Inflammation and the immune system

Chapter 30 Inflammation and the immune system

It is difficult to separate the immune system from the anti-inflammatory system; the two are interrelated and any defect in the immune system has far-reaching effects on a patient’s health.

To properly understand the immune system it is necessary to have a reasonable understanding of its working components. The explanation here is very simplified but is more than adequate for the scope of the book and for a basic understanding of the underlying principles of the complicated processes of the immune and anti-inflammatory systems.

Origins of the Immune System

Communication in early evolution was cell to cell. This means of communication survived as we evolved to become the immune system and the inflammatory response.

The Function of the Immune System

The immune system is the body’s defence system against bacteria, fungi, parasites, viruses and other pathogens entering the body. It is also a means of eliminating these pathogens before they cause serious harm.

The construction of the immune system allows it to adapt so as to mount a more rapid and vigorous attack each time it encounters a particular pathogen.

Why is An Anti-Inflammatory Response Necessary?

The anti-inflammatory response is a defensive response to tissue injury or damage. It is designed to remove the irritant and repair damaged tissue.

Components of the Immune System

Leucocytes

Leucocytes – white blood cells – are part of the body’s mobile defence system. There are five types of white blood cell:

• Neutrophils • Eosinophils • Basophils		Granulocytes produced in bone marrow; 6-day supply in the marrow.
• Lymphocytes: continually in the circulatory and lymph systems. Produced mainly in the lymph system (lymph glands, spleen, thymus tonsils, etc.). • Monocytes: change to macrophages after entering the tissues.

• Neutrophils

• Respond to the chemicals released by bacteria and dead tissue cells, moving to the area of highest concentration.

• Phagocytose the foreign cells and destroy them.

• Die soon after phagocytosis, as the process uses up their glycogen reserves. The dead neutrophils accumulate, with tissue fluid, to create pus.

• Eosinophils

• Increase in allergic reactions.

• Increase in most parasitic infections.

• Have surface receptors for immunoglobulin E (IgE).

• Basophils

• Similar to mast cells but mobile.

• Highly specific receptors to IgE (see mast cells, below).

• Lymphocytes

• Increase in viral infections.

• Two major types: B and T lymphocytes.

• Monocytes

• Leave the bloodstream to become tissue macrophages, which remove dead cell debris. Also attack some bacteria and fungi (neutrophils do not deal with these effectively).

• Have a longer life than neutrophils as they are able to replace their digestive enzymes.

Other Components

• Mast Cells

• Found in connective tissue and contains granules of histamine (p. 175) and heparin (see Figure 28.2, p. 213).

• Involved in wound healing and defence against pathogens.

• Involved in allergic (Chapter 34 ‘Respiratory diseases’, p. 267) and anaphylactic reactions.

• Highly specific receptors to IgE.

How Does the Immune System Work?

Pathogens that invade the body stimulate the immune system, which has three main stages of response:

1. To neutralize the pathogen by:

• secreting cytotoxic proteins: proteins lethal to pathogens

• phagocytosis: engulfing the pathogen and effectively digesting it.

2. To fragment the pathogen by phagocytosis: the fragments are presented on the surface of antigen-presenting cells (APCs) in the lymph tissue and provide a marker that enables the cells of the immune system to recognize that type of pathogen. The APCs also release a cytokine (interleukin-1; see below), which encourages the proliferation of B and T cells.

3. To secrete interleukins: the above stimulates the cells of the immune system to secrete interleukins, which further stimulate the immune system. The B and T lymphocytes are cloned in the lymph nodes. Some cells produce a pool of memory cells (M) specific to a particular antigen, which will enable the body to respond much faster with another exposure. This takes place in the lymph node and is known as the induction phase. The other cells go on to the effector phase.

The effector phase is one of the following:

• Humoral-mediated phase: involves antibodies, which act in the fluid of the blood and tissues to involve the B cells. There is also some added stimulation from interaction between the B cells and T helper cells.

• Cell-mediated phase: this works where the antibodies cannot reach, deals with pathogens in cells and involves the T cells.

Humoral Response

A humoral-mediated response (Figure 30.1):

• Is an immediate reaction. Hence the speed of anaphylactic shock, hay fever, asthma and some food allergies. It is a type 1 reaction.

• The T helper cells not only activate B cells but also release interleukins (signalling molecules and part of a group classed as cytokines). These interleukins stimulate eosinophils, mast cell production and the generation of IgE, which are the mediators in chronic inflammation.

• IgE has a strong tendency to attach to mast cells and basophils, changing the composition of their cell membranes so that they release their contents. People with atopic allergies have high levels of IgE in their blood.

• Some of the components are histamine, protease, platelet-activating factors, etc., which open-up the local blood vessels, attracting the eosinophils and neutrophils to the site. The eosinophils and neutrophils attack and destroy bacteria. The site is also damaged by the contents such as the proteases. There is loss of fluid into the tissues and contraction of the local smooth muscles.

Figure 30.1 Humoral (antibody)-mediated response showing points of immunosuppressant intervention.

Antibodies or immunoglobulins (hence the shorthand Ig) have two main functions:

1. To recognize and interact specifically with particular antigens (Figure 30.2): this can provide some damage limitation.

2. To activate the immune system: the tails act as a tag to activate the complement sequence (see below).

Figure 30.2 Structure of an antibody showing its attachment to antigens.

There are five classes of antibody: IgA, IgD, IgE, IgG and IgM.

• The Complement System

This is similar in mechanism to the coagulation cascade (see Figure 28.1, p. 212). It is activated by interaction in several ways:

• Antigen–antibody complex (classical pathway)

• the antigen (alternative pathway)

• complex carbohydrates (see Chapter 9 ‘Carbohydrates’ p. 71).

The final part of complement activation produces a membrane attack complex, which creates holes in the outer membrane of Gram-negative bacteria (see Figure 29.1, p. 218).

The complement cascade has a feedback mechanism, which in theory should limit its action. However, several of the products of the complement cascade are powerful inflammatory stimulants, so it is possible for the inflammatory response to get out of hand.

Figure 30.3 Diagram demonstrating the cell-mediated response showing points of immunosuppressant interventions.

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Jul 22, 2016 | Posted by admin in PHARMACY | Comments Off

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