Type III hypersensitivity reactions develop as a result of excess formation of immune complexes (Ag-Ab complexes) which initiate an inflammatory response through activation of complement system leading to tissue injury (Fig. 1).

- Antigen involved: Immune complexes can involve exogenous antigens such as bacteria and viruses or endogenous antigens such as DNA

- Removal of immune complexes: Mere formation of immune complexes does not result in type III hypersensitivity reaction

* Under normal circumstances, the immune complexes are rapidly cleared by activation of complement system

* Immune complexes coated with complements are either directly phagocytosed by macrophages/ monocytes or are bound to RBCs and carried to liver and spleen where they are phagocytosed.

- However, in some situations, the immune system may be exposed to excess dose of antigen over long period of time such as in chronic infection, autoimmune diseases, and repeated exposure to environmental pollutants. This leads to formation of excessive immune complexes.

Fig1. Mechanism of systemic type III hypersensitivity reaction.

Soluble vs Insoluble Immune Complexes

 Balance between level of antigen and antibody decides the nature of immune complex that is going to be formed.

- In case of antibody excess or antigen-antibody equivalence, immune complexes formed are large and insoluble; which tend to localize near the site of antigen administration to produce a localized type III reaction

- However, in situations when the antigen is in excess (particularly monovalent antigens), small soluble complexes are formed which tend to travel through blood and get deposited in various sites producing a generalized type III reaction.

Mechanism of Tissue Injury

 Classical Complement Activation

The Ag-Ab-immune complexes stimulate the classical pathway of complement; the products of which mediate the tissue injury in type III reaction.

- Anaphylatoxin: Complement by-products C3a and C5a being anaphylatoxins, induce localized mast cell degranulation with consequent increase in vascular permeability

- Chemoattractant: C3a and C5a also act as chemo attractants, causing recruitment of neutrophils to the site of immune complex deposition

- Role of neutrophils: Neutrophils attempt to phagocytose the large immune complexes, but fail in doing so. Instead, they release large number of lytic enzymes from the secretory granules (through frustrated phagocytosis) which causes extensive tissue damage.

Platelet Activation

 Immune complexes bind to the Fc receptors on platelets leading to their activation. Platelet aggregation (leads to microthrombi formation) and vasoactive amines released from activated platelets, both together cause tissue ischemia leading to further tissue damage.

Activation of Hageman Factor

Activation of Hageman factor leads to activation of kinin, which in turn causes vasodilatation and edema.

Types of Type III Hypersensitivity

 Reaction Type III reactions are either localized or generalized.

Localized or Arthus Reaction

 Arthus reaction is defined as localized area of tissue necrosis due to vasculitis resulting from acute immune complex deposition at the site of inoculation of antigen.

The reaction is produced experimentally (NM Arthus, 1903) by injecting an antigen into the skin of a previously immunized animal, e.g. rabbit (i.e. excess of preformed antibodies against the injected antigen are already present in the circulation). The circulating antibodies bind with the antigen in the dermis and form immune complexes. These immune complexes fix the complement, resulting in localized immune complex mediated inflammatory response called Arthus reaction.

 In humans, localized Arthus reaction is seen in some situations, such as:

- In skin: (1) following insect bites or (2) during allergic desensitization treatment wherein repeated injections of the same antigen is given for long periods

- In lungs, following inhalation of bacteria, fungi, spores or proteins may produce intrapulmonary lesions. Examples include conditions causing extrinsic allergic alveolitis, such as:

* Farmer’s lung: It develops following inhalation of actinomycetes (Saccharopolyspora species) from mouldy hay

* Bird-Fancier’s disease: This develops following inhalation of serum proteins in dust derived from dried pigeon’s feces.

Generalized or Systemic Type III Reactions

 The pathogenesis of systemic immune complex disease can be divided into two phases:

 1. Formation of small sized soluble Ag-Ab complexes in the circulation, which occurs following the entry of a large dose of antigen into the body

 2. Induces inflammatory reaction: Deposition of the immune complexes in various tissues, thus initiating an inflammatory reaction in various sites throughout the body such as; blood vessels (vasculitis), glomerular basement membrane (glomerulonephritis), and synovial membrane (arthritis). This has been linked to the pathogenesis of various diseases (Table 1).

Table1. Diseases associated with generalized type iii hypersensitivity reactions.

Serum Sickness

This is another historical example of type III reaction. This condition is not seen nowadays, it was seen in the past, following serum therapy, i.e. administration of foreign serum, e.g. horse anti-tetanus serum, to treat tetanus cases.

- The horse serum proteins being foreign can induce antibody formation in the host, leading to generation of large number of immune complexes

- Typically, after 7–8 days, the individuals begin to show various manifestations which are collectively called serum sickness. The symptoms include fever, weakness, vasculitis, edema, erythema and rarely lymphadenopathy and glomerulonephritis

- It subsides gradually once the immune complexes are cleared and free antibodies accumulate.

اخر الاخبار

اخبار العتبة العباسية المقدسة

جامعة العميد تنظم ورشة تدريبية عن برنامج منصة التعليم العالي

قسم الشؤون الفكرية ينظم برنامجًا دينيًّا لكشافة الكفيل في النجف الأشرف

العتبة العباسية المقدسة تقدم دعوة لجامعتي الكوفة والطوسي للمشاركة في مشروعها القرآني الخاص بطلبة الجامعات

قسم الشؤون الفكرية يصدر مجموعة جديدة من الإصدارات المعرفية والثقافية

المزيد

الآخبار الصحية

كيف يمكن لحفنة من الجوز أن تؤثر على نومك وتركيزك؟

دراسة: كوب ميلك شيك واحد قد يكون "قنبلة دماغية"

هل يعد "الباراسيتامول" خيارا آمنا للنساء الحوامل؟

دراسة تكشف الرابط بين العلاقات العاطفية والرضا عن الحياة

المزيد

الآخبار التكنلوجية

كارثة صامتة.. "الهواء الملوث" يسرق نور عيون الأطفال

دراسة: رصد أول دليل على وجود "إشعاع هوكينغ"

رسالة بلغة لا تعرفها؟.. "واتساب" يترجمها لك فورا

"إنستغرام".. ميزة جديدة لكشف "الكذب في العمر"

المزيد

مواضيع ذات صلة

Humoral Immunodeficiency (B Cell Defects)

Type IV Hypersensitivity Reaction

Type II Hypersensitivity Reaction

Detection of Type I Hypersensitivity

Manifestations of Type I Reaction

Mechanism of Type I Hypersensitivity

Self-Recognition (Tolerance)

Hypersensitivity Reactions

Humoral/Antibody-Mediated Immune Response

Cell-Mediated Immune Response

Helper T Cells (Activation AND Differentiation)

Type III (Immune Complex) Reactions