hypersensitivity and skin immunity

Question 1

what are the key players in skin immunology

Answer 1

• keratinocytes (epidermal)
• langerhans cells (epidermal)
• melanocytes (epidermis and dermis)
• dermal dendritic cells (dermis)
• mast cells (dermis)
• lymphocytes (dermis, occasionally epidermis)
• other effector cells (dermis and epidermis)

Question 2

what are the roles of the skin immune system

Answer 2

• reduced surveillance and collaboration with commensals
• recognition and elimination of non-commensal organisms/pathogens (including commensal organisms in excess)
• unhelpful immune responses in allergy and immune mediated disease

Question 3

explain how the skin immune system allows for reduced surveillance and collaboration with organisms

Answer 3

keratinocytes produce host defence peptides to control microorganisms on the skin. commensals also produce AMPs which kill other bacteria and also activate T-regulatory cells reducing immune responses
in addition langerhans cells are less active when presenting commensal bacteria antigens

Question 4

explain how the skin immune system allows for recognition and elimination of organisms

Answer 4

• bacteria induce cytokine production from keratinocytes (danger signals sent to circulating neutrophils)
• neutrophils leave circulation and migrate into the epidermis
• neutrophils phagocytose bacteria and destroy them

Question 5

what are the 4 types of hypersensitivity reactions and how are they mediated

Answer 5

• Type 1: immedite hypersensitivity mediated by IgE activating mast cells
• type 2: IgG antibodies against cell surface/matrix antigens
• type 3: antigen antibody complex mediated
• type 4: T cell mediated

Question 6

what is a hypersensitivity reaction

Answer 6

an immune response to innocuous antigens that lead to symptomatic reactions upon re-exposure

Question 7

what is sensitisation

Answer 7

before any specific immune reaction, the body must have encountered the organism before. the type of allergen, the dose and the timing of exposure all influence the type of immune response that will result
the process of priming a specific immune response is called sensitivity (vaccines)
the cytokines produced by T-helper cells determines the type of response

Question 8

discuss type 1 hypersensitivity reaction

Answer 8

• IgE mediated hypersensitivity
• sensitisation occurs in the past
• on subsequent exposure allergen-specific IgE on mast cells and basophils binds allergen, causing crosslinking and degranulation releasing many mediators. immediate response is within 30 minute
• IgE bound to the mast cell by the high affinity IgE receptor is crosslinked by soluble antigens causing release of mast cell mediators (histamine, protease, prostoglandins, leukotrines, cytokines)
• resuklts in vascular dilation, smooth muscle contraction, airway constriction, swelling and redness of skin, and (worst case anaphylaxis) cellular recruitment and pruritus

Question 9

discuss type 2 hypersensitivity

Answer 9

• IgG antibody recognises cell surface or matrix antigens
• reactions occur within 5-10 hours
• results in complement lysis of the cell, removal by the reticuloendothelial system, destruction of the target by effector cells, antibody allows immune cells to be directed to target

Question 10

discuss type 3 hypersensitivity

Answer 10

• IgG and/or IgM binds to soluble antigens and then is carried to areas where it becomes entrapped in the vessel. common sites in the skin are small vessels in the tail, ears, and feet. the antigen/antibody complex is not cleared by the reticuloendothelial system
• reactions occur maximally at 4-8 hours
• results in complement damage to the vessel wall, macrophages, neutrophils and mast cells may be activated by the complexes and cause additional damage, variable locally to more generalized patterns of disease, swelling, partial ischaemia and tissue necrosis
• vasculitis may be an acute event but due to damage to the blood vessels the effects on the skin and other organs can be very severe

Question 11

discuss type 4 hypersensitivity

Answer 11

• in sensitized animals, antigen is processed by local dendritic cells and antigen specific (primed) T cells
• reactions occur maximally at 24-78 hours
• results in T cell recruitment and activation of other cells (monocytes and macrophage) to produce a local inflammatory response and leads to cytotoxicity

Question 12

list classifications of type 4 hypersensitivities and their appearance/cells involved/timing/antigens

Answer 12

allergic (Th2)
- 28-72 hours
- pruritus and eczema
- lymphocytes followed by eosinophils
- house dust mite, yeasts etc are entigens

contact (Th-1)
- 48-72 hour
- eczema
- lymphocytes followed by macrophages
- epidermal antigens (organic chemicals, poison ivy, heavy metals)

tuberculin
- 48-72 hours
- local induration
- lymphoctyes, monocytes, macrophages
- tuberculin is antigen

granuloma:
- 21-28 days
- hardening
- macrophages, epitheloid and giant cells, fibrosis
- persistent antigen or foreign body presence