Final Exam (Lecture 21) - Type III (Immune-Complex) and Type IV (DTH and Contact Dermatitis) Hypersensitivities Flashcards
List the components of a Type III reaction and their role in the reaction. (Type of antibody, type of antigen, complement components (key molecules and their major function), neutrophils (why do they arrive, how are they activated, and what are the products of their activation), mast cells (how they are activated and the contribution of mediators). Review complement activation and mast cell degranulation if needed.
1) Antibody
- IgG in significant amounts
2) Antigen
- Soluble antigen in sufficient amounts
3) Complement components
- MAC = lysis
- C3b = opsonization of immune complexes
- C5a = chemotaxis of neutrophils, oxidative burst,
increased vascular permeability, up regulation of
addressins, and anaphylation
4) Neutrophils
- Chemotaxis attracts them so they can kill and
phagocytose
- Activated by C5a or immune complexes bound to
neutrophil Fc-gamma/C3b receptors
- Products of activation is oxidants and defensins
5) Mast cells:
- Fc gamma receptors bind to C3a, C5a, or Fc
portion of immune complexes
- Increased vascular permeability, smooth muscle
contraction, platelet accumulation, vessel occlusion
Compare Type I and Type III local hypersensitivity reactions (antibody, antigen, cause of the reaction observed, cellular infiltrate, and timing).
1) Type 1:
- 15-30 minutes
- Antibody: IgE
- Antigen: Allergen (soluble)
- Eosinophils
2) Type 3:
- 6-8 hours
- Antibody: IgG
- Antigen: Soluble protein
- Neutrophils
Describe a classic example of a local immune-complex reaction (e.g. a booster vaccination).
1) Antigen is injected into SQ tissue of a sensitized individual
2) High-titered IgG antibody will diffuse into tissue of injection site and bind to the antigen resulting in large amounts of immune-complexes at equivalence points
3) Inflammation induced with complement activation, mast cells, and their mediators and neutrophils in 6-8 hours
Describe a classic example of a systemic immune-complex disease (e.g. serum sickness) including the common sites of immune complex deposition, and explain the resulting clinical signs.
A large amount of passive IgG from another species.
Ex: Dog bitten by rattlesnake
- Treatment includes a transfusion of RBC to
replace already lysed cells and equine
antivenin to neutralize the venom
Equine-origin antivenin: foreign antibody that can cause a systemic type 3 hypersensitivity
Common sites: Plasma filtration sites
- blood vessels
- glomeruli
- choroid plexus
Clinical signs:
- skin rash
- joint pain
- urinary issues
- neurologic issues
Label a graph describing the timing and sequence of events for a generalized immune-complex disease (like serum sickness), including relative amounts of free antigen, complement levels in the body, immune complexes, clinical signs, and free antibody. Explain why this can occur in an individual after the first exposure to the antiserum produced in a different species.
IN PPT
Explanation:
- First exposure to antiserum from another
species will elicit an immune response (its a
large foreign protein) and complement
activation
List the components of a T-cell mediated hypersensitivity (Type IV), including types of T cells, how they recognize antigens, and key molecules that bring about the clinical signs.
Type: TH1 and CTLs
Recognize:
- Antigens presented on:
- MHC I and MHC II from
Langerhans/macrophages
Key molecules:
- Proingflammatory cytokines
- TH1 releases IL-2, INF-gamma and TNF
IL-2:
- Proliferation of T cell chemokines
INF-gamma:
- Increase MHC II, activate M1 macrophages
TNF:
- Upregulate adhesion molecules, chemokines,
and leaky vessels
Describe the series of events that occur to result in a positive intradermal skin test for tuberculosis and what a positive intradermal skin test means.
1) PPD is injected
2) Sentinel cells with PRR recognize the PAMPs
3) Proinflammatory cytokines are secreted
- IL-1, IL-6, TNF
4) Act on blood vessels to increase selectins and
addressins
5) Memory TH1 cells bind to addressins
6) Memory TH1 recognizes PPD on the MHC I
receptor
7) Secretes INF-gamma
8) Attract mononuclear cells
- Monocytes and lymphocytes
9) Positive result = induration
- Means that the animal has been infected with
TB
Compare a positive intradermal skin test for determining allergen selection for a dog with a atopy and a positive intradermal skin test for a cow infected with Mycobacterium bovis, including the antigen, antigen-specific component of the immune system, the reaction seen clinically, the cause of the reaction, and the timing of the observable reaction.
1) Positive intradermal skin test (dog):
- IgE on mast cells
- Wheal and flare due to mast cell
degranulation
- 15-30 minutes
2) Positive intradermal skin test (cow):
- TH1
- Induration (hard nodule) due to accumulation
of mononuclear cells
- 72 hours
There is a product on the market called VenomVet for the treatment of people for all North American pit vipers envenomations. Use labeled drawings and brief notes to describe how the antivenin was treated to make this product. Give a brief explanation for why it will still work as an antivenin and decrease the risk of developing serum sickness.
Antibody that is typically ovine or equine (foreign to dog) is cleaved at hinge region
Still works as antivenin due to the Fab region still being in tact (will still neutralize the venom).
Less likely to cause serum sickness due to cleaving a large portion of the foreign protein. (Fc region is unique to each species and with it cleaved from the ovine/equine sample, it is less likely to stimulate an immune reaction in the dog).
Poison Ivy contact dermatitis is a Type IV (T-cell mediated) hypersensitivity. The urushiol oil of the plant is a small lipid-soluble chemical. It covalently binds to extracellular host proteins and it crosses the host cell membranes, and covalently binds to intracellular proteins; the newly formed molecule induces and immune response.
- Do you think urushiol oil alone would be a good antigen? What makes a good antigen? Explain.
- What is the general term used to describe this type of new antigen (immunogen)?
- Based on the description of this immunogen, describe how it would be processed and presented to the immune system, including the antigen-specific cells stimulated.
1) No; a good antigen is a large foreign protein that stimulates T cells.
2) Hapten
3) Recognized by sentinel cells and presented on MHC II to activate T helper cells
