Immunology/Biochem of Skin Flashcards
How does the structure of skin contribute to its function as an immunological system?
Keratin layer (stratum corneum), stratifications
What cell types are involved in the immune response in the skin?
Immune system cells, keratinocytes
What are some examples of chemical signals/molecules that influence cell behaviour or help target pathogens?
Cytokines, chemokines, eicosanoids, antimicrobial peptides
What are the different immune responses?
Normal (innate and adaptive), hypersensitivity, immunodeficiency, autoimmunity
What occurs in hypersensitivity?
Over-reaction to antigen
What occurs in immunodeficiency?
Infection not controlled (tumours may form)
What occurs in autoimmunity?
Reaction to host (chronic inflammation)
How is the keratin layer of the skin formed?
Terminal differentiation of keratinocytes to corneocytes
What are some important proteins in the keratin layer?
Filaggrin, keratin and involucrin
What is another name for the keratin layer?
Stratum corneum
What are keratinocytes?
Structural and functional cells of the epidermis
How are keratinocytes involved in the immune response?
Sense pathogens via cell surface receptors and help mediate an immune response
What are some examples of things which can activate keratinocytes?
UV and sensitisers (e.g allergic contact dermatitis)
What do keratinocytes produce that aids in the immune response?
Antimicrobial peptides (AMP), cytokines, chemokines
What do AMPs do?
Directly kill pathogens
What do cytokines and chemokines do?
Recruit and regulate cells of the adaptive and innate immune system
In what skin condition are high levels of AMP found in the skin?
Psoriasis
What are Langerhans cells?
Type of dendritic cell that intersperse with the keratinocytes in the epidermis
What are the main skin-resident immune cells?
Langerhans cells
How do Langerhans cells work?
Antigen presenting cells (APCs) that process lipid antigen and microbial fragments and present them to effector T cells (help activate T cells)
What are Langerhans characterised by, and what do they act as in the skin?
Birbeck granules; act as sentinels
Where are T cells found in healthy skin
Both the epidermis and dermis
What kind of T cells are found in the epidermis?
Mainly CD8+ T cells
What kinds of T cells are found in the dermis?
CD4+ and CD8+ T cells
What other kind of T cells can be found in the epidermis and dermis?
Natural killer cells
What are some CD4+ Th cells associated with inflammation of the skin?
Th1 (psoriasis), Th2 (atopic dermatitis), Th17 (psoriasis and atopic dermatitis)
Where are T cells produced and synthesised?
Produced in the bone marrow and synthesised in the thymus
What cells form the basis of cell-mediated immunity?
T cells
What are involved in antigen recognition and T cell activation?
Interaction between the T cell receptor and the Major Histocompatibility complex (MHC), enhanced by co-receptors (CD4+ and CD8+)
What are the two CD4+ helper cells?
Th1 and Th2
How does Th1 work?
Activate macrophages to destroy micro-organisms (e.g IL-2, IFNg)
How does Th2 work?
Helps B cells make antibodies (e.g IL-4/5/6)
How do CD8+ cytotoxic T cells work?
Ca kill cells directly (important in protection against viruses and cancer)
What are some dermal dendritic cells?
Dermal dendritic cells (involved in antigen presenting and secretion of chemo/cytokines), Plasmacytoid dendritic cells (produce IFNa, found in diseased skin)
How do cytokines and chemokines work during the inflammatory response?
Modulate the response and recruit/activate different cell types to the locus
What are other cells involved in the immune response found in the dermis?
Macrophages, Neutrophils, Mast cells
What are neutrophils?
Circulating leukocytes attracted to tissue by chemokines
Where do mast cells tend to be found?
In “barriers”
What are mast cells?
Effector cells of the IgE-mediated immune response (allergy)
How are mast cells activated and what does this cause?
IgE binds causing activation and release of inflammatory mediators
What else can activate mast cells?
Trauma, some drugs, certain micro-organisms
What are some preformed mediators of inflammation found in mast cells?
Tryptase, chymase, TNF, histamine
What are some inflammatory mediators that are newly synthesised by mast cells?
IL-3/5/6/8, TNF, TGFb, IFNy, PGD2
What chromosome is linked to MHC molecules?
Chromosome 6
What is MHC class I?
Found on almost all cells, presents endogenous antigen to CD8+ T cells
What is MHC class II?
Found on antigen presenting cells (B cells, macrophages), presents exogenous antigen to Th cells (CD4+)
How does MHC control the immune system?
Through recognition of “self” and “non-self”
What are some skin conditions linked to an inappropriate immune response?
Psoriasis, Atopic dermatitis, Bullous pemphigoid, Contact dermatitis, Morphea/systemic sclerosis, Urticaria, SLE, Skin tumours
How is psoriasis triggered?
Environmental factors in genetically susceptible individuals
What is the hallmark of skin lesions in psoriasis?
Inflammation
Are the plaques in psoriasis reversible?
Yes
What do keratinocytes release when they are under stress in psoriasis?
Factors that stimulate plasmacytoid dendritic cells and produce IFNa, release IL-1b/6 and TNF
Where do the dendritic cells migrate to in psoriasis once activated?
Skin draining lymph nodes-present to and activate T cells (Th1 and Th7)
Where are T cells attracted to in psoriasis?
Attracted to dermis by chemokines and then secrete IL-17A/17F/22 (stimulates keratinocyte proliferation, AMP release and neutrophil-attracting chemokines)
How is atopic eczema different from psoriasis?
Histologically different, non-lesioning skin is not normal
Why does atopic eczema occur?
Impairment of skin barrier-mutations in filaggrin gene associated with severe/early onset, decreased AMP in skin
What cells are involved in atopic eczema?
T cells (Th2), dendritic cells, keratinocytes, macrophages and mast cells (all found in lesions)
How does the defective skin barrier in atopic eczema cause disease?
Allows access/sensitisation to allergen and promotes colonisation by micro-organisms
What are some factors in autoimmunity?
Lymphocyte abnormalities, intercell communication, genetic predisposition, anatomic abnormalities, hormonal influence, infection
What are some diseases caused by autoimmunity?
Psoriasis, vitiligo, systemic lupus erythematous
What are the two kinds of immunodeficiency?
Primary (genetic)-inherited defect (specific/non-specific)
Secondary (acquired)-AIDS, malignancy, aging, diabetes
What mediates a type 1 hypersensitivity reaction?
IgE
How do allergies arise?
Early exposure to allergen causes production of IgE which binds to FceR1 receptor on mast cells
What occurs on later exposure to an antigen in allergy?
Rapid cross-linking of receptors, signal transduction and degranulation of the mast cell
How long can an allergic response take?
Minutes (very early onset, Wheal and flare), hours (cellular infiltration nodule)
What is a type II hypersensitivity mechanism important in?
Autoimmunity and transplantation (haemolytic disease)
What occurs in skin testing for a type III hypersensitivity response?
Leads to Arthus reaction (slower than type I skin response but faster that type IV response)
What mediates type II and III hypersensitivity responses?
IgG and IgM
What mediates type IV hypersensitivity responses?
Th1-based on T-cell mediated response which then recruits other cells to site (tuberculin reaction)
When does a type IV hypersensitivity reaction peak?
24-48 hrs after contact with allergen
What cells are found in the epidermis of the skin?
Keratinocytes, Langerhans cells, CD8+ T cells, melanocytes
What cells are found in the dermis of the skin?
Dendritic cells, macrophages CD4+ and CD8+ T cells, natural killer cells, fibroblasts, lymph/vasculature
