Hypersensitivity Flashcards
Describe what makes a good antigen.
- Large foreign molecules >1400 kd
- Complex molecule
- Stable shape for recognition by cell surface receptors
=Proteins!
- polysaccharides are easily degraded
- lipids are simple molecules, easily degraded and widely distributed
Describe the general structure of an antibody
Antibody= soluble B cell receptor
- 160kD glycoprotein composed of 4 polypeptide chains
- 2 heavy chains (50-60kD)
- 2 light chains, half the length and weight of heavy chain
- Structure is Y shaped with two identical halves, linked by disulfide bonds
- Groove between the light and heavy chain forms the antigen binding site
When treated with papain, where are the cleavage sites?
Papain cleavage occurs above the S-S bond of hinge region
Produces 3 fragments
- 2 identical Fab regions- antigen binding region
- 1 Fc region- fragment crystallizable region
List the functions of antibodies
- Complement activation
- Antibody dempendent cell cytotoxicity (ADCC)
- Mast cell degranulation
- Agglutination
- Opsonization
- Precipitation
- Neonatal immunity
- Neutralization of toxins
What is the order in which isotype switching occurs?
IgM
IgD
IgG
IgE
IgA
Which cytokines are involved in isotype switching?
- Class switching occurs while B cell is still in germinal center
- IL-4, IFNg, TGFb
- Results from deletion of unwanted heavy chain gene segmens, then joining with variable regions
- variable regions remain the same but has new heavy chain constant regions which defines antibody class
Describe the main function of each Ig isotype
IgA
- Secretory
- Shortest serum half life (2-3 days)
- Highest antiviral activity
IgE
- Immunity to parasites
- Most mast cell/basophil degranulation activity
IgG
- Most abundant in circulation
- Longest serum half life
- Most effective at neutralizing toxins
- Crosses placenta
IgM
- Produce during primary immune response
- Most efficient at fixing complement
- Naive B cell receptor (also IgD)
IgD
- Naive B cell receptor
Which antibody isotypes have ability to fix complement?
IgG and IgM
IgA cannot activate classical pathway, can activate alternative pathway
List examples of each type of hypersensitivity reaction
- Type I (immediate, IgE)
- IgE mediated
- Ex asthma, anaphylaxis
- Type II (cytotoxic)
- Ab binding (IgG, M) to Ag on body tissues
- Ex pemphigus, cryglobulinemia
- Type III (immune complex)
- deposition of Ab-Ag complexes in vesssel walls
- Ex SLE, leukocytoclastic vasculitis, serum sickness
- Type IV (delayed, cell mediated)
- Antibodies NOT involved
- Contact HS, flea bite HS, graft rejection
Drug eruptions can be any type of HS reaction
Histamine release during Type I HS reaction creates what kind of response?
Triple response of Lewis
- Mucus secretion
- Bronchoconstriction
- Vasodilation
- Vascular permeability
Describe antibody dependent cell mediated cytotoxicity
- ADCC only occurs when target cell is covered with antibodies that are attached to antigens on cell
- Fc region is recognized by Fcg receptor on killer cell
- Cells that mediate ADCC: NK cells, neut, eos, macrophoage
- Killer cells have FcgRIII sepcific for antigen bound IgG, not antigen specific
- MHC is not involved
- Cytotoxic mechanisms dependent on type of killer cell involved
- NK cells- perforines
- Macrophage, neuts/eos- proteases, toxic oxygen species
List some infectious agents that may trigger formation of immune complexes and Type III hypersensitivity reaction.
- FIP
- FeLV
- canine adenovirus
- ehrlichiosis
- leishmaniasis
- dirofilaria
- Staphylococcus
- Streptococcus
What is the most common etiologic agent of purpura hemorrhagica
Streptococcus equi
Which medication has been documented to cause formation of antinuclear antibodies in dogs?
Hydralazine
What is the classic example of delayed hypersensitivity reaction?
Tuberculin (Montaux) reaction