Immunity Aims: Must be able to define the term immunity. Should be able to outline the different forms of immunity. Could be able to outline the stages of non-specific immunity.

Basics Immune system differentiates between ‘SELF’ and ‘NON- SELF’. ‘SELF’: material made by the body’s cells. ‘NON-SELF’: foreign material, includes material such as snake venom, dust, pollen, viruses and micro-organisms, such as bacteria. If infected with foreign material, the immune system is activated - attempts to remove the foreign material before it causes harm to tissues in the body.

Two Types of Immunity The two kinds of response of the immune system interact together to provide immunity for an individual: NATURAL / INNATE immunity non-specific it acts in the same way for every infection involves many physical and chemical barriers to infection it has no ‘memory’ of a prior infection Acquired or adaptive immunity highly specific involves the production of specialised cells and chemical substances known as antibodies has a ‘memory’

Non-Specific Immunity First Line of Defence – Prevent entry to the body Skin – continuous barrier to microbe entry Mucous Membranes – Secreted by cells in respiratory system – trap bacteria and swept by cilia – swallowed, sneezed, coughed Natural Secretions – Tears, Saliva contain lysozyme causing bacteria to burst. Stomach contains acid. Also bacterial agents in Milk and Semen. Natural Flora – Bacteria found on skin in gut and in vagina, non-pathogenic in given areas – inhibits the growth of pathogenic bacteria.

Non-Specific Immunity Second Line of Defence – Kicks in after microbe entry Made up of a number of parts: Phagocytes and Killer Cells – Complement Proteins – Interferon – Cytokines – Inflammation -

The Second Line of Defense Eosinophils: Produce toxic proteins against certain parasites, some phagocytosis Antimicrobial substances Basophils: Release heparin and histamine which promote inflammation Inflammation and fever Neutrophils, monocytes: These cells engulf and destroy foreign material (e.g. bacteria) Phagocytic white blood cells 40°C 37°C A range of non- specific defenses inside the body inhibit or destroy pathogens. These non-specific defenses react to the presence of any pathogen, regardless of which species it is. White blood cells are involved in most of these responses. The 1st line of defense The 2nd line of defense The 3rd line of defense 6

Mast Cell - Secretes hisatmines phagocytes

Phagocytes Phagocytes respond by engulfing and destroying micro-organisms and foreign materials. Phagocytes are produced by cells in the bone marrow and include neutrophils and monocytes/ macrophages. (When monocytes leave the bloodstream, they become macrophages) A bacterium or other micro-organism is engulfed by a phagocyte. Enzymes and other factors are released into the vacuole containing the bacterium and the bacterium is killed. Some white blood cells that kill virus-infected body cells are called natural killer (NK) cells.

The Action of Phagocytes Phagocytes are white blood cells that ingest microbes and digest them by phagocytosis. Detection Phagocyte detects microbes by the chemicals they give off (chemotaxis), and the microbes stick to its surface. Microbes Nucleus Ingestion The phagocyte wraps pseudopodia around it the microbe, engulfing it and forming a vesicle. Phagosome Phagosome forms A phagosome (phagocytic vesicle) is formed, enclosing the microbes in a membrane. Lysosome Fusion with lysosome Phagosome fuses with a lysosome (containing powerful enzymes that can digest the microbe). Digestion The microbes are broken down by enzymes into their chemical constituents. Discharge Indigestible material is discharged from the phagocyte.

Microbial Abuse of Phagocytes Microbes evade immune system Some microbes evade the immune system by entering phagocytes. The microbes prevent fusion of the lysosome with the phagosome. They multiply inside the phagocyte, almost filling it. e.g. Chlamydia, Shigella, Mycobacterium tuberculosis, and malarial parasites. Some microbes kill phagocytes Some microbes produce toxins that kill phagocytes. e.g. toxin-producing staphylococci and the dental plaque-forming bacteria Actinobacillus. Dormant microbes hide inside cells Some microbes can remain dormant inside the phagocyte for months or years at a time. e.g. the microbes that cause brucellosis and tularemia.

Complement Proteins Blood proteins called complement proteins assist phagocytes to recognise foreign material. In the second line of defence: Some stick to invading micro-organisms that then become more readily identifiable as foreign to phagocytes. Some stimulate phagocytes to become more active. Some attract phagocytes to the site of infection. Other complement proteins destroy the membranes of invading micro-organisms.

Complement proteins: bacteriophage bacteria Complement protein

Interferons Some virally infected cells secrete interferons. Induce resistance to viral infection in the surrounding cells. Acts as a warning signal from the cell already doomed Causes changes in the surfaces of the surrounding cells, making it more difficult for a virus to infect Play an important role in reducing or slowing down the growth, reproduction or development of the pathogen and minimising the symptoms that arise Prevents viral protein synthesis 14

Cytokines A group of proteins and peptides that are used in organisms as signaling compounds. These chemical signals are similar to hormones and neurotransmitters and are used to allow one cell to communicate with another. Cytokines are involved in a variety of immunological, inflammatory and infectious diseases. Each cytokine binds to a specific cell-surface receptor.

Inflammation Damage to the body’s tissues caused by physical agents (e.g. sharp objects), microbial infection, or chemical agents triggers a defensive response called inflammation. Usually characterized by four symptoms: pain, redness, heat, and swelling. The inflammatory response is beneficial has the following functions: To destroy the cause of the infection and remove it and its products from the body. If this fails, to limit the effects on the body by confining the infection to a small area. To replace or repair tissue damaged by the infection by improving blood flow.

The Process of Inflammation Bacteria entering on knife or other sharp object. Blood clot forms Chemicals released by damaged cells (e.g. histamines and prostaglandins) attract phagocytes to the infection. Epidermis Dermis Blood vessels increase in diameter and permeability in the area of damage. This increases blood flow to the area and allows defensive substances to leak into tissue spaces. Phagocytes reach the damaged area within one hour of injury. They squeeze between cells of blood vessel walls to enter the region and destroy invading microbes. An abscess starts to form after a few days. This collection of dead phagocytes, damaged tissue and various body fluids is called pus. Subcutaneous tissue

Fever A fever (pyrexia) is defined as a body temperature above 37°C (98.6°F) measured in the mouth. Normal body temperature range is: 36 to 37°C / 96.8 to 98.6°F Fevers are usually caused by bacterial or viral infections. Fevers of less than 40°C (104°F) do not need treatment. Excessive fever requires prompt attention as death usually results if body temperature rises above 44.4°C to 45.5°C (112°F to 114°F).

The Cause of Fever Infection by pathogen or toxin Macrophages respond. The presence of endotoxins induces the macrophage to produce a small protein called interleukin-1. Thermostat is reset Interleukin-1 induces the hypothalamus to increase production of prostaglandins. This resets the body's 'thermostat' to a higher temperature, producing fever. Bacterial toxins Bacterium Macrophage releases interleukin-1 into the blood stream. Macrophage Hypothalamus Temperature increases beyond the normal range of 36.2–37.2 °C (96.8–98.6 °F)

The Stages of a Fever Fever Onset Chill Phase Crisis Phase The body responds to the new thermostat setting, raising the body temperature by: • Blood vessel constriction • Increased metabolic rate • Shivering Fever Onset Even though the body temperature is increasing above normal, the skin remains cold, and shivering occurs. This condition, called a chill, is a definite sign that body temperature is rising. When the body reaches the setting of the thermostat, the chill disappears. Chill Phase Crisis Phase Body temperature will be maintained at the higher setting until interleukin-1 has been eliminated. As the infection subsides, the thermostat is then reset to 37°C. Heat losing mechanisms, such as sweating and vasodilation cause the person to feel warm. This crisis phase of the fever indicates that body temperature is falling.

The Benefits of Fever Up to a point, fever is beneficial. Fever has the following effects: Intensifies the effect of interferons (antiviral proteins that inhibit viral replication). Increases the production of T cells. Speeds up the metabolic reactions, which helps to increase the rate of tissue repair. Increases heart rate, so that white blood cells are delivered to sites of infection more rapidly.