Imunitas pada kulit

Pathogens (such as bacteria, fungi, and viruses)

INNATE IMMUNITY (all animals) Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Rapid response

Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response Humoral response: Antibodies defend against infection in body fluids.

ADAPTIVE IMMUNITY (vertebrates only) Recognition of traits specific to particular pathogens, using a vast array of receptors
Slower response

Cell-mediated response: Cytotoxic cells defend against infection in body cells.

Components of the immune system

Innate immune system

Adaptive immune system Pathogen and antigen specific response Lag time between exposure and maximal response Cell-mediated and humoral components Exposure leads to immunologic memory Found only in vertebrates

Response is non-specific Exposure leads to immediate maximal response Cell-mediated and humoral components No immunological memory Found in nearly all forms of life (plants & animals)

Roles of the Skin

The skin or integumentary system has four roles It acts as a barrier against infection and injury It helps to regulate body temperature It removes waste products from the body Provides protection against UV radiation from the sun It also serves as a way through which sensations are transmitted to the nervous system

The immune system protects organisms with layered defenses of increasing specificity
Most simply, 1. physical barriers prevent pathogens such as bacteria and viruses from entering the body If a pathogen breaches these barriers, the 2. innate immune system provides an immediate, but non-specific response
Innate immune systems are found in all plants and animals

If pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the 3. adaptive immune system
Here, the immune system adapts its response during an infection to improve

its recognition of the pathogen This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered

Innate Immune Features of the Skin

Cells
Phagocytes: Macrophages, neutrophils, NK cells Mast cells

Circulating chemicals
Complement

Locally produced chemicals

Cytokines, histamine

Mast Cells
Bone marrow-derived Dermal resident Perivascular Mediators
Preformed (histamine, e.g.) Newly synthesized (cytokines, e.g.)

Various stimuli mediator release

Immunologic:

IgE

binding antigen Nonimmunologic: Physical, drugs, complement

Cells of the Cutaneous Adaptive Immune Response

Langerhans cell Dermal dendrocytes Keratinocytes T-cells Endothelial cells

Langerhans Cells
Bone marrow-derived
Monocyte lineage

Transient epidermal cells Dendritic cell

Cell surface molecules: CD1a, MHC II, ATPase, Fc receptor for IgG, C3 receptor, B7, several CAMs

Electron microscopy: Birbeck granules, convoluted nucleus

Langerhans Cells: Epidermal Transients

Migration and maturation
Bone marrow Blood Epidermis (LC) Afferent lymph Lymph node Functions Antigen capture and processing Presentation of antigen Costimulation of nave T-cells Produce activating cytokines

Antigen

Langerhans Cell Migration

Keratinocytes As Immune Cells

Old view: Keratinocytes... Are passive barrier cells Are passive victims of immune attack

Keratinocytes As Immune Cells

Newer view: Keratinocytes... Produce cytokines
e.g., IL-1, TNF-, Chemokines

Respond to cytokines
e.g., IFN, IL-1

Upregulate ICAM-1 Present antigen Antimicrobial peptide

Endothelial Cells & Cutaneous Inflammation

Increase permeability When activated, endothelial cells...

cell surface expression of P-selectin for enhanced leukocyte margination synthesis & expression of E-selectin for selective T-cell (CLA +) homing to the skin expression of VCAM-1 & ICAM-1 to stop leukocytes and allow diapedesis

Immune response amplified

Cutaneous Lymphocyte Antigen (CLA)

Specific skin homing marker on T-cells CLA+ lymphocytes are memory/effector cells (CD45RO +) Cell adhesion to endothelial cell
E-selectin is ligand

With cutaneous inflammation, E-selectin upregulated, CLA+ cells selected

The Skin Immune System

Components 1. APCs: Langerhans cells, dermal dendrocytes, dermal macrophages 2. Keratinocytes 3. Endothelial cells 4. Skin-homing T-cells 5. Draining regional lymph vessels and nodes