10: The Immunological Structure of the Skin Flashcards

1
Q

What is the primary role of the skin as a border organ?

A

The skin serves as a border organ, separating the host’s structural constituents from the environment while allowing communication between the inside and outside world. This dual role is commonly referred to as ‘skin barrier function’.

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2
Q

What are the major tasks of the skin in maintaining tissue homeostasis?

A

The major tasks of the skin include securing and maintaining tissue homeostasis and preserving host integrity. In response to major danger signals, it allows for the rapid generation and mobilization of effective host defense reactions to neutralize pathogens.

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3
Q

What components make up the skin immune system?

A

The skin immune system consists of various cells and molecules, including:

  • Macrophages: Phagocytosis and cytokine production
  • Dendritic cells: Antigen presentation and activation of T cells
  • T cells: Adaptive immune response
  • B cells: Antibody production
  • Mast cells: Release of histamine and other mediators
  • Neutrophils: First responders to infection
  • Eosinophils: Defense against parasites and allergic reactions.
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4
Q

What are the two components of the skin immune system?

A

The skin immune system has two components: an innate component, which provides immediate defense against pathogens, and an adaptive component, which involves a more specific and long-lasting immune response.

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5
Q

What is the dual role of the skin as a ‘Grenzorgan’ and how does it contribute to immune responses?

A

The skin acts as a ‘Grenzorgan’ by separating the host’s structural constituents from the environment while allowing communication between the inside and outside. This dual role is known as ‘skin barrier function’, which secures tissue homeostasis and preserves host integrity. In response to pathogenic microorganisms, it enables rapid host defense reactions to neutralize threats.

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6
Q

What are the key components of the skin immune system and their roles?

A

The skin immune system consists of both innate and adaptive components. Key cellular constituents include:

  • Macrophages: Phagocytosis and antigen presentation
  • Dendritic cells (DC): Antigen capture and presentation to T cells
  • T cells: Adaptive immune response
  • Mast cells: Release of mediators in allergic responses
  • Neutrophils: First responders to infection
  • Eosinophils: Defense against parasites and modulation of allergic responses.
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7
Q

What are pattern recognition receptors (PRRs) and their role in innate immunity?

A

Pattern recognition receptors (PRRs) are a large family of surface-bound and/or cytoplasmic receptors that enable leukocytes and non-leukocytes involved in innate immunity to rapidly sense danger signals such as microbes, their constituents, hapten, and UV radiation.

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8
Q

How do innate immunocytes respond to pathogens?

A

Innate immunocytes either expand in situ or are recruited from circulation to elaborate mediators that neutralize and/or eliminate pathogens.

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9
Q

What is the difference in onset between innate and adaptive immunity?

A

Innate immunity has a rapid onset, while adaptive immunity takes 10-14 days to develop.

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10
Q

What is the capacity of innate immunity in terms of danger discrimination?

A

Innate immunity has the capacity to discriminate between danger and non-danger signals only.

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11
Q

What is the role of neutrophils in the innate immune system?

A

Neutrophils act as the first responders after most forms of injury in the innate immune system.

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12
Q

A patient with a bacterial skin infection shows rapid recruitment of immune cells to the site of injury. Which innate immune cells are the first responders?

A

Neutrophils act as the first responders after most forms of injury.

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13
Q

A patient with a history of UV radiation exposure shows activation of pattern recognition receptors (PRRs). What is the role of PRRs in this context?

A

PRRs, such as Toll-like receptors (TLRs), rapidly sense danger signals like UV radiation and initiate immune responses.

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14
Q

A patient with a skin infection shows a lack of memory response upon repeated antigen exposure. Which component of the immune system is likely involved?

A

The innate immune system, which lacks memory, is likely involved in this scenario.

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15
Q

What is the role of pattern recognition receptors (PRRs) in innate immunity?

A

Pattern recognition receptors (PRRs) are essential for both leukocytes and non-leukocytes in innate immunity, enabling them to rapidly sense danger signals such as microbes, haptens, and UV radiation.

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16
Q

How do innate immunocytes respond to the presence of pathogens?

A

Innate immunocytes either expand in situ or are recruited from circulation to elaborate mediators that neutralize and/or eliminate pathogens.

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17
Q

What are the key differences between innate and adaptive immunity in terms of response time and memory?

A

Innate immunity has a rapid onset, while adaptive immunity takes 10-14 days to develop. Innate immunity lacks memory, whereas adaptive immunity reacts in an enhanced fashion to repeated antigen challenges.

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18
Q

What is the function of neutrophils in the innate immune system?

A

Neutrophils act as the first responders after most forms of injury, playing a crucial role in the initial immune response.

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19
Q

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

A

Eosinophils are much less efficient phagocytes than polymorphonuclear neutrophils. They release preformed cationic proteins that are toxic to several parasites, providing efficient protection against them.

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20
Q

What role do basophils play in allergic tissue inflammation?

A

Basophils contain histamine-filled granules and are a rich source of cytokines such as interleukin (IL)-4 and IL-13. They resemble mast cells and play an important role in allergic tissue inflammation.

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21
Q

What are the key functions of mast cells in the immune system?

A

Mast cells exhibit membrane-bound and cytoplasmic granules containing preformed mediators (e.g., histamine, serotonin) and molecules upon activation (e.g., TNF, IL-3,4,13). They release mediators through the interaction of complement cleavage products with their receptors and Fc-mediated binding of IgE, leading to type 1 hypersensitivity reactions.

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22
Q

How do macrophages contribute to the elimination of invading microbes?

A

Macrophages are heavily involved in the elimination of invading microbes through phagocytosis and the subsequent killing of pathogens by reactive oxygen species. They also clean up the stage and promote tissue regeneration and repair.

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23
Q

What is the role of dendritic cells in antiviral defense?

A

Dendritic cells play a major role in antiviral defense by producing type 1 interferons upon activation of TLR7 and TLR9. Imiquimod provides a strong activation signal, enhancing both interferon production and expression of lytic molecules, which is significant in treating conditions like genital warts and basal cell carcinomas.

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24
Q

What are innate lymphocytes and their primary function?

A

Innate lymphocytes are a family of non-T non-B lymphoid cells that include cytotoxic natural killer (NK) cells and helper ILCs. NK cells are responsible for the recognition and killing of virally infected and neoplastic cells, as well as the secretion of IFN-γ, a main immunoregulatory cytokine.

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25
Q

A patient with a history of allergic reactions shows elevated levels of histamine in the skin. Which immune cell is most likely responsible for this, and what triggers its activation?

A

Mast cells are responsible for releasing histamine. Their activation is triggered by the interaction of complement cleavage products (C3a and C5a) with their receptors or by Fc-mediated binding of IgE crosslinked by the respective antigen.

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26
Q

A patient with a viral skin infection is treated with imiquimod. What is the mechanism of action of this treatment?

A

Imiquimod activates dendritic cells with innate immune functions, leading to massive production of type 1 interferons and expression of lytic molecules, which are effective against viral infections.

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27
Q

A patient with an exaggerated immune response to plant pollen is diagnosed with an allergic condition. Which immune cells and cytokines are likely involved?

A

Basophils, which contain histamine-filled granules and are a rich source of cytokines such as IL-4 and IL-13, play an important role in allergic tissue inflammation.

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28
Q

A patient with a parasitic skin infection shows elevated levels of eosinophilic cationic proteins. What is the role of these proteins?

A

Eosinophilic cationic proteins are toxic to several parasites and provide efficient protection against them.

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29
Q

A patient with a viral skin infection shows increased production of type 1 interferons. Which immune cells are responsible for this response?

A

Dendritic cells with innate immune functions play a major role in antiviral defense by producing type 1 interferons.

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30
Q

A patient with a skin condition shows the secretion of IFN-γ by innate lymphocytes. What is the role of this cytokine?

A

IFN-γ is a main immunoregulatory cytokine secreted by natural killer (NK) cells, which are part of the innate lymphocyte family.

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31
Q

A patient with a skin condition shows the secretion of IL-4 and IL-13 by immune cells. Which cells are likely responsible for this secretion?

A

Basophils, which are rich sources of cytokines like IL-4 and IL-13, are likely responsible for this secretion.

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32
Q

A patient with a skin condition shows the secretion of reactive oxygen species by immune cells. Which cells are involved in this process?

A

Macrophages are involved in the elimination of invading microbes by phagocytosis and the subsequent killing of the pathogen using reactive oxygen species.

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33
Q

A patient with a skin condition shows the therapeutic efficacy of topical imiquimod. What is the mechanism behind this efficacy?

A

Topical imiquimod provides a strong activation signal for dendritic cells, leading to the production of type 1 interferons and lytic molecules, which are effective against conditions like genital warts and basal cell carcinomas.

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34
Q

A patient with a skin condition shows type 1 hypersensitivity reactions. Which immune cells and mechanisms are involved?

A

Mast cells are involved in type 1 hypersensitivity reactions, which occur due to Fc-mediated binding of IgE crosslinked by the respective antigen.

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35
Q

What is the primary role of eosinophils in the immune response, and how do they achieve this?

A

Eosinophils provide efficient protection against parasites by releasing preformed cationic proteins that are toxic to several parasites. They are much less efficient phagocytes compared to polymorphonuclear neutrophils.

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36
Q

How do basophils contribute to allergic tissue inflammation?

A

Basophils contain histamine-filled granules and are a rich source of cytokines such as interleukin (IL)-4 and IL-13. They resemble mast cells and play an important role in mediating allergic responses.

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37
Q

Describe the function of mast cells in the immune system and their mechanism of action upon activation.

A

Mast cells exhibit membrane-bound and cytoplasmic granules containing preformed mediators like histamine and serotonin. Upon activation, they release these mediators and interact with complement cleavage products C3a and C5a, as well as IgE, leading to type 1 hypersensitivity reactions.

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38
Q

What is the significance of NK cells in the innate immune response?

A

NK cells are crucial for the recognition and killing of virally infected and neoplastic cells. They secrete IFN-γ, which is a main immunoregulatory cytokine, enhancing the immune response against infections and tumors.

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39
Q

Explain the role of macrophages in the elimination of invading microbes.

A

Macrophages are heavily involved in eliminating invading microbes through phagocytosis and subsequent killing of pathogens using reactive oxygen species. They also promote tissue regeneration and repair after an immune response.

40
Q

What role do dendritic cells play in antiviral defense, and how does Imiquimod enhance this function?

A

Dendritic cells play a major role in antiviral defense by producing type 1 interferons upon activation of TLR7 and TLR9. Imiquimod provides a strong activation signal that enhances not only interferon production but also the expression of lytic molecules, contributing to its therapeutic efficacy in certain skin conditions.

41
Q

What is the significance of NK cells in the innate immune response?

A

NK cells are crucial for the recognition and killing of virally infected and neoplastic cells. They also secrete IFN-γ, which is a main immunoregulatory cytokine, enhancing the immune response.

42
Q

Explain the role of macrophages in the elimination of invading microbes.

A

Macrophages are heavily involved in eliminating invading microbes through phagocytosis and subsequent killing of pathogens using reactive oxygen species. They also promote tissue regeneration and repair after the immune response.

43
Q

What role do dendritic cells play in antiviral defense, and how does Imiquimod enhance their function?

A

Dendritic cells play a major role in antiviral defense by producing type 1 interferons upon activation of TLR7 and TLR9. Imiquimod provides a strong activation signal that enhances not only interferon production but also the expression of lytic molecules, contributing to its therapeutic efficacy.

44
Q

What are the three distinct populations of antigen presenting dendritic cells found in normal human skin?

A

The three distinct populations of antigen presenting dendritic cells in normal human skin are:
- Epidermal Langerhans cells
- Dermal DC
- Plasmacytoid DC (CD141+)

45
Q

What is the primary location of T lymphocytes in human skin?

A

Most T lymphocytes are localized in the dermis, with only 10% found in the epidermis.

46
Q

What are the criteria used to subdivide T cells?

A

T cells can be subdivided based on the following criteria:
1. Antigenic experience
2. Type of T-cell receptors
3. Type of accessory molecules expressed (CD4 vs CD8)
4. Functional differentiation (type of transcription factor; helper vs cytotoxic; cytokine secretion pattern)

47
Q

What are the requirements for maintaining cellular and tissue homeostasis in the skin?

A

The maintenance of cellular and tissue homeostasis requires:
1. Prevention of exaggerated responses to innocuous substances (e.g., human dander, plant pollen, nutrients)
2. Occurrence of host-defense reactions at a subclinical level, that is, in the absence of inflammation.

48
Q

How does Psoriasin function in the skin’s immune response?

A

Psoriasin is an antimicrobial peptide (AMP) produced by keratinocytes with a baseline production. Its antimicrobial effect is mainly directed against Escherichia coli.

49
Q

What role do commensals like Staphylococcus epidermidis play in skin immunity?

A

Commensals such as Staphylococcus epidermidis colonizing the epidermis can induce an immune response that depends on the interplay between different types of dendritic cells (DC).

50
Q

A patient presents with a skin infection caused by Escherichia coli. Which antimicrobial peptide (AMP) is likely involved in the defense mechanism, and what is its primary source?

A

Psoriasin, an AMP with baseline production by keratinocytes, is primarily involved in defending against Escherichia coli.

51
Q

A patient with a skin condition shows a predominance of CD4+ T cells in the dermis. What does this indicate about the localization of T cells in the skin?

A

Most T cells are localized in the dermis, with dermal T cells being mainly CD4+.

52
Q

A patient with a skin condition shows a predominance of CD8+ T cells in the epidermis. What does this indicate about the localization of T cells in the skin?

A

Epidermal T cells preferentially display the CD8+ phenotype.

53
Q

A patient with a skin condition shows a lack of inflammation despite the presence of host-defense reactions. What does this indicate about the immune system’s state?

A

This indicates that host-defense reactions are occurring at a subclinical level, maintaining tissue homeostasis without inflammation.

54
Q

A patient with a skin condition shows exaggerated immune responses to innocuous substances like plant pollen. What does this indicate about the immune system’s regulation?

A

This indicates a failure in preventing exaggerated responses to innocuous substances, which is essential for maintaining tissue homeostasis.

55
Q

A patient with a skin condition shows the presence of commensal bacteria like Staphylococcus epidermidis. What is the role of these commensals in the immune response?

A

Commensals like Staphylococcus epidermidis colonizing the epidermis can induce an immune response dependent on the interplay between different types of dendritic cells.

56
Q

A patient with a skin condition shows the presence of ribonucleotidases with antimicrobial properties. What is the role of these proteins?

A

Ribonucleotidases, such as types 1, 4, 5, and 7, are constitutively produced mediators that prevent the overgrowth of pathogenic microorganisms in normal skin.

57
Q

A patient with a skin condition shows the presence of Psoriasin. What is the primary target of this antimicrobial peptide?

A

Psoriasin, an antimicrobial peptide, primarily targets Escherichia coli.

58
Q

What are the three distinct populations of antigen presenting dendritic cells found in normal human skin, and what is their significance in the adaptive immune system?

A

The three distinct populations of antigen presenting dendritic cells in normal human skin are:
1. Epidermal Langerhans cells
2. Dermal DC
3. Plasmacytoid DC (CD141+)

These cells are crucial for initiating and regulating immune responses in the skin, derived from bone marrow precursors.

59
Q

How do T lymphocytes contribute to the maintenance of skin immune homeostasis, and what are the main subtypes identified?

A

T lymphocytes are the largest population of lymphocytes in the skin, primarily localized in the dermis. They contribute to skin immune homeostasis by:
- Preventing exaggerated immune responses to harmless substances.
- Engaging in host-defense reactions at subclinical levels.

The main subtypes of T lymphocytes include:
- CD4+ T Cells: Mainly found in the dermis, involved in helper functions.
- CD8+ T Cells: Preferentially displayed by epidermal T cells, cytotoxic functions.
- T naїve: Inexperienced T cells that have not yet encountered an antigen.
- T memory: Long-lived cells that respond more rapidly upon re-exposure to an antigen.
- Recirculating T Cells: Move between lymphoid tissues and skin.
- Tissue-resident Memory T Cells (Trm): Provide localized immune protection in the skin.

60
Q

What role do antimicrobial peptides (AMPs) play in the prevention of pathogenic microorganisms in normal skin, and what is an example of such an AMP?

A

Antimicrobial peptides (AMPs) play a critical role in preventing the overgrowth of pathogenic microorganisms in normal skin by:
- Providing a first line of defense against infections.
- Exhibiting direct antimicrobial properties against a range of pathogens.

An example of an AMP is Psoriasin, which is produced by keratinocytes and has a baseline production level. It primarily targets Escherichia coli, demonstrating its role in skin immunity.

61
Q

How do commensal microorganisms like Staphylococcus epidermidis influence the immune response in the skin?

A

Commensal microorganisms such as Staphylococcus epidermidis influence the immune response in the skin by:
- Inducing an immune response that is dependent on the interplay between different types of dendritic cells (DC).
- Contributing to the maintenance of skin homeostasis by preventing pathogenic overgrowth and modulating local immune responses.

62
Q

What are the three distinct populations of antigen presenting dendritic cells found in normal human skin, and what is their significance in the adaptive immune system?

A

The three distinct populations of antigen presenting dendritic cells in normal human skin are:
1. Epidermal Langerhans cells
2. Dermal DC
3. Plasmacytoid DC (CD141+)

These cells play a crucial role in initiating and regulating immune responses by presenting antigens to T lymphocytes, thus influencing the adaptive immune system.

63
Q

How do T lymphocytes contribute to the skin’s immune response, and what are the main criteria for their subdivision?

A

T lymphocytes are the largest and most important lymphocyte population in the skin, primarily localized in the dermis. They contribute to the immune response by recognizing and responding to antigens. T cells can be subdivided based on:
1. Antigenic experience
2. Type of T-cell receptors
3. Type of accessory molecules expressed (CD4 vs CD8)
4. Functional differentiation (helper vs cytotoxic; cytokine secretion pattern)

64
Q

What mechanisms are involved in maintaining cellular and tissue homeostasis in the skin, and how do they prevent overgrowth of pathogenic microorganisms?

A

Maintenance of cellular and tissue homeostasis in the skin requires:
1. Prevention of exaggerated responses to innocuous substances (e.g., human dander, plant pollen).
2. Host-defense reactions at a subclinical level, in the absence of inflammation.

The overgrowth of pathogenic microorganisms is prevented by:
- Proteins with antimicrobial properties (e.g., ribonucleotidases 1, 4, 5, and 7)
- Different proteases
- Certain antimicrobial peptides (AMPs), such as Psoriasin, which is produced by keratinocytes and targets Escherichia coli.

65
Q

What role do commensal microorganisms play in the skin’s immune response, and how does this relate to dendritic cells?

A

Commensal microorganisms, such as Staphylococcus epidermidis, colonizing the epidermis can induce an immune response that is dependent on the interplay between different types of dendritic cells. This relationship helps to maintain skin homeostasis and modulate immune responses, preventing overreactions to harmless antigens.

66
Q

What role does IL-17 play in the immune response of the skin?

A

IL-17, produced by CD8+ T cells, binds to IL-17 receptors on keratinocytes, triggering the production of mediators that help prevent the overgrowth of pathogens like Staphylococcus aureus.

67
Q

What is the significance of Langerhans cells (LCs) in skin immune responses?

A

Langerhans cells (LCs) are considered principal sensitizing cells in skin-derived immune responses, but they are dispensable for protective immune responses against certain microorganisms, such as herpes simplex virus.

68
Q

How do T cells of the Th17 lineage contribute to skin conditions like acne and rosacea?

A

T cells of the Th17 lineage have been identified in lesional skin of acne and rosacea, where they recognize Propionibacterium acnes-derived peptides, contributing to the inflammatory response.

69
Q

What factors contribute to the recurrence of inflammatory skin diseases?

A

The recurrence of inflammatory skin diseases is caused by both the influx of pathogenic leukocytes from the blood and the activation of T memory cells in the skin, particularly Trm cells.

70
Q

What is the relationship between immune cell presence and prognosis in skin cancers?

A

High numbers of intratumoral and peritumoral granulocytes, pDCs, and M2 macrophages are associated with a bad prognosis, while large numbers of CD3+ T cells, CD8+ cytotoxic T lymphocytes, and CD45RO+ memory T cells are linked to longer disease-free survival.

71
Q

A patient with rosacea has a predominance of Th17 cells in their skin lesions. What is the likely antigen these cells are recognizing?

A

Th17 cells in rosacea lesions are likely recognizing Propionibacterium acnes-derived peptides.

72
Q

A patient with a cutaneous Leishmania infection shows an unusual presence of B cells in the skin. Why is this observation significant?

A

B cells generally avoid the skin, but their presence in cutaneous Leishmania infection is a notable exception.

73
Q

A patient with recurrent inflammatory skin disease shows activation of T memory cells in the skin. What type of T memory cells are likely involved?

A

T resident memory cells (Trm) are likely involved in the recurrence of inflammatory skin diseases.

74
Q

A patient with a primary skin tumor shows a high number of intratumoral granulocytes and M2 macrophages. What does this indicate about the prognosis?

A

The presence of high numbers of intratumoral granulocytes and M2 macrophages, which produce IL-4, IL-10, IL-13, and TGF-β, heralds a poor prognosis.

75
Q

A patient with a skin infection caused by herpes simplex virus shows a lack of protective immune response. What does this suggest about the role of Langerhans cells (LCs)?

A

LCs are dispensable for the occurrence of protective immune responses against certain microorganisms, such as herpes simplex virus.

76
Q

A patient with a skin infection caused by Staphylococcus aureus shows activation of keratinocytes. Which cytokine and receptor are involved in this process?

A

IL-17 produced by CD8+ T cells binds to IL-17 receptors on keratinocytes, triggering the production of mediators to prevent the overgrowth of Staphylococcus aureus.

77
Q

A patient with a skin condition shows trafficking of antigen-bearing Langerhans cells (LCs) to lymph nodes. What is the significance of this observation?

A

Antigen-bearing LCs and dendritic cells (DCs) constantly traffic between the skin and lymph nodes, playing a role in immune responses.

78
Q

A patient with a skin condition shows the presence of plasmacytoid dendritic cells (pDCs) at the margins of lesions. What is the role of pDCs in this context?

A

Plasmacytoid dendritic cells (pDCs) are involved in the innate immune response and are usually detected at the active margins of individual lesions.

79
Q

A patient with a skin condition shows the presence of T cells of the Th17 lineage. What is the significance of this observation?

A

T cells of the Th17 lineage are involved in inflammatory skin diseases, such as acne and rosacea, and recognize specific antigens like Propionibacterium acnes-derived peptides.

80
Q

A patient with a skin condition shows the recurrence of inflammation despite treatment. What is the likely cause of this recurrence?

A

The recurrence of inflammation is likely caused by the activation of T resident memory cells (Trm) in the skin.

81
Q

A patient with a skin condition shows trafficking of Langerhans cells (LCs) carrying melanosomes to lymph vessels. What does this indicate about the role of LCs?

A

LCs carrying melanosomes and/or apoptotic bodies are involved in antigen presentation and trafficking between the skin and lymph nodes.

82
Q

A patient with skin cancer shows a high number of CD3+ T cells and CD8+ cytotoxic T lymphocytes. What does this indicate about the prognosis?

A

The presence of high numbers of CD3+ T cells and CD8+ cytotoxic T lymphocytes is associated with a longer disease-free survival.

83
Q

A patient with skin cancer shows a weakening of the immune system’s cancer-destructive capacity over time. What does this indicate about the tumor’s progression?

A

The weakening of the immune system’s cancer-destructive capacity over time indicates that the primary tumor is persisting and evading immune responses.

84
Q

A patient with skin cancer shows the presence of myeloid-derived suppressor cells. What is the significance of this observation?

A

The presence of myeloid-derived suppressor cells, which produce immunosuppressive cytokines like IL-4, IL-10, and TGF-β, is associated with a poor prognosis.

85
Q

A patient with skin cancer shows the presence of peritumoral granulocytes. What does this indicate about the immune contexture?

A

The presence of peritumoral granulocytes is associated with a poor prognosis in skin cancer.

86
Q

A patient with skin cancer shows the presence of transforming growth factor (TGF)-β. What is the role of this cytokine in the tumor microenvironment?

A

Transforming growth factor (TGF)-β is an immunosuppressive cytokine produced by cells like M2 macrophages, contributing to a poor prognosis in skin cancer.

87
Q

What role do Langerhans cells (LCs) play in skin-derived immune responses?

A

Langerhans cells (LCs) are considered principal sensitizing cells in skin-derived immune responses, playing a key role in initiating and regulating immune responses.

88
Q

What does the presence of peritumoral granulocytes indicate about the immune contexture?

A

The presence of peritumoral granulocytes is associated with a poor prognosis in skin cancer.

89
Q

What is the role of transforming growth factor (TGF)-β in the tumor microenvironment?

A

Transforming growth factor (TGF)-β is an immunosuppressive cytokine produced by cells like M2 macrophages, contributing to a poor prognosis in skin cancer.

90
Q

What role do Langerhans cells (LCs) play in skin-derived immune responses?

A

Langerhans cells (LCs) are regarded as principal sensitizing cells in skin-derived immune responses. They are dispensable for protective immune responses against certain microorganisms, such as herpes simplex virus. LCs are involved in antigen trafficking between skin and lymph nodes, leading to the hypothesis that they are intrinsically destined to generate downregulating or tolerizing T-cell responses.

91
Q

How do different T-cell subsets influence the classification of inflammatory skin diseases?

A

Many inflammatory skin diseases can be classified according to the T-cell subset(s) involved. For example, Th1 cells are associated with conditions like lichen planus and allergic contact dermatitis, while Th2/Th22 cells are linked to atopic dermatitis. This classification helps in understanding the immune mechanisms underlying various skin diseases.

92
Q

What is the significance of T memory cells in the recurrence of inflammatory skin diseases?

A

The recurrence of an inflammatory skin disease is influenced not only by the influx of pathogenic leukocytes from the blood but also by the activation of T memory cells (notably Trm) in the skin. This highlights the role of memory T cells in maintaining immune responses and potentially contributing to disease persistence.

93
Q

What is the relationship between immune cell presence in tumors and disease prognosis in skin cancers?

A

The presence of high numbers of intratumoral and peritumoral granulocytes, pDCs, myeloid-derived suppressor cells, and M2 macrophages is associated with a bad prognosis in skin cancers. In contrast, large numbers of CD3+ T cells, CD8+ cytotoxic T lymphocytes, and CD45RO+ memory T cells are linked to a longer disease-free survival, indicating the importance of immune contexture in cancer outcomes.

94
Q

What role do Langerhans cells (LCs) play in skin-derived immune responses?

A

Langerhans cells (LCs) are considered principal sensitizing cells in skin-derived immune responses. They are dispensable for protective immune responses against certain microorganisms, such as herpes simplex virus. LCs are involved in antigen trafficking between skin and lymph nodes, leading to the hypothesis that they are intrinsically destined to generate downregulating or tolerizing T-cell responses.

95
Q

How does the presence of different T-cell subsets influence the classification of inflammatory skin diseases?

A

Inflammatory skin diseases can be classified according to the T-cell subset(s) involved. For example, diseases associated with Th1 cells include lichen planus and acute graft-versus-host disease (GVHD), while Th2/Th22 cells are linked to atopic dermatitis and psoriasis. This classification helps in understanding the underlying immune mechanisms and potential therapeutic targets.

96
Q

What is the significance of T memory cells in the recurrence of inflammatory skin diseases?

A

The recurrence of inflammatory skin diseases is influenced not only by the influx of pathogenic leukocytes from the blood but also by the activation of T memory cells in the skin, particularly Trm cells. This suggests that memory T cells play a crucial role in maintaining immune responses and potentially contributing to disease persistence.

97
Q

What is the relationship between immune cell presence in tumors and disease prognosis in skin cancers?

A

The presence of high numbers of intratumoral and peritumoral granulocytes, pDCs, and M2 macrophages producing IL-4, IL-10, and TGF-β is associated with a bad prognosis in skin cancers. Conversely, large numbers of CD3+ T cells, CD8+ cytotoxic T lymphocytes, and CD45RO+ memory T cells correlate with a longer disease-free survival, indicating the importance of immune context in cancer outcomes.