Students lectures

1. Physical barriers to prevent infections (virus and microbes) and the complement system
Ch. 2 and 12
2. Innate immunity - the cells responsible of pattern recognition of pathogens
Ch. 1 (pag. 1 to pag. 11), and Ch. 3
3. B-cells and T-cells
Ch. 4 (pag. 127 to pag. 138), Ch. 7 (very mild)
4. Development of lymphocytes and thymic selection
Ch. 8
5. Antigen Presentation Mechanisms
Ch. 6
6. T-cell mediated immunity
Ch. 9
7. Humoral Response
Ch. 10
8. Allergies and B-cell malfunction
Ch. 14
9. Autoimmunity and transplant rejection
Ch. 15
10. Failure of immune system: immune deficiencies
Ch. 13
11. Exploiting the immune system: manipulation of immune responses
Ch. 16
12. Use of antibodies as research tool
pag. 723 to pag 778
Immune System:

- It is the body's defense against infectious organisms and other invaders. Through a series
of steps called the immune response.

- It is made up of a network of cells, tissues, and organs that work together to protect the
body.
Immunity:
3 types

Innate Immunity:
- Everyone is born with innate (or natural) immunity, a type of general protection. 

- It includes the external barriers of the body, like the skin and mucous membranes (like
those that line the nose, throat, and gastrointestinal tract), which are the first line of
defense in preventing diseases from entering the body. If this outer defensive wall is
broken (as through a cut), the skin attempts to heal the break quickly and special immune
cells on the skin attack invading germs.

Adaptive Immunity (or active) immunity

It develops throughout our lives. It involves the lymphocytes and develops as people are
exposed to diseases or immunized against diseases through vaccination.

Passive Immunity

It is "borrowed" from another source and it lasts for a short time. For example, antibodies in
a mother's breast milk give a baby temporary immunity to diseases the mother has been
exposed to. This can help protect the baby against infection during the early years of
childhood.
Innate Vs. Adaptive immunity
Problems of the Immune System:

Disorders of the immune system fall into four main categories:

1. Immunodeficiency Disorders (primary or acquired)

- They happen when a part of the immune system is missing or not working properly.
- Some people are born with an immunodeficiency (known as primary
immunodeficiencies), although symptoms of the disorder might not appear until later in
life.
- Immunodeficiencies also can be acquired through infection or produced by drugs (these
are sometimes called secondary immunodeficiencies).

- Immunodeficiencies can affect B lymphocytes, T lymphocytes, or phagocytes.

- Examples of primary immunodeficiencies :
• IgA deficiency
• Severe combined immunodeficiency (SCID) is also known as the "bubble boy disease“

 - Acquired (secondary) immunodeficiencies include:

• HIV (human immunodeficiency virus) infection/AIDS (acquired immunodeficiency

syndrome) 
• Immunodeficiencies caused by medications. Some medicines suppress the immune
system. One of the drawbacks of chemotherapy treatment for cancer
2. Autoimmune Disorders
The immune system mistakenly attacks the body's healthy organs and tissues as though they
were foreign invaders. They include: Lupus, Scleroderma

3. Allergic Disorders
- They happen when the immune system overreacts to exposure to antigens in the
environment. The immune response can cause symptoms such as swelling, watery eyes, and
sneezing. Medicines called antihistamines can relieve most symptoms.
They include: Asthma, Eczema

4. Cancers of the Immune System

Cancer happens when cells grow out of control. This can include cells of the immune system. 
Examples :

Leukemia, which involves abnormal overgrowth of leukocytes, is the most common childhood
cancer. 
Lymphoma involves the lymphoid tissues and is also one of the most common childhood
cancers.
 Components
Cells :

1) lymphocytes :
- come from a distinct lineage of stem cells and are responsible for the adaptive response
- They are the only cells in the body that are capable of recognizing specific antigens through
an array of highly specific receptors.
- Lymphocytes develop from stem cells in the bone marrow and differentiate into three
populations of cells that are important in immune responses: B cells, T cells and natural
killer (NK) cells.

(a) B cells
They are the only cells capable of producing antibodies and are the cells that mediate humoral
immunity.

Antibodies
- They are specialized proteins that lock onto specific antigens. And once produced, they stay
in a person's body, so that if the  immune system encounters that antigen again, the
antibodies are already there to do their job.
- Antibodies also can neutralize toxins (poisonous or damaging substances) produced by
different organisms.
- Antibodies can recognize an antigen and lock onto it, but they are not capable of
destroying it without help.
- antibodies can activate a group of proteins called complement that are also part of the
immune system. Complement assists in killing bacteria, viruses, or infected cells.

Immunizations
An immunization introduces the body to an antigen in a way that doesn't make someone sick,
but does allow the body to produce antibodies that will then protect the person from future
attack by the germ or substance that produces that particular disease.

(b) T cells:
-They are involved in cell-mediated immunity.
- There are a number of different T lymphocytes:

1. Helper T cells: secrete cytokines that help B cells to mount potent antibody responses
and assist macrophages in killing phagocytosed microbes.

2. Cytotoxic T cells: (also known as natural killer T cells) , directly kill infected cells.

3. Memory T cells:  will be present after the body has fought off an infection and help the
body to deal more easily with any future infection of the same type.

4. Regulatory T cells (also known as suppressor T cells) help to regulate other T cells to

prevent them targeting the body's own cells.
Maturation:

B cells and T cells mature in the bone marrow and thymus, respectively.
The bone marrow and thymus are considered “primary lymphoid organs.”
During this process of maturation, random changes occur in the regions of DNA that encode
the antigen receptors for each developing B and T cell. Thus, by the time any one B or T cell
has matured, mutations will have occurred in its DNA that allow its antigen receptors
to recognize a single antigen with very high specificity. The net result is a population of
mature lymphocytes that can recognize millions of different antigens. (Of course, in this
process of B and T cell maturation, some receptors are randomly produced that react against
self antigens. For the most part, these self-reactive lymphocytes are killed, or “deleted” from
the total population of lymphocytes. This process is called self-tolerance because it ensures
that we don’t make lymphocytes that react against our own antigens and that our immune
system “tolerates” our own cells. Failures in the process result in autoimmune disease.

Recirculation:

Mature B and T cells leave the primary lymphoid organs and continually circulate through
peripheral sites of the body “looking” for antigens to recognize and respond to. This process
of continual migration from one peripheral lymphoid tissue to another is known as
lymphocyte recirculation. These recirculating lymphocytes are known as “naïve”
lymphocytes because they have not yet encountered the antigen for which they have
specific receptors. If naïve lymphocytes encounter an antigen for which they are specific in
one of these peripheral lymphoid tissues, they will become activated and initiate an
adaptive response.

(b) NK cells :

Like cytotoxic T cells, also kill infected or damaged cells but have receptors that are much
less specific. NK cells are considered part of innate immunity, while B and T cells
participate in adaptive immunity.

2) Antigen presenting cells:

- The main job is to capture and display antigens to lymphocytes to initiate the adaptive
response
- Most APCs are located in the periphery where they survey tissues for antigens.
- Unlike lymphocytes, which recognize very specific antigens, an APC has receptors that
recognize broad classes of microbial antigens. When stimulated, these receptors
cause the stimulating antigen to be endocytosed. This initiates several responses by
the APC that occur simultaneously: the APC displays the antigen on its surface via
MHC II molecules; the APC synthesizes molecules that facilitate its migration into the
lymph and to a local lymph node; the APC synthesizes and displays additional
molecules on its surface that will act as co-activators of lymphocytes in the lymph
node.
- The best understood antigen presenting cell is the dendritic cell.
- Other cells in the body that possess the special MHC II molecules needed to display
endocytosed antigens are macrophages and B cells. Thus, macrophages and B cells
can also act as antigen presenting cells.

3) Effector cells:
The cells that actually eliminate the microbe are called effector cells. This group
is made up of activated lymphocytes and other leukocytes. Activated helper T cells stimulate
macrophages to kill endocytosed microbes; activated cytotoxic T cells and NK cells directly kill
infected cells; plasma cells (antibody-secreting B cells) secrete antibodies, which target
antigens for destruction. Non-lymphoid leukocytes such as macrophages and granulocytes
participate in the elimination of microbes in both the innate and adaptive immune responses.

Organs :
There are three important types of peripheral lymphoid organs: 

1) lymph nodes
antigen presenting cells that have engulfed antigens migrate to lymph nodes where they can
display those antigens to groups of naïve lymphocytes.

2) submucosal lymphoid tissues:

Tonsils and other submucosal lymphoid tissues (such as Peyer’s patches in the gut) survey
antigens that may enter via the oral cavity, gastrointestinal tract and other mucosal surfaces.
Antigens from these sites are directly conveyed to underlying lymphoid tissues via specialized
epithelial cells.

3) The spleen :
is an organ that brings lymphocytes together with antigens that may be circulating in the
blood. Blood that enters the spleen flows through a vast network of channels that are lined
with phagocytes and dendritic cells.
These antigen presenting cells can then convey the antigens to lymphocytes in the spleen.

What happens ?

I) Before the microbe invades:

Before the microbes invade, naïve B and T lymphocytes are circulating throughout the body,
moving between the blood and peripheral lymphoid tissues such as the spleen and lymph
nodes. This makes sense: antigens that enter through the periphery will eventually be
captured and concentrated in local lymph nodes and antigens in the blood will be captured
and concentrated in the spleen. Naïve lymphocytes go to those areas because it is in those
tissues that they have the best chance of detecting a foreign antigen. Simultaneously, cells of
the innate immune system are mostly inactive in the periphery, waiting to be stimulated by an
invading microbe.

II) Antigen recognition and the innate response:

Invading microbes breach the epithelium and are encountered by mechanisms of innate
immunity. These innate mechanisms promote local inflammation and try to kill the invaders.
Simultaneously, some of the microbes are detected by receptors on antigen presenting cells,
activating them. The APCs endocytose the microbes, display pieces of them on their surfaces
and migrate to a local lymph node to “look” for a lymphocyte that can recognize the microbial
antigens they are displaying.
A lymphocyte that has a receptor specific for the displayed antigen will bind the displayed
antigen, causing the lymphocyte to become activated. At this point, the adaptive immune
response begins…

III) The adaptive immune response:

The adaptive immune response consists of the activation and differentiation of B and/or T
lymphocytes. Activated lymphocytes divide and mature, producing effector cells that will
eventually eliminate the microbe. Non-lymphoid leukocytes assist lymphocytes in their
work. Differentiated T cells migrate from the lymph nodes toward the site of infection .At
the site of infection , helper T cells activate macrophages to kill phagocytosed microbes .
Activated cytotoxic T cells migrate toward the infected tissues and directly mediate the
killing of infected cells .
Differentiated B cells , which are known as plasma cells , unlike Differentiated T cells do
not migrate from the lymph nodes, instead they remain and produce a large number of
antibodies . These antibodies leave the lymph nodes and enter the circulation
 Some basics
• white Blood Cells : 3 major types

1. Granulocytes:
- They are phagocytes, that is they are able to ingest foreign cells such as bacteria,
viruses and other parasites.
- They are so called because they have granules of enzymes which help to digest the
invading microbes. Granulocytes account for about 60% of our white blood cells.
- 3 different forms:

a. Neutrophils : are by far the most prevalent of these cells. Each neutrophil cell can
ingest up to between around 5 and 20 bacteria in its lifetime.
b. Eosinophils : are involved in allergic reactions and can attack multicellular parasites
such as worms.
c. Basophils: are also involved in allergic reactions and are able to release histamine,
which helps to trigger inflammation, and heparin, which prevents blood from clotting.

2.Monocytes:
They can develop into two types of cell:
Dendritic cells:
 are antigen-presenting cells.
Macrophages:
 are phagocyte cells which are larger and live longer than neutrophils. They are also able
to act as antigen-presenting cells.
3. Lymphocytes

• Humoral immunity:  is the type of adaptive immunity that is mediated by antibodies
produced by plasma cells. It is the main mechanism for defending against extracellular
microbes and their toxins.
• Cell-mediated immunity : is the type of adaptive immunity mediated by T
lymphocytes; it is the main defense mechanism against microbes that survive within
phagocytes (i.e. the bacteria that causes Tuberculosis) or that infect the cytosol of
non-phagocytic cells (i.e. many viruses).
• Cytokines : are secreted proteins that work as mediators of immune and inflammatory
reactions. Cytokines provide a mechanism for cells of the immune system to “talk” to
one another to coordinate a response. Interleukin is another term for a cytokine that
acts on other leukocytes.