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Introduction

Our bodies are constantly under attack from pathogens, and therefore, we must be able to distinguish between self and non-self-antigens so that the immune system knows which cell to target.

This is made possible by the Major Histocompatibility Complex, which is a group of genes in vertebrates responsible for producing proteins that are expressed on the surface of the cells. All nucleated cells have MHC Class I markers and only antigen presenting cells have MHC Class II markers. These markers identify cells as being self and can present non-self-antigens to the immune system. Any molecule which triggers an immune response is an antigen e.g. cell surface proteins

Innate Immunity

Innate immunity or natural/passive immunity has the same reaction for any antigen, it is non-specific, comprises of physical, chemical and microbiological defences and has no memory of prior exposure

First Line of Defence

• Intact Skin: hard-keratinised outer layer, which serves as a physical barrier to pathogens. The waterproof nature of the keratin helps to keep the skin dry, acid and salt in sweat and antibacterial secretion of sebum from the sebaceous glands inhibit pathogenic growth by preventing the optimal conditions for pathogenic growth
• Mucous Membranes: mucous secreted by cells lining the respiratory tract help to trap microorganisms and other particles. With the help of the cilia on these cells, they sweep the foreign cells up to the throat. Mucous lining the digestive tract also form a protective barrier against penetration by microbes
• Natural Secretions: lysozymes are an enzyme found in tears and saliva. They have powerful digestive capabilities and can cause the lysis of foreign agents before they enter the body. The stomach also produces hydrochloric acid which is highly acidic and thus can kill harmful agents
• Natural Flora: there are bacteria that live naturally on the skin and gastrointestinal tract which inhibit the growth of pathogens mainly through competition. An example includes bacteria living in the gut which produces lactic acid, creating an acidic condition for other microorganisms. They also prevent opportunistic infections

Second Line of Defence

This is the innate cell mediated defence

Interferons

Interferons are proteins that are released by viral affected cells that act on uninfected cells to increase their resistance to infection. They assist the immune response by inhibiting viral replication within other cells of the body by stimulating the production of antiviral proteins and warn nearby cells making them more resistant to infection

Complement Proteins

Complement proteins are inactive enzymes present in the plasma which are activated when they make direct contact with non-self-antigens. This starts a sequence of reactions that activates many complement proteins

• Opsonisation: they coat the surface of a pathogen making it more susceptible to phagocytosis
• Lysis: they can assemble into a membrane-attack complex which can actively damage the plasma membrane destroying the membrane integrity. Therefore, the cell loses osmotic pressure and water enters causing lysis
• Immune Clearance: the removal of immune complexes from the circulation – cleans dead pathogens and antibodies

They also promote inflammation, attract macrophages and neutrophils through chemotaxis and cluster and bind pathogens together through agglutination

Phagocytes

The function of phagocytes is to engulf and destroy foreign pathogens and to engulf antigen-antibody complexes. In doing so, certain phagocytes can display the antigens of ingested pathogens on their MHC markers to T helper & Cytotoxic T cell

• Neutrophils: these phagocytose bacteria and release enzymes that kill bacteria, they also die in the process. They have a flexible plasma membrane, which enables them to squeeze between capillary cells into tissue
• Macrophages: these are large phagocytic cells, which can digest a large range of infections agents. They are stationary cells generally found lining blood channels in the tissue of the liver, spleen and in the lymph nodes.
• Monocytes: these are found in the bloodstream and once they leave circulation they differentiate into macrophages
• Mast cells: these have granules that upon contact with non-self-antigens releases histamine and thereby promotes inflammation

Antigen Presenting Cells

These are immune cells that specialise in presenting an antigen to a T-cell. The main types of professional APCs are dendritic cells, macrophages and B cells. APCs phagocytose a pathogen, take up the antigen, process it, and display it on both their MHC markers. Cytotoxic T cell cells interact with MHC Class I. T helper cells interact with MHC Class II

• Dendritic Cells: these act as messengers between the innate and the adaptive immune systems. After phagocytosing a pathogen, they migrate to the lymph node where they present the antigen

Cytokines

These are small glycoproteins which indicate the presences of potentially harmful invaders. They act as messengers between cells of the immune system and can promote the growth and proliferation of T lymphocytes, induce fever, promote antibody responses, activate macrophages and initiate or reduce inflammation.

Inflammation

Inflammation can occur when tissues are killed, damaged or burned. When damage occurs in a tissue, mast cells in the tissue secrete chemicals including histamine into the surrounding tissue fluid

• Capillaries dilate and more blood flows to the area and therefore there is increased permeability of the local capillaries causing the site to become swollen, hot and red
• Phagocytes – neutrophils and macrophages are attracted to the site of infection, into the damaged tissue
• Blood clot and pus form to seal the wound

Fever

Fever helps to inhibit the growth of some bacteria and viruses which are often temperature sensitive. It increases metabolic processes and the heart rate to allow the blood to deliver leukocytes to affected areas more rapidly.

Adaptive Immunity

Adaptive immunity is also called acquired immunity and produces cells and antibodies against specific antigens. It has memory and on re-exposure has a rapid response

Third Line of Defence

• B Lymphocytes, these mature in the bone marrow and differentiate into plasma cells which produce antibodies and B memory cells
• T Lymphocytes, these mature in the thymus gland and differentiate into cytotoxic T cells which attach and kill virus-infected cells, T helper cells which coordinate immune response and T memory cells
• Mature B and T cells are those which have developed receptors

Humoral Immune Response

The humoral response is active against non-self-antigens outside host cells, for example some bacteria, viral particles and free antigens

When antigen presenting cells phagocytose a pathogen, they present the foreign antigens on their MHC Class II markers and then migrate to the lymph nodes via the lymphatic vessels, where a corresponding naïve T helper cells use their receptors to recognise the presented antigens on the APCs. They are then regarded as selected (clonal selection). Meanwhile, free antigens will bind with specific naïve B-cells. They are then also regarded as being selected.

The selected B cell and T helper cell travel through the body to find each other. When they find each other, the B cell would then present its antigens on its MHC Class II markers to the previously selected T helper cells. The T helper cell then releases cytokines, causing the proliferation and differentiation of T helper cells into active T helper, including some memory T helper cells and the B cells will produce plasma and memory B-cells. This is known as clonal expansion.

The plasma cells produce and secrete vast quantities of specific antibodies which flood into circulation. The memory cells retain memory of the antigen and specific antibody and can respond quickly and strongly to any subsequent experience of the same antigen

Cell Mediated Response

The cell mediated response is active against non-self-antigens located inside cells for example viruses, cancer cells and transplant tissue.

When infected, the cell will present the viral antigens or stress-induced antigens on their MHC Class I markers. Cytotoxic T cell cells then bind to this presented antigen and with the help of cytokines produced by T helper cells, they proliferate and differentiate into active Cytotoxic T cell cells and memory Cytotoxic T cell cells. The active Cytotoxic T cell cells then recognise the specific infected/cancerous cells and secrete perforin which ruptures the plasma membrane. Or they can bind to death receptors initiating apoptosis

Antibodies

Antibodies do not directly destroy pathogens but defend against infectious pathogens and toxins by binding to pathogens. They block their receptors so that the pathogens cannot infect other healthy cells and bind to pathogens tagging them for destruction (Agglutination). Immunity involving antibodies circulating in in the body is called humoral immunity. Each antibody is specific for one antigen only due to the antigen binding site of the antibody molecule being complementary in shape for the antigen

Antibodies

Secondary Response

After natural exposure or vaccination, T helper cells initiate the response and the presence of memory cells results in a much faster response. Antibodies are produced faster and in large quantities. Secondary response occurs within hours while primary takes days

Lymphatic System

The lymphatic system is a network of thin walled lymphatic vessels containing lymph which reaches all tissues of the body and connects the lymphoid organs. Primary lymphoid organs include the bone marrow and thymus, secondary lymphoid organs include appendix, spleen, tonsils and lymph nodes. This wide distribution of lymphoid tissue around the body enables foreign antigens to be rapidly detected

• Tissue fluid drains into lymph vessels
• Fluid in lymph vessels pass through masses of tissue called lymph nodes
• Lymph nodes contain lymphocytes, which are involved in the immune response

Physical Plant Defences

• Waxy Cuticle: forms a barrier against degrading enzymes used by pathogens to gain entry
• Galls: abnormal swelling due to the sealing of infected areas to help inhibit the spread of a pathogen

Chemical Plant Defences

• Naturally secreted antibiotics, inhibit pathogenic development on the surface of the plant
• Toxins, inhibit pathogenic development on the surface of the plant
• Tannins, Resin, Phytotoxins