Transcript Immunology of Skin Diseases

Immunology of Skin Diseases
Dr. Nadisha Badanasinghe
Senior Lecturer/ Consultant Microbiologist
FOM, Ragama
UNIVERSITY OF KELANIYA
Outline
Immune response
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Skin as an immune organ
Immune imbalance
Immunologically mediated skin diseases
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Immunological basis
Hypersensitivity skin diseases
Autoimmune skin diseases
Skin diseases in immune deficiency
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Immune system - Function
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The body’s defense against disease causing organisms, malfunctioning cells,
and foreign particles
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Can recognize and remember millions of different enemies
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Immune cells have specific receptors to recognize harmful pathogens
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Immune cells have to distinguish these pathogens from the body's own
healthy tissue/ cells
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Immune response
1) Innate immunity (Natural or Non specific/ 1st line defense)
Barriers, Cells (Neutrophils, Macrophages, NK cells, Dendritic cells), Secretions (Cytokines)
2) Acquired immunity (Adaptive or Specific/ 2nd line)
Cell-mediated immunity
(T lymphocytes)
Th1, Th2, Tc, Treg
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Humoral immunity
(B lymphocytes)
Antibodies
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Skin as an immune organ
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Barrier function - innate
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Physical barrier
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Dead keratinocytes in stratum corneum
Chemical barrier
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acidic, hydrolipidic nature of the skin, as a result of sweat, sebum, lipids, and
antimicrobial peptides
Microbiological barrier
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Normal flora
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Skin as an immune organ
• Cells
• Secretions
• Epidermis
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Keratinocytes
Melanocytes
Langerhan cells
T lymphocytes
• Dermis
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Dendritic cells
NK cells
Mast cells
Macrophages
T cells
• Th1, Th2, Tc, Treg, memT
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• Cytokines
• Chemokines
• AMPs
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Balanced Immune response
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To achieve an efficient immune response without damaging the host
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Any breakdown in cutaneous immunity therefore leads to the development of
immune-mediated skin disorders
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If exaggerated------> Hypersensitivity/ Allergy
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If inappropriate -------> Autoimmunity -----> immune response to self tissues
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If supressed --- immune deficiency - infections and cancers
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Immune balance
Infections and cancers
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Immunological skin diseases
Autoimmune
Skin specific
Hypersensitivity
Systemic with skin
manifestations
Immune deficiency
Infections
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•Type I
•Type II
•Type III
•Type IV
Hypersensitivity reactions
•‘Over
reaction’ of the immune system to harmless environmental antigens
•Genetic and environmental factors play a role
Type
Immune mechanism
Time of onset
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IgE mediated
(immediately)
2-30 mins
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Ab & complement
(intermediate)
5-8 hrs
III
Ag/ab complexes
(intermediate)
2-8hrs
IV
T cell mediated
(delayed)
24-72 hrs
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Type 1 HS
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Mediated by IgE Abs , mast cells, inflammatory cells
Mild  severe
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Urticaria
Atopic dermatitis/ eczema
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Type 1 Hypersensitivity/ Immediate
reaction
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Pathogenesis of atopic dermatitis
SKIN
BARRIER
IMMUNOLOGI
CAL
Type I HS reaction
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GENETIC
•Altered lipid composition of the
stratum corneum
• Decrease in skin ceramides
ENVIRONMENT
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•Inhalants (HDM, Animal
dander)
•Food
•Clothing
Type 1 Hypersensitivity
Sensitization occurs when the person is exposed t the antigen/allergen
for the first time
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Type-I Hypersensitivity:
Allergen Interaction with IgE on the Surface of Mast Cells triggers the Release of
Inflammatory Mediators
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Type 1 Hypersensitivity/ Immediate reaction
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Type IV – delayed type HS
Mediated by cells
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TH cells
Macrophages
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Cytokines
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Persistent presence of antigen leads to chronic inflammation and
granuloma formation
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Ex: Allergic contact dermatitis
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Allergic contact dermatitis
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Nickle/metals
Sunscreens/Cosmetics
Paraphenylenediamine (PPD) (hair dye, henna, photographic chemicals)
Latex
Plastic/ rubber
Ethylenediamine
CAPB (Cocamidopropyl Betaine) - shampoo, bath products, facial
cleansers
Topical medications
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Allergic contact dermatitis
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Immuno-pathology
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Type 4 Hypersensitivity/ Delayed reaction
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Investigation of a Hypersensitivity
reaction
Type I HS
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Skin prick test
Pick to prick test
Specific IgE
Type IV HS
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Patch test
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Skin Prick Test
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Patch Test
Autoimmune diseases
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Genetic + Environmental
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The response of the adaptive immune system to self antigens that
occurs when mechanisms of self tolerance fails.
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Self tolerance – “ unresponsiveness to self antigens”
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This happens when central and peripheral tolerance mechanisms fail
and produce
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Auto-reactive T cells
Auto-reactive B cells Auto-antibodies
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B cell tolerance
Peripheral LO
Self Tolerence Mechanisms
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Causes of autoimmunity
Failure of tolerance mechanisms
Availability of normally sequestered self antigens (Lens of eyes,
thyroid, testes)
Altered or modified self antigens
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Physical (irradiation)
Chemical (drugs)
Microbial (viruses)
Cross reacting antigens (Foreign Ag = Self Ag)
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Infections (Strep M protein and heart muscle , Strep A and GBM)
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Other autoimmune mechanisms
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Decreased T reg cells
Deregulated cytokines
Disturbances of apoptosis
Pre-existing organ damage
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Mechanisms of damage
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Direct autoantibody reaction with cell membranes
• Eg: anti-Ro/La antibodies in SLE
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Autoantibodies form immune-complexes
• Eg; antineutrophil cytoplasmic antibody [ANCA] in vasculitides or anti-DNA in SLE
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Direct antibody penetration into the cells  interfere signal transduction
• Eg: Antifibroblast autoantibodies in Systemic sclerosis
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Cell-mediated destruction
• Eg: T helper cells in Psoriasis, Pemphigus, Alopecia
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Excess inflammatory response
• Exaggerated production of distinct cytokines and chemokines by keratinocytes
(Psoriasis)
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Autoimmune skin diseases
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Skin specific autoimmune diseases
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Systemic autoimmune diseases with skin involvement
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Skin specific autoimmune diseases
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Pemphigus
Bullous pemphigoid
Dermatitis Herpetiformis
Psoriasis
Vitiligo
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desmoglein 1 and 3
BP230
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V
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Systemic autoimmune diseases with
skin involvement
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First manifestation of a systemic disease
Concomitant with systemic involvement
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SLE
Systemic sclerosis/ Scleroderma
Dermatomyositis
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Auto-antioodies associated with skin
damage
Anti-fibroblast antibodies
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Systemic sclerosis
Anti-endothelial antibodies
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Systemic sclerosis
Anti-Ro/SSA
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SLE
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Diagnosis of Autoimmune skin diseases
Biopsy and histology
Immuno-fluorescence –
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To detect tissue bound/ circulating auto-antibodies
Other autoantibody tests – ANA, dsDNA
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Skin diseases associated with immune
deficiency
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T h1cell deficiency
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Infections
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Herpes zoster
Bacillary angiomatosis
Cryptococcosis
Kaposi sarcoma
Autoimmune
Type I HS
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Leprosy and Immune response
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The immunological response mounted by the host dictates the clinical
phenotype
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approximately 95% of patients infected with the bacterium do not
develop overt disease
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Genetic susceptibility
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Associations of HLA-DR2 alleles with susceptibility to leprosy
polymorphisms within the TLR1 and TLR2 genes
Modulate helper T immune response
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Immune response
Effective response is mediated by Th1 cells (type IV HS)
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Infection is localized to Schwann cells and macrophages
strong cell-mediated responses clear antigens, but cause local tissue
destruction
Pro-inflammatory cytokines produced (IFN-γ, IL-2)
Polarize to tuberculoid disease
Ineffective Th1 response
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have specific T cell failure and macrophage dysfunction
produce Th2-type cytokins  antibody production
Polarize to lepromatous disease
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Delayed Type HS (Th1, macrophages and cytokines)
NK
IL12/IL18
IFN
IL-12
M
IFN
TH1
IL-2 (autocrine action)
IL-2
Mycobacterial killing
CTL
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Leprosy spectrum (Ridley Jopling 1966)
Cell-mediated immunity
Antibody
TH1
TH2
Bacterial
index
TT
BT
BB
BL
LL
Paucibacillary
Multibacillary
IL-2/IFN
IL-10/IL4
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Immunology of Skin Diseases
Appropriate immune response
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Innate (Barriers, cells, secretions)
Adaptive (T cells and Bcells)
Inappropriate/ altered immune response  skin diseases
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Hypersensitivity reactions
Autoimmune reactions
Immune deficiency  infections
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