Lecture 23 - Type 3 hypersensitivities Flashcards Preview

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Flashcards in Lecture 23 - Type 3 hypersensitivities Deck (22)
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Which antibodies are involved in type 3 hypersensitivities?

IgG and IgM


In type 3 hypersensitivities, what does antibody bind to?

Soluble antigens

(I.e. not cells or cell matrices)


How are immune complexes normally cleared from the body without causing tissue damage?

  1. Immune complexes activate complement.
  2. C3b opsonizes immune complexes.
  3. C3b binds to C3b receptor on RBCs or platelets.
  4. Macrophages in liver and spleen strip the immune complexes off the RBC.  Complex is broken down by the macrophage.


What is meant by "immune complex?"

Antibody bound to antigen.


When antibody binds to antigen, it can activate complement and activate Fc receptors on phagocytic cells.  (This is true for all isotypes except IgE and IgA.  IgE binds to mast cells, and the Fc portion of IgA is bound by the J chain)


Learning Objective 1


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).

  • IgG binds to soluble antigen.
  • Complement fixation through the classical pathway.  Formation of the MAC, causing cell lysis.
  • C3a and C5a are chemotactic for neutrophils.  They are also anaphylatoxins (cause mast cell degranulation).
  • Mast cell degranulation and complement fixation results in vasodilation and increased vascular permeability.


Learning Objective 2


List the common sites of immune complex deposition and explain the resulting clinical signs. 

Immune complexes get deposited at common plasma filtration sites - Blood vessels, glomeruli, synovial cavities.

Diseases associated with immune complex deposition at theses sites:

  • Vasculitis
  • Glomerulonephritis
  • Synovitis, arthritis


What factors contribute to deposition of immune complexes?

  • Size of circulating immune complex
  • Ability of host to clear complexes from circulation
  • How tightly antibody is bound to antigen
  • Amount of circulating immune complexes


Learning Objective 3


Compare and contrast Type I and Type III hypersensitivity reactions - antibody, antigen, cellular infiltrate, and timing.

Type 1 reaction

  • Antigen cross-links IgE bound to mast cells, causing degranulation.  Reaction within 15 minutes.  Chemotactic for eosinophils.

Type 3 reaction

  • Free-floating IgG binds to antigen and activates complement.  Chemotactic for neutrophils.  Cellular infiltrate in 6-8 hours.


Learning Objective 4


Describe a local type III reaction, including the conditions necessary for it to occur.

Antigen is introduced into a tissue.  Pre-formed antibodies form complexes with the antigen.  Immune complexes stay localized.


Ex: insect bite, vaccine


Learning Objective 5


Describe a generalized (systemic) type III reaction, including the conditions necessary for it to occur.

Antigen is present in high amounts in the blood stream.  Circulating antibody binds with the antigen, forming immune complexes.  Immune complexes get deposited at sites of plasma filtration.


Ex: serum sickness


How might an individual develop a type 3 sensitivity to horse serum after only 1 injection with the serum?

If the serum is in high enough concentration, it will hang around in the blood stream long enough for the body to develop high titer IgG against the serum components.  This will result in immune complex formation.

This process usually takes 10-14 days.


A dog presents to your in a hemolytic crisis from a snake bite.  You administer equine-derived antivenom to treat the snake venom and cross-matched canine erythrocytes to replace the lost red blood cells.  The dog appears to improve, but one week later starts acting lethargic and has a fever.  What do you suspect is going on, doc?

Serum sickness.  The dog has developed IgG against the equine antibodies.

The patient's symptoms are due to immune complex formation and complement fixation.  The patient should improve in a few days after the equine antibody titers decrease.


You administered equine antivenom to a dog that got bit by a snake.  Will this dog be immune to snake bites in the future?

Lol nope


You administered equine antivenom to a dog who got bit by a snake.  About a week later, he showed signs of serum sickness, but improved.

Two years later, the dog got bit by a snake again (d'oh!).  You should probably proceed with the same treatment, right?


The dog reacted to the equine antibodies, so will have formed memory cells.  If you administer equine antivenom again, the dog will have a secondary immune response and produce high titer, high affinity IgG against the antivenom.

Formation of immune complexes will result in lots of complement fixation, which could lead to shock and death.


Learning Objective 6 Part 1


Use a graph to describe the timing and sequence of events for a generalized immune-complex disease (like serum sickness)


Learning Objective 6 part 2


For type 3 hypersensitivity reactions, discuss relative amounts of free antigen, complement levels in the body, immune-complexes, clinical signs and free antibody. Explain why this can occur on the first exposure to the serum. 

  • High antigen levels in the serum stimulates formation of IgG.  Rising IgG levels causes formation of immune complexes.
  • Clinical signs peak as antibody levels peak.  As antigen levels decrease, the amount of free antibody begins to rise.
  • Complement levels decrease as immune complex levels rise due to fixation of complement.
  • Serum sickness can happen at first exposure because foreign serum remains in the blood stream for an extended period, allowing antibodies to form.  This usually happens in about 10 days.


Where does FIP virus replicate in the body?

Macrophages and monocytes


Is humoral immunity protective against FIP?


Antibodies will bind to the virus, but will not inactivate it.  Opsonized virus is taken up by macrophages, where the virus can replicate freely.


Learning Objective 7


Explain how FIP can result in an immune-complex disease.

Antibodies against FIP virus are not protective, but instead speeds up phagocytosis of the virus by macrophages, which speeds up viral replication.

Large amounts of antigen and antibody in the serum result in formation of immune complexes, causing clinical disease through complement fixation and immune complex deposition in sensitive sites like the glomeruli.


True or False

Both Type 2 and Type 3 hypersensitivities can be seen in systemic lupus erythematosus (SLE)


Type 2 results from auto-antibody to RBCs.

Type 3 results from immune complex formation between auto-antibodies and nuclear DNA and histones.


Learning Objective 8


Explain the pathogenesis of the clinical signs that result from immune complex deposition in SLE and those that result from the autoantibody to RBCs and the cytotoxic response (Type II reaction) in SLE.

  • Auto-antibody is formed against nuclear DNA and histone components.
    • Immune complex formation results in dermatitis, glomerulonephritis, and arthritis (type 3 reaction)
  • Auto-antibody to RBCs causes cell lysis and anemia (type 2 reaction)


How would you go about treating systemic lupus erythematosus (SLE)?

High dose glucocorticoids and other immunosuppressive drugs


Prognosis is often guarded to poor, especially if immune complexes have been deposited in the kidney (resulting in glomerulonephritis).