Lecture 26

Type II Hypersensitivity

Known as cytotoxic hypersensitivity

Results in an immune response against cell membrane-bound antigens and then cell destruction

Antigens can be:

• Normal part of the cell membrane e.g blood type antigens

• Covalently bind to the cell membrane e.g penicillin

Cell destruction is mediated by antibodies and the complement system

Two mechanisms:

1. Antibody dependent cell-mediated cytotoxicity by natural killer cells

2. Complement mediated reactions through the classical pathway

Blood Transfusion Reactions

This is when RBCs from the donor have antigens that recipient can recognise as foreign

Antibodies may form IgM and IgG following transfuion

Some species such as cats can have naturally occurring antibodies

Reaction leads to agglutination due to antibody complement is bound malong them clump, and haemolysis

Cats have A, B and Ab blood types:

Cats with A type blood tend not to have such a strong response compared to type B blood cats

Dogs have 7 RBC antigens

Only DEA 1.1 (and 1.2) is sufficiently antigenic to cause transfusion reactions which means transfusion with the other blood types would be less reactive

Dogs don’t have naturally occurring blood type antibodies

Horses also have 7 blood groups but for every group there are a variable umber of “factors” for each group

They have around 400 000 different blood types = no universal donor

Aa and Qa blood types are the most antigenic

Horses don’t have naturally-occurring antibodies

Cattle 11 blood groups and sheep have 6 blood groups

They also have complex blood types

Some may have naturally occurring antibodies

Finding a Donor

Best way is to blood type → best seen used in cats and dogs

Small animals usually have like cards that allow for rapid agglutination testing for different blood antibodies

However if you can’t, you can cross match to identify whether there is a major or minor cross match

• Major – recipient antibodies to donor RBCs

• Minor – donor antibodies to recipient RBCs

Neonatal Isoerythrolysis

Known as the haemolytic disease of the newborn

Common in foals and kittens

The mare can produce Ab against foreign RBC antigens after exposure to foreign RBC antigens via previous pregnancy or blood transfusion. After birth the foal ingests antibodies in colostrum from the dam (mum) . Large quantities of Ab against RBC are in the colostrum, and following ingestion by the foal results in haemolytic disease and anaemia. In horses Ab are unable to cross the palacenta so foals are unaffected during pregnanc. Ab production requires prior sensitization so first foals are normally unaffected.

In kittens neonatal isoerythrolysis is also a problem as type B cats (queen) have high levels of antibodies against type A antigens on RBC in kitten. So even 1st pregnancies are a risk if the kitten has different blood type from the queen as these Ab can be transferred via colostrum to the kitten.

Type III Hypersensitivity

This is when you have excess antigen or antibody

Usually when you had an infection of some type

You develop soluble antigen-antibody complexes where they can travel in the circulation and deposit in tissues → once bound they can activate classical complement → cellular damage

Tissues such as blood vessel walls and glomerular basement membranes tend o be a site of deposition

Rhodococcus equi infection in foals

Immune complexes deposit in the glomerular basement membranes or in the joints leading to either kidney disease or polyarthritis

Pupura haemorrhagica

This is vasculitis that follows strep equi (which causes strangles)

Administration of vaccine following strangles infection can cause this but is also seen naturally following strangles disease

Serum sickness

This is when you get many doses of blood products

Seen in situations such as anti-venom administration

Type IV Hypersensitivity Reactions

No antibodies are not involved

This is a T-cell mediated process only:

Either a Th1 CD4+ sensitivity or CD8+ sensitivity

Needs to be a sensitisation phase

Takes 48-72 hours for clinical signs to develop leading to a delayed response

3 subtypes:

• Contact dermatitis

• Tuberculin-type hypersensitivity

• Granulomatous hypersensitivity

Contact Dermatitis

Haptens penetrate the skin either directly or through insect bites

APCs (langerhan cells in skin) then present antigen (hapten) to CD4+ and CD8+

Activated CD8+ T cells secrete cytokines which can recruit other immune cells

Suppression begins once anti-inflamm cytokines are secreted

Tuberculin Reaction

Describes a diagnostic test used to identify animals previously exposed to mycobacterium tuberculosis (usually in cattle)

Animals exposed to M. tuberculosis develop Th1 response (sensitisation)

Tuberculin = fragments of the M. tuberculosis organism is injected intradermally to test for disease → local dendritic cells phagocytose tuberculin antigen and migrate to local lymph node → memory T cells recognise it and are activated → proliferate → accumulate at site of antigen in the skin

Humans/mice – α/β T cells accumulate, cattle – γ/δ T cells accumulate

Positive reactions show a big firm swelling = induration

Granuloma Formation

This happens we have persistent antigen stimulation → causes granuloma formation due to high cell recruitment and activation of macrophages to multi-nucleated giant cells

Results from not being able to destroy the antigen by APCs

Fibroblasts are recruited to wall off the area and prevent spread

Diabetes Mellitus

This is a CD8+ process where they are sensitised against pancreatic islet cells → T cell mediated cytotoxic destruction

This leads to inability to produce insulin and therefore unable to to regulate their sugar