Diagram of cell cooperation in the adaptive immune response. Cytokines play a key role in these processes

As we saw in previous chapters about cell cooperation in the immune response, the activation of T and B lymphocytes takes place through a complex process in which antigen presenting cells and antigens take part, as well as both lymphocytes.

Cytokines are also involved in this important process of the adaptive immune response, favouring the activation of T and B lymphocytes.

Two signals are required for the T lymphocytes to be activated and enter into the G1 phase of the cell cycle. One results from interaction with antigen and the other is a co-stimulator.

The cytokine IL 2 is secreted as a result of this stimulation, permitting the expansion and differentiation of the T lymphocytes in two cell subtypes of CD4+ T helper lymphocytes, Th 1 lymphocytes (T helper 1) and Th 2 lymphocytes (T helper 2). 

Both populations produce different types of cytokine.

Th 1 lymphocytes. These are basically linked to macrophage activation in processes of intracellular antigen removal through the activation of phagocytosis, or in processes of NK cell activation, inducing cytotoxicity in infected cells. They also produce pro-inflammatory cytokines as a response to antigenic stimulation.  

These cytokines promote the differentiation of cytotoxic effectors, with the most important being:

Th 2 lymphocytes. These are linked to the activation and differentiation of B lymphocytes. Th 2 lymphocytes recognise the antigen on the surface of the B lymphocytes, along with the SLA-II molecules, and induce clonal expansion of B cells and the resulting differentiation to antibody-producing plasma cells. Th 2 cells also are related to the activation of eosinophils. 

The main cytokines secreted by these cells are:

As well as the subtypes of Th 1 and Th 2 helper lymphocytes, the Th 0 helper lymphocyte has been found which appears to be linked to an intermediary process of differentiation between Th1 and Th2. Th 0 can secrete cytokines of both cell groups (Th 1 and Th 2).

Up to now, clones of helper lymphocytes with defined cytokine patterns have not been generated in the porcine species, but immune responses mainly of the type Th1 or Th2 have been described.

Regarding CD8+ lymphocytes , which are mainly cytotoxic lymphocytes, it has been found that they secrete cytokines of the type Interferon (IFN-g) and Tumour Necrosis Factor (TNF-b) which activate cytotoxic mechanisms in macrophages and granulocytes, and therefore have a Tc1 pattern, similar to Th 1 

MAIN CYTOKINES RELATED TO THE ADAPTIVE IMMUNE RESPONSE
CYTOSINE	STRUCTURE	PRODUCER C.	FUNCTION
IL 1	Monomer (18 kD)	Macrophages.	Raising of temperature Activation of T lymphocytes and macrophages
IL 6	Monomer (26 kD)	Th2 Lymphocytes Macrophages.	Activation of T and B lymphocytes
IL 12	Heterodimer (75 kD)	Macrophages. Neutrophils Dendritic cells	Th1 lymphocyte differentiation  NK cell activation
IL 16	Homodimer (13 kD)	CD8 T lymphocytes	IL2 receptor induction
TNF a	Homotrimer (17 kD)	Macrophages. Lymphocytes  NK cells Mast cells	Local inflammation Changes in permeability Raising of temperature
IFN a	Monomer (18 kD)	Lymphocytes	SLA I activation
IFN b	Monomer (20 kD)	Fibroblasts	NK activation
IFN g	Homodmer	Lymphocytes  NK cells	SLA I and SLA II induction Antigen presentation

How are cytokines studied?

The study of cytokines presents several problems. Some are linked to their own characteristics such as their low concentration, short half-life and redundancy of their biological effects, which makes them difficult to study. Other problems are related to the lack of reagents for the study of cytokines in any species other than murines or humans. However, thanks to recombinant cytokines, this last factor is on the way to being solved.

The most commonly used methods are:

Immunological methods . Obtaining different recombinant cytokines has enabled the production of monoclonal antibodies and the development of various methods of immunological assessment for several cytokines. These methods are on the whole immunoenzymatic and of the ELISA, type, offering high sensitivity and specificity for cytokine capture and quantification. Their disadvantage is that cytokines which are not biologically active can be detected and quantified.

Molecular methods have been able to develop thanks to knowledge of the different sequences of a large number of cytokines, permitting the adaptation of PCR amplification techniques, meaning that different cytokines can be identified in different tissues or cells. These techniques, which nowadays can also be quantitative, can detect and quantify the different cytokines, although as is the case with immunological methods, their detection does not necessarily imply biological activity.