Chapter 15: Resistance and immunity

Question 1

Specific defense mechanisms

Answer 1

•These are grouped together under the term immunity. Resistance is directed against only one specific invader. In addition, immunological memory develops, which confers long-term immunity to specific infections. An antigen is anything that stimulates an immune response.

Question 2

Non-specific defense mechanisms

Answer 2

•These are the first lines of general defense; they prevent entry and minimize further passage of microbes and other foreign material into the body.
•There are five main non-specific defense mechanisms:
-defense at body surfaces
-phagocytosis
-natural antimicrobial substances
-the inflammatory response
-immunological surveillance.

Question 3

Defense at body surfaces

Answer 3

• Healthy, intact skin and mucous membranes provide an efficient physical barrier protecting the body’s exposed surfaces. Few pathogens can establish themselves on healthy skin. Sebum and sweat secreted onto the skin surface contain antibacterial and antifungal substances.
• Epithelial membranes lining body cavities and passageways exposed to the external environment (e.g., the respiratory, genitourinary, and digestive tracts) are more delicate but are also well defended. Epithelia produce antibacterial secretions, often acidic, containing antibodies and enzymes, as well as sticky mucus for trapping passing microbes.
• Hairs in the nose act as a coarse filter, and the sweeping action of cilia in the respiratory tract moves mucus and inhaled foreign materials towards the throat. Then it is coughed up (expectorated) or swallowed.
• The one-way flow of urine from the bladder minimizes the risk of infection ascending through the urethra into the bladder. In the female, the acidity of vaginal secretions discourages microbial growth.

Question 4

Phagocytosis

Answer 4

Process by which certain living cells called phagocytes ingest or engulf other cells or particles. The phagocyte may be a free-living one-celled organism, such as an amoeba, or one of the body cells, such as a white blood cell.

Question 5

Hydrochloric acid

Answer 5

This is present in high concentrations in gastric juice and kills most ingested microbes.

Question 6

Lysozyme

Answer 6

This antibacterial enzyme is present in granulocytes, tears, and other body secretions, but not in sweat, urine, or cerebrospinal fluid. It destroys bacterial cell walls but does not affect viruses or other pathogens.

Question 7

Antibodies

Answer 7

These protective proteins are found coating membranes and in body fluids, and inactivate bacteria

Question 8

Saliva

Answer 8

This is secreted into the mouth and washes away food debris that may otherwise encourage bacterial growth. It contains antibodies, lysozyme, and buffers to neutralize bacterial acids that promote dental decay.

Question 9

Interferons

Answer 9

These chemicals are produced by T-lymphocytes, macrophages, and body cells that have been invaded by viruses. They prevent viral replication within infected cells and the spread of viruses to healthy cells.

Question 10

Complement

Answer 10

Complement is a system of about 20 proteins found in the blood and tissues. It is activated by the presence of immune complexes (an antigen and antibody bound together) and by foreign sugars on bacterial cell walls. Complement:

• binds to, and damages, bacterial cell walls, destroying the microbe
• binds to bacterial cell walls, stimulating phagocytosis by neutrophils and macrophages
• attracts phagocytic cells such as neutrophils into an area of infection, i.e. stimulates chemotaxis.

Question 11

The inflammatory response

Answer 11

This is the physiological response to tissue damage and is accompanied by a characteristic series of local changes. Its purpose is protective: to isolate, inactivate and remove both the causative agent and damaged tissue, so that healing can take place. The cardinal signs of inflammation are redness, heat, swelling, and pain.

Question 12

Causes of inflammation

Answer 12

Any form of tissue damage stimulates the inflammatory response, even in the absence of infection. The wide range of causative agents includes extremes of temperature, trauma, corrosive chemicals including extremes of pH, abrasion, and infection by pathogens.

Question 13

Acute inflammation

Answer 13

• Acute inflammation is typical of short duration, e.g., days to a few weeks, and may range from mild to very severe, depending on the extent of the tissue damage. Most aspects of the inflammatory response are hugely beneficial, promoting the removal of the harmful agent and setting the scene for healing to follow.
• The acute inflammatory response is described here for convenience as a collection of separate events: increased blood flow, accumulation of tissue fluid, migration of leukocytes, increased core temperature, pain, and suppuration. These events significantly overlap and develop together.

Question 14

Increase blood flow

Answer 14

• Following injury, both the arterioles supplying the damaged area and the local capillaries dilate, increasing blood flow to the site.
• This is caused mainly by the local release of several chemical mediators from damaged cells, e.g., histamine and serotonin. Increased blood flow to the area of tissue damage provides more oxygen and nutrients for the increased cellular activity that accompanies inflammation. Increased blood flow causes the increased temperature and reddening of an inflamed area and contributes to the swelling (edema) associated with inflammation.

Question 15

Increased tissue fluid formation

Answer 15

• This is partly due to increased capillary permeability caused by inflammatory mediators such as histamine, serotonin, and prostaglandins, and partly due to elevated pressure inside the vessels because of increased blood flow. Most of the excess tissue fluid drains away in the lymphatic vessels, taking damaged tissue, dead and dying cells, and toxins with it.
• Plasma proteins, normally retained within the bloodstream, also escape into the tissues through the leaky capillary walls; this increases the osmotic pressure of the tissue fluid and draws more fluid out of the blood. These proteins include antibodies, which combat infection, and fibrinogen, a clotting protein. Fibrinogen in the tissues is converted by thromboplastin to fibrin, which forms an insoluble mesh within the interstitial space, walling off the inflamed area and helping to limit the spread of any infection. Some pathogens, e.g., Streptococcus pyogenes, which cause throat and skin infections, release toxins that break down this fibrin network and promote the spread of infection into adjacent, healthy tissue.

Question 16

Migration of leukocytes

Answer 16

• Loss of fluid from the blood thickens it, slowing the flow and allowing the normally fast-flowing white blood cells to contact, and adhere to, the vessel wall. In the acute stages, the most important leukocyte is the neutrophil, which adheres to the blood vessel lining, squeezes between the endothelial cells and enters the tissues (diapedesis) where its main function is in phagocytosis of antigens. Phagocyte activity is promoted by the raised temperatures (local and systemic) associated with inflammation.
• After about 24 hours, macrophages become the predominant cell type at the inflamed site, and they persist in the tissues if the situation is not resolved, leading to chronic inflammation. Macrophages are larger and longer-lived than neutrophils. They phagocytose dead/dying tissue, microbes and other antigenic material, and dead/dying neutrophils. Some microbes resist digestion and provide a possible source of future infection

Question 17

Chemotaxis

Answer 17

This is the chemical attraction of leukocytes, including neutrophils and macrophages, to an area of inflammation.

Question 18

Increased temperature

Answer 18

• The increased temperature of inflamed tissues has the twin benefits of inhibiting the growth and division of microbes, whilst promoting the activity of phagocytes.
• The inflammatory response may be accompanied by a rise in body temperature (fever, pyrexia), especially if there is a bacterial infection.
• Pyrexia increases the metabolic rate of cells in the inflamed area and, consequently, there is an increased need for oxygen and nutrients.

Question 19

Pain

Answer 19

This occurs when local swelling compresses sensory nerve endings. It is exacerbated by chemical mediators of the inflammatory process, e.g., bradykinin and prosta­glandins which potentiate the sensitivity of the sensory nerve endings to painful stimuli. Although pain is an unpleasant experience, it may indirectly promote healing, because it encourages protection of the damaged site.

Question 20

Suppuration (pus formation)

Answer 20

Pus consists of dead phagocytes, dead cells, fibrin, inflammatory exudate, and living and dead microbes. A localized collection of pus in the tissues is called an abscess. The most common pyogenic (pus-forming) bacteria are Staphylococcus aureus and Streptococcus pyogenes.

Question 21

Resolution

Answer 21

This occurs when the cause has been successfully overcome. Damaged cells and residual fibrin are removed, being replaced with new healthy tissue, and repair is complete, with or without scar formation

Question 22

Development of chronic inflammation

Answer 22

Acute inflammation may become chronic if the resolution is not complete, e.g., if live microbes remain at the site, as in some deep-seated abscesses, wound infections, and bone infections.

Question 23

Chronic inflammation

Answer 23

The processes involved are very similar to those of acute inflammation but, because the process is of longer duration, considerably more tissue damage is likely. The inflammatory cells are mainly lymphocytes instead of neutrophils, and fibroblasts are activated, leading to the laying down of collagen, and fibrosis. If the body defenses are unable to clear the infection, they may try to wall it off instead, forming nodules called granulomas, within which are collections of defensive cells. Tuberculosis is an example of an infection that frequently becomes chronic, leading to granuloma formation. The causative bacterium, Mycobacterium tuberculosis, is resistant to body defenses and so pockets of organisms (Ghosn foci) are sealed up in granulomas within the lungs.

Question 24

Immunological surveillance

Answer 24

A population of lymphocytes, called natural killer (NK) cells, constantly patrol the body searching for abnormal cells. Cells that have been infected with a virus, or mutated cells that might become malignant, frequently display unusual markers on their cell membranes, which are recognized by NK cells. Having detected an abnormal cell, the NK cell immediately kills it. Although NK cells are lymphocytes, they are much less selective about their targets than the other two types discussed in this chapter (T- and B-cells).

Question 25

Immunity

Answer 25

The body’s first line of defense is its collection of non-specific defenses, including phagocytes such as macrophages. If these are overwhelmed, activation of the powerful immune system follows. Immunity possesses three key attributes not seen with non-specific defenses: specificity, memory, and tolerance.

Question 26

Memory

Answer 26

Unlike general defense mechanisms, an immune response against a particular antigen will usually generate immunological memory of that antigen. This means that the immune response on subsequent exposures to the same antigen is generally faster and more powerful.

Question 27

Tolerance

Answer 27

The cells of the immune system are aggressive and potentially extremely destructive. Control of their activity is essential for the protection of healthy body tissues. As immune cells travel around the body, they check the marker proteins that cells show on their cell membranes. Healthy body cells display the expected ‘self’ markers and are ignored by the patrolling immune cells. However, non-self-cells, such as cancer cells, foreign (transplanted) cells, or pathogens, possess different patterns of markers, which immediately activate the immune cell and usually lead to the destruction of the non-self-cell.

Question 28

Lymphocytes

Answer 28

• Lymphocytes make up 20–30% of circulating white blood cells but at any one time, most of them are found in lymphatic and other tissues rather than in the bloodstream. They include natural killer cells involved in immunological surveillance, T-cells (the majority), and B-cells. T- and B-cells are responsible for immunity (specific defense) and are produced in the bone marrow and some lymphatic tissues, although T-cells migrate to the thymus gland for final maturation.
• For each of the millions of possible antigens that might be encountered in life, there is a corresponding T- and B-cell programmed to respond to it. There are, therefore, vast numbers of different T- and B-cells in the body, each capable of responding to only one antigen (antigen specificity).

Question 29

T-cells

Answer 29

The hormone thymosin, produced by the thymus gland, is responsible for promoting T-cell maturation, which leads to the formation of fully specialized (differentiated), mature, functional T-cells. It is important to recognize that a mature T-cell has been programmed to recognize only one type of antigen, and during its subsequent travels through the body will react to no other antigen, however dangerous it might be. Thus, a T-cell manufactured to recognize the chickenpox virus will not react to a measles virus, a cancer cell, or a tuberculosis bacterium.

Question 30

B-cells

Answer 30

These are both produced and matured in the bone marrow. They produce antibodies (immunoglobulins), proteins designed to bind to and destroy an antigen. As with T-cells, each B-cell targets one specific antigen; the antibody released reacts with one type of antigen and no other. B-cells provide antibody-mediated immunity.

Question 31

Cell-mediated immunity

Answer 31

Cell-mediated immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

Question 32

Cytotoxic t-cells

Answer 32

• These directly inactivate any cells carrying antigens. They attach themselves to the target cell and release powerful toxins, which are very effective because the two cells are so close together. The main role of cytotoxic T-cells is in destruction of abnormal body cells, e.g., infected cells and cancer cells.

Question 33

Helper t-cells

Answer 33

• These are essential not only for cell-mediated immunity but also antibody-mediated immunity. Their central role in immunity is emphasized in situations where they are destroyed, as by the human immunodeficiency virus (HIV). When helper T-cell numbers fall significantly, the whole immune system is compromised. T-helpers are the commonest of the T-cells; their main functions include:
• Production of chemicals called cytokines, e.g., interleukins and interferons, which support and promote cytotoxic T-cells and macrophages
• Cooperating with B-cells to produce antibodies; although B-cell is responsible for antibody manufacture, they require to be stimulated by a helper T-cell first.

Question 34

Suppressor t-cells

Answer 34

These cells act as ‘brakes’, turning off activated T- and B-cells. This limits the powerful and potentially damaging effects of the immune response. Suppressor T-cells are also thought to help prevent the development of autoimmunity and to protect the fetus in pregnancy.

Question 35

Memory t-cells

Answer 35

These long-lived cells survive after the threat has been neutralized and provide cell-mediated immunity by responding rapidly to another encounter with the same antigen.

Question 36

Antibody-mediated (humoral)immunity

Answer 36

B-cells are much less mobile than T-cells and spend much of their time in lymphoid tissue, e.g., the spleen and lymph nodes. B-cells, unlike T-cells, recognize and bind antigen particles without having to be presented with them by an antigen-presenting cell. Once its antigen has been detected and bound, and with the help of an activated helper T-cell, the B-cell enlarges and begins to divide (clonal expansion). It produces two functionally distinct types of cells, plasma cells, and memory B-cells.

Question 37

Plasma cells

Answer 37

These secrete massive quantities of antibodies (immunoglobulins, Ig) into the blood. Antibodies are carried throughout the tissues. Plasma cells live no longer than a day and produce millions of molecules of only one type of antibody, which targets the specific antigen that was originally bound to the B-cell. Antibodies:

• bind to antigens, labeling them as targets for other defense cells such as cytotoxic T-cells and macrophages
• bind to bacterial toxins, neutralizing them
• activate complement

Question 38

Memory b-cells

Answer 38

• Like memory T-cells, these cells remain in the body long after the initial episode has been dealt with, and rapidly respond to another encounter with the same antigen by stimulating the production of antibody-secreting plasma cells. The interdependence of the two parts of the immune system.
• The fact that the body does not normally develop immunity to its own cells is due to the fine balance that exists between the immune reaction and its suppression. Autoimmune diseases are due to the disturbance of this balance.

Question 39

Acquired immunity

Answer 39

The immune response to an antigen following the first exposure (primary immunization) is called the primary response. Second and subsequent exposures give rise to a secondary response.

Question 40

The primary response

Answer 40

Exposure of the immune system to an antigen for the first time leads to a slow and delayed rise in antibody levels, peaking 1–2 weeks after infection. This delayed response reflects the time required to activate the T-cell system, which then stimulates B-cell division. Antibody levels start to fall once the infection is cleared, but if the immune system has responded well, it will have generated a population of long-lived memory B-cells, making the individual immune to future infection.

Question 41

The secondary response

Answer 41

On subsequent exposures to the same antigen, the immune response is much faster and 10–15 times more powerful, because the memory B-cells generated after the first infection rapidly divide and antibody production begin almost immediately.

Question 42

The five types of antibodies

Answer 42

• lgA- Found in body secretions like breast milk and saliva, and prevent antigens from crossing epithelial membranes and invading deeper tissues.
• lgD-This is made by B-cells and displayed on their surfaces. Antigens bind here to activate B-cells
• lgE-Found on cell membranes of, e.g., basophils and mast cells, and if it binds its antigen, activates the inflammatory response. This antibody is often found in excess in allergy
• lgG-This is the largest and most common antibody type. It attacks many different pathogens and crosses the placenta to protect the fetus
• lgM-Produced in large quantities in the primary response and is a potent activator of complement

Question 43

Active naturally acquired immunity

Answer 43

The body may be stimulated to produce its own antibodies by:

• Having the disease. During the illness, B-cells develop into plasma cells that produce antibodies in sufficient quantities to overcome the infection. After recovery, the memory B-cells produced confer immunity to future infection by the same antigen.
• Having a subclinical infection. Sometimes the infection is not sufficiently severe to cause clinical disease but stimulates sufficient memory B-cells to establish immunity, e.g., hepatitis A. In other cases, the subclinical infection may be too mild to stimulate an adequate response for immunity to develop.

Question 44

Active artificially acquired immunity

Answer 44

This type of immunity develops in response to the administration of dead or live artificially weakened pathogens (vaccines) or deactivated toxins (toxoids). The vaccines and toxoids retain antigenic properties that stimulate the development of immunity, but they cannot cause the disease. Many infectious diseases can be prevented by artificial immunization.

Question 45

Passive naturally acquired immunity

Answer 45

This type of immunity is acquired before birth by the passage of maternal antibodies across the placenta to the fetus, and to the baby in breast milk. The variety of different antibodies provided depends on the mother’s active immunity. The baby’s lymphocytes are not stimulated, and this form of immunity is short-lived.

Question 46

Passive artificially acquired immunity

Answer 46

In this type, ready-made antibodies, inhuman or animal serum, are injected into the recipient. The source of the antibodies may be an individual who has recovered from the infection, or animals, commonly horses, that have been artificially actively immunized. Specific immunoglobulins (antiserum) may be administered prophylactically to prevent the development of disease in people who have been exposed to the infection, e.g., rabies, or therapeutically after the disease has developed.