Hypersensitivity, Autoimmunity and Skin, Muscle and Joints Flashcards
What are the four types of hypersensitivity reactions?
Type I/Immediate hypersensitivity (allergies)
Type II/Antibody-mediated diseases
Type III/Immune complex-mediated diseases
Type IV/T cell-mediated diseases
What is a type I hypersensitivity reaction?
Common allergies
Atopy
Propensity to develop immediate hypersensitivity
What causes Type I hypersensitivity?
Triggered by environmental antigens that elicit strong Th2 response and IgE production
What signalers are attributed to immediate hypersensitivity?
Vasoactive amines and lipid mediators
What signalers are attributed to late phase reaction in allergies?
Cytokines
What does IgE bind to in Type I reactions?
FcERI on mast cells
What does release of vasoactive amines (histamine) cause?
Vascular dilation
Smooth muscle contraction
Secretion of what two cytokine causes inflammation?
TNF
IL-4
(occurs in late-phase/re-exposure)
What does anaphylaxis cause?
Fall in BP caused by vasodilation leading to shock and airway obstruction due to laryngeal edema
What causes hives?
Localized mast cell degranulation and dermal microvascular hyperpermeability
What is Type II hypersensitivity most commonly caused by?
Antibodies specific for normal cell or tissue antigens
What causes phagocytosis in type II?
IgG binding to tissue and phagocytes binding to FcyRI receptors
C3b binding to C3b receptor on phagocytes
What antibodies are found in type II?
IgM and IgG for complement fixation
What complements are chemoattractants causing inflammation?
C3a and C5a
When does pemphigus vulgaris present in life?
40-60 years
What causes pemphigus vulgaris?
IgG autoantibodies specific for desmogleins in desmosomes
What are the three phases in immune complex-mediated hypersensitivity type III?
- ) Immune complex formation
- ) Immune complex deposition
- ) Inflammation and tissue injury
What are the therapeutic approaches to Type II and Type III hypersensitivity?
1.) Corticosteroids (anti-inflammatory)
2,) Plasmapheresis
3.) Administration of IV IgG: may turn off B cells and inflammatory binding cells
4.) Biologics: monoclonal antibodies, soluble receptors
How do Th1 cells facilitate Type IV?
Helper T cells release IFN-y activating macrophages which release TNF, IL-1, chemokines
How do CD8+ T cells facilitate Type IV?
Kill antigen-expressing cells via specific recognition of class I MHC-peptide complex
What facilitates hypersensitivity in rheumatoid arthritis?
CD4+ helper T cells
What CD4 helper T cells produce inflammatory cytokines in RA?
Th1 -> IFN-y -> Mac activation
Th17-> IL-17 -> neutrophil and monocytes
Macrophages -> TNF and IL-1 -> inflammation; proteases that degrade hyaline
Antibodies produced in RA are specific for what?
Citrullinated peptides
How are Citrullinated proteins made?
Self proteins in RA have arginine converted into citrulline
What happens to Citrullinated proteins?
Antibodies against Citrullinated proteins form immune complexes which deposit in joints (Type III)
What promotes Citrullinated proteins?
Inflammation such as infection or smoking
What are rheumatoid factors?
IgM and IgA antibodies specific for their own IgG
What are the three therapies for Type IV?
Corticosteroids
Methotrexate: inhibits DNA synthesis by blocking metabolism of folic acid
Biologics
