Chapter 1: Immunity

Objectives of the chapter 2 Immunity is the ability of the body to defend against diseases or damages.
By the end of this chapter students should be able: Immune system is the body’s defense system or group of organs working
 to explain the meaning of the term immune response together to defend or fight the body against diseases.
 to explain the difference between the terms antibody Immune response is any reaction of immune system.
and antigen.
 To explain the origin and maturation of leucocytes. Immunology is the study of immune system or the study of the physiological
 To explain and differentiate nonspecific and specific defenses by which the body destroys or neutralizes foreign matter, both living
immune systems. and non-living things.
 to describe the role of phagocytes and lymphocytes  Function of immune system:
in defense against pathogens
 to distinguish between B lymphocytes and T
The three major functions of the immune system:
lymphocytes in fighting infection 1. It protect against infection by microbes.
 to distinguish between active, passive, natural and 2. It removes non-microbial foreign substances.
artificial immunity 3. It destroys cancer cells that arise in the body (immune surveillance).
 to describe the function of antibodies
 to explain how vaccination can control disease

 Types of immunity:
Immunity (immune defense) can be divided into two categories; specific or non-specific.
Non-specific immune defense (innate immunity): immune Specific immune defense (acquired immunity): immune
response which protects against foreign substances or cells response protects against foreign substances or cells which
without having recognized their specific identifies. recognize their specific identifies.
- NOT unique for to the particular foreign substance or cells. - Unique for to the particular foreign substance or cell.

 Non-specific immunity:
It’s a defense which its response is the same for every invader (pathogen) and this operates immediately after
appearance microbes in the body and it consist of 2 lines:
 First line of defense
This is the external barrier defense which prevents pathogen into body. Skin and mucous membranes of the body are
first line of defense against pathogens. In man; for example;
1. The skin: acts as physical barrier that stops pathogen.
2. Mucous membranes: epithelial layer of mucous membranes which lines body cavities; secretes a fluid
called mucus that lubricates and moistens the cavity surface.
- Mucus membrane of the nose has mucus-coated hairs that trap and filter microbes, dust and pollutants
from inhaled air.
- Mucus membrane of the upper respiratory tract contains cilia which propels inhaled dust and microbes
towards the throat.
Other fluids produced by various organs which also helps skin and mucus membranes for protection:
3. Tear: the lacrimal glands of the eyes produce a tear which dilutes microbes and keeps them from setting
on the surface of the eye.
4. Saliva: the salivary glands produce saliva. It washes microbes from the surfaces of the teeth and from the
mucus membranes of the mouth.
5. Urine: the cleansing of the urethra by the flow or it slow down microbial growth of the urinary system.
- Vaginal secretions: moves microbes out of the body in females.
- Defecation and vomiting: expel microbes.
6. Sebum: sebaceous glands of the skin secrete an oily substance known as sebum that forms a protective
covering over the surface of the skin. It inhibit the growth of a certain pathogenic bacteria and fungi.
7. Blood clotting: helps to seal wounds rapidly, until a more permanent repair is produced by mitosis of the
cells surrounding the wounds.
If this defense is broken, the second line of defense within your body is activated.
 The second line of defense
This is the internal defense which consist cells and molecules that work together to protect the body. When pathogens
invade or penetrate the physical and chemical barriers of the skin and mucus membranes, they encounter a second line
defense. Complement proteins, interferons, phagocytes, neutrophils, natural killer cells, inflammation and fever are
common actors of the second line of defense.
  Special proteins that kill or inhibit pathogens:
1. complement system 2. Interferon:
This is system consists of about 20 different proteins. This is a proteins produced by cells infected with virus.
Complement proteins circulate in the blood and become Function of interferon:
active when they encounter certain pathogens. - It prevents the virus from spreading.
 It destructs of the pathogen’s membrane Interferon binds to un-infected neighboring cells and
 It activates the phagocytes stimulates these cells to produce antiviral proteins which
These proteins aggregate to inserts into itself into the foreign can prevent viral replication in these cells.
cell’s cell walls or plasma membrane such as bacteria and
fungi, forming a pore. So water enters the foreign cell
through this pore and causing to swells, burst and die.
Aggregation of complement proteins also triggered by the
binding of antibodies into invading microbes.

 White blood cells which attack and kill pathogens:

The most important cellular counterattacks in the second line
of nonspecific defenses are carried out by three kinds of white
blood cells: neutrophils, macrophages, and natural killer
cells. These cells circulate through the body within the
bloodstream, wait within the tissues for pathogens, and then
attack the pathogens. Each kind of cell uses a different
mechanism to kill pathogens.

1. Neutrophils Special type of phagocytes which form 60% of white blood cells. They are produced and stored by the bone
marrow until them becoming mature. They travel through the body by squeezing the capillary walls to
tissue. Functions of neutrophils are:
- They ingest and kill pathogen (bacteria) by phagocytosis.
- They also release chemicals that kill other bacteria in the neighborhood as well as neutrophils themselves.
During infection; a large number of neutrophils are released but they are short lived.
2. Macrophages: These are phagocytes larger than neutrophils. They are produces bone marrow by stem cells and they travel
in blood as monocytes which develop into macrophages “big eaters” once they settle in the body organs
such as the lungs, liver, spleen, kidneys, lymph nodes and thymus. They paly role initiating immune
response. Functions of macrophages are:
- It ingests and kills pathogens they encounter by phagocytosis.
- They also clear dead cells and other debris from the body.
Macrophages are long – lived cells.
3. Natural killer Natural killer cells (also known as NK cells) are a type of lymphocyte.
cells Function of NK cells:
- It kill tumor & virus-infected cells.
NK cells kill NOT by phagocytosis, they release perforins (proteins
that destroys abnormal by making pores in their cell membranes and
then allow water enters into the target cells, which then swells and
burst). Also release granzymes “granule-secreted enzyme” (protease
enzymes that destroy or breaking down the intracellular substrates of
the abnormal cells).
 The vigilant surveillance by NK cells is one of the body’s most potent defenses against cancer.
 Phagocytosis:
Phagocytosis is the process by which phagocytes fight against pathogen.
− If pathogens invade the body and
cause an infection, some of the cells
under attack respond by releasing
chemicals such as histamine. These,
with any chemicals released by the
pathogens themselves, attract passing
neutrophils to the site. (This
movement towards a chemical
stimulus is called chemotaxis.) The
phagocytes destroy the pathogens by
phagocytosis.
− The diagram below shows the stages
of phagocytosis.

 the inflammatory response:

It is a localized, non-specific response to infection and a series of events that suppress infection and speed recovery.
When a pathogen enters body and damage body tissues
then infected or injured cells/ tissues in your body
release chemical alarm signals, including histamine
which promote dilation of local blood vessels which
increases the flow of blood to site of infection or
injury and causes the area to became red and warm.
And also increase the permeability of capillaries in the
area, producing the edema (tissue swelling) and this
allows phagocytes (monocytes and neutrophils) to
migrate the blood to the external fluid, where they can
attack pathogen (bacteria).
- Neutrophils arrive first, spilling out chemicals that kill the bacteria in the vicinity. The pus associated with some
infections is a mixture of dead or dying pathogens, tissue cells and neutrophils.
- Monocytes follows next, become macrophages that engulf pathogens and the remains of the dead cells.
 The temperature response:
Macrophages that encounters invading microbes release a regulatory chemical molecule called interleukin-1 and others
pyrogens such as bacterial endotoxins which cause body temperature increases several degrees above the normal value of
about 37°C (98.6°F). This higher or elevated temperature known as a fever.
- Fever is helpful because many disease-causing bacteria do not grow well at high temperatures.
- Fever contributes to the body’s defense by stimulates phagocytosis.
- Also it cause to store iron in the liver and spleen, this reduce blood levels of iron, which bacteria need in large
amounts to grow.
Although fever may slow the growth of bacteria, very high fever is dangerous because extreme heat can destroy important
cellular proteins. Temperatures greater than 39.4°C are considered dangerous, and those greater than 40.6 °C can be fatal.
 Specific immunity:
Its ability to recognize, respond to, and remember a particular substance. It also known as acquired immunity or adaptive
immunity. Main characteristics of adaptive immunity:
1. Specificity is the ability of adaptive immunity to recognize a particular substance. For example, innate immunity can act
against bacteria in general, whereas adaptive immunity can distinguish among different kinds of bacteria.
2. Memory is the ability of adaptive immunity to remember previous encounters with a particular substance and, as a result, to
respond to it more rapidly.
in adaptive immunity; the response during the second exposure is faster and stronger than the response to the first exposure
because the immune system remembers the bacteria from the first exposure. For example, following initial exposure to the
bacteria, the body can take many days to destroy them. During this time, the bacteria damage tissues and produce the
symptoms of disease. After the second exposure to the same bacteria, however, the response is very rapid and effective.
Bacteria are destroyed before any symptoms develop, and the person is said to be immune.
 Antigen and antibody:
An antigen is a molecule that stimulates (provokes) a specific immune response. It’s a large complex molecule such as
proteins and are generally foreign to the body, usually present of the surface of pathogens.
Antibody: is a protein produced by B-cells against these specific antigens.
- Particular lymphocytes have receptor proteins on the surfaces that recognize an antigen and direct a specific
immune response against the antigen and the cell that carries the antigen. (N.B. Antigens and antibodies are
specific to one another.

 How third line defense works:

The immune defense mechanisms of the body involve the action of white blood cells (leucocytes). Leucocytes that include
− Phagocytes are involved in the second line defense (nonspecific immune response)
− Lymphocytes (B-cells and T-cells) are involved to third line of defense (specific immune response)
 B-cells direct the humoral immune response  T-cells direct the cell mediated response
(Lymphocytes are produced by bone marrow. B-cells and T-cells are named based on where they mature; while mature
bone marrow and T-cells mature in thymus gland that found just above the heart and below the sternum)

Humoral immunity “antibody-mediated immunity” Cell mediated immunity

Humoral immunity is the component of specific immunity Cell mediated immunity is component/type of specific
which mediated by antibodies secreted from B-cells that immunity mediated by T-cells that attack the cells that carry
circulating in blood or others body fluids. the specific antigen.
 It involves B-Cells  It involves cytotoxic T-Cells
 Antibodies are presence  Lack antibodies
 Rapidy  Delay
 It does NOT provide immunity against cancer.  It provides immunity against cancer.
 It does NOT act on the transplant.  It act on the transplant.

 Major Histocompatibility Complex proteins:

MHC proteins are glycoproteins found the surface of most vertebrate cells. In humans; (Human leukocyte antigen HLA).
- It helps immune system to distinguish its cells from foreign cells (self-versus non-self-recognition)
There are two major classes of MHC molecules:
1. MHC I: glycoproteins are present on almost every cell in the body.
2. MHC II: glycoproteins are only present on specialized antigen-presenting immune cells, including macrophages.
The genes encoding the MHC proteins are polymorphic (have many forms) so that the MHC proteins are thus different
for each individual, much as finger prints are.

 T – Lymphocytes: the cell mediated response:

T-cells are type of lymphocytes that produced in the bone marrow but mature in the thymus gland. The cell mediated
immune response carried out by T-cells. “It protect the body from virus infection and cancer or killing abnormal and virus-
infected cells”.
There are four kinds of T- cells:
1- Helper T-cells: cells activate other defensive cells of the body (it stimulates the immune response)
2- T Killer cells (cytotoxic T-cells):- cells attack and kill cells of the pathogens. (It destroy and kills viral infected cells).
3- Inducer T-cells: cells induces the thymus gland to maturate more T-cells. (It oversee the development of T-cells in the
thymus.)
4- Suppressor T- cells: cells stops the action of other lymphocytes. (It terminates the immune response.)

When macrophages process the foreign antigens; they secrete interleukin -1 which stimulates division and proliferation of T-cells.
One helper T-cells have been activated by the antigen presented to them by the macrophages, they secrete the cytokines known as
macrophage colony–stimulating factor and gamma interferon (this promotes the activity of macrophages). Also helper T cells
secretes interleukin -2 (this stimulates the proliferation of Cytotoxic T-cells). Cytotoxic T cells can destroy infected cells only
those cells display the foreign antigen together with their glycoproteins (MHC-I proteins)
  B – lymphocytes: humoral immune response
B – Lymphocytes remain in the bone marrow until maturity and then spread throughout the body concentrating in lymph
nodes and the spleen. Like cytotoxic T- cells; B-cells have receptor proteins on their surface, one type of receptor for each
type of B- cell. So it works on 1 specific antigen; therefore produces only 1 type of antibody to that specific antigen.

Unlike the receptors of T-cells which bind only to antigen MHC protein complex on antigen presenting cells, B cells
receptors can bind to free unprocessed antigen. When pathogen enters the body, the B-cells encounters and enters antigen
particles by endocytosis and get processed.
Helper T cells recognize the specific antigen will bind to the antigen-glycoprotein complex on the B-cells and release
interleukin2 (this stimulates division of B –cells).
Some of these activated B-cells divides and became plasma cells (short lived antibody factories) and others into memory
B- cells (long lived).
The plasma cells secrete large amount of antibodies into the blood plasma and lymph which transports to all parts of the
body to destroy pathogens. After the pathogens are destroyed by the antibodies; the concentration of antibodies decreases.
However, the memory cells remain in the blood circulation. If some antigen again introduced into body, the memory B-
cells divide to form many plasma cells and memory cells.
− This is why; when a new antigen is introduced into the body, the response (primary response) is slow and the body
may get infected.
− The next time when the same antigen enters, the response (secondary response) is fast and the body might not be
infected.
  Primary response and secondary response:
Primary response: is the response to the first invasion of the pathogen.
− The first or primary response is slow because, at this stage, there are
very few B cells that are specific to the antigen. So fewer antibodies
are produced in the primary response.
Secondary response: is the response to which subsequent invasion
generates.
− The secondary response is faster because there are now many memory
cells, which quickly divide and differentiate into plasma cells. There are
many more B cells specific to the pathogen that has invaded the body.
Many more antibodies are produced in the secondary response.
 Active and passive immunity:
Immunity is categorized as:
1. Innate (inherited) immunity: is the ability that the body born to recognize and destroy foreign substances.
2. Acquired (adaptive) immunity: is not present at birth. It is learned. It may be
classified into active and passive.
a) Active immunity: is the immunity gained when an antigen enters the body.
During this, an immune response occurs and antibodies are produced by
plasma cells.
This form of immunity is active because the person makes their own antibodies.
This happens when the lymphocytes are activated by antigens on the surface of
pathogens that have invaded the body.
I. Natural active immunity: is immunity gained when a pathogen naturally enters the body.
II. Artificial active immunity: is immunity gained when an antigen is introduced to individual’s body to
stimulate his or her immune system. This system is also called vaccination.
b) Passive immunity: the immunity gained when antibodies introduced into body
of a person from outside. This form of immunity is a passive because the
person has not produced the antibodies themselves.
I. Natural passive immunity: is immunity gained when antibodies are
passed from a mother to a developing foetus via the placenta or to a
newborn baby through the colostrum (the thick yellowish fluid produced
by a mother’s breasts for the first four or five days after birth, contains a
type of antibody known as IgA.)
II. Passive artificial immunity: is immunity gained when antibodies transferring from animal/person who has
developed immunity to another requiring immunity.
 However, passive artificial immunity is only temporary b/c the antibodies are used up or eliminated by recipients.
 Antibodies:
Antibodies (also known as immunoglobulins, Igs)are specialized proteins that
defend against foreign substances in the body. They are produced by white
blood cells known as B cell.
Each antibody consists of four polypeptides– two heavy chains and two light
chains joined to form a "Y" shaped molecule.
− Disulfide bonds hold the chains together.
 Antigen binding site: is a region on an antibody that binds to antigens.
Antigens (also known as immunogens) are any foreign substance that cause an immune response.
 Epitope: The specific region on an antigen that an antibody recognizes and binds.
Functions of antibodies:
1. It prevents bacterial toxins &viruses from entering the host cell.
2. It makes bacteria less active by attaching to its flagella
3. It agglutinates bacteria, preventing them spreading throughout the body. “Antibodies with multiple binding sites”
4. It causes lysis (destruction) of bacteria by punching holes on the cell membrane.
5. It combine with toxin, neutralizing toxins them and making them harmless; these antibodies are called antitoxins.
  Classes of antibodies:
Antibodies are divided into five major classes:
Class Description
IgG IgG is the only class of immunoglobulin capable of crossing the placenta. These molecules are the most
plentiful in blood and body or tissue fluids. This type can cross the placenta. Its functions are: It acts as
antitoxins, It cause agglutination and It provide protection to a fetus
IgA IgA is produced by B cells located in the mucous membranes of the body. Its located in sweat, saliva,
tears, mucus secretion of small intestine, vaginal and prostate secretion, nasal fluid and bronchial
secretions and colostrum (breast milk. Its main functions: It inhibits bacteria adhering to the host cell and
it prevent bacteria forming colonies on the mucus membranes.
IgD These are located on the surface membranes of the most mature B cells. Its main functions: It regulate B-
cell activation and protects against worms
IgE Found mostly in tissues. Its main Functions: It activate mast cells to release histamine that are involved
in allergic responses. And It help protect against parasitic infections such as worms
IgM the most massive or largest antibody. Its located blood and tissue fluid (Cannot cross placenta)and their
functions are: It cause agglutination and It activate the complement proteins.
 Vaccination:
Vaccination (also known as immunization )is the introduction of vaccine (a small amount of an inactive form of a pathogen)
into the body. Vaccines can contain dead pathogens, harmless live pathogens (attenuated organisms), harmless fragments
(antigens) of the pathogen and harmless form of toxin (toxoid)
- Toxins: a type of natural poison produced by an organism, often as a form of protection. These all act as antigens and
trigger an immune response.
When take or injected into the body, they stimulate white blood cells to produce antibodies to fight the pathogen. N.B: The
vaccine contains only a weakened or harmless version of a pathogen, which means that the vaccinated person is in no
danger of developing the disease. Vaccines can be given orally or by injection (into veins or muscle). For example;
− The poliomyelitis vaccine “taken orally contains harmless virus” – OPV.
− The diphtheria and pertussis vaccine “taken as injection contains weakened bacteria” and the tetanus vaccine
“taken as injection contains weakened toxins” - DPT as one vaccine
Some vaccines are highly effective, and one injection may well give a lifetime’s protection. Less effective vaccines need
booster injections to stimulate secondary responses that give enhanced protection.
Advantage of vaccination:
 It activates the immunity without causing symptoms of disease.
 It enhances the production of memory cells that remembers quickly and protects the re-infection.
 Problems of vaccine:
1) Poor response: Some people do not respond at all, or not very well, to vaccinations. This may be because
− They have a defective immune system and as a result do not develop the necessary B and T cell clones. Or
− They suffer from malnutrition, particularly protein-energy malnutrition (an inadequate intake of protein), and do not
have enough protein to make antibodies or clones of lymphocytes. These people are at a high risk of developing
infectious diseases and transmitting them to people who have no immunity.
2) Antigenic variation:
The mechanism by which a pathogen such as a protozoan, bacterium or virus alters the proteins or carbohydrates on
its surface. It caused by mutations.
a. Antigenic drift “small changes and still recognize memory cells”
b. Antigenic shift “large changes and no longer recognize”

For example; the influenza virus mutates regularly to give different antigens.
− When there are only minor changes in the viral antigen, memory cells will still recognize them and start a secondary
response. These minor changes are called antigenic drift.
− More serious are major changes in antigen structure – known as antigenic shift – when influenza viruses change their
antigens considerably and the protective immunity given by vaccination against a previous strain is ineffective against
the new one.
3) Antigenic concealment: Some pathogens evade attack by the immune system by:
 Some living inside cells such as Plasmodium enters liver cells or red blood cells
 Some covering their bodies in host proteins such as parasitic worms
 Some live inside and infects T- helpers such as HIV.
 Some living where is beyond the reach of many antibodies such as Vibrio cholera lives walls of intestine.