Know the modes of action of Complete Freund’s adjuvant

 

Freund’s adjuvant is of two types and both types are unique components of induction procedures of several experimental animal replicas of autoimmune disease. Aside from the early studies conducted during the 1950s and 1960s, a no more direct investigation has been undertaken on the mode of action of these adjuvants.

It is commonly supposed that the complete as well as the incomplete type of adjuvant work by prolonging the life span of injected autoantigen. It increases the lifetime by motivating its efficient delivery to the immune system and by supplying an intricate set of signals to the inborn compartment of the immune system. This causes an altered leukocyte propagation as well as differentiation.

Both types of Freund’s adjuvant have been the most frequently used immunoadjuvants for experimental purposes for 50 years. However, the mode of action of these adjuvants is still not totally understood. Moreover, in spite of huge advancement in the knowledge of the cellular and molecular basis of the immune system, immunologists have continued to utilize the complete form of adjuvant without taking care of its mode of action.

The regular use of CFA in investigational protocols is concealed in the Methods and Materials sections of trial studies without additional consideration of the insinuations in the Discussion sections. The use of CFA is obligatory in the introduction procedures of several experimental autoimmune disease models, such as:

·         Experimental autoimmune neuritis

·         Experimental autoimmune encephalomyelitism

·         Experimental autoimmune uveitis

·         Experimental autoimmune thyroiditis

·         Experimental autoimmune orchitis

Some of the actions of the complete form of Freund’s adjuvant include:

·         Facilitation and hyper immunization of autoimmune disease introduction

·         Granuloma formation

·         Local inflammation

·         Protection against fetal loss

·         introduction of cells with suppressor action

·         avoidance of diabetes in NOD or non-obese diabetic mice

The modes of action of CFA include:

·         augmentation of antigen uptake by antigen-presenting cells

·         Emission of risk signals causing T-helper 1 skewing

·         Chemokine induction

·         Cytokine induction

·         Growth as well as successive reduction of activated cluster of differentiation 4 and T-helper cells

·         Haemopoietic dysfunction

Immunologists have used complete Freund’s adjuvant for over 50 years to induce autoimmune infections in experimental animals.

During the early days of work with Freund’s adjuvant, three action mechanism categories were proposed. Among them, two categories, such as the long life span of autoantigens introduced in CFA or IFA and their changed trafficking to important sites in the immune system remain fully valid. IFA is essentially paraffin oil that contains mannide mono‐oleate as a surfactant. Of note, these two methods apply to CFA as well as to IFA, as they both are caused by implanting the antigen in an oily excipient. Uptake of antigens by antigen-presenting cells and succeeding trafficking of these cells are now hot topics of study in immunology.

Relevant systems of molecules and particularly, the chemokines and their receptors, are in the untangled process. Unfortunately, the way the management of IFA as well as Complete Freund’s adjuvant affects these networks at a cellular and molecular basis is not yet a key point of concern.

 The third mechanism category, which the early staff had to leave mostly anonymous, can at least be partly specified at present and accommodated into a possible scenario, which involves mainly innate immunity mechanisms.