a.

Antigens are any foreign molecules specifically recognized by lymphocytes which

trigger an immune response in the body (frequently protein but not always). Antigens
may enter the body from the environment (for example, through inhalation or ingestion)
or may be generated within the cells of the body (for example, aberrant proteins encoded
by mutant genes of cancerous cells). Antigens contain epitopes (antigenic
determinants) are variable regions on the antigen capable of inducing specific
recognition by antibodies that bind to these variable sites. These epitopes help
lymphocytes (such as B-cells, helper T-cells, and Cytotoxic T-cells) mark these antigens as
non-self and trigger a subsequent rejection by the immune system.

In a skin graft, antigens on the site of the new skin cells (glycoproteins involved in cell-
to-cell recognition or other molecules) may trigger antibody production by plasma cells or
T-cells, which may lead to subsequent rejection of the graft. MHC molecules are
responsible for activating the immune response to most tissue grafts. Alien MHC molecules
may be recognized and marked as non-self, which leads to rejection of the graft. Unless
the MHC molecules of the donor and recipient are well-matched, the rejection reaction
occurs, and leads to unsuccessful transplantation.

Antibodies (also called immunogloulins, abbreviated Ig), are proteins produced by

plasma cells (undifferentiated B-cells) which bind to antigens and marks antigens for
elimination, thus inactivating foreign particles. Antibodies are composed of heavy chains
and light chains joined by disulfide bridges. Antibodies also include an antigen-binding site
(variable region) specific to epitopes on the antigen.

The diversity of antibodies is due to genes and Clonal selection: antigen-driven cloning of
lymphocytes “Each antigen, by binding to specific receptors, selectively activates a tiny
fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number
of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to
eliminating the antigen.”

Antibodies of the B/T cells: Antigens (w/ epitopes):

Plasma cells produce 5 types of antibody proteins:

IgG is the most abundant antigen and is able to cross the placenta and the walls of blood
vessels. IgG confers passive immunity to the fetus and may be involved in Rh
complications. (In Rh complications, a Rh positive fetus passes some IgG antibodies to the
Rh negative mother through the placenta, and the mother develops immunity toward
them, leading to rejection of the fetus by the mother; fortunately, Rh complications can be
lessened with the help of anti-Rh proteins that momentarily supress the mother's immune
system).

IgA is produced by cells in mucous membranes and prevents the attatchment of

viruses/bacteria to epithelial surfaces; IgA is also found in saliva, tears, and perspiration.
IgM indicates infection and is too large to cross the placenta.

IgD does not activate complement and does not cross the placenta. IgD is found on
the surfaces of B cells and probably helps in the differentiation of B cells into plasma and memory
cells.

IgE is a very large antibody and is released in small quantities. IgE triggers histamines
involved in allergic reactions.

Antibodies have five ways of inactivating antigens: Viral neutralization, whereby an antigen
prevents a virus from binding to it's host; Opsonization, which increases phagocytosis;
Agglutinization of antigen-bearing particles such as microbes , Precipitation of soluble
antigens, all of which increase the effectiveness of Phagocytosis, and finally Activation of the
complement system and pore formation which leads to cell lysis of infected cells.

Effector cells and Memory cells may also play an important role in immune response.
Effector cells are short-lived cells that combat the antigen. Memory cells are long-lived
cells that bear receptors for the antigen and circulate in the blood stream long after the
infection/immune response has ceased, lying dormant in wait for the next antigen attack.
Opposed to the primary immune response, lymphocyte proliferation and differentiation the
first time the body is exposed to an antigen, memory cells lead to a quicker secondary
immune response the next time an individual is exposed to the same antigen. The
primary immune response and memory cells help develop an individual’s immunological
memory, so that if the skin graft was rejected, it would probably be rejected if a second
grafting attempt was undertaken.
Antibodies combine with Antigens in the Antigen-Combining site. (determined genetically)

Our body contains many nonspecific lines of defense

In Primary Immune Response, B-cells may be activated in a Humoral response or

Cytotoxic T-cells may be activated in a Cell-mediated response. Both reactions produce
memory B and T cells which persist and aid in secondary immune response.
 • Helper T lymphocytes function in both humoral & cell-mediated immunity. Helper T
cells are stimulated by antigen presenting cells (APCs) and secrete Cytokines to
stimulate other lymphocytes like interleukin-2 (IL-2) which activates B cells and
cytotoxic T cells and interleukin-1 (IL-1): activates helper T cell to produce IL-2. These
interleukins are involved in positive feedback since interleukins further increase the
activity of helper T cells to stimulate other cells.

In
In

Humoral immunity: B cells are activated and produce antibodies which defend against
bacteria, toxins, and viruses free in the lymph and blood plasma.

• B cells are stimulated by T-dependent antigens. In humoral immunity,

Macrophages (antigen presentation complexes) with class II MHC proteins
 stimulated Helper T cells with CD4 protein. The activated T cell with CD4 protein
secretes cytokines which activate the B cell. The B cell then differentiates into
memory and plasma B cells which produce antibodies to destroy foreign antigens.
•
Humoral Response:
 •
•
•
In Cell-mediated immunity, Cytotoxic T-cells are activated and bind to or lyse cells.
Activated Cytotoxic T-cells defend against cells infected with bacteria, viruses, fungi,
protozoa, and parasites; nonself interaction.

• In Cell-mediated response, cytotoxic T cells destroy cells that have been infected
by intracellular pathogens and cancer cells. Cytotoxic T cells are activated by Class
I MHC molecules (nucleated body cells) which expose foreign proteins, and the
binding activity is enhanced by CD8 surface protein present on most cytotoxic T
cells.
• To destroy foreign antigens/invaders, the cytotoxic T cell releases perforin, a
protein that forms pores in the target cell membrane, and leads to cell lysis.

Cell-mediated Response:
 •

b. The inflammatory response is also characterized by redness and swelling of the

affected site, due to vasodilation (histamine) and increased temperature (pyrogens).

Swelling of the site of tissue injury is caused by the release of chemical signals which
trigger the release of histamine from basophils and mast cells. The release of
histamine causes the release of prostaglandins which increases blood flow & vessel
permeability. This increased permeability of the capillaries surrounding the wound leads to
vasodilation, Increased blood flow allows phagocytotic migration of White Blood Cells to
the affected site which is mediated by chemokines secreted by blood vessel endothelial
cells. which increases the flow of macrophages, and other leukocytes to the site of injury.
The leukocytes (white blood cells, including neutrophils, basophils, eosinophils,
monocytes) invade the infection site and destroy bacteria or wall off the site.

Heat (and perhaps fever) is caused by pyrogens, leukocyte-released molecules which

increase body temperature. Raised temperature at the affected site also helps impede
bacterial infection by denaturing some of their proteins/enzymes.

At the site of injury, white blood cells, dead cells, and fibin proteins conglomerate to form
a clot that seals the wound.

Formation of the clot:

The wound is sealed by blood clotting, caused by platelets and fibrin proteins

Thromboplastin and Ca2+ convert Prothrombin to Thrombin.

Thrombin converts Fibrinogin to Firbin

(From Wikipedia: Fibrin is “fibrillar protein that is polymerised to form a "mesh" that forms
a hemostatic plug or clot (in conjunction with platelets) over a wound site.”)

Fibrin: