Hypersensitivity and Immunopathologies Flashcards
Hypersensitivity reactions def
excessive or inappropriate immune response due to prolonged or repeated exposure to antigen.
• Can target self antigens OR foreign antigens
Types of hypersensitivity reactions
- Type I = immediate IgE
- Type II = antibody mediated IgM and/or IgG
- Type III = Immune Complex IgM and/or IgG
- Type IV = cell mediated T cells
Type I hypersensitivity
immediate or allergic reactions that occur within minutes to hours after exposure
- Reactions are known as ALLERGIES
- suffered by 54% of pop
Initial exposure of type I hypersensitivity
- allergen enters body
- APC eats it
- APC presents peptides from allergen to MHC II
- Helper T cells activated and differentiate into Th2 for STRONG response
- Th2 activate B cells (PLASMA CELLS) specific for antigen
- B cells make IgE
Plasma cells
B cells that mass-produce antibodies
IgE half-life
IGE antibodies only live in blood for a day, but can attached to mast cells for half-life of several weeks
Steps in hypersensitivity type I
- first exposure
- sensitization
- re-exposure
- allergic reaction
first exposure (step1 hypersensitivity type I)
person may or may not have an initially allergic reaction to first exposure because IgE antibodies take time to accumulate in load onto mast cells
sensitization (step 2 hypersensitivity type I)
Fc region of IgE binds to mast cells located throughout the body. This allows a second exposure of allergen to activate mast cells
re-exposure (step 3 hypersensitivity type I)
allergen binds to IgE antibody and creates clusters which causes degranulation and release of chemistry
allergic reaction (step 4 hypersensitivity type I)
chemistry live release by mast cells includes:
- early phase: immediate release of histamines, proteases, prostaglandins
- late phase: 6-24 hours which includes IL-4, TNF and WBC
Cells involved with allergies
- mast cells = located in tissue for immediate response
- basophils = rapid response brought by blood due to signal from mast cell. Will degranulation upon antigen exposure
- eosinophils = delayed response that are recruited from bone marrow
Non-atopic individuals
nonallergic people
- respond weakly to allergens
- produce mainly IgG
Atopic individuals
Allergic people
• produce large amounts of IgE
Hygiene hypothesis
theory that chronic inflammation (especially allergies and asthma) is an unintended consequence of greed adduction and exposure to microbes in the first year of life
Type II hypersensitivity
antibody mediated (IgM or IgG)
- antibodies bind to surface of cells (cell membrane) or extracellular matrix
- means of destruction include: antibody dependent cell mediated cytotoxicity, complement system, functional derangements
antibody dependent cell mediated cytotoxicity (ADCC)
complement INDEPENDENT destruction of target cell and hypersensitivity type II
- antibodies (IgG or IgA) bind to antigens on target cell’s surface.
- Complex is recognized to WBCs (monocytes, neutrophils, eosinophils, NK cells)
- WBC mediates destruction of pathogen
Complement system
complement proteins (MAC) destroy target cells in hypersensitivity type II
- IgM and IgG are good it fixing complement
- production of complement proteins activates macrophages and neutrophils
functional derangement
antibodies act as agonists or antagonists to cell receptors in hypersensitivity type II
• may occur with or without inflammation
Hemolytic Anemias
what are the five carbon protein on RBC. RBC are then phagocytized. When complemented fixed, RBCs are quickly lysed
rheumatic heart disease
streptococcal throat infection activate helper cells
- helper T cells cross react with a protein present on mitral valve the heart
- cross reacting helper T cells direct an inflammatory attack on the heart
hypersensitivity reaction type III
deposition of antibody-antigen complexes accumulate (MAC), are first cleared
- IgM and IgG fixed complement
- complement attracts neutrophils and macrophages
- FC region on neutrophil in macrophage bind to FC region of IgM and IgG
- phagocytes eat the antigen-antibody complex thus releasing inflammatory chemistry
Lupus Erythemoatosus
an inflammatory disease of the in T-cell intolerance
- IgG recognizes many antigens that form self antigen-antibody complexes
- example than autoimmune hypersensitivity type III
Hypersensitivity reaction type IV
cell mediated = inappropriate or excessive immune response from T cells
- types: delayed type hypersensitivity (DTH), cell mediated cytotoxicity
- they do not involve antibodies. But stimulated by intercellular parasites
- may be directed against self or exogenous antigens
- require prior exposure
Delayed type hypersensitivity
form of hypersensitivity type IV reaction
- Th1 secretes INFγ Which stimulates macrophages
- macrophage does damage and stimulates fibrosis
- examples include: contact dermatitis, Crohn’s disease, type I diabetes, multiple sclerosis
Multiple sclerosis
it example of delayed hypersensitivity (hypersensitivity type IV)
- initiated by self reactive T cells that target myelin base proteins
- helper T cells emit cytokines attracting macrophage which do damage
Cell mediated cytotoxicity (hypersensitivity type IV reaction)
CTL cells display foreign antigens
- perforin or granzyme B
- CTLs release INFγ (Activates macrophage –> fibrosis)
- major reason organ transplants are rejected
- example = viral hepatitis
