Type III hypersensitivities

immune complex mediated inflammation

What IS a type III hypersensitivity

Kupffer cells

Antigen-antibody complexes form constantly in the body, but are usually phagocytized by ______________ so the red blood cells they're attached to can be recycled

stage of immune response, amount of antibody and antigen present

Proper removal of antibody antigen complexes is highly dependent on what two things?

early in the response,

LOTS of antigen vs small amounts of antibodies, AND the complexes that form are small and difficult to clear

Is proper removal of antibody-antigen complexes more difficult in the early, intermediate or late stages of the immune response?

Why?

cleared, immune complex deposition, classical complement, neutrophils

Type III hypersensitivity reactions occur when antigen-antibody complexes form in the circulation and are not adequately ________. THEN ___________________ can occur in blood vessels of various tissues which then activates the _______________ pathway, producing chemotactic factors that recruit ___________ and other inflammatory cells

False; small immune complexes DO NOT fix complement

true/false: it takes longer, but given enough time, small immune complexes will eventually fix complement in order to be cleared from the tissues.

Fc portion, vascular endothelium

BECAUSE they dont fix complement, the ________ portion of an antibody molecule from an immune complex will embed itself where?

platelet activation, vasoactive amines increase vascular permeability, leukocyte activation

what are the sequela to immune complex deposition?

(sequela = the consequence of a previous disease or injury... which, if you knew that, gold star, my vocab is worse than yours)

more susceptible to immune complex deposition (think small capillary networks)

What do all these sites have in common?

Blood vessel walls, Dermal/epidermal junction, Renal glomerulus, Synovial membrane, Ciliary body, Choroid plexus, Pulmonary alveolus.

vasculitis - blood vessel walls; nephritis - renal glomeruli, arthritis - joint spaces

high IV exposure to antigen in Hypersensitivity III reactions leads to what three diseases? (Give disease - and the site of immunocomplex deposition)

arthus reaction - perivascular area

high SubQ exposure to antigen in Hypersensitivity III reactions leads to what disease? (Give disease - and the site of immunocomplex deposition)

farmer's lung - alveolar/capillary interface

high inhaled exposure to antigen in Hypersensitivity III reactions leads to what disease? (Give disease - and the site of immunocomplex deposition)

serum sickness, purpura hemorrhagica, systemic lupus erythematosus

what are three examples of systemic reactions to a type III hypersensitivity?

neutrophils, macrophages, mast cells, inflammation, tissue destruction, Arthus

Repeated exposure in subcutaneous tissue leads to the presence of preformed antibodies that quickly form immune complexes upon rexposure.

These activate _______, _________ and _________ which promote LOCALIZED _______ and _________ when they degranulate.

This is the ________ reaction

True (duh... I think? Maybe not duh)

true/false: Arteritis and vasculitis on a systemic scale can affect a variety of organ systems.

But clinical manifestations are directly attributed to which organ is affected and the severity

antigen-antibody complexes, vascular walls

During the early phase of systemic type III hypersensitivity reactions, ________________________ deposit in the __________throughout the body.

complement, neutrophils, lysosomal enzymes, fibrinoid necrosis

Deposition of immune complexes into vessel walls can activate _________ and ________ which leads to the release of __________ and to ____________________ of the vessel wall.

^ this is the LATE PHASE response

Infectious canine hepatitis (CAV-1), feline infectious peritonitis (corona), classical swine fever (pestivirus [flaviviridae])

What three common infectious diseases have significant type III immunopathologic features

the blue eye (virus-antibody complexes deposited in corneal endothelium, causes fluid exchange ans swelling)

Which part of infectious canine hepatitis is from a type III hypersensitivity?

small and medium immune complexes are not cleared effectively.

These lodge in vessels in the abdomen/kidneys/chest, so, turbulent blood flow and high pressure around these places get the complexes trapped (vessel bifurcation especially)

What part of FIP is from a type III hypersensitivity?

vasculitis and petechial hemorrhages (kind of the whole disease), from immune complexes in blood vessels leading to inflammation and tissue damage

What part of classical swine fever is from a type III hypersensitivity response?

serum sickness

______________: systemic hypersensitivity condition resulting from immune complex deposition in tissue and blood vessels that causes tissue damage through complement activation.

horse serum, snake bites, botulism, pneumococcal, meningiococcal, streptococcal, diphtheria, tetanus, rabies

Historically, antisera derived from _________ were the most common causes of serum sickness. These antisera were used to treat _________, __________, and ________, __________ and ___________ infections, and to immunize patients against ________, __________ and _________

human proteins, heterologous (non-human) proteins, vaccinations, immune modulating agents, anti-venoms

The symptoms of serum sickness arise as a result of the formation of immune complexes between __________ and ______________________

The most common sources were __________, __________ and _________

false; in individuals who have prior exposure, the immune response is faster because antibodies are already present (immediate onset or 1-3 day onset of symptoms)

true/false: on first exposure, serum sickness typically shows symptoms 7-10 days after exposure because the body needs time to make antibodies against it.

In individuals with previous exposure, these symptoms will appear SLOWER (12-15 days later) because the body is better at fighting off the initial stages of the reaction.

fever, rash, joint pain, swollen lymph nodes, GI issues

whata re some symptoms of serum sickness

The Fc portion of the antibody is removed; no cross-linking of Fc means no formation of immune complexes

What is done in many anti-venin products to prevent serum sickness? Why does this help?

immunofluorescence

diagnosis of a type III hypersensitivity often utilizes ___________ to directly visualize the location and nature of deposited immune complexes