition is rapid and does not require prior exposure to the pathogen.

Question 4

What is the basis of the adaptive immune system’s response?

Answer 4

The adaptive immune system’s response is based on antigen receptor or antibody diversity, allowing for a specific response to various pathogens.

Question 5

How do innate and adaptive immune systems differ in their recognition mechanisms?

Answer 5

The innate immune system recognizes proteins, lipids, and nucleotides, while the adaptive immune system is based on antigen receptor or antibody diversity.

Question 6

What are the primary cells involved in the first line of defense against pathogens?

Answer 6

Dendritic cells and macrophages are the primary cells that provide rapid first line of defense against pathogens.

Question 7

What is the role of T helper 1 (TH1) cells in the immune system?

Answer 7

TH1 cells are the main mediators of cell-mediated immunity, playing a crucial role in the immune response against intracellular pathogens.

Question 8

How do B cells function in the immune system?

Answer 8

B cells form the humoral arm of the immune system by binding to and neutralizing pathogens, preventing their ability to enter and infect cells.

Question 9

What is the significance of T regulatory cells (Tregs) in the immune response?

Answer 9

Tregs maintain tolerance to self-antigens in the periphery, suppressing activation, cytokine production, and proliferation of other T cells, thus preventing autoimmune responses.

Question 10

What are the characteristics of naïve T cells?

Answer 10

Naïve T cells are cells that have completed their primary development but have not yet encountered their specific antigen, making them ready to respond to future infections.

Question 11

What are the functions of tissue-resident lymphocytes in the immune system?

Answer 11

Tissue-resident lymphocytes act as sensors of disturbed tissue integrity from infection or injury and help recruit additional immune cells from the blood.

Question 12

A patient with atopic dermatitis has elevated levels of a specific immune cell type. Which cell type is likely elevated, and what is its role?

Answer 12

B cells are likely elevated in atopic dermatitis. They produce antibodies that bind and neutralize pathogens and bacterial toxins.

Question 13

A patient with a bacterial skin infection shows activation of a specific T cell subset. Which subset is involved, and what is its primary function?

Answer 13

TH17 cells are involved in bacterial skin infections. They mediate antigen responses against extracellular pathogens.

Question 14

A patient with a bacterial skin infection shows activation of TH1 cells. What is the primary function of TH1 cells?

Answer 14

TH1 cells are the main mediators of cell-mediated immunity.

Question 15

A patient with a bacterial skin infection shows activation of TH17 cells. What skin condition is TH17 implicated in?

Answer 15

TH17 cells are implicated in psoriasis.

Question 16

A patient with a bacterial skin infection shows activation of TH2 cells. What is the primary function of TH2 cells?

Answer 16

TH2 cells facilitate humoral (antibody) responses and inhibit some cell-mediated immune responses.

Question 17

What distinguishes naive T cells from effector T cells?

Answer 17

Naive T cells have not yet encountered their specific antigen, while effector T cells can mount a response to antigens once a naive T cell meets its specific antigen.

Question 18

In what conditions are B cells infrequently found, and what is their primary function?

Answer 18

B cells are infrequently found in normal skin but are present in chronic inflammatory skin conditions. Their primary function is to bind to and neutralize pathogens and bacterial toxins.

Question 19

What is the significance of tissue-resident lymphocytes in the immune response?

Answer 19

Tissue-resident lymphocytes act as sensors of disturbed tissue integrity from infection or injury and help recruit additional immune cells from the blood.

Question 20

What are the three populations of Innate Lymphoid Cells (ILCs) found in human skin?

Answer 20

The three populations of ILCs found in human skin are:

1. ILC-1 - Surface Molecule: CD161, Activated by: IL-12, IL-15, Primary Cytokines: TNF-α, IFN-γ, Implicated in: ACD
2. ILC-2 - Surface Molecule: KLRG1, CRTH2, CCR4, Activated by: IL-25, IL-33, TSLP, PGD2, Primary Cytokines: IL-5, IL-13, Implicated in: Atopic dermatitis
3. ILC-3 - Surface Molecule: NKp44, Activated by: IL-1, IL-23, Primary Cytokines: IL-7, IL-22, Implicated in: Psoriasis

Question 21

What is the role of invariant Natural Killer T (iNKT) cells in the immune response?

Answer 21

Invariant Natural Killer T (iNKT) cells recognize glycolipid antigens presented by the MHC class 1-like molecule CD1d and are activated by potent bacterial ligands such as cell wall sphingolipids.

Question 22

What are Mucosal-associated Invariant T (MAIT) cells and their function?

Answer 22

MAIT cells are a special subset of T cells characterized by expressing a semi-variant T cell receptor and being activated by bacterial riboflavin biosynthesis intermediates presented by the MHC class 1-like molecule MR1.

Question 23

A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What antigens do these cells recognize, and how are they activated?

Answer 23

iNKT cells recognize glycolipid antigens presented by the MHC class I-like molecule CD1d and can be activated by bacterial ligands such as cell wall sphingolipids.

Question 24

A patient with a fungal skin infection shows activation of a specific innate lymphoid cell (ILC) population. Which ILC population is involved, and what cytokines do they produce?

Answer 24

ILC-3 is involved in fungal skin infections. They produce cytokines such as IL-7 and IL-22.

Question 25

A patient with a bacterial infection shows activation of mucosal-associated invariant T (MAIT) cells. What activates these cells, and what cytokines do they produce?

Answer 25

MAIT cells are activated by bacterial riboflavin biosynthesis intermediates presented by the MHC class I-like molecule MR1. They produce cytokines such as IFN-γ and IL-17.

Question 26

A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What transcription factor is essential for their development?

Answer 26

The transcription factor PLZF is essential for the development of invariant natural killer T (iNKT) cells.

Question 27

A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What are the five major subsets of iNKT cells, and what do they mirror?

Answer 27

The five major subsets are iNKT1, iNKT2, iNKT17, TH1, and TH2. They mirror T helper cell subsets in cytokine production.

Question 28

A patient with a bacterial skin infection shows activation of innate lymphoid cells (ILCs). Which ILC population is involved, and what cytokines do they produce?

Answer 28

ILC-1 is involved in bacterial skin infections. They produce cytokines such as TNF-α and IFN-γ.

Question 29

A patient with a bacterial skin infection shows activation of unconventional T cells. How do these cells differ from conventional T cells?

Answer 29

Unconventional T cells respond more quickly than conventional T cells and have limited TCR arrangement but can recognize a wide range of antigens.

Question 30

A patient with a viral infection shows activation of mucosal-associated invariant T (MAIT) cells. What is unique about their T cell receptor (TCR)?

Answer 30

MAIT cells express a semi-variant TCR combining a unique TCRα chain with a restricted set of TCRβ chains.

Question 31

A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What changes in host metabolism can these cells sense?

Answer 31

iNKT cells can sense changes in host lipid metabolism through recognition of transiently expressed or unstable endogenous lipids.

Question 32

A patient with a bacterial skin infection shows activation of innate lymphoid cells (ILCs). What are the three populations of ILCs found in human skin?

Answer 32

The three populations of ILCs in human skin are ILC-1, ILC-2, and ILC-3.

Question 33

A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What bacterial ligands can activate these cells?

Answer 33

Bacterial ligands such as cell wall sphingolipids can activate invariant natural killer T (iNKT) cells.

Question 34

What are the three populations of Innate Lymphoid Cells (ILCs) found in human skin and their primary cytokines?

Answer 34

| ILC Type | Surface Molecule | Activated by | Primary Cytokines | Implicated in | |----------|------------------|--------------|-------------------|----------------| | ILC-1 | CD161 | IL-12, IL-15 | TNF-α, IFN-γ | ACD | | ILC-2 | KLRG1, CRTH2, CCR4 | IL-25, IL-33, TSLP, PGD2 | IL-5, IL-13 | Atopic derm | | ILC-3 | NKp44 | IL-1, IL-23 | IL-7, IL-22 | Psoriasis |

Question 35

How do invariant Natural Killer T (iNKT) cells recognize antigens and what are their major subsets?

Answer 35

iNKT cells recognize glycolipid antigens presented by the MHC class 1-like molecule CD1d and can be activated by bacterial ligands such as cell wall sphingolipids. They have 5 major distinct subsets that mirror T helper cell subsets in cytokine production: iNKT1, iNKT2, iNKT17, TH1, and TH2.

Question 36

What is the role of Mucosal-associated Invariant T (MAIT) cells in the immune response?

Answer 36

MAIT cells are a special subset of T cells that express a semi-variant T cell receptor combining a unique TCRα chain with a restricted set of TCRβ chains. They are evolutionarily conserved and have a capacity for rapid effector function.

Question 37

What is the main function of dendritic cells in the immune response?

Answer 37

The main function of dendritic cells is to process antigen material and present it on the cell surface to activated T cells, playing a crucial role in the adaptive immune response.

Question 38

How do natural killer (NK) cells kill altered cells?

Answer 38

Natural killer (NK) cells kill altered cells directly via perforin/granzyme/granulysin or Fas/Fas-ligand dependent mechanisms or indirectly via the secretion of cytokines.

Question 39

What are the three types of dendritic cell subsets found in human skin?

Answer 39

The three types of dendritic cell subsets found in human skin are: 1. Myeloid Dendritic Cells/Conventional DC - Arise from myeloid progenitors in the bone marrow and migrate to tissues. 2. Plasmacytoid Dendritic Cells - Act as sentinels against pathogens.

Question 40

What are the three types of dendritic cell subsets found in human skin?

Answer 40

The three types of dendritic cell subsets found in human skin are: 1. **Myeloid Dendritic Cells/Conventional DC**: Arise from myeloid progenitors in the bone marrow and are abundant at barrier tissue sites. 2. **Plasmacytoid Dendritic Cells**: Act as sentinels against viral infections and express Toll-like receptors. 3. **Langerhans Cells**: Reside in the epidermal layer of the skin, derived from bone marrow, and account for 2-5% of epidermal cells.

Question 41

What cytokines do Langerhans cells require for their development and epidermal residence?

Answer 41

Langerhans cells require the cytokines **IL-34** and **TGF-B**, both derived from keratinocytes, for their development and epidermal residence.

Question 42

What role do dermal dendritic cells play in inflammatory conditions such as psoriasis?

Answer 42

Dermal dendritic cells are the **major source of cytokines** in inflammatory conditions such as **psoriasis**, producing **TNF-a** and inducible nitric oxide synthetase.

Question 43

Which dendritic cell subset is implicated in psoriasis, and how does treatment affect it?

Answer 43

Inflammatory dendritic cells (Tip-DCs) are implicated in psoriasis. They produce TNF-α, IL-20, and IL-23, which are rapidly downregulated during effective treatment.

Question 44

Which dendritic cell subset plays a sentinel role in early defense against viral infections?

Answer 44

Plasmacytoid dendritic cells act as sentinels in early defense against viral infections and express Toll-like receptors 7 and 9.

Question 45

How do plasmacytoid dendritic cells differ from conventional dendritic cells in antigen processing?

Answer 45

Plasmacytoid dendritic cells express fewer MHC class II and co-stimulatory molecules on their surface and process antigens less efficiently compared to conventional dendritic cells.

Question 46

Which dendritic cell subset is the major source of cytokines in chronic inflammatory conditions?

Answer 46

Dermal dendritic cells are the major source of cytokines in inflammatory conditions such as psoriasis.

Question 47

Where do myeloid dendritic cells originate, and what is their role?

Answer 47

Myeloid dendritic cells originate from myeloid progenitors in the bone marrow. They process antigen material and present it on the cell surface to activate T cells.

Question 48

What intracellular sensor do plasmacytoid dendritic cells use to detect single-stranded RNA viruses?

Answer 48

Plasmacytoid dendritic cells use the intracellular sensor RIG-1 to detect single-stranded RNA viruses.

Question 49

What is the state of myeloid dendritic cells under normal conditions, and how does it change during inflammation?

Answer 49

Under normal conditions, myeloid dendritic cells are in an immature state. During inflammation, an additional population of inflammatory dendritic cells appears.

Question 50

What is the primary function of dendritic cells in the immune response?

Answer 50

Dendritic cells primarily function to **process antigen material** and **present it** on their surface to activated T cells, playing a crucial role in the **adaptive immune response**.

Question 51

How do plasmacytoid dendritic cells differ from conventional dendritic cells in terms of function and surface markers?

Answer 51

Plasmacytoid dendritic cells act as **sentinels** against viral infections and express **Toll-like receptors 7 and 9**. They have fewer **MHC class II** and co-stimulatory molecules on their surface compared to conventional dendritic cells.

Question 52

What are the characteristics and functions of Langerhans cells in the skin?

Answer 52

Langerhans cells are a specialized subset of dendritic cells residing in the **epidermal layer** of the skin. They account for **2-5%** of epidermal cells and contain unique **Birbeck granules**.

Question 53

What role do natural killer (NK) cells play in the immune system?

Answer 53

Natural killer (NK) cells are large granular lymphocytes that survey the body for altered cells, including those infected with viruses or parasites, killing these cells **DIRECTLY** via **perforin/granzyme/granulysin**.

Question 54

What is the role of macrophages in the immune system?

Answer 54

Macrophages are essential components of **innate immunity** and play a **central role in inflammation**.

Question 55

What are the two main populations of macrophages and their functions?

Answer 55

The two main populations of macrophages are: 1. **M1 Macrophages**: Activated primarily by **IFN-γ**, produce proinflammatory cytokines, and kill **intracellular bacteria**. 2. **M2 Macrophages**: Involved in response to **parasites**, **tissue remodeling**, and **resolution of skin inflammation**.

Question 56

What are the characteristics and functions of mast cells?

Answer 56

Mast cells are the most abundant at epithelial sites such as the **skin** and **mucosal tissues**, serving as the **first line of defense** against external pathogens.

Question 57

Which macrophage type is involved in parasitic infections?

Answer 57

M2 macrophages are involved in parasitic infections, playing a central role in tissue remodeling and resolution of inflammation.

Question 58

What are the two main populations of macrophages, and how do they differ?

Answer 58

The two main populations are M1 macrophages, which produce proinflammatory cytokines, and M2 macrophages, which are involved in tissue remodeling.

Question 59

What is the origin of mast cells, and how long do they survive in tissues?

Answer 59

Mast cells are derived from pluripotent bone marrow precursors and can survive in tissues for months to years.

Question 60

What receptors do macrophages use to sense tissue invasion?

Answer 60

Macrophages use scavenger, pattern recognition, and phagocytic receptors to sense tissue invasion.

Question 61

What are the primary functions of macrophages in the immune response?

Answer 61

Macrophages are essential components of **innate immunity** and play a central role in **inflammation**.

Question 62

What are the key differences between M1 and M2 macrophages?

Answer 62

| Type | Activation | Cytokines Produced | Function | |------|------------|-------------------|----------| | M1 | Activated primarily by **IFN-γ** | IL-1β, TNF-α, IL-12, IL-18 | Proinflammatory, phagocytize pathogens | | M2 | Alternatively activated | IL-4, IL-10, IL-13, M-CSF, TGF-β | Response to **parasites**, **tissue remodeling** |

Question 63

What role do mast cells play in the immune system?

Answer 63

Mast cells serve as the **first line of defense** against **external pathogens** and can survive in tissues for **months to years**.

Question 64

How do mast cells differ from submucosal or connective tissue mast cells?

Answer 64

Mast cells are **heterogeneous** and differ in some properties from **submucosal** or **connective tissue mast cells**.

Question 65

What are the primary functions of mast cells in the immune response?

Answer 65

Mast cells play a crucial role in the immune response by releasing various **cytokines** and **mediators** such as **Histamine**, **Cytokines**, and **Lipid mediators**.

Question 66

What distinguishes neutrophils from other leukocytes in terms of their role in inflammation?

Answer 66

Neutrophils are characterized as the **hallmark cells of acute inflammation** due to their **high mobility** and **powerful effector functions**.

Question 67

What are the two types of granules found in neutrophils and their functions?

Answer 67

| Granule Type | Function | |--------------------------|--------------------------------------------| | Peroxidase-negative | Involved in **neutrophil recruitment** and **tissue breakdown**. | | Peroxidase-positive | Contains **antimicrobial proteins** such as **alpha-defensins**. |

Question 68

How do eosinophils respond to stimuli in the immune system?

Answer 68

Eosinophils are recruited into tissues in response to specific stimuli, including **Interleukins-5** and **Eotaxin chemokines**.

Question 69

Which immune cells would be the first to respond to a skin infection?

Answer 69

Neutrophils are the first responders to skin infections, using mechanisms such as phagocytosis and degranulation.

Question 70

What cytokine produced by mast cells contributes to chronic inflammation?

Answer 70

TNF-α is a cytokine produced by mast cells that contributes to increased vascular permeability.

Question 71

What preformed compounds are released from mast cell granules during an allergic reaction?

Answer 71

Mast cell granules release preformed compounds such as histamine, serotonin, TNF-α, and various proteases.

Question 72

What is the hallmark process of neutrophil recruitment?

Answer 72

The hallmark process is 'neutrophil swarming.' Neutrophils have two types of granules: peroxidase-negative and peroxidase-positive.

Question 73

What lipid mediators are produced by mast cells?

Answer 73

Mast cells produce lipid mediators such as leukotrienes and prostaglandins, contributing to increased vascular permeability.

Question 74

What cytokines are produced by mast cells following activation?

Answer 74

Mast cells produce cytokines such as TNF-α, IL-3, IL-4, IL-5, and IL-6 following activation.

Question 75

How do neutrophils respond to sites of injury?

Answer 75

Neutrophils respond to sites of injury by being rapidly recruited, engaging in phagocytosis, and producing reactive oxygen species.

Question 76

What distinguishes eosinophils from neutrophils in terms of structure and function?

Answer 76

Eosinophils can be distinguished by their **bilobed nuclei**, large specific granules, and their primary involvement in responses to parasitic infections.

Question 77

How can eosinophils be distinguished from neutrophils?

Answer 77

Eosinophils have bilobed nuclei, while neutrophils have multilobed nuclei. Eosinophils contain large specific granules with major proteins, whereas neutrophils have peroxidase-positive and peroxidase-negative granules. Eosinophils are primarily involved in responses to parasitic infections and allergic reactions, while neutrophils are the first responders to bacterial infections.

Question 78

What is the role of basophils in the immune system?

Answer 78

Basophils are involved in mediating allergic disease and immunity against parasites. They secrete large quantities of IL-4 and are an important source of Th2-type cytokines. Basophils complete their maturation in the bone marrow before entering the peripheral blood and have a short lifespan of several days.

Question 79

How do keratinocytes contribute to the immune response?

Answer 79

Keratinocytes are the most abundant cell type in the skin and play an active role in inflammatory responses. They express multiple different Toll-like receptors and are an important source of cytokines and a broad range of chemoattractants, such as the S100A family of proteins and chemokines, which attract various inflammatory cell types, including neutrophils, macrophages, and dendritic cells.

Question 80

Which granulocyte is involved in allergic reactions and what cytokines does it release?

Answer 80

Basophils are involved in allergic reactions. They release large quantities of IL-4 and other Th2-type cytokines.

Question 81

What role do keratinocytes play in inflammatory responses?

Answer 81

Keratinocytes play an active role in inflammatory responses by expressing Toll-like receptors and producing cytokines and chemokines that attract inflammatory cells.

Question 82

What are the major proteins found in eosinophil granules?

Answer 82

Eosinophil granules contain major basic protein, eosinophil peroxidase, eosinophilic cationic protein, and eosinophil-derived neurotoxin.

Question 83

What chemokines do keratinocytes produce, and what is their role?

Answer 83

Keratinocytes produce chemokines such as the S100A family, which attract inflammatory cell types like neutrophils and macrophages.

Question 84

What stimuli recruit eosinophils into tissues?

Answer 84

Eosinophils are recruited into tissues in response to stimuli such as interleukin-5, eotaxin chemokines, and CCL26.

Question 85

What is the role of basophils in the immune response, particularly in relation to allergic diseases?

Answer 85

Basophils are involved in mediating allergic disease and immunity against parasites. They secrete large quantities of IL-4, which is a Th2-type cytokine, suggesting their significant role in the immune response to allergens.

Question 86

How do keratinocytes contribute to inflammatory responses in the skin?

Answer 86

Keratinocytes play an active role in inflammatory responses by expressing multiple different Toll-like receptors. They are also an important source of cytokines and a broad range of chemoattractants, such as the S100A family of proteins and chemokines, which attract various inflammatory cell types, including neutrophils, macrophages, and dendritic cells.

Question 87

What distinguishes the maturation process of basophils from that of mast cells?

Answer 87

Basophils complete their maturation in the bone marrow before entering the peripheral blood, while mast cells mature in the tissues. This results in basophils having a shorter lifespan of several days compared to mast cells, which can live for weeks to years.

Question 88

What is the significance of eosinophils being found in proximity to mast cells in tissues?

Answer 88

Eosinophils are usually found in proximity to mast cells, with which they communicate extensively. This relationship may enhance the immune response in allergic reactions and parasitic infections, as both cell types play crucial roles in these processes.