Hypersensitivity and immune responses in the skin Flashcards
Which are the key immunological cells in the skin and where are they found?
Keratinocytes - epidermis
Langerhans - epidermis
Melanocytes - epidermis and dermis
Dermal dendritic cells - dermis
Dermal macrophages - dermis
Mast cells - dermis
Lymphocytes - dermis
What is the function of dermal dendritic cells
Migrate to lymph node to cause an immune response
How do keratinocytes and commensals reduce immune response to normal bacteria on the skin
Keratinocytes and other commensals produce AMPs (antimicrobial peptides) to control microorganisms on the skin.
Commensals also activate T-reg cells reducing immune responses
How does the skin recognise and eliminate non-commensal organisms?
Bacteria induces keratinocytes to produce IL-6 and IL-8 -> attract neutrophils which enter the epidermis to phagocytose and destroy bacteria
What is bacterial pyoderma?
Neutrophils accumulated at the mouth of hair follicles making a distinct pustule
What is a hypersensitivity reaction?
immune responses to innocuous antigens that lead to symptomatic reactions upon re-exposure
Explain Type I (immediate) hypersensitivity
IgE-mediated
Sensitisation to the allergen occurs in the past
On next exposure - allergen specific IgE (on mast cells and basophils) binds allergen -> crosslinking and degranulation releasing many mediators (histamine, cytokines etc)
Response within 30 mins
What are the results of a type I hypersensitivity reaction?
Vascular dilation
Increased vascular permeability
Smooth muscle contraction
Airway constriction
Swelling and oedema
Worst case = anaphalaxis
Cellular recruitment
Pruritus
Explain Type IIa hypersensitivity
IgG antibody recognises cell surface or matrix antigens (self or non-self) and binds to it leading to ->
Complement lysis of the cell (complement mediated cell cytotoxicity)
Or
Removal by the reticuloendothelial system
Result in 5-10 hrs
Explain type IIb hypersensitivity
IgG antibody recognises cell surface or matrix antigens and binds to it (self or non-self) leading to ->
Destruction of the target cell by effector cells (macrophages, NK cells, eosinophils, neutrophils)
Anti-body dependent cellular toxicity (ADCC)
Result in 5-10 hrs
Explain type III hypersensitivity
IgG and/or IgM binds to soluble antigens which is then carried to an area where it becomes trapped in a vessel e.g., tail, ears, feet
This leads to complement damage to vessel wall
Macrophages, neutrophils and mast cells may be activated by the complexes and cause more damage
Results in swelling, partial ischaemia and tissue necrosis
Occurs after 4-8hrs
Explain type IV hypersensitivity
T-cells orchestrate specific immune responses through production of cytokines or through direct cell contact
Reactions occur after 24-72 hours
What is canine atopic dermatitis
a genetically predisposed inflammatory and pruritic allergic skin disease associated with IgE antibodies
What type of hypersensitivity reactions are seen in canine atopic dermatits
I and IV