PHYSIOLOGY1

CHAPTER 34: Resistance of the Body to Infection: II. Immunity and Allergy

Immunity – capability of the body to resist almost all types of organisms or toxins that tend
to damage the tissues and organs.

Innate immunity – results from general processes rather than from processes directed at
specific disease organisms.
1. Phagocytosis of bacteria and other invaders by white blood cells and cells of the
tissue macrophage system.
2. Destruction of swallowed organisms by the acid secretions of the stomach and the
digestive enzymes.
3. Resistance of the skin to invasion by organisms.
4. Presence in the blood of certain chemical compounds that attach to foreign
organisms or toxins and destroy them. Some of these compounds are
a. Lysozyme – a mucolytic polysaccharide that attacks bacteria and causes them
to dissolute;
b. Basic polypeptides – which react with and inactivate certain types of gram-
positive bacteria;
c. The complement complex – a system of about 20 proteins that can be
activated in various ways to destroy bacteria; and
d. Natural killer lymphocytes that can recognize and destroy foreign cells, tumor
cells, and even some infected cells.

- Innate immunity makes the human body resistant to such diseases as some paralytic
viral infections of animals, hog cholera, cattle plague, and distemper— a viral disease
that kills a large percentage of dogs that become afflicted with it.

Acquired Immunity – immunity does not develop until after the body is first attacked by a
bacterium, virus, or toxin often requiring weeks or months to develop the immunity
- The human body has the ability to develop extremely powerful specific immunity
against individual invading agents such as lethal bacteria, viruses, toxins, and even
foreign tissues from other animals.
- Is caused by a special immune system that forms antibodies and/or activated
lymphocytes that attack and destroy the specific invading organism or toxin.

Basics Types of Acquired Immunity:

1. Humoral Immunity or B-cell immunity (because B lymphocytes produce the
antibodies) - develops circulating antibodies, which are globulin molecules in the
blood plasma that are capable of attacking the invading agent

2. Cell-mediated Immunity or T-cell immunity (because the activated lymphocytes

are T-lymphocytes) - is achieved through the formation of large numbers of activated
T lymphocytes that are specifically crafted in the lymph nodes to destroy the foreign
agent

Antigens (antibody generations) – proteins or large polysaccharides substances

(molecular weight of 8000 or greater) that initiate the acquired immunity
– The process of antigenicity usually depends on regularly recurring molecular groups,
called epitopes, on the surface of the large molecule.

Lymphocytes – are responsible for acquired immunity [if destroyed, no immunity develop]
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– Located extensively in the lymph nodes but can also be found in some special
lymphoid tissues (spleen, submucosal areas of gastrointestinal tract, thymus, and
bone marrow)

Two Types of Lymphocytes that Promote Cell-Mediated or Humoral Immunity

(Both lymphocytes are derived from pluripotent hematopoietic stem cells then are pre
processed)
1. T lymphocytes - responsible for forming the activated lymphocytes that provide
“cell-mediated” immunity
Preprocessed: thymus gland
2. B lymphocytes - responsible for forming antibodies that provide “humoral”
immunity
Preprocessed: liver (during mid fetal life) and bone marrow (in late fetal life
and after birth)
First discovered in birds: Bursa of Fabricius

Clone of lymphocytes - all the different lymphocytes are capable of forming specificity of
antibody or T cell
B lymphocyte - its progeny will eventually secrete the specific type of antibody that
then circulates throughout the body.
T lymphocyte - its progeny are specific sensitized T cells that are released into the
lymph and then carried to the blood and circulated through all the tissue fluids
and back into the lymph, sometimes circulating around and around in this
circuit for months or years.

Origin of Lymphocytes: The whole gene for forming each type of T cell or B cell is never
present in the original stem cells from which the functional immune cells are formed.
Instead, there are only “gene segments”—actually, hundreds of such segments—but not
whole genes. During preprocessing of the respective T- and B-cell lymphocytes, these gene
segments become mixed with one another in random combinations, in this way finally
forming whole genes.

Each clone of lymphocytes is responsive only to a single type of antigen:

In the case of the B lymphocytes, each of these has on the surface of its cell membrane
about 100,000 antibody molecules that will react highly specifically with only one specific
type of antigen. Therefore, when the appropriate antigen comes along, it immediately
attaches to the antibody in the cell membrane; this leads to the activation process. In the
case of the T lymphocytes, molecules similar to antibodies, called surface receptor proteins
(or T-cell markers), are on the surface of the T-cell membrane, and these too are highly
specific for one specified activating antigen.

Role of Macrophage: Most invading organisms are first phagocytized and partially
digested by the macrophages, and the antigenic products are liberated into the macrophage
cytosol. The macrophages then pass these antigens by cell-to-cell contact directly to the
lymphocytes, thus leading to activation of the specified lymphocytic clones. The
macrophages, in addition, secrete a special activating substance called interleukin-1 that
promotes still further growth and reproduction of the specific lymphocytes.

Helper cells – secret specific substance that activate the specific B lymphocytes

Specific Attributes of the B-Lymphocyte System—Humoral Immunity and the

Antibodies
Formation of Antibodies by Plasma Cells:
Before exposure to a specific antigen, the clones of B lymphocytes remain dormant in
the lymphoid tissue. On entry of a foreign antigen, macrophages in the lymphoid tissue
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phagocytize the antigen and then present it to adjacent B lymphocytes. In addition, the
antigen is presented to T cells at the same time, and activated helper T cells are formed.
These helper cells also contribute to extreme activation of the B lymphocytes.
Those B lymphocytes specific for the antigen immediately enlarge and take on the
appearance of lymphoblasts. Some of the lymphoblasts further differentiate to form
plasmablasts, which are precursors of plasma cells. In the plasmablasts, the cytoplasm
expands and the rough endoplasmic reticulum vastly proliferates. The plasmablasts then
begin to divide at a rate of about once every 10 hours for about nine divisions, giving in 4
days a total population of about 500 cells for each original [Link] mature plasma
cell then produces gamma globulin antibodies at an extremely rapid rate—about 2000
molecules per second for each plasma cell. In turn, the antibodies are secreted into the
lymph and carried to the circulating [Link] process continues for several days or weeks
until finally exhaustion and death of the plasma cells occur.

Formation of “Memory” Cells—Difference between Primary Response and

Secondary Response
A few of the lymphoblasts formed by activation of a clone of B lymphocytes do not go on to
form plasma cells but instead form moderate numbers of new B lymphocytes similar to
those of the original clone. In other words, the B cell population of the specifically activated
clone becomes greatly enhanced, and the new B lymphocytes are added to the original
lymphocytes of the same clone. They also circulate throughout the body to populate all the
lymphoid tissue; immunologically, however, they remain dormant until activated once again
by a new quantity of the same antigen. These lymphocytes are called memory cells.
Subsequent exposure to the same antigen will cause a much more rapid and much more
potent antibody response this second time around, because there are many more memory
cells than there were original B lymphocytes of the specific clone.

Immunoglobulins – are gamma globulins antibodies

Molecular weight: 160,000 – 970,000
- Constitute about 20% of plasma protein
- Composed of light and heavy polypeptide chains (heavy-light pair)
Specificity of antibody: When the antibody is highly specific, there are so many bonding sites
that the antibody-antigen coupling is exceedingly strong, held together by (1) hydrophobic
bonding, (2) hydrogen bonding, (3) ionic attractions, and (4) Van der Waals forces.

Classes of Antibody [Ig means immunoglobulin]: IgM, IgG (75% of antibodies of normal
person), IgA, IgD, and IgE (involved in allergy)

Mechanisms of Action of Antibodies:

Direct Action of Antibodies on Invading Agents
1. Agglutination, in which multiple large particles with antigens on their surfaces, such as
bacteria or red cells, are bound together into a clump
2. Precipitation, in which the molecular complex of soluble antigen (such as tetanus toxin)
and antibody becomes so large that it is rendered insoluble and precipitates
3. Neutralization, in which the antibodies cover the toxic sites of the antigenic agent
4. Lysis, in which some potent antibodies are occasionally capable of directly attacking
membranes of cellular agents and thereby cause rupture of the agent

Activation of the Complement System

Complement – collective term that describes a system of about 20 proteins, many of which
are enzyme pre cursors. Eleven proteins (designated as C1 through C9, B, and D) are
present normally among the plasma proteins in the blood as well as among the proteins that
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leak out of the capillaries into the tissue spaces. The enzyme precursors are normally
inactive, but they can be activated mainly by the so-called classic pathway.

Classic Pathway – initiated by antigen – antibody reaction.

When an antibody binds with an antigen, a specific reactive site on the “constant” portion of
the antibody becomes uncovered, or “activated,” and this in turn binds directly with the C1
molecule of the complement system, setting into motion a “cascade” of sequential
reactions, beginning with activation of the proenzyme C1 itself. The C1 enzymes that are
formed then activate successively increasing quantities of enzymes in the later stages of the
system, so that from a small beginning, an extremely large “amplified” reaction occurs.
Multiple end products are formed, and several of these cause important effects that help to
prevent damage to the body’s tissues caused by the invading organism or toxin. Among the
more important effects are the following:
1
1. Opsonization and phagocytosis
2. Lysis
3. Agglutination.
4. Neutralization of viruses
5. Chemotaxis
6. Activation of mast cells and basophils
7. Inflammatory effects
Several Types of T Cells
and their Functions:
1. Helper T cells – form series of protein mediators called lymphokines (Interleukin-2,
Interleukin-3, Interleukin-4, Interleukin-5, Interleukin-6, Granulocyte-monocyte
colony-stimulating factor, Interferon-γ)

2. Cytotoxic T cells (killer cells) – is a direct-attack cell that is capable of killing

micro-organisms and, at times, even some of the body’s own cells. The receptor
proteins on the surfaces of the cytotoxic cells cause them to bind tightly to those
organisms or cells that contain the appropriate binding-specific antigen. Then, they
kill the attacked cell. After binding, the cytotoxic T cell secretes holeforming proteins,
called perforins that literally punch round holes in the membrane of the attacked
cell. Then fluid flows rapidly into the cell from the interstitial space. In addition, the
cytotoxic T cell releases cytotoxic substances directly into the attacked cell. Almost
immediately, the attacked cell becomes greatly swollen, and it usually dissolves
shortly thereafter. Also, these cytotoxic killer cells can pull away from the victim cells
after they have punched holes and delivered cytotoxic substances and then move on
to kill more cells

3. Suppressor T cells – are capable of suppressing the functions of both cytotoxic and
helper T cells. It is believed that these suppressor functions serve the purpose of
preventing the cytotoxic cells from causing excessive immune reactions that might
be damaging to the body’s own tissues. For this reason, the suppressor cells are
classified, along with the helper T cells, as regulatory T cells. It is probable that the
suppressor T-cell system plays an important role in limiting the ability of the immune
system to attack a person’s own body tissues, called immune tolerance

Passive Immunity - transfusion of antibodies or T lymphocytes to confer immunity

Undesirable effect of immunity:

Allergy caused by active T-cells: Delayed reaction allergy

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Delayed-reaction allergy is caused by activated T cells and not by antibodies.

In the case of poison ivy, the toxin of poison ivy in itself does not cause much harm to the
tissues. However, on repeated exposure, it does cause the formation of activated helper
and cytotoxic T cells. Then, after subsequent exposure to the poison ivy toxin, within a
day or so, the activated T cells diffuse from the circulating blood in large numbers into
the skin to respond to the poison ivy toxin. And, at the same time, these T cells elicit a
cell-mediated type of immune reaction. Remembering that this type of immunity can
cause release of many toxic substances from the activated T cells as well as extensive
invasion of the tissues by macrophages along with their subsequent effects, one can well
understand that the eventual result of some delayed-reaction allergies can be serious
tissue damage. The damage normally occurs in the tissue area where the instigating
antigen is present, such as in the skin in the case of poison ivy, or in the lungs to cause
lung edema or asthmatic attacks in the case of some airborne antigens.

Allergies in the Allergic Person, who has excess IgE Antibodies

Atopic allergies – are caused by non ordinary response of the immune system. The allergic
tendency is genetically passed from parent to child and is characterized by the presence of
large quantities of IgE antibodies in the blood. These antibodies are called reagins or
sensitizing antibodies to distinguish them from the more common IgG antibodies. When
an allergen (defined as an antigen that reacts specifically with a specific type of IgE reagin
antibody) enters the body, an allergen-reagin reaction lakes place, and a subsequent allergic
reaction occurs.

A special characteristic of the IgE antibodies (the reagins) is a strong propensity to

attach to mast cells and basophils. Indeed, a single mast cell or basophil can bind as many
as half a million molecules of IgE antibodies. Then, when an antigen (an allergen) that has
multiple binding sites binds with several IgE antibodies that are already attached to a mast
cell or basophil, this causes immediate change in the membrane of the mast cell or basophil,
perhaps resulting from a physical effect of the antibody molecules to contort the cell
membrane. At any rate, many of the mast cells and basophils rupture; others release special
agents immediately or shortly thereafter, including histamine, protease, slow-reacting
substance of anaphylaxis (which is a mixture of toxic leukotrienes), eosinophil chemotactic
substance, neutrophil chemotactic substance, heparin, and platelet activating factors. These
substances cause such effects as dilation of the local blood vessels; attraction of eosinophils
and neutrophils to the reactive site; increased permeability of the capillaries with loss of fluid
into the tissues; and contraction of local smooth muscle cells. Therefore, several different
tissue responses can occur, depending on the type of tissue in which the allergen-reagin
reaction occurs.

Different types of allergic reactions:

 Anaphylaxis - When a specific allergen is injected directly into the circulation, the
allergen can react with basophils of the blood and mast cells in the tissues located
immediately outside the small blood vessels if the basophils and mast cells have
been sensitized by attachment of IgE [Link], a widespread allergic
reaction occurs throughout the vascular system and closely associated tissues. This
is called anaphylaxis. Histamine is released into the circulation and causes body-wide
vasodilation as well as increased permeability of the capillaries with resultant marked
loss of plasma from the circulation. An occasional person who experiences this
reaction dies of circulatory shock within a few minutes unless treated with
epinephrine to oppose the effects of the histamine. Also released from the activated
basophils and mast cells is a mixture of leukotrienes called slow-reacting substance
of [Link] leukotrienes can cause spasm of the smooth muscle of the
bronchioles, eliciting an asthma-like attack, sometimes causing death by suffocation.
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 Urticaria - results from antigen entering specific skin areas and causing localized
anaphylactoid reactions. Histamine released locally causes (1) vasodilation that
induces an immediate red flare and (2) increased local permeability of the capillaries
that leads to local circumscribed areas of swelling of the skin within another few
minutes. The swellings are commonly called hives. Administration of antihistamine
drugs to a person before exposure will prevent the hives.

 Hay Fever - the allergen-reagin reaction occurs in the nose. Histamine released in
response to the reaction causes local intranasal vascular dilation, with resultant
increased capillary pressure as well as increased capillary permeability. Both these
effects cause rapid fluid leakage into the nasal cavities and into associated deeper
tissues of the nose; and the nasal linings become swollen and secretory. Here again,
use of antihistamine drugs can prevent this swelling reaction. But other products of
the allergenreagin reaction can still cause irritation of the nose, eliciting the typical
sneezing syndrome.

 Asthma - often occurs in the “allergic” type of person. In such a person, the allergen-
reagin reaction occurs in the bronchioles of the lungs. Here, an important product
released from the mast cells is believed to be the slow-reacting substance of
anaphylaxis, which causes spasm of the bronchiolar smooth muscle. Consequently,
the person has difficulty breathing until the reactive products of the allergic reaction
have been removed.