Immunity

Introduction to immunity

You have met immunity in earlier classes. This chapter looks at how the body defends itself, with most emphasis on the immune system. The body's response to foreign particles, such as the production of antibodies directed against one particular antigen, is called an immune response.

Immune response

The body's response to foreign particles, such as the production of antibodies directed against a specific antigen.

Immunity

The ability to resist damage from foreign substances such as microorganisms and harmful chemicals, for example toxins released by microorganisms.

Immunology

The study of foreign particles that can affect the living body and of the defence mechanisms the body uses to eliminate them.

The human body has three lines of defence against microbial attack.

• First line: external barriers that keep microbes out of the body.
• Second line: nonspecific internal defence that combats all invading microbes.
• Third line: specific internal defence, also called adaptive or acquired immunity.

The first and second lines of defence together make innate immunity. The third line is adaptive (acquired) immunity.

9.1First line of defence

The first and obviously best defence is to keep microbes out in the first place. The human body has two surfaces exposed to the environment: the skin, and the mucous membranes of the digestive and respiratory tracts. These surfaces are external barriers to microbial invasion.

Because these barriers inhibit nearly all kinds of microbes in the same way, the first line of defence is a nonspecific defence.

9.1.1Skin: an impenetrable barrier against microbial invasionOften examined

The skin is made of two layers, the epidermis and the dermis. Together they give a physical, a chemical and an immune barrier, so unbroken skin blocks microbes extremely well.

Epidermis: the physical barrier

• The epidermis is the outermost layer, made of tightly packed cells that form a physical barrier.
• Most epidermal cells contain the protein keratin, which strengthens them and makes them resistant to abrasion and water loss.
• The outer surface consists of dry dead cells, so most microbes that land on it cannot get the water and nutrients they need.
• The surface has a slightly acidic pH (around 5.5), which inhibits the growth of many pathogens.
• Desquamation is the shedding of dead skin cells. It removes microbes that have attached to the surface.

Dermis: glands and the immune barrier

The dermis is the inner, comparatively thick layer. It contains glands, hair follicles, receptors, nerves and blood vessels.

• Sebaceous (oil) glands secrete sebum, an oily substance. Sebum contains fatty acids that lower skin pH and have antimicrobial properties.
• Sweat glands secrete sweat, a salty fluid that generally cools the body. Sweat contains lysozyme, an enzyme that breaks down bacterial cell walls, and its high salt concentration can dehydrate bacteria.
• Secretions from sweat and sebaceous glands contain natural antibiotics such as lactic acid, which inhibit the growth of bacteria and fungi.

9.1.2Epithelium of digestive tract: an impenetrable barrier against microbial invasion

The gastrointestinal tract (GIT) is covered by a mucous membrane. This protects the GIT against microbial invasion by means of its various secretions.

• Hydrochloric acid is secreted in the stomach by the oxyntic (parietal) cells. It kills the bacteria present in food.
• Various digestive enzymes in gastric juice, intestinal juice and pancreatic juice also digest the bacteria present in food.

9.1.3Epithelium of respiratory tract: an impenetrable barrier against microbial invasion

The anterior (front) part of the nasal cavities, which contains hairs, is called the vestibule. The respiratory tract defends itself in the following ways.

• Vestibular hairs filter the large dust particles from inhaled air.
• The inner surface of the nasal cavities is lined with ciliated mucous epithelium. Its mucus traps fine dust particles and microbes.
• The cilia of this epithelium sweep the trapped fine dust and microbes backwards to the pharynx, where they are swallowed and eliminated by the digestive system.
• The trachea and the air passages inside the lungs (bronchi and bronchioles) are also lined with ciliated mucous epithelium. Its cilia propel mucus and foreign particles towards the larynx, where they enter the pharynx and are swallowed.

9.2Second line of defence: nonspecific defenceOften examined

If microbes succeed in penetrating the skin or mucous membranes, a second line of defence takes action. It is made up of nonspecific internal defences.

• A standing army of phagocytic cells and natural killer cells.
• The inflammatory response, provoked by the invasion of microbes.
• Fever, which the body often produces.
• Protective proteins (the complement system and interferons).

These defences are nonspecific because they attack a wide variety of microbes, rather than targeting specific invaders as the immune response does.

9.2.1Killing cells of bloodOften examined

Some white blood cells are called phagocytes. A phagocyte is a cell that destroys other abnormal body cells (cancerous cells) or invaded microorganisms by engulfing them. This process is called phagocytosis.

The main phagocytic white blood cells are macrophages, dendritic cells and neutrophils. Natural killer (NK) cells kill infected body cells and cancer cells in a different way, by releasing proteins.

9.2.1Macrophages and dendritic cellsOften examined

Monocytes are formed in the bone marrow. They typically circulate in the blood for 1 to 3 days before migrating into the tissues, where they become macrophages or dendritic cells. Through the blood, macrophages and dendritic cells are carried to the areas of the body where they are needed.

Macrophages

• Macrophages are generally found in organs such as the lungs, liver, spleen, kidney and lymph nodes, not in the blood. There they patrol within the free spaces among the cells and trap and destroy microorganisms entering the tissue.
• As macrophages interact with microbes they engulf and destroy them, and they also display some parts of the microbes on their surface so that other body cells may be informed. Such cells are called antigen presenting cells (APCs).
• During phagocytosis macrophages secrete many proteins. Some trigger the maturation of monocytes into macrophages, increasing their number. Interleukin-1 signals the brain to raise the body temperature, producing fever. Some other proteins stimulate the specific immune response.
• Macrophages also play an essential role in wound healing and tissue repair by removing dead cells and debris.

Dendritic cells

Dendritic cells (DCs) are found in tissue that is in contact with the outside environment. They become antigen-presenting cells that capture, process and present antigens to lymphocytes to initiate and regulate the adaptive immune response.

9.2.1NeutrophilsOften examined

Neutrophils belong to the granulocyte type of white blood cells.

• They are highly short-lived and highly mobile: they squeeze between the cells of capillary walls and can enter parts of tissue where other cells cannot.
• They move like Amoeba, forming pseudopodia.
• They proceed rapidly to the infected area and often die after a single phagocytic event.
• Neutrophils also release lysosomal enzymes by extracellular degranulation; these kill microorganisms and cause inflammation.
• Neutrophils can release neutrophil extracellular traps (NETs) to kill microbes.

9.2.1Natural killer cellsOften examined

Natural killer (NK) cells are a type of lymphocyte that provide innate immunity. In general, NK cells do not directly attack invading microbes. Instead they attack cancerous cells and body cells infected by viruses.

An NK cell kills its target by releasing proteins called perforins. The pores formed by these proteins allow certain apoptotic proteases, known as granzymes, to diffuse passively into the target cell. The cell then dies by apoptosis, and a macrophage engulfs and digests the dying cell.

Perforins

Proteins released by NK cells that punch holes in the membrane of an infected or cancerous cell.

Granzymes

Apoptotic proteases that enter the target cell through the perforin pores and make it die by apoptosis.

Apoptosis

Programmed death of a cell.

9.2.2Protective proteins of complement systemOften examined

The complement system consists of over fifty types of small proteins found in the blood. They are synthesised by the liver and normally circulate in an inactive state. They are activated when foreign particles enter the body.

Once one complement protein is activated, it activates another protein, which activates other proteins of the system, and so on. As a result:

• phagocytes clear foreign and damaged material;
• inflammation develops, which attracts additional phagocytes to the site of infection;
• cell-killing membrane attack complexes are activated.

The complement system is an important supporter of the immune system. It enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body, promotes inflammation, and attacks the plasma membrane of the pathogen.

An example of the protective proteins of the complement system is the membrane attack complex (MAC). It produces holes in the bacterial cell wall and the plasma membrane of pathogens. The holes allow fluids and salts to enter the bacterial cell, so the bacterium swells and eventually bursts.

9.2.2InterferonsOften examined

Interferons belong to the large class of proteins known as cytokines, molecules used for communication between cells during infection. They are released by host cells in response to several pathogens, especially viruses. Interferons are named for their ability to "interfere" with viral replication.

Interferons are antiviral agents produced by virus-infected cells. On infection, virus-infected cells mount an innate immune response to protect themselves from the virus and to warn neighbouring cells by means of interferon.

Interferons have a wide range of functions used to combat infection at all stages of a pathogen's life cycle. For a viral infection they:

• signal virus-infected cells to undergo apoptosis;
• prohibit entry of the virus into uninfected cells;
• stop viral replication;
• prevent the virus from leaving an infected cell;
• activate immune cells to generate an immune response.

The many forms of interferon are rapidly produced to defend against viruses. Interferons can also combat bacterial and parasitic infections, inhibit cell division, and promote or slow down the differentiation of cells.

9.2.3Inflammatory responseOften examined

The inflammatory response is a major component of the nonspecific defence. Any damage to tissue, whether caused by an infectious microorganism or by physical injury, even just a scratch or an insect bite, triggers this response. Inflammation can be localised or systemic (widespread).

Local inflammation

An inflammatory response confined to a specific area of the body.

The classical signs of inflammation are heat, pain, redness, swelling and loss of function.

Figure 9.10 shows the chain of events when a pin has pricked the skin and infected it with bacteria. The first thing that happens is that the damaged cells release chemical alarm signals such as histamine. The chemical sparks the mobilisation of various defences. Histamine induces neighbouring blood vessels to dilate and to start leaking. Blood supply to the damaged area increases, and blood plasma passes out of the leaky vessels into the interstitial fluid of the affected tissues, causing inflammation.

Function of inflammation

• Eliminate the initial cause of cell injury.
• Clear out necrotic cells and tissues damaged by the original insult (to attack physically) and by the inflammatory process.
• Initiate tissue repair.
• Help prevent the spread of infection to the surrounding tissues.

9.2.4Temperature responseOften examined

Fever or pyrexia is a body temperature raised above normal. The invading microorganisms often release certain chemicals, generally termed pyrogens. Pyrogens cause the temperature set point of the hypothalamic thermostat of the body to rise. As a result all the mechanisms for raising body temperature are brought into play, such as heat conservation and increased heat production.

Certain white blood cells, in response to infection, also release hormones collectively called endogenous pyrogens. These further increase the temperature set point of the hypothalamus, because a higher body temperature increases the activity of the phagocytic white blood cells that attack bacteria.

Ways fever affects microbes

• Higher body temperature increases the activity of phagocytic white blood cells that attack bacteria.
• The endogenous pyrogens cause other cells to reduce the concentration of iron in the blood. Many bacteria need more iron to reproduce at 38 or 39 degrees Celsius than at 37 degrees Celsius, so fever and reduced iron combine to slow down their rate of reproduction.
• Fever increases the production of interferons, which travel to other cells and increase their resistance to viral attack.
• The higher temperature may directly inactivate virus particles, particularly enveloped viruses, which are more heat-sensitive than non-enveloped viruses.
• Replication of some viruses is reduced at higher temperatures, so fever may inhibit replication.

Fever is a nonspecific defence against microbial infections. However, a high degree of fever often becomes destructive to the body's own metabolic system and can ultimately collapse the body. Therefore physicians prescribe antipyretic drugs to patients with a high degree of fever.

9.3Third line of defence: the specific defencesOften examined

If a pathogen gets past the body's nonspecific defence, the third line of defence interferes with a series of defence responses, often called immune responses, that attack the particular pathogens having specific antigens. These antigens serve as the stimulus to produce an immune response. Viruses, bacteria and other pathogens have specific antigens on their surface.

Antigen

A substance that stimulates an immune response. The term comes from ANTI-body GENerating substances.

Specific defence

The third line of defence. It responds against particular infections and acts as the most powerful means of resisting infections.

The response of the third line of defence can be of two types: the humoral immune response and the cell-mediated immune response. These responses are carried out by two components: B lymphocytes (B cells) and T lymphocytes (T cells). The third line of defence also involves the role of monocytes (macrophages), which take part in the activation of these lymphocytes.

9.3.1Role of monocytes in third line of defenceOften examined

Monocytes are a kind of white blood cell. They circulate in the blood for one to three days and then leave the blood and come into the intercellular spaces of the tissues. In the tissues they swell and reach a larger size to become tissue macrophages or dendritic cells, which are irregular in shape with many projections.

When these cells perform phagocytosis of invaded microorganisms, after digesting them they not only display microbial antigens on their surfaces, they also secrete substances:

• Macrophages begin to secrete about 100 different compounds, including various enzymes, interferons and a protein called interleukin-1.
• The interleukin-1 secreted by macrophages activates T cells, which in turn begin to secrete interleukin-2, and interleukin-2 then activates B cells.
• Interleukin-1 also promotes a general response to injury, causing fever and activating other mechanisms that defend the body against invasion.
• Dendritic cells, after phagocytosis, become antigen-presenting cells for T cell activation.

9.3.2Role of T cells in third line of defence (cell mediated immune response)Often examined

T cells originate from stem cells in the bone marrow. After early embryonic development, the newly forming T cells migrate to the thymus gland for processing. The thymus makes T cells immunocompetent, that is, capable of an immunological response. The immune response provided by T cells is called the cell mediated immune response.

Activation of T cells

In case of infection, macrophages perform phagocytosis of the invading microorganism and detect particular antigens (nonself molecules) of the organism. Macrophages isolate these antigens and display them on their surface with the help of their own proteins (self-protein) called major histocompatibility complex (MHC). In this way macrophages become antigen-presenting cells (APCs).

Macrophages also secrete interleukin-1, which stimulates and attracts helper T cells towards the displayed antigens. Helper T cells have a specific receptor on their surface called the T cell receptor (TCR), by which they bind with a particular antigen displayed on the APC. Interleukin-1 also stimulates the helper T cells to secrete another protein, interleukin-2, which not only compels the helper T cells to divide but also causes the proliferation of certain cytotoxic T cells and B cells.

The activation of T cells by a specific antigen is called cell-mediated immunity. The body contains millions of different T cells, each able to respond to one specific antigen.

Major histocompatibility complex (MHC)

The cell's own (self) proteins that macrophages use to display antigens on their surface.

Antigen-presenting cell (APC)

A cell, such as a macrophage, that displays antigens on its surface so that T cells can recognise them.

T cell receptor (TCR)

The specific receptor on a helper T cell that binds a particular antigen displayed on an APC.

Cell-mediated immunity

The activation of T cells by a specific antigen.

9.3.2Types of T cellsOften examined

Two main categories of T cells have been identified. The first group is known as CD8 cells, because they have a surface marker designated CD8, and includes cytotoxic T cells and suppressor T cells. The second group, the helper T cells, are also known as CD4 cells because they have a surface marker designated CD4.

When T cells are activated they divide and produce four types of cells that have specific roles in the cell-mediated immune response.

• Cytotoxic T cells secrete cytotoxin, which triggers destruction of the pathogen's DNA, or perforin, a protein that creates holes in the pathogen's plasma membrane. The holes cause the pathogen to lyse (rupture).
• Helper T cells secrete interleukin-2, which stimulates cell division of T cells and B cells. In other words, these cells recruit even more cells to help fight the pathogen.
• Suppressor T cells: when infection is successfully removed, these cells begin to secrete certain proteins that inhibit further proliferation of T cells. Therefore they shut down the immune response.
• Memory T cells remain dormant after the initial exposure to an antigen. If the same antigen presents itself again, even years later, the memory cells are stimulated to convert themselves into helper T cells and help fight the pathogen.

9.3.3Role of B cells in third line of defence: humoral or antibody mediated immune responseOften examined

Stimulated helper T cells secrete interleukin-2, which causes the proliferation of cytotoxic T cells and B cells. B cells are differentiated in the bone marrow. B cells express specific receptors on their cell membrane, the B cell receptors (BCRs). A BCR allows the B cell to bind a specific antigen, against which it will start an antibody response. Like T cells, there are millions of B cell types in the body, each specific for one particular antigen.

9.3.3Activation of B cellsOften examined

B cell activation begins when the B cell binds to an antigen via its BCR. B cells are stimulated to bind the specific antigen by interleukin-2 proteins secreted by helper T cells. After binding a specific type of antigen, the B cell divides to produce two types of cells: plasma clone cells and memory B cells.

• Plasma cells are specialised to secrete antibodies in bulk. After B cells become plasma cells they live only for a few days, but they secrete a great deal of antibody during that time. A plasma cell can produce more than 10 million antibody molecules per hour.
• Memory B cells: if the same antigen enters the body later, the memory B cells divide to make more plasma cells and memory cells that can protect against future attacks by the same antigen.

The stimulation of B cells to divide into plasma clone cells and memory B cells, and the secretion of antibodies by plasma clone cells, is called the humoral mediated immune response.

9.3.3Structure of an antibodyOften examined

Antibodies (also called immunoglobulins or Ig) are Y-shaped proteins that circulate through the bloodstream and bind to specific antigens, thereby attacking microbes. The antibodies are transported through the blood and the lymph to the site of pathogen invasion.

A typical antibody is a Y-shaped molecule made of four polypeptide chains: two identical long chains called heavy chains and two identical short chains called light chains. Each chain has a constant segment, a functional segment and a variable segment.

• In the constant segment (C) of the heavy chains, the amino acid sequence is constant within a particular immunoglobulin class.
• The variable segments (V) consist of different amino acid sequences in every antibody. Therefore they act as the antigen-binding site.
• Each antibody has two antigen-binding sites.

Antibody (immunoglobulin, Ig)

A Y-shaped protein of two heavy and two light polypeptide chains that binds a specific antigen.

Constant segment

Part of a chain whose amino acid sequence is the same within one immunoglobulin class.

Variable segment

Part of a chain whose amino acid sequence differs in every antibody; it forms the antigen-binding site.

9.3.3Mode of action of an antibodyOften examined

Antibodies work in four different ways.

9.3.3Primary and secondary immune responseOften examined

The action of the immune system can be classified into two parts: the primary and the secondary immune response. The primary immune response is the first contact of the immune system with an infectious agent. All following contacts with the same pathogen are called the secondary immune response.

• The secondary immune response is faster and stronger than the primary response.
• The primary response forms memory cells, while the secondary response uses existing memory cells.
• The primary response sets the stage for the secondary response, allowing the immune system to "remember" and mount a more effective defence against future infections.

9.3.3Monoclonal antibodyOften examined

Whenever a person falls ill, the body responds by producing antibodies to counteract the antigens of the pathogen. These antibodies are specific to a particular antigen. Scientists can replicate these antibodies and use them in the treatment of a disease. Monoclonal antibodies (mAbs) are artificially engineered in laboratories by scientists as a form of medication. They help the human body combat diseases better because each can target only one specific type of antigen.

The discovery of mAbs by Köhler and Milstein in 1975 revolutionised various aspects of biological research, diagnostics and therapy. mAbs are a single type of antibody produced by identical immune cells (clones). They bind specifically to a particular antigen. This uniqueness allows precise targeting and recognition of specific molecules.

Monoclonal antibodies (mAbs)

Antibodies of a single type, produced by identical immune cells (clones), engineered in laboratories to bind one specific antigen.

Impact on biological research

1. Specificity and sensitivity: mAbs enabled researchers to detect and quantify specific molecules with precision, which helped in the study of complex biological processes.
2. Immunological research: mAbs helped explain immune responses, cell signalling and antigen-antibody interactions.
3. Cancer research: mAbs aided understanding of cancer cell biology, so targeted therapies and diagnostic tools were developed.
4. Protein analysis: mAbs facilitated the detection and characterisation of specific proteins and increased understanding of protein function and expression.
5. Drug development: mAbs are responsible for the creation of new targeted therapies of cancer and autoimmune diseases.

Impact on diagnostics

1. ELISA (Enzyme Linked Immunosorbent Assay) and Western blot: mAbs enabled the development of sensitive and specific diagnostic tests such as ELISA and Western blot.
2. Imaging agents: mAbs combined with radioactive or fluorescent labels help imaging techniques like PET and fluorescence microscopy. Positron Emission Tomography (PET) is a medical imaging technique that uses radioactive tracers to create 3D images of metabolic and physiological processes in the body. PET helps doctors diagnose and monitor various diseases such as cancer, neurological disorders and cardiovascular conditions.

Impact on therapy

1. Targeted therapies: mAbs have revolutionised disease treatment. They are used to treat cancer, COVID-19, cardiovascular disease and autoimmune diseases.
2. Immunotherapy: mAbs can make use of the immune system to combat cancer.

9.3.4Inborn and acquired immunity

The two basic types of immunity are (a) inborn (innate) immunity and (b) acquired immunity. The ability of the innate immune system to kill microorganisms is not specific. The first and second lines of defence that you have already studied in this chapter are the part of innate or inborn immunity.

Highly specific protection is provided by the acquired (adaptive) part of the immune system, but it takes several days for this system to become fully functional. The two components of the acquired immune system are cell-mediated immunity and antibody mediated (humoral) immunity.

9.4Types of acquired immunityOften examined

There are two ways to acquire adaptive immunity: (a) active immunity and (b) passive immunity. Both types may be acquired naturally or artificially. Providing immunity artificially is called immunisation.

Natural active immunity

This is the kind of immunity obtained as a result of an infection. The body manufactures its own antibodies when exposed to an infectious agent. This type of immunity is most effective and generally persists for a long time, sometimes even for life. For example, you can get measles only once in your life, as it gives lifelong natural active immunity.

Artificial active immunity

Artificial active immunity (vaccination) is achieved by injecting (or administering orally) small amounts of antigen, called the vaccine, into the body of an individual. The process is called vaccination. The antigen stimulates the body to manufacture antibodies against that antigen. Often a second dose, a booster, is given and this stimulates a much quicker production of antibody, which is long lasting and protects the individual from the disease for a considerable time. Several types of vaccine are currently in use.

Passive immunity

In passive immunity, antibodies from one individual are passed into another individual. They give immediate protection, unlike active immunity, which takes a few days or weeks to build up. However, it only provides protection against infection for a few weeks, because the antibodies are broken down by the body's natural processes, so their number slowly falls and protection is lost.

Natural passive immunity

This may be gained naturally. For example, antibodies from a mother can cross the placenta and enter her foetus. In this way they protect the baby until its own immune system is fully functional. Passive immunity may also be provided by colostrum, the first secretion of the mammary glands. The baby absorbs the antibodies through its gut.

Artificial passive immunity

Antibodies that have been formed in one individual are extracted and then injected into the blood of another individual, who may or may not be of the same species. They can be used for immediate protection if a person has been, or is likely to be, exposed to a particular disease. For example, specific antibodies used for combating tetanus and diphtheria used to be cultured in horses and injected into humans. Only antibodies of human origin are now used for humans. Antibodies against rabies and some snake venoms are also available. Antibodies against the human rhesus blood group antigen are used.

9.3.5Disorders of immune systemOften examined

Some conditions stimulate a defective immune response or destroy the immune system. They are called disorders of the immune system.

Allergies

Allergies are defective immune responses leading to chronic health conditions such as hay fever, eczema, asthma and food allergy. The immune system of allergy patients overreacts when allergens (like pollen, dust or mould) are inhaled, ingested or enter through the skin. The body starts producing a large quantity of special antibodies, IgE (immunoglobulin E). This IgE binds with basophils to release inflammatory chemicals like histamine.

Histamine increases capillary leakiness, swelling, mucus secretion, inflammation and other allergic responses. Antihistamine drugs block some of the effects of histamine, relieving the symptoms of allergies. Vaccination can be an effective treatment of allergy, especially for asthma.

Autoimmune disease

In autoimmune disease, the immune system attacks the healthy cells of the body's organs and tissues by mistake. Antibodies are produced against the body's own components and begin to destroy them. There are more than 80 types of autoimmune disease. They can affect almost any part of the body. For example:

1. Some types of anaemia are caused by antibodies that destroy a person's red blood cells.
2. Many cases of insulin-dependent (juvenile-onset) diabetes occur because the insulin-secreting cells of the pancreas are the victims of a misdirected immune response.
3. Vitiligo is a chronic autoimmune disorder that causes patches of skin to lose pigment or colour.

Unfortunately, at present there is no way to cure autoimmune diseases. The autoimmune response can be suppressed with drugs.

9.3.5Transplant rejectionsOften examined

It is occasionally desirable to transplant some tissue or an organ such as the skin, kidney, heart or liver from one person to another to replace a non-functional, damaged or lost body part. In such cases there is a danger that the recipient's cells may recognise the donor's organ or tissue as being foreign. This triggers the recipient's immune mechanisms, which may act to destroy the donor tissue. Such a response is called transplant rejection.

Role of T cells in transplant rejection

The mechanism of rejection probably varies with the nature of the tissue and the degree of incompatibility. All the mechanisms require that the host helper T cells come into contact with the graft tissue's major histocompatibility complex (MHC) antigens. This contact is probably mediated by the dendritic cells of the graft tissue itself. At this point three different possibilities exist.

1. In the first, antigen-specific TH cells stimulate the activation and proliferation of appropriate T cells, which then enhance a focused attack on the transplant tissue.
2. In the second, responsive antigen-specific TH cells move to the graft site, where they release lymphokines. These recruit monocytes/macrophages and T cells to the graft site and maintain them at the scene while they destroy the tissue.

Role of B cells in transplant rejection

There is a third mechanism in which antibodies play a role. The responsive helper T cell interacts with the appropriate B cell clone, producing a shower of antibodies to the implanted tissue's MHC antigens. These can trigger either complement-mediated graft damage or facilitate the phagocytosis of the grafted tissue by macrophages.

Immunosuppressant drugs

9.3.5STEAM activity 9.1

STEAM activity 9.1: Recognising phagocytes and lymphocytes while observing prepared slides.

The book gives only the title of this activity. Use the notes of this unit to recognise the cells you see on a prepared slide of blood.

Key terms

Immune response

The body's response to foreign particles, such as the production of antibodies directed against a specific antigen.

Immunity

The ability to resist damage from foreign substances such as microorganisms and harmful chemicals, for example toxins released by microorganisms.

Immunology

The study of foreign particles that can affect the living body and of the defence mechanisms the body uses to eliminate them.

Innate immunity

The first and second lines of defence together: nonspecific defence present from birth.

Adaptive (acquired) immunity

The third line of defence: the specific internal defence.

Desquamation

The shedding of dead skin cells, which removes attached microbes.

Sebum

An oily secretion of the sebaceous glands containing fatty acids that lower skin pH and are antimicrobial.

Lysozyme

An enzyme in sweat that breaks down bacterial cell walls.

Vestibule

The anterior part of the nasal cavities, which contains hairs.

Phagocyte

A white blood cell that destroys abnormal body cells or invaded microorganisms by engulfing them.

Phagocytosis

The process of engulfing and destroying cancerous cells or invaded microorganisms.

Macrophage

A phagocyte found in organs such as lungs, liver, spleen, kidney and lymph nodes; it engulfs microbes and acts as an antigen presenting cell.

Dendritic cell

A cell found in tissue in contact with the outside environment; an antigen presenting cell whose main function is the activation of T cells.

Neutrophil

A short-lived, mobile granulocyte that phagocytoses microbes, releases lysosomal enzymes by degranulation and releases extracellular traps.

Antigen presenting cell (APC)

A cell that displays parts of microbes on its surface so that other cells are informed, for example macrophages, dendritic cells and B cells.

Interleukin-1

A protein secreted by macrophages that activates T cells and signals the brain to raise body temperature.

Interleukin-2

A protein secreted by helper T cells that makes helper T cells divide and causes proliferation of cytotoxic T cells and B cells.

Natural killer (NK) cell

A lymphocyte of innate immunity that kills virus-infected and cancerous cells with perforins and granzymes.

Perforin

A protein that punches holes in the membrane of the target cell.

Granzymes

Apoptotic proteases that enter the target cell through perforin pores.

Apoptosis

Programmed cell death.

Complement system

More than fifty small blood proteins, made by the liver, that are activated in a chain and complement antibodies and phagocytes.

Membrane attack complex (MAC)

A complement product that makes holes in bacterial cell walls and plasma membranes so that the bacterium swells and bursts.

Cytokine

A chemical messenger that regulates cell differentiation, production and gene expression to affect immune responses.

Interferon

A cytokine released by virus-infected cells that interferes with viral replication and warns neighbouring cells.

Inflammatory response

A nonspecific defence triggered by tissue damage, with heat, pain, redness, swelling and loss of function.

Histamine

A chemical alarm signal released by damaged cells that makes blood vessels dilate and leak.

Fever (pyrexia)

A body temperature raised above normal.

Pyrogens

Chemicals released by invading microorganisms that raise the set point of the hypothalamic thermostat.

Endogenous pyrogens

Hormones released by white blood cells in response to infection that further raise the set point of the hypothalamus.

Antipyretic

A drug prescribed for high fever; it blocks the elevation of the hypothalamic set point.

Antigen

A substance that stimulates an immune response (from ANTI-body GENerating substances).

Specific defence

The third line of defence, the most powerful means of resisting infection.

Humoral immune response

The immune response in which B cells become plasma cells that secrete antibodies.

Cell-mediated immune response

The immune response carried out by T cells.

Major histocompatibility complex (MHC)

The cell's own (self) proteins used to display antigens on the surface of antigen presenting cells.

T cell receptor (TCR)

The receptor on a helper T cell that binds a particular antigen displayed on an APC.

Immunocompetent

Capable of an immunological response; T cells become so in the thymus.

Cytotoxic T cell

A CD8 cell that kills infected cells with cytotoxin or perforin.

Helper T cell

A CD4 cell that secretes interleukin-2 to stimulate T cells and B cells.

Suppressor T cell

A CD8 cell that secretes proteins that inhibit proliferation of T cells and shut down the immune response.

Memory T cell

A dormant cell that converts into helper T cells when the same antigen returns.

B cell receptor (BCR)

The specific receptor on a B cell that binds one antigen.

Plasma cell

An activated B cell specialised to secrete antibodies in bulk.

Memory B cell

A long-lived cell that divides into plasma cells and memory cells if the same antigen enters again.

Antibody (immunoglobulin)

A Y-shaped protein of two heavy and two light chains that binds a specific antigen.

Opsonisation

Binding of antibody to an antigen so that macrophages phagocytose it.

Antibody dependent cell mediated cytotoxicity (ADCC)

Killing of antibody-coated infected or tumour cells by NK cells, which induce apoptosis.

Primary immune response

The first contact of the immune system with an infectious agent; it forms memory cells.

Secondary immune response

All later contacts with the same pathogen; faster and stronger, using existing memory cells.

Monoclonal antibodies (mAbs)

Antibodies of a single type produced by identical immune cells (clones) and engineered to bind one antigen.

Active immunity

Immunity in which the body makes its own antibodies.

Passive immunity

Immunity in which antibodies from one individual are passed into another; protection lasts a few weeks.

Vaccination

Injecting or giving orally small amounts of antigen (a vaccine) to give artificial active immunity.

Colostrum

The first secretion of the mammary glands, which gives the baby natural passive immunity.

Allergy

A defective immune response to allergens, with IgE binding basophils to release histamine.

Autoimmune disease

A disease in which the immune system attacks the body's own healthy cells by mistake.

Transplant rejection

The destruction of donor tissue by the recipient's immune system.

Lymphokines

Signalling molecules released by immune cells that coordinate the immune response.

FBISE 2026 questions

Questions from the FBISE HSSC-II 2026 (1st Annual) papers that belong to this unit, answered the way an examiner expects.

Exam focus

1. Draw and label the structural model of an antibody (heavy and light chains, variable and constant segments, antigen-binding sites). (long)
   Asked in both 2026 sets (Set B Q.4 (a), Set D Q.5 (b) OR); book short question 4.
   Go to answer
2. Describe the role of B cells in the humoral immune response: BCR, interleukin-2, plasma cells and memory B cells. (long)
   Set D Q.5 (a) OR (4 marks); book long question 9.
   Go to answer
3. Differentiate between active and passive immunity, and classify natural and artificial examples (colostrum, placenta, vaccination). (long)
   Set B Q.4 (b), MCQ 10 and Set D MCQ 11; book long question 10.
   Go to answer
4. Monoclonal antibodies: definition, specificity and therapeutic use. (short)
   Set B MCQ 7, Set D MCQ 8 and Set D Q.2 (v); book long question 13.
   Go to answer
5. Types of T cells (cytotoxic, helper, suppressor, memory) and their actions. (short)
   Set B Q.2 (x) OR; book short question 11 (d) and long question 8.
   Go to answer
6. Skin as a barrier, complement system and macrophages: three-point short answers. (short)
   Set D Q.2 (vi) OR and Q.2 (x), Set B Q.2 (vi); book long questions 1 to 3.
   Go to answer
7. How antibodies kill pathogens (neutralisation, opsonisation, complement fixation, ADCC) and why each antibody binds one antigen. (short)
   Supports the antibody-structure questions (Set B Q.4 (a), Set D Q.5 (b) OR); book short questions 6 and 7.
   Go to answer
8. Primary and secondary immune response: memory cells and why a booster works. (short)
   No direct 2026 question; the book's graph and short question 11 (h) make it a likely 3-mark question.
   Go to answer