What are Antibodies (Immunoglobulins)?
Antibodies are also known as Immunoglobulins (Ig). These are proteins produced by the immune system’s plasma cells (type of white blood cell) in response to antigens.
| WHITE BLOOD CELLS (WBC) ↓ |
| Lymphocytes (type of WBC) ↓ |
| B-cells (type of lymphocyte that produce antibodies) ↓ |
| Plasma cells (type of B-cell) a.k.a. plasma B cells or plasmocytes ↓ |
| Placental mammals such as humans and dogs have 5 categories of antibodies which include ↓ IgA, IgD, IgE, IgG and IgM. |
IgE is of particular importance regarding the issue of allergies. When allergens and IgE bind, it triggers specialized cells (mast and basophiles) to release various inflammatory chemical mediators such as histamine, resulting in the symptoms associated with an allergy response. IgE is not only associated with allergies and microbial/parasitic infections but also autoimmune diseases (Dimson et al.2003) and anti-tumoral defense (Gould et al.1999).
What is Hypersensitivity?
Dogs and humans have immune systems that aim to protect them against foreign substances and disease. Hypersensitive reactions can occur when the immune system of a pre-sensitized individual overreacts and mounts an amplified response when re-exposed to a substance. Though traditionally viewed as detrimental responses, hypersensitivity reactions can also be considered as a host-protective (Rajan 2003) such as through helping to isolate and eliminate specific antigens.
Hypersensitive reactions are immune-mediated responses that range in severity from the mild, albeit irritating or uncomfortable (common), through to damaging (less common) and severe/anaphylaxis (relatively rare) or even fatal (rare).
Alloimmunity, Autoimmunity and Hypersensitivity
Alloimmunity is the term used to describe an immune response directed to antigens from the same species e.g. grafts and transplant rejections.
Autoimmunity refers to when the immune system mounts a response against its own cells and tissues e.g. rheumatoid arthritis and allergies.
Hypersensitivity refers to an undesirable reaction by the immune system with an outcome that is detrimental to the body. Allergic reactions represent an undesirable immune response and are grouped by ‘type’. Type 1 Hypersensitivity is associated with the ‘classic’ allergy response; it represents what people typically think of as “having an allergy” and includes aspects such as atopy, anaphylaxis and allergic asthma.
Hypersensitivity Types and Characteristics
Classification of hypersensitivity into various ‘types’ is achieved based on factors such as the underlying mechanism and mediators involved (e.g. IgE, IgG, IgM, T-cells), as well as the severity and latency of the response. Although the 4 type model advocated by Gell and Coombs in 1963 is still most widely used, variations do exist between authorities.
4 Type Model (Gell and Coombs):
| TYPE 1 | TYPE 2 | TYPE 3 | TYPE 4 | |
| ALSO KNOWN AS |
Immediate Hypersensitivity or Atopic, Anaphylactic or Reaginic Allergy |
Cytotoxic Hypersensitivity (antibody-dependent) |
Immune Complex-Mediated Hypersensitivity | Cell-Mediated Hypersensitivity or Delayed Type Hypersensitivity |
| RESPONSE TIME |
Acute Response: Seconds – Minutes Late-Phase Response: |
Minutes – Hours | Hours – Day | 2 – 3 days |
| EXAMPLES |
Chemotherapy drugs Dog allergens Food allergy Hay fever |
Erythroblastosis fetalis
Goodpasture’s syndrome Membranous nephropathy Transfusion reactions |
Widespread, systemic diseases for example: Farmer’s Lung (Hypersensitivity pneumonitis) Rheumatoid arthritis Serum sickness Systemic lupus erythematous |
Allergic contact dermatitis related to allergens such as to poison ivy (as opposed to chemical-related skin damaged inflammation termed ‘irritant contact dermatitis’ or sometimes simply ‘contact dermatitis’) Multiple sclerosis |
| MECHANISM |
Acute response: Late-Phase response: |
Antibodies (IgG or IgM) bind to foreign cell antigen ↓ Antibody/antigen complex (complement fixation) activates pathways ↓ Cell damage then cell death by Membrane Attack Complex (MAC) |
Antibody (IgG) bind to foreign cell antigen ↓ Antibody (IgG) /antigen complexes typically form in circulation/body fluids before being deposited in tissue ↓ Antibody/antigen complex (complement fixation) activates pathways ↓ Cell damage then death by neutrophils + lysosomal enzymes released |
T–cells (rather than antibodies) recognize foreign substance ↓ Immune response involving monocytes/macrophages ↓ Target cells destroyed |
| NOTES |
Discussed in greater depth in: Possible role played by IgG/IgG4 is uncertain and debatable at present (e.g. Boluda et al. 1997), as is the scientific value offered by food allergy diagnostic tests for it. For example, IgG/IgG4: |
Possible role played by IgM is uncertain and debatable at present |
Type 4 Hypersensitivity is not the same as late-phase Type 1 Hypersensitivity |
Variations:
| 5 Type Model |
Some systems choose to divide Type 2 Hypersensitivity into 2 subcategories, whilst others classify one of these subcategories as being Type 5 Hypersensitivity. Thus, the 5 type model e.g. in UK, differs from the 4 type system because: |
| 7 Category Model (Sell et al. 1996) |
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Other: |
Revised nomenclature for allergy in order to present a more unified definition of hypersensitivity based on allergy, IgE and atopy but regardless of target tissue or organ. |
How Hypersensitivity Relates to Dog Allergies
People:
When referring to allergies that affect humans, the term ‘dog allergies’ is quite specific; it implies people who are allergic to dog allergens associated with dog dander or their urine etc. Remember dog related allergies refer to people who are not allergic to dog allergens but rather to other allergens carried on them e.g. dietary or environmental. Furthermore, a person may have concurrent allergies that are both dog specific and dog related.
Thus, Type 1 Hypersensitivity would account for the various symptoms observed in a person sensitized to dog allergens. However, humans can experience allergic reactions/conditions associated with other types of hypersensitivity e.g. Type 2 Hypersensitivity and autoimmune haemolytic, but these are not relevant in the context of people allergic to dogs, dog allergens and the topic of dog allergies.
Dogs:
When referring to allergies that affect dogs (allergies in dogs), the term ‘dog allergies’ is broader in scope; although Type 1 Hypersensitivity is responsible for the vast majority of allergies that affect canines e.g. to food or pollen, there exists a variety of conditions that result from allergic reactions associated with other types of hypersensitivity e.g. systemic lupus/discoid lupus erythematosus (Type 3 Hypersensitivity) or allergic contact dermatitis (Type 4 reaction).
