Immunology - Immunology of the Skin Flashcards
What 4 factors contribute to the skin as an immunological system?
Genetics
Structure (keratin layer, stratification)
Cell types (immune cells, keratinocytes)
Chemical signals/ molecules (cytokines, chemokines, eicoanoids, antimicrobial peptides
What are cytokines?
Proteins that are involved in cell communication
What are chemokines?
Chemical messengers that induce chemotaxis
What are eicosanoids?
Signalling molecules made by oxidation of 20-Carbon fatty acids
What is an antigen?
a protein/ peptide or polysaccharide that elicits an immune response
What is hypersensitivity?
over reaction to antigen
What is autoimmunity?
Reaction to host tissue
What is the stratum corneum made up of?
Corneocytes (terminally differentiation keratinocytes)
What are 3 important structural proteins in the keratin layer?
Filaggrin
Involucrin
Keratin
What is filaggrin?
Filament-associated protein that binds to keratin
What does involucrin do?
Contributes to formation of cell envelope that protects corneocytes
How do keratinocytes in the epidermis sense pathogens?
Via cell surface - then help mediate an immune response
What 2 things (other than pathogens) can activate keratinocytes in the epidermis leading to an immune response?
UV
Sensitisers (e.g. contact dermatitis)
What can keratinocytes in the epidermis produce that can kill pathogens directly?
Anti-microbial peptides (AMPs)
In what condition are AMPs found in high levels in the skin?
Psoriasis
What do keratinocytes in the epidermis produce that recruit and regulate cells of the adaptive and innate immune system?
Cytokines and chemokines
Where are Langerhans cells found?
Interspersed with keratinocytes in the epidermis
What is the main skin resident immune cell?
Langerhans cells
What organelle is characteristic of Langerhans cells?
Birbeck granule
What type of immune cell are Langerhans cells?
Dendritic cells - antigen presenting cells
What shape are Birbeck granules?
“tennis-racket” cytoplasmic organelle
What do Langerhan cells do?
“Keep watch” in the epidermis
Process lipid Ag and microbial fragments and present them to effector T cells
Help to activate T cells
What type of T lymphocytes are located in the epidermis?
Mainly CD8+ (Killer) T cells
What type of T lymphocytes are located in the dermis?
CD4+ and CD8+ T cells
Other subsets of T cells are also found e.g. NK cells
What type of CD4+ Th cells are associated with psoriasis?
Th1 and Th17
What type of CD4+ Th cells are associated with atopic dermatitis?
Th2 and Th17
What interleukin does Th17 produce?
Interleukin 17
What are interleukins?
A group of cytokines expressed by WBCs
Where are T cells produced?
Bone marrow
Where are T cells sensitised?
Thymus
What does Ag recognition and T cell activation involve integration with?
T cell receptor (TCR) and major histocompatibility complex (MHC) - this is enhanced by co-receptors
What do Th1 T cells do? what do they release (2)?
Activate macrophages to destroy micro-organisms - release IL2 and IFNgamma
What do Th2 cells do? What do they release (3)?
Help B cells to make Ab, release IL4, IL5 and IL6
What is the purpose of CD8+ cytotoxic T cells?
To kill infected cells directly
Important protection against viruses and cancer
What are 2 examples of dendritic cells found in the dermis?
Dermal dendritic cell
Plasmacytoid dendritic cell (pDC)
What are dermal dendritic cells involved in?
Ag presenting and secreting cyto/ chemokines
What is the purpose of plasmacytoid dendritic cells?
Ag presenting and to produce IFNalpha -> found in diseased skin
Apart from dendritic cells, what 3 other immune cells are present in the dermis?
Macrophages
Neutrophils
Mast cells
What attracts circulating neutrophils to tissue?
Chemokines
What cells are the effects of IgE-mediated immune response?
Mast cells
What happens when IgE binds to mast cells?
Activation of the mast cell and release of inflammatory mediators
What are 4 examples of pre-formed mediators released from mast cells?
Tryptase
Chymase
TNF
Histamine
What are examples of newly synthesised mediators released from mast cells?
IL (3, 5, 6, 8, 13, 16, 18), TNF, TGFbeta, PGD2, PGE2, LTB4, LTC4, VEGF, bFGF, IP-10, MIP-1alpha, MIP-1beta
Apart from IgE, what else can activate mast cells? (3)
Physical trauma, certain drugs, micro-organisms
What chromosome is the gene for MHC found?
Chromosome 6
Where are class 1 MHC found?
On almost all cells
What is the purpose of class 1 MHC?
To present Ag to cytotoxic T cells - present endogenous Ag
What is the purpose of class 2 MHC?
To present exogenous Ag to Th cells
Where are Class 2 MHC found?
On APC (B cells, macrophages)
Skin conditions associated with inappropriate immune response/ inflammation? (9)
Skin infection Skin tumours Psoriasis Atopic dermatitis Bullous pemphigoid Contact dermatitis Morphea/ systemic sclerosis Urticaria Systemic lupus erythematous
Give 3 examples of autoimmune skin conditions?
Psoriasis
Vitiligo
Systemic lupus erythematous
What mediates type 1 hypersensitivity?
IgE - immediate
What happens in type 1 hypersensitivity?
Early exposure to allergen causes the production of IgE, which binds to FceRI receptor on mast cells
Laster exposure causes rapid cross linking of the receptors, signal transduction and degranulation of mast cell
What 2 time frames of responses are involved in type 1 hypersensitivity?
Very rapid early response = minutes (wheal and flare)
Later réponse = hours (cellular infiltration, nodule)
What mediates type 2 and 3 hypersensitivity?
Antibodies - IgG and IgM
What conditions are type 2 hypersensitivity important in?
Auto-immunity and transplantation e.g. haemolytic disease the newborn
What type of reaction does skin testing in type 3 hypersensitivity lead to?
Arthus reaction- slow than type 1 but faster than type 4
What mediates type 4 hypersensitivity?
Th1 cells - delayed type hypersensitivity based on a t cell resoles which then recruits other cells to the site
2 examples of a type 4 hypersensitivity reaction?
Tuberculin reaction
Contact allergy
when does a type 4 hypersensitivity reaction peak?
24 - 48 hours after exposure
How does ageing affect skin immunity?
Changes in skin structure = easier access
Decreased ability to detect malignant cells
Decreased ability to detect Ag = infection risk
Decreased ability to detect self from non-self = autoimmunity
Non-immune cells of the epidermis?
Keratinocytes
Melanocytes
Immune cells of the epidermis?
Langerhans cells T cells (Esp. CD8+ cells)
Immune cells in the dermis?
Dendritic cells
Macrophages
NK cells
T cells (CD4+ and CD8+)
Non-immune cells in the dermis?
Fibroblasts
Lymph/ vasculature
