11: Cellular Components of the Cutaneous Immune System Flashcards
What are the components of the skin immune system?
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
What are the dual characteristics of innate and adaptive immune cells?
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.
How does the innate immune system recognize pathogens?
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.
What is the basis of the adaptive immune system’s response?
The adaptive immune system’s response is based on antigen receptor or antibody diversity, allowing for a specific response to various pathogens.
How do innate and adaptive immune systems differ in their recognition mechanisms?
The innate immune system recognizes proteins, lipids, and nucleotides, while the adaptive immune system is based on antigen receptor or antibody diversity.
What are the primary cells involved in the first line of defense against pathogens?
Dendritic cells and macrophages are the primary cells that provide rapid first line of defense against pathogens.
What is the role of T helper 1 (TH1) cells in the immune system?
TH1 cells are the main mediators of cell-mediated immunity, playing a crucial role in the immune response against intracellular pathogens.
How do B cells function in the immune system?
B cells form the humoral arm of the immune system by binding to and neutralizing pathogens, preventing their ability to enter and infect cells.
What is the significance of T regulatory cells (Tregs) in the immune response?
Tregs maintain tolerance to self-antigens in the periphery, suppressing activation, cytokine production, and proliferation of other T cells, thus preventing autoimmune responses.
What are the characteristics of naïve T cells?
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.
What are the functions of tissue-resident lymphocytes in the immune system?
Tissue-resident lymphocytes act as sensors of disturbed tissue integrity from infection or injury and help recruit additional immune cells from the blood.
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?
B cells are likely elevated in atopic dermatitis. They produce antibodies that bind and neutralize pathogens and bacterial toxins.
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?
TH17 cells are involved in bacterial skin infections. They mediate antigen responses against extracellular pathogens.
A patient with a bacterial skin infection shows activation of TH1 cells. What is the primary function of TH1 cells?
TH1 cells are the main mediators of cell-mediated immunity.
A patient with a bacterial skin infection shows activation of TH17 cells. What skin condition is TH17 implicated in?
TH17 cells are implicated in psoriasis.
A patient with a bacterial skin infection shows activation of TH2 cells. What is the primary function of TH2 cells?
TH2 cells facilitate humoral (antibody) responses and inhibit some cell-mediated immune responses.
What distinguishes naive T cells from effector T cells?
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.
In what conditions are B cells infrequently found, and what is their primary function?
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.
What is the significance of tissue-resident lymphocytes in the immune response?
Tissue-resident lymphocytes act as sensors of disturbed tissue integrity from infection or injury and help recruit additional immune cells from the blood.
What are the three populations of Innate Lymphoid Cells (ILCs) found in human skin?
The three populations of ILCs found in human skin are:
- ILC-1 - Surface Molecule: CD161, Activated by: IL-12, IL-15, Primary Cytokines: TNF-α, IFN-γ, Implicated in: ACD
- 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
- ILC-3 - Surface Molecule: NKp44, Activated by: IL-1, IL-23, Primary Cytokines: IL-7, IL-22, Implicated in: Psoriasis
What is the role of invariant Natural Killer T (iNKT) cells in the immune response?
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.
What are Mucosal-associated Invariant T (MAIT) cells and their function?
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.
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?
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.
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?
ILC-3 is involved in fungal skin infections. They produce cytokines such as IL-7 and IL-22.
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?
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.
A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What transcription factor is essential for their development?
The transcription factor PLZF is essential for the development of invariant natural killer T (iNKT) cells.
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?
The five major subsets are iNKT1, iNKT2, iNKT17, TH1, and TH2. They mirror T helper cell subsets in cytokine production.
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?
ILC-1 is involved in bacterial skin infections. They produce cytokines such as TNF-α and IFN-γ.
A patient with a bacterial skin infection shows activation of unconventional T cells. How do these cells differ from conventional T cells?
Unconventional T cells respond more quickly than conventional T cells and have limited TCR arrangement but can recognize a wide range of antigens.
A patient with a viral infection shows activation of mucosal-associated invariant T (MAIT) cells. What is unique about their T cell receptor (TCR)?
MAIT cells express a semi-variant TCR combining a unique TCRα chain with a restricted set of TCRβ chains.
A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What changes in host metabolism can these cells sense?
iNKT cells can sense changes in host lipid metabolism through recognition of transiently expressed or unstable endogenous lipids.
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?
The three populations of ILCs in human skin are ILC-1, ILC-2, and ILC-3.
A patient with a viral infection shows activation of invariant natural killer T (iNKT) cells. What bacterial ligands can activate these cells?
Bacterial ligands such as cell wall sphingolipids can activate invariant natural killer T (iNKT) cells.
What are the three populations of Innate Lymphoid Cells (ILCs) found in human skin and their primary cytokines?
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 |
How do invariant Natural Killer T (iNKT) cells recognize antigens and what are their major subsets?
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.
What is the role of Mucosal-associated Invariant T (MAIT) cells in the immune response?
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.
What is the main function of dendritic cells in the immune response?
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.
How do natural killer (NK) cells kill altered cells?
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.
What are the three types of dendritic cell subsets found in human skin?
The three types of dendritic cell subsets found in human skin are:
- Myeloid Dendritic Cells/Conventional DC - Arise from myeloid progenitors in the bone marrow and migrate to tissues.
- Plasmacytoid Dendritic Cells - Act as sentinels against pathogens.
What are the three types of dendritic cell subsets found in human skin?
The three types of dendritic cell subsets found in human skin are:
- Myeloid Dendritic Cells/Conventional DC: Arise from myeloid progenitors in the bone marrow and are abundant at barrier tissue sites.
- Plasmacytoid Dendritic Cells: Act as sentinels against viral infections and express Toll-like receptors.
- Langerhans Cells: Reside in the epidermal layer of the skin, derived from bone marrow, and account for 2-5% of epidermal cells.
What cytokines do Langerhans cells require for their development and epidermal residence?
Langerhans cells require the cytokines IL-34 and TGF-B, both derived from keratinocytes, for their development and epidermal residence.
What role do dermal dendritic cells play in inflammatory conditions such as psoriasis?
Dermal dendritic cells are the major source of cytokines in inflammatory conditions such as psoriasis, producing TNF-a and inducible nitric oxide synthetase.
Which dendritic cell subset is implicated in psoriasis, and how does treatment affect it?
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.
Which dendritic cell subset plays a sentinel role in early defense against viral infections?
Plasmacytoid dendritic cells act as sentinels in early defense against viral infections and express Toll-like receptors 7 and 9.
How do plasmacytoid dendritic cells differ from conventional dendritic cells in antigen processing?
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.
Which dendritic cell subset is the major source of cytokines in chronic inflammatory conditions?
Dermal dendritic cells are the major source of cytokines in inflammatory conditions such as psoriasis.
Where do myeloid dendritic cells originate, and what is their role?
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.
What intracellular sensor do plasmacytoid dendritic cells use to detect single-stranded RNA viruses?
Plasmacytoid dendritic cells use the intracellular sensor RIG-1 to detect single-stranded RNA viruses.
What is the state of myeloid dendritic cells under normal conditions, and how does it change during inflammation?
Under normal conditions, myeloid dendritic cells are in an immature state. During inflammation, an additional population of inflammatory dendritic cells appears.
What is the primary function of dendritic cells in the immune response?
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.
How do plasmacytoid dendritic cells differ from conventional dendritic cells in terms of function and surface markers?
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.
What are the characteristics and functions of Langerhans cells in the skin?
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.
What role do natural killer (NK) cells play in the immune system?
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.
What is the role of macrophages in the immune system?
Macrophages are essential components of innate immunity and play a central role in inflammation.
What are the two main populations of macrophages and their functions?
The two main populations of macrophages are:
- M1 Macrophages: Activated primarily by IFN-γ, produce proinflammatory cytokines, and kill intracellular bacteria.
- M2 Macrophages: Involved in response to parasites, tissue remodeling, and resolution of skin inflammation.
What are the characteristics and functions of mast cells?
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.
Which macrophage type is involved in parasitic infections?
M2 macrophages are involved in parasitic infections, playing a central role in tissue remodeling and resolution of inflammation.
What are the two main populations of macrophages, and how do they differ?
The two main populations are M1 macrophages, which produce proinflammatory cytokines, and M2 macrophages, which are involved in tissue remodeling.
What is the origin of mast cells, and how long do they survive in tissues?
Mast cells are derived from pluripotent bone marrow precursors and can survive in tissues for months to years.
What receptors do macrophages use to sense tissue invasion?
Macrophages use scavenger, pattern recognition, and phagocytic receptors to sense tissue invasion.
What are the primary functions of macrophages in the immune response?
Macrophages are essential components of innate immunity and play a central role in inflammation.
What are the key differences between M1 and M2 macrophages?
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 |
What role do mast cells play in the immune system?
Mast cells serve as the first line of defense against external pathogens and can survive in tissues for months to years.
How do mast cells differ from submucosal or connective tissue mast cells?
Mast cells are heterogeneous and differ in some properties from submucosal or connective tissue mast cells.
What are the primary functions of mast cells in the immune response?
Mast cells play a crucial role in the immune response by releasing various cytokines and mediators such as Histamine, Cytokines, and Lipid mediators.
What distinguishes neutrophils from other leukocytes in terms of their role in inflammation?
Neutrophils are characterized as the hallmark cells of acute inflammation due to their high mobility and powerful effector functions.
What are the two types of granules found in neutrophils and their functions?
Granule Type | Function |
|————————–|——————————————–|
| Peroxidase-negative | Involved in neutrophil recruitment and tissue breakdown. |
| Peroxidase-positive | Contains antimicrobial proteins such as alpha-defensins. |
How do eosinophils respond to stimuli in the immune system?
Eosinophils are recruited into tissues in response to specific stimuli, including Interleukins-5 and Eotaxin chemokines.
Which immune cells would be the first to respond to a skin infection?
Neutrophils are the first responders to skin infections, using mechanisms such as phagocytosis and degranulation.
What cytokine produced by mast cells contributes to chronic inflammation?
TNF-α is a cytokine produced by mast cells that contributes to increased vascular permeability.
What preformed compounds are released from mast cell granules during an allergic reaction?
Mast cell granules release preformed compounds such as histamine, serotonin, TNF-α, and various proteases.
What is the hallmark process of neutrophil recruitment?
The hallmark process is ‘neutrophil swarming.’ Neutrophils have two types of granules: peroxidase-negative and peroxidase-positive.
What lipid mediators are produced by mast cells?
Mast cells produce lipid mediators such as leukotrienes and prostaglandins, contributing to increased vascular permeability.
What cytokines are produced by mast cells following activation?
Mast cells produce cytokines such as TNF-α, IL-3, IL-4, IL-5, and IL-6 following activation.
How do neutrophils respond to sites of injury?
Neutrophils respond to sites of injury by being rapidly recruited, engaging in phagocytosis, and producing reactive oxygen species.
What distinguishes eosinophils from neutrophils in terms of structure and function?
Eosinophils can be distinguished by their bilobed nuclei, large specific granules, and their primary involvement in responses to parasitic infections.
How can eosinophils be distinguished from neutrophils?
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.
What is the role of basophils in the immune system?
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.
How do keratinocytes contribute to the immune response?
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.
Which granulocyte is involved in allergic reactions and what cytokines does it release?
Basophils are involved in allergic reactions. They release large quantities of IL-4 and other Th2-type cytokines.
What role do keratinocytes play in inflammatory responses?
Keratinocytes play an active role in inflammatory responses by expressing Toll-like receptors and producing cytokines and chemokines that attract inflammatory cells.
What are the major proteins found in eosinophil granules?
Eosinophil granules contain major basic protein, eosinophil peroxidase, eosinophilic cationic protein, and eosinophil-derived neurotoxin.
What chemokines do keratinocytes produce, and what is their role?
Keratinocytes produce chemokines such as the S100A family, which attract inflammatory cell types like neutrophils and macrophages.
What stimuli recruit eosinophils into tissues?
Eosinophils are recruited into tissues in response to stimuli such as interleukin-5, eotaxin chemokines, and CCL26.
What is the role of basophils in the immune response, particularly in relation to allergic diseases?
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.
How do keratinocytes contribute to inflammatory responses in the skin?
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.
What distinguishes the maturation process of basophils from that of mast cells?
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.
What is the significance of eosinophils being found in proximity to mast cells in tissues?
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.
