22. Immune System and the Bodys Defense

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22. Immune System and the Body's Defense
I. Overview of Diseases Caused by Infectious Agents

Disease can be caused by a variety of factors, some have causes within our bodies (e.g., genetic
disorders and cancer) and some have external causes (e.g., injury or infection). Infectious agents
that cause harm to the body are often called pathogens. Your textbook describes five categories
of infections agents (Table 22.1): bacteria, viruses, fungi, protozoans, and multicellular parasites.

II. Overview of the Immune System

Mechanisms your body employs to defend against pathogens, cancers, etc. make up your body's
immune system. This system differs from other systems studied in the class in that it is a system
composed primarily of individual cells spread throughout the body, rather than a discrete system
of organs. However, the cells of the immune system do work in a cooperative manner to provide
a clear function for the body.

Immune cells and their locations
The primary cells of the immune system are the leukocytes:
     The granulocytesneutrophils, eosinophils, and basophils.
     Monocyteswhich become macrophages when they leave the blood and enter other
        tissues.
     Lymphocyteswhich include T-cells, B-cells, and natural killer (NK) cells.

Although leukocytes circulate in the blood, most of the leukocytes in the body are found in other
locations:
      Lymphatic tissuemacrophages and lymphocytes are housed in secondary lymphatic
        structures.
      Select organsmacrophages can be found in most organs of the body, including the
        lungs, brain, etc.
      Epithelial layers of the skin and mucous membranesdendritic cells are phagocytes
        (related to monocytes) that patrol the skin and mucous membranes looking to devour
        pathogens.
      Connective tissuesmast cells (which are similar to basophils) are located throughout
        the body's connective tissues, especially in the dermis of the skin and those tissues that
        line the respiratory, digestive, and urogenital tracts. You should recall their functions
        from A&P I.

Comparison of innate immunity and adaptive immunity
Defense is provided by the immune system in two general ways: (1) The innate (or nonspecific)
system attempts to protect the body from all invaders. The first line of defense in the innate
system is provided by the skin and mucosae, which act as physical barriers to invasion. The
second line of defense includes phagocytic cells and antimicrobial proteins, which attempt to
contain the spread of any invaders that get past the first line of defense. The innate system
provides a generic but immediate defense against toxins and pathogens. (2) The adaptive (or
specific) system can mount specific attacks against specific invaders. This system can provide a
more effective defense against a specific invader, but it takes more time for the adaptive system

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to coordinate an attack. The two systems generally act together in fighting an infection.

III. Innate Immunity

Preventing entry
The thick, keratinized stratum corneum provides a nearly impenetrable barrier to pathogens that
might try to enter the body through intact skin. Mucous membranes also provide an effective
barrier against most potential invaders. Various secretions also help prevent entry into the body:
        1. Fluids secreted onto the skin (e.g., sweat and sebum) contain chemicals that inhibit
                growth of microorganisms.
        2. The stomach secretes hydrochloric acid and proteases that kill microorganisms in the
                food we eat.
        3. Saliva and tears contain lysozyme to kill bacteria residing in the mouth or on the
                surfaces of the eye.
        4. Mucous membranes produce mucus to trap microorganisms. Cilia lining internal
                passages sweep mucus out of the body or into the digestive tract. Mucus also
                contains lysozyme.

Various harmless (an often beneficial) microorganisms live on your skin and within exposed
tracts of the body. Many of these microorganisms inhibit the growth of potentially harmful
microorganisms.

Cellular defenses
Phagocytic cells patrol the body's tissues in search of invaders that have breached the surface
barriers. The chief phagocytes are macrophages and neutrophils. They engulf pathogens (as
well as damaged cells or cellular debris) and chemically digest them inside of structures called
phagolysosomes (Fig. 22.3a).

In response to an infection, basophils and mast cells release chemicals that cause inflammation
and serve as attractants for other cells of the immune system (Fig. 22.3b). You should already
be familiar with the chemicals histamine and heparin.

Natural killer (NK) cells are lymphocytes that specialize in detecting and killing cancer cells
and cells infected by viruses. Whereas other lymphocytes act against specific targets, NK cells
are less particular and can kill a broad range of targets. NK cells destroy cells by attacking the
target cell's membrane. They produce chemicals called perforins, which create channels in the
target cell membrane and lead to destruction of the target cell (Fig. 22.3c).

Eosinophils are most important in defending against invaders too large for phagocytosis, such as
parasitic worms ( (Fig. 22.3d). They can also phagocytize antigen-antibody complexes.

Antimicrobial proteins
A variety of antimicrobial proteins assist in defense by attacking pathogens directly or hindering
their ability to reproduce. Interferons (IFNs) are released by some cells that have been infected
by viruses. IFNs are able to hinder reproduction of viruses, and they activate macrophages and
NK cells to seek out and destroy other virus-infected cells (Fig. 22.4).



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Complement is a system of at least thirty proteins that circulate in the blood in an inactive state.
Activated complement amplifies the inflammatory response and it directly kills cells. Activation
of the complement system results in several effects that assist in defense of the body (Fig. 22.5):
         Opsonizationbinding of complement proteins or antibodies to a pathogen makes it
           an easier target for phagocytosis.
         Inflammationcomplement enhances the inflammatory response by activating mast
           cells and basophils.
         Cytolysisseveral complement proteins work together to form a membrane attack
           complex (MAC), which puts holes in the target cell plasma membrane, causing lysis
           of the target cell.

Inflammation
Infection, chemicals, heat, and physical trauma produce the inflammatory response in tissue.
Inflammation involves redness, heat, swelling, and pain in the injured or infected area. The
inflammatory response begins with the release of chemicals from injured tissue, phagocytes,
lymphocytes, mast cells, basophils, and the blood. These chemicals include histamine,
leukotrienes, prostaglandins, and others (Table 22.4).

One effect of these chemicals is dilation of small blood vessels and increased permeability of
capillaries in the vicinity of the injury or infection. This causes both hyperemia, increased
blood flow, and edema, swelling, at the site of infection or injury.

Also, endothelial cells of the capillaries produce cell-adhesion molecules (CAMs) that enable
leukocytes to stick to capillary walls. Leukocytes traveling through the blood can stick to the
CAMs, exit the blood vessel, and migrate to where they are needed.

Inflammation has the result of a net movement of fluid from the blood to the infected/injured
tissue. This fluid brings with it chemicals, nutrients, and cells that are able to fight infection and
heal damaged tissue. Edema causes an increase of pressure in the interstitial fluid, which drives
more fluid into the lymphatic system. This fluid is likely to contain pathogens that have entered
the body, and they can be detected by cells in the lymphatic system.

Fever
Fever, which is defined as an abnormally high body temperature, is a systemic response to
infection. After exposure to foreign invaders, leukocytes may release chemicals called
pyrogens, which cause the body temperature to rise. Fever appears to cause the spleen to
sequester zinc and iron, which are required by bacteria to multiply. Increased temperature also
elevates the body's metabolic rate, which speeds up the process of tissue repair.

IV. Adaptive Immunity: An Introduction

Introduction of a foreign substance into the body may initiate an adaptive immune response.
The result is multiplication (cloning) of lymphocytes to create an army of cells that are able to
recognize and fight the specific invader. Whereas the innate defenses are able to act
immediately (or at least very quickly), the adaptive system takes several days to develop a full
response. T-lymphocytes are responsible for carrying out what is called the cell-mediated
response of adaptive immunity, and B-lymphocytes carry out the humoral response.

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Antigens
An antigen is a substance that can provoke an adaptive immune response. Most antigens are
proteins; some are polysaccharides. It makes sense that most antigens are proteins, as proteins
are the organic molecules with the most diversity among organisms. Consider that sugars like
glucose, fructose, and sucrose, and lipids such as cholesterol and fatty acids are used by many
(maybe most?) organisms. Thus, you would not want these molecules to trigger the immune
system.

An antigen that is foreign to the body is, simply enough, called a foreign antigen. For example,
if a streptococcus bacterium enters my body, various proteins on the surface of the bacterium
would be recognized by my cells of my adaptive immune system. These molecules would be
considered foreign antigens.

The term self-antigen is used to describe various proteins found on the surfaces of cells that are
recognized as self by that person's immune system, but would be seen as foreign if placed in
another individual.

It is typical that the immune system recognizes only part of an antigen molecule as being
antigenic. The part of the antigen that the immune system recognizes is called the antigenic
determinant (or epitope). Many antigens are large enough molecules that they have more than
one epitope. Also be aware that a particular pathogen may contain numerous different molecules
that are antigenic. So, a bacterium may have multiple antigens, some with more than one
epitope, all capable of triggering a host's immune system.

General structure of lymphocytes
Each T-cell and B-cell produces a rather unique receptor for a particular antigen (Fig. 22.9).
Each receptor is composed of several proteins that form a "receptor complex," and each
lymphocyte may have about 100,000 copies of the receptor complex on its outer surface. The
receptor complex is referred to as a TCR on a T-cell or a BCR on a B-cell.

As noted above, a given lymphocyte makes receptors that will bind to a particular antigen. This
is not the result of any specific intent for the cell to recognize a particular antigen. In other
words, your body does not intentionally make cells with receptors to match an antigen on the
streptococcus bacterium. Rather, your body makes billions of lymphocytes, each with receptors
that will recognize something. Because there are so many lymphocytes, if streptococcus (or any
other pathogen) gets into your body, chances are pretty much 100% that some lymphocytes in
the body will be able to recognize it.

A B-cell is able to bind directly to an antigen and begin its response. A T-cell requires that
antigen be presented to the T-cell and its receptors by another cell. Each T-cell has coreceptors
(Fig. 22.9a) that allow it to recognize this other cell:
      Cells known as helper T-cells have coreceptors called CD4 receptors. Each TCR on a
         helper T-cell is associated with a CD4 receptor.
      Cells known as cytotoxic T-cells have coreceptors called CD8 receptors. Each TCR on
         a cytotoxic T-cell is associated with a CD8 receptor.




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Antigen presentation and MHC molecules
As mentioned in the previous section, in order for a T-cell to recognize an antigen, the antigen
must be presented. There are certain cells of the immune system that have the specific function
of presenting antigen to helper and cytotoxic T-cells. These calls are called antigen-presenting
cells (APCs), and they include dendritic cells, macrophages, and B-lymphocytes. However, you
will soon learn that most cells of your body have the ability to present antigens to the immune
system.

The presentation of antigen to T-cells requires that the antigen be attached to a special group of
glycoproteins, called MHC, found on the surfaces of cells. These proteins are coded by a group
of genes called the major histocompatibility complex (hence the abbreviation MHC).

Millions of different combinations of MHC genes can be found in the human population, so
generally only identical twins have the same MHC molecules. The combination of MHC
molecules on cells in a person's body is the combination that is recognized as self. If cells with
another combination of MHC enter the body (as may occur during an organ transplant), then
they will be recognized as foreign.

There are two general classes of MHC molecules found within a person:

Class I MHC molecules are displayed by nearly all cells of the body. Class I MHC molecules
are made in the rough ER, and they bind fragments of protein (peptides) that come from within
the cell (Fig. 22.10). These MHC molecules and associated peptides are then displayed on the
cell's outer surface. Most of the time, these peptides are parts of normal cellular proteins, and
they are recognized by the immune system as self. However, if a cell has been infected or
become cancerous, it will typically produce abnormal proteins. Fragments of these abnormal
proteins are displayed on the cell's surface with the class I MHC molecules, where cytotoxic T-
cells can recognize the abnormal particles as foreign antigens. The T-cell's CD8 receptors bind
to the class I MHC molecules and its TCR binds to the antigen (Fig. 22.12).

This is essentially a way for an infected or cancerous cell to advertise its condition to the
immune system and set itself up for destruction by cytotoxic T-cells.

Class II MHC molecules are displayed on the surfaces of APCs (APCs also display class I
MHC). Class II MHC molecules are made in the rough ER, and they bind peptide fragments
from foreign molecules that have been engulfed by the APC (Fig. 22.11). Because these
antigens have been brought into the APC from the outside, they are called exogenous antigens.
After the exogenous antigen is bound to the MHC molecule, the MHC molecule migrates to the
cell's surface to display the exogenous antigen (which is foreign). Class II MHC molecules are
recognized by helper T-cells, with CD4 receptors binding to the class II MHC molecules and
TCR binding to the antigen (Fig. 22.12).

This alerts helper T-cells to the presence of an infection or other danger to the body that requires
action by the immune system.




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