4. Cutaneous Immune System

Haut

1. Epidermis

2. Dermis

3. Hypodermis

• stratum corneum (mainly dead kerationytes & lipids)

  • strong impenetrable layer, prevents water loss

• stratum granulosum

• stratum spinosum

  • contains the immune cells of the epidermis

• stratum basale

  • where keratinocytes regenerate

  • location of melanoytes

• connects skin to muscle and bone

• fat depot, insulation and cushion

• rich in lympathics

• sweat gland & hair follicles

• moisturizers of skin

• nerve endings of sensory neurons

stratified cornea at the top of epidermis

-> preventing pathogen entry and water exchange

dermis

• sweat and sebaceous(talk) glands

• hair follicles

1. eccrine

   • nearly everywhere

   • regulare temperature

2. apoccrine

   • associated with hair follicles & reproductive organs

   • mature in puberty

   • linked to pheromone production

• color

• hair and nails

• produce water/sweat

• major sensory organ

• makes vitamin D

• keratinoytes (epihtelial cells)

barrier and interface with the environment

Langerhans cells

keratinocytes

DETCs - dendritic epidermal t cells (mouse)

• embyonically derived

• APC

• coordinate a number of adaptive and innate immune responses

• can migrate to draining lymph nodes

• mouse specific

• key innate immune roles

• important for wound healing

• mast cells

• eosinophils

IL-17 producing yd T cells

hair follicles

sensory neurons in the skin actively regulate protective and patogenic imunne responses through cellular and molecular interactions with local immune cells

• main cells in epidermis

• proliferate to nucleus cells -> stratum corneum

• protective

• but also pathogenic when they are disregulated

• potent apc functions

• important role in allergy & inflammation

• can activate Th1,2 and 17

• they are migratory and prime t cell in draining LN

• they balance immuna activationd & tolerance

• mouse specific

• epidermis

• Long-lived, self-renewing.

1. Surveillance: Constantly interact with keratinocytes and monitor for stress signals.

2. Stress recognition: Respond to ligands upregulated by damaged or transformed keratinocytes (not classical MHC presentation).

3. Cytokine/growth factor production:

   • Release IFN-γ, TNF-α for antimicrobial defense.

   • Produce growth factors like KGF (keratinocyte growth factor), IGF-1 for wound healing.

4. Bridge innate and adaptive immunity: Rapid first responders, but also influence later immune responses.

• only inflammation in human

• develop in embyronic neonatal life

• important in many mouse skin infection models

• Activation:

  • Can be activated rapidly and without classical antigen presentation.

  • Respond to cytokines like IL-1β, IL-23 from stressed or infected tissue.

• Produce IL-17A, IL-22 → recruit neutrophils, enhance antimicrobial peptide production by epithelial cells.

• Provide early defense against extracellular bacteria and fungi (e.g., Candida).

• derive from stem cell dactor responsive progenitors

• alomot excluively in tissues (dermis, mucosa, subdermis)

• fast alarm

• IgE activated (when allergie)

• Schnelle Alarmzellen → setzen Histamin frei (granulate)→ Vasodilatation, erhöhte Gefäßpermeabilität, Rekrutierung von Immunzellen.

• importand role asthma and allergy

• mostly tissue but also blood

• respond to IL-5 und 3 und GM-CSF

• also important for asthma and allergy

• granulate

An immune-privileged site is an anatomical location in the body where immune responses are naturally limited or actively suppressed to protect vital tissues from collateral damage caused by inflammation.

• specalized KCs

• CCL20, 2 and 8 attracts monoytes and inflammatory cells

• “hole” that hair breaks in statum corneum so that microbes can get in

• propionibacterium

• sebocytes produce IL-6, IL-1ß, TGFß

• cytokines + dermal DC priming lead to overreaction of Th17

Stimulus → Nerves release neuropeptides → activate immune cells → cytokines/mediators → feedback to nerves →Outcome = protection (wound healing, defense) OR pathology (chronic inflammation, itch)

1. skin dendritic cells capture antigen

2. migrant to draining lymph nodes

   1. prime naice t cells

   2. imprinting them with skin homing molecules (CLA,CCR4, CCR10)

3. T cells recirulate or persist

• SALT = Skin-Associated Lymphoid Tissue

• Healthy skin: no organized SALT (uses resident cells + draining LNs).

• Diseased skin: tertiary lymphoid structures (“SALT-like”) can form.