Immunology in the skin
Summary
TLDRThe skin, as the body's primary barrier, hosts a complex ecosystem of immune cells and skin cells that work together to maintain homeostasis and respond to threats. It comprises the epidermis, dermis, and subcutaneous tissue, with commensal microbes aiding in protection and healing. Keratinocytes form the epidermal barrier, while dendritic cells and T cells in the dermis and epidermis play crucial roles in immune response. Specialized immune cells like Langerhans cells and various T cell subsets contribute to defense and can become disregulated, leading to skin disorders such as psoriasis. The script delves into the intricate balance of the skin's immune system and its potential for both protection and disease.
Takeaways
- 🛡️ The skin acts as the body's primary barrier against physical harm and pathogens, maintaining tissue homeostasis and inducing immune responses.
- 🌱 The skin is composed of the epidermis, dermis, and subcutaneous fatty region, and hosts commensal bacteria, fungi, and viruses beneficial for protection and healing.
- 🔬 The epidermis is made up of specialized epithelial cells called keratinocytes, which are continuously replenished and form the skin's barrier.
- 🧬 In the dermis, fibroblasts secrete elastin and collagen fibers, creating a dense extracellular matrix, while blood and lymphatic vessels support the skin's functions.
- 🕵️♂️ Langerhans cells in the epidermis are specialized dendritic cells that sample antigens and have both anti-inflammatory and activatory roles.
- 🔎 Dendritic cells in the dermis efficiently capture dead cells and present antigens to T-cells, acting as immune sentinels.
- 💪 T-cells are the immune effectors in the skin, with memory T-cells being more abundant in healthy skin than in the blood, ready for rapid reactivation.
- 🔄 CD8 T-cells in the epidermis are cytotoxic, killing target cells upon activation, while CD4 T-cells in the dermis have a more regulatory role.
- 🤒 Other immune cells like natural killer cells, eosinophils, and mast cells may be involved in allergic reactions in the skin.
- 🚨 Dendritic cells and keratinocytes sense tissue damage through receptors that recognize pathogen-derived or host-derived molecules.
- 🛡️ Keratinocytes produce antimicrobial peptides and inflammatory mediators that activate immune cells and recruit additional immune effectors.
- 🔄 Activated T-cells migrate to lymph nodes, where they are primed to differentiate into effector cells that return to the skin to control infections.
- 🛑 Memory CD8 cells persist in the epidermis to provide immunity against future encounters with the same pathogen.
- 🤕 Skin disorders like psoriasis can result from disregulated immune responses, with genetic and environmental factors contributing to the disease's onset.
- 🧬 Genetic studies have linked psoriasis susceptibility to specific genes, including those associated with the Th17 subset of T-cells, which produce IL-17 and play a role in psoriasis pathogenesis.
Q & A
What is the primary function of the skin in the human body?
-The skin serves as the body's primary barrier against physical insults and microbial pathogens, helping to maintain tissue homeostasis and induce immune responses.
What are the main components of the skin structure?
-The skin is composed of the epidermis, dermis, and a subcutaneous fatty region.
What beneficial effects do commensal bacteria, fungi, and viruses living on the skin have?
-Commensal bacteria, fungi, and viruses on the skin have beneficial effects in protecting against pathogens and aiding in wound healing.
What are the specialized epithelial cells in the epidermis called, and what is their role?
-The specialized epithelial cells in the epidermis are called keratinocytes, which are continuously replenished and are largely responsible for the skin's barrier function.
What do fibroblasts in the dermis secrete that contributes to the extracellular matrix?
-Fibroblasts in the dermis secrete elastin and collagen fibers that form a dense extracellular matrix.
How do Langerhans cells in the epidermis function in the immune response?
-Langerhans cells in the epidermis sample antigens and can have both anti-inflammatory and activatory roles, depending on the context.
What is the role of dendritic cells in the dermis regarding antigen presentation?
-Dendritic cells in the dermis are highly efficient at capturing dead cells and presenting antigens, such as viruses or other intracellular pathogens, to T cells.
What types of T cells are predominantly found in the epidermis and dermis, and what are their functions?
-CD8 T cells, which can become cytotoxic and kill target cells upon activation, are mostly found in the epidermis. In the dermis, helper CD4 T cells, which have a more modulatory role in the immune response, are predominant.
How do immune cells, such as dendritic cells and keratinocytes, respond to tissue damage?
-Dendritic cells and keratinocytes sense tissue damage through receptors that recognize pathogen-derived molecular patterns or host-derived molecules exposed by cell death, such as DNA.
What is the process that leads to the formation of acute psoriatic lesions?
-Acute psoriatic lesions form when stressed keratinocytes might release self DNA, which, in complex with an antimicrobial peptide, activates dermal plasmacytoid dendritic cells to secrete high amounts of the antiviral mediator IFN, along with pro-inflammatory IL1 Alpha.
How do genetic studies contribute to our understanding of psoriasis?
-Genetic studies have identified psoriasis-associated susceptibility genes, some of which link the subset of T cells that produce IL17 to psoriasis pathogenesis.
Outlines
🛡️ Skin's Immune Defense Mechanisms
The skin serves as the body's first line of defense against physical harm and pathogens. It is a unique environment where immune cells interact with skin cells to maintain tissue health and trigger immune responses. The skin is structured into the epidermis, dermis, and a subcutaneous fatty layer, and is home to beneficial commensal organisms that aid in protection and healing. The epidermis is composed of specialized epithelial cells called keratinocytes, which are continuously replenished and form the skin's barrier. In the dermis, fibroblasts produce extracellular matrix components and blood capillaries provide nourishment. The skin is populated by a variety of immune cells including Langerhans cells in the epidermis and dendritic cells in the dermis, which are crucial for antigen sampling and presentation. T cells, particularly memory T cells, are abundant in the skin and play a significant role in immune responses. Other immune cells like natural killer cells, eosinophils, and mast cells may also contribute to allergic reactions. The skin's immune cells can detect tissue damage and respond to it, while keratinocytes produce antimicrobial peptides for direct bacterial killing. Activated dendritic cells migrate to lymph nodes to prime naive T cells, which then differentiate into effector T cells to combat infections. Memory T cells persist to provide long-term immunity.
🔬 Psoriasis: An Autoimmune Skin Disorder
Psoriasis is a chronic inflammatory skin condition characterized by the formation of scaly, reddish plaques. It is influenced by a combination of environmental and genetic factors, with physical injury or inflammation potentially triggering acute lesions. The exact antigenic trigger is not known, but it is hypothesized that stressed keratinocytes might release self-DNA, which could activate plasmacytoid dendritic cells to secrete antiviral and pro-inflammatory cytokines. This leads to the differentiation and accumulation of T cells around blood vessels in the dermis, eventually causing epidermal infiltration and thickening. Specialized T cell subsets secrete mediators that stimulate keratinocyte proliferation, contributing to tissue remodeling and the amplification of the immune response. Without treatment, acute psoriatic lesions can become chronic. Genetic studies have linked psoriasis to susceptibility genes, some of which are associated with the Th17 subset of T cells, implicating them in the disease's pathogenesis. The skin's immune cells are thus vital for barrier function and defense against pathogens, but can also become dysregulated, leading to autoimmunity or allergies.
Mindmap
Keywords
💡Skin Barrier
💡Keratinocytes
💡Commensal Microbes
💡Dermis
💡Langerhans Cells
💡Dendritic Cells
💡T Cells
💡Inflammatory Mediators
💡Psoriasis
💡Autoimmunity
💡Memory T Cells
Highlights
The skin serves as the body's primary barrier against physical and microbial threats, with a unique environment where immune cells interact with skin cells to maintain tissue homeostasis and induce immune responses.
Commensal bacteria, fungi, and viruses on the skin have beneficial effects in protecting against pathogens and aiding wound healing.
The epidermis is composed of highly specialized epithelial cells called keratinocytes, which are continuously replenished from a single layer of basal keratinocytes.
Dead cells called corneocytes form the outermost layer of the skin, playing a significant role in its barrier function.
In the dermis, fibroblasts secrete elastin and collagen fibers, creating a dense extracellular matrix that supports the skin structure.
Lymphatic vessels in the dermis drain lymph fluid to lymph nodes, where immune cells are activated upon pathogen encounter.
Langerhans cells in the epidermis are specialized dendritic cells that sample antigens and have both anti-inflammatory and activatory roles depending on the context.
Dendritic cells in the dermis efficiently capture dead cells and present antigens to T cells, acting as immune sentinels.
Healthy skin contains more than twice the number of T cells found in the blood, with most being memory T cells capable of rapid reactivation.
CD8 T cells in the epidermis become cytotoxic upon activation, killing target cells and playing a crucial role in the immune response.
Helper CD4 T cells in the dermis have a modulatory role in the immune response, influencing the overall immune activity.
Other immune cells like natural killer cells, eosinophils, and mast cells may be involved in allergic reactions in the skin.
Dendritic cells and keratinocytes sense tissue damage through receptors that recognize pathogen-derived or host-derived molecules.
Keratinocytes produce antimicrobial peptides that can directly kill bacteria and contribute to the skin's defense mechanisms.
Activated dendritic cells migrate to lymph nodes to present antigens to naive T cells, initiating their activation and differentiation.
Memory CD8 cells persist in the epidermis to provide immunity for future encounters with the same virus, ensuring a rapid response.
Disregulated immune responses can lead to skin disorders such as psoriasis or atopic dermatitis, impacting skin health and appearance.
Psoriasis is a lifelong inflammatory skin disease characterized by scaly reddish plaques, influenced by a combination of environmental and genetic factors.
Genetic studies have identified psoriasis-associated susceptibility genes, some linking the subset of T cells that produce IL-17 to psoriasis pathogenesis.
Skin immune cells play a critical role in maintaining barrier function against pathogens but can also cause autoimmunity or allergies when activated by self-antigens or harmless antigens.
Transcripts
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the skin is the body's primary barrier
against physical insults and microbial
pathogens it represents a unique
environment in which immune cells
interact with skin cells to maintain
tissue homeostasis and induce immune
responses the skin is composed of
epidermis dermis and a subcutaneous
fatty region commensal bacteria fungi
and viruses living on the skin have
beneficial effects in the protection
against pathogens and in wound
healing the epidermis is composed of
Highly specialized epithelial cells
known as kattin aites they are
continuously replenished from just one
layer of Basil kattin aites which divide
frequently dead cells called corneocytes
form the outermost layer and are largely
responsible for the barrier function of
the
skin in the dermis cells known as fiber
blasts secrete elastin and coll fibers
that form a dense extracellular
Matrix blood capillaries irrigate the
dermis while lymph fluid is drained
through lymphatic vessels to lymph nodes
specialized immune structures in which
immune cells are activated after
pathogen
encounter diverse and functionally
specialized immune cells populate the
skin in the epidermis A specialized
subset of dendritic cells called lahan
cells sample antigen they project dend
upward towards the cornified epithelial
layer and Sample bacterial antigen such
as toxins lahan cells appear to be both
anti-inflammatory and activatory
depending on
context dendritic cells in the dermis
are highly efficient at capturing dead
cells and presenting antigen such as
viruses other intracellular pathogens or
skin Associated self antigen to te-
cells if dendritic cells are the immune
Sentinels t cells are the immune
effectors healthy skin contains more
than twice the number of tea cells found
in the blood most of them are memory tea
cells that have previously encountered
antigen and can be rapidly reactivated
tea cells in the epidermis are mostly
cd8 te- cells a subset that becomes
cytotoxic and kill target cells upon
activation they're long-term residents
in the epidermis mostly disconnected
from the
circulation tea cells in the dermis are
mostly helper CD4 te- cells which have a
more modulatory role in the immune
response a variety of other immune cells
such as natural killer cells eosinophils
and mast cells are present in the dermis
and might be involved in allergic
reactions in the
skin dendritic cells and catinos sites
sense tissue damage such as wounds or
cold sore lesions that occur when latent
herpes virus reactivates and they do
that through evolutionarily conserved
receptors that recognize pathogen
derived molecular patterns or host
derived molecules that are exposed by
cell death such as
DNA kattin Ayes produce antimicrobial
peptides which can kill bacteria
directly inflammatory mediators such as
interlukin 1 or il1 which activate
dendritic cells and chemokines which
recruit neutrophils macrophages and tea
cells activated dendritic cells migrate
to the lymph nodes where they present
antigen from the site of infection to
naive tea cells priming them to activate
and differentiate into infecta tea
cells activated tea cells return to the
skin and kill infected cartinos sites to
control viral infection or secrete
signals that recruit additional immune
affector
cells following viral clearance memory
CDH cells persist in the epidermis to
provide immunity for future encounters
with the same virus
immune responses can become disregulated
and cause skin disorders such as
psoriasis or atopic
dermatitis psoriasis is a lifelong
inflammatory skin disease characterized
by scaly reddish plaques a combination
of environmental and genetic factors
confer susceptibility to the
disease physical injury or inflammation
can trigger the formation of an acute
lesion the antigenic trigger is unknown
but current models proposed that
stressed carattino sites might release
self DNA which in complex with an
antimicrobial peptide activates dermal
plasmacytoid dendritic cells to secrete
high amounts of the antiviral mediator
into feon together with pro-inflammatory
il1 Alpha released by stressed kattin
Ayes interferon activates dermal
dendritic cells to promote te- cell
differentiation the earliest
recognizable change in the affected skin
is the accumulation of tea cells and
dendritic cells around blood vessels in
the
dermis an overt lesion occurs when cd8 T
cells dendritic cells and neutrophils
infiltrate the
epidermis specialized subsets of tea
cells secrete soluble mediators like
interferon gamma and il17 which
stimulate the proliferation of coratin
aites and this produces a marked
thickening of the
epidermis signals from the proliferating
coratin aites act as chemoattractants
for infiltrating
nutrifil cross talk between immune cells
cartin aites and dermal cells thus
contributes to tissue Remodeling and
amplification of this disregulated
immune
response without treatment acute
psoriatic lesions become chronic lesions
genetic Studies have identified
psoriasis Associated susceptibility
genes some of them linking th17 cells
the subset of te- cells that produce
il17 to psoriasis pathogenesis thus
immune cells in the skin exert important
roles in maintaining the barrier
function against pathogens but can also
become activated by self antigen or
harmless antigen to cause autoimmunity
or
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allergies
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and
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