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Chapter 15 Introduction to the

Immune Response and Inflammation


BODY DEFENSES - Genetic information code is carried on a
I. Barrier Defenses chromosome and is called the major
- Certain anatomical barriers exist to: histocompatibility complex
 prevent the entry of foreign pathogens - MHC contains histocompatibility antigens or
 to serve as important lines of defense in human leukocyte antigens (HLAs)
protecting the body - The antigens (proteins) are located on cell
membrane and allow body to recognize cells as
a. Skin being self-cells
- First line of defense - Cells without these proteins are identified as
- Physical barrier to protect internal tissues and foreign and are targeted for destruction
organs
- Glands secrete chemicals to destroy pathogens II. Cellular Defenses
- Top layer of skin falls off daily, making it difficult - Foreign pathogens that manage to get past
for pathogens to colonize skin barrier defences will encounter human
- Normal bacterial flora help destroy disease- inflammatory and immune systems, or
causing pathogens mononuclear phagocyte system (MPS)
- Previously called reticuloendothelial system
b. Mucous membranes - Composed primarily of leukocytes, lymphocytes,
- Line areas of the body that are exposed to lymphoid tissues, and chemical mediators
external influences but do not have the benefit of - Stem cells in bone marrow produce 2 types of
skin protection WBC or leukocytes
- Respiratory tract (exposed to air), GI tract o Lymphocytes – key components of
(exposed to anything ingested by mouth), GU immune system; consist of T cells, B cells,
tract (exposed to pathogens from perineal and and natural killer cells
rectal area o Myelocytes – develop into different cell
- Secreted sticky mucus capable of trapping types that are important for basic
invaders and inactivating them for destruction and inflammatory and immune response;
removal includes neutrophils, basophils,
- Lined with tiny, hair-like processes called cilia that eonsinophils, and
sweep any captured pathogen monocytes/macrophages
- In GI tract, mucous membrane serves as protective
coating, preventing erosion of GI cells by acidic a. Neutrophils
environment of the stomach - Polymorphonuclear leukocytes
- Also secreted mucous that serves as lubricant for - Capable of moving outside of the blood stresm
movement of food bolus and waste products (diapedesis) and engulfing and digesting foreign
- Acts as thick barrier to prevent foreign pathogens material (phagocytosis)
from penetrating GI tract and entering the body - Rapidly produced when body is injured or
invaded by a pathogen, and move to site of injury
c. Gastric acid to attack foreign substance
- Acid secreted by stomach in response to stimuli - Called phagocytes
- Aids digestion, destroys would-be pathogens that - Able to identify non-self cells by use of the MHC
are ingested or swallowed after removal from the - Can engulf non-self cells or mark them for
respiratory tract destruction by cytotoxic T lymphocytes

d. Major histocompatibility complex b. Basophils


- Last barrier of defense - Myelocytic leukocytes
- Ability to distinguish between self-cells and foreign - Not capable of phagocytosis
cells - Contains chemical substances or mediators that
are important for initiating and maintaining an

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immune or inflammatory response (histamine, o Plasminogen system – initiates dissolution
heparin, etc) of blood clots
- Mast cells – basophils that are fixed and do not [Last 2 systems are discussed in Part VIII]
circulate; found in respiratory tract, GI tract, and a. Kinin system
skin; stimulated by local irritation - Hageman factor activates kallikrein, a substance
found in the local tissues, which causes the
c. Eosinophils precursor substance kininogen to be converted to
- Circulating myelocytic leukocytes bradykinin and other kinins
- Exact function is not understood - Bradykinin caused local vasodiation
- Often found at site of allergic reaction o Brings more blood to the injured area
- May be responsible for removing proteins and o Allows WBC to escape into tissues
active components of the immune reaction from o Stimulates nerve endings to cause pain,
the site of an allergic response alerting the body to injury
- Bradykinin also causes release of arachidonic
d. Monocytes/Macrophages acid from cell membrane
- Mononuclear phagocytes o Causes release of autacoids
- Mature leukocytes capable of phagocytizing an  Acts like local hormones
antigen  Released from cells, cause effect in
- Help remove foreign material from the body so immediate area, then broken down
the body can heal  Includes:
- Can also process antigens and present them to  Prostaglandins – some augment the
active lymphocytes for destruction inflammatory reaction, some block it
- Can circulate in blood stream or can be fixed in  Leukotrienes – some cause
specific tissue vasodilation and increased capillary
- Release chemicals necessary to elicit a strong permeability, some block it
inflammatory reaction  Thromboxanes – cause local
- Also respond to chemical mediators released by vasoconstriction and facilitate
other cells to increase intensity of a response and platelet aggregation and blood
facilitate body’s reaction coagulation

b. Histamine release
e. Lymphoid tissues - Occurs while Hageman factor-initiated events are
- Includes lymph nodes, spleen, thymus gland, proceeding
bone marrow, and lymphoid tissue throughout - Release is caused by injury to a cell membrane
respiratory and GI tracts - Histamine causes vasodilation
- Bone marrow and thymus gland are important in o Brings more blood and blood
creating cellular components of the MPS components to the area
- Bone marrow has a role in differentiation of the T - Also alters capillary permeability
cells and regulating the actions of the immune o Neutrophils and blood chemicals leave
system bloodstream and enter injured area
- Lymph nodes and lymphoid tissue store - Stimulates pain perception
concentration populations of neutro-, baso-, - Brings neutrophils to the area and engulf and get
eosinophils, and lymphocytes in areas of the body rid of the invader or to remove the injured cell
that facilitate their surveillance for and destruction
of foreign proteins c. Chemotaxis
- Ability to attract neutrophils and to stimulate then
III. Inflammatory Response and other macrophages in the area to be very
- Local reaction of the body to invasion or injury aggressive
- Cell injury causes the activation of a chemical in - Property of some leukotrienes activated by
the plasma called factor XII or Hageman factor arachidonic acid
- Hageman factor is responsible for activating at - Activation of neutrophils and release of other
least 3 systems in the body: chemicals can lead of cell injury and destruction
o Kinin system - When destroyed, the cell releases various
o Clotting cascade – initiates blood clotting lysosomal enzymes that dissolve or destroy cell
membranes and proteins
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- Lysosomal enzymes are important in biological ii. Helper T cells
recycling and breakdown of one-living tissues o Respond to chemical indicators of
after death immune activity
- They can cause local cellular breakdown and o Stimulate other lymphocytes to be more
further inflammation aggressive and responsive
o Develops into cycle leading to cell death
iii. Suppressor T cells
d. Clinical presentation o Respond to rising levels of chemicals
o Calor / Heat – occurs due to increased associated with an immune response to
blood flow to area suppress or sow the reaction
o Tumor / Swelling – occurs due to fluid o Balance of helper and suppressor T cells
that leaks into the tissues as a result of the allow for rapid response to body injury or
change in capillary permeability invasion
o Rubor / Redness – related again to o Allows body to conserve energy and
increase in blood flow caused by components
vasodilation
o Dolor / Pain – comes from activation of b. B Cells
pain fibers by histamine and the kinin - Found throughout MPS in groups called clones
system - Programmed to identify specific proteins or
- Once neutrophils become active, they release a antigens
chemical that is a natural pyrogen, or fever- - Changes into a plasma cell when it reacts with a
causing substance specific antigen
- Pyrogen resets neurons in hypothalamus to o Produces antibodies or immunoglobulins
maintain higher body temperature to act as which circulate and react with this
catalyst to many of the body’s chemical reactions, specific antigen when it is encountered
making inflammatory and immune responses more o When antigen and antibody react, they
effective form antigen-antibody complex which
- Leukotrienes affect brain to induce slow-wave reveals a new receptor site on the
sleep, which is an energy conservation measure antibody that activates a series of plasma
for fighting the invader proteins in the body called complement
o Also causes myalgia and arthralgia proteins
(muscle and joint pain)
c. Complement proteins
IV. Immune Response - React in cascade fashion to form a ring around
- Stimulated by more specific invasion the antigen-antibody complex
- Can destroy the antigen by altering membrane,
a. T Cells allowing osmotic inflow of fluid that causes cell to
- Programmed in the thymus gland burst
- Provides cell-mediated immunity - Also induces chemotaxis, increasing activity of
phagocytes, and release histamine
i. Effector or Cytotoxic T cells
o found throughout the body d. Antibody formation
o aggressive against self-cells, releasing - Aka acquired or active immunity
cytokines or chemicals that directly - Lifelong reaction
destroy a foreign cell of mark is for - Initial formation of antibodies, or primary
destruction by phagocytes via response, takes several days
inflammatory response - Activated B cell form memory cells that will
o Has membrane-identifying antigens produce antibodies for immediate release in the
different from those established by future if antigen is encountered
person’s MHC - Antibodies are released in the form of
o May be body’s own cells invaded by a immunoglobulins
virus
i. IgM – contains antibodies produced at the
first exposure to the antigen

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ii. IgG contains antibodies made by the - Activates cellular immunity or the immune system’s
memory cells that circulate and enter tissue; response is mild or absent
mostly found in serum
iii. IgA – secreted in plasma cells in GI,  Autoimmune disease
respiratory tract, and epithelial cells; react - Occurs when the body responds to specific self-
with specific pathogens encountered in antigens to produce antibodies or cell-mediated
exposed areas; found in tears, saliva, immune responses against its own cells
sweat, mucus, bile - Speculations:
iv. IgE – present in small amounts, related to o A result of response to a cell that was
allergic responses and the activation of mast invaded by a virus, leading to antibody
cells production to similar cells;
v. IgD – role is not determined o Production of autoantibodies is a normal
process that goes on all the time, but in a
e. Other mediators state of immunosuppression, the
- Interferons suppressor T cells do not suppress
o Chemicals secreted by cells that have autoantibody production; or
been invaded by viruses and possibly by o There is a genetic predisposition to
other stimuli develop autoantibodies
o Prevent viral replication and suppress  Transplant rejection
malignant cell replication and tumor - Self-transplantation, or auto transplantation, results
growth in no immune response
- Interleukins - All other transplants produce an immune reaction
o Chemicals secreted by active leukocytes - Matching a donor’s HLA markers as closely as
to influence other leukocytes possible to those of the recipient for
 IL-1 – stimulated T and B cells to histocompatibility is essential
initiate immune response o The more closely the foreign cells can be
 IL-2 – released from active T cells matched, the less aggressive will the
to stimulate the production of immune reaction be to the donated tissue
more T cells and to increase the
activity of B cells, cytotoxic cells,
and natural killer cells

V. Interrelationship of the immune and inflammatory


responses
- Work together to protect the body and to
maintain a level of homeostasis within the body
- Helper T cells stimulate the activity of B cells and
effector T cells.
- Suppressor T cells monitor the chemical activity in
the body and act to suppress B-cell and T-cell
activity when the foreign antigen is under control.
- Both B cells and T cells ultimately depend on an
effective inflammatory reaction to achieve the end
goal of destruction of the foreign protein or cell

PATHOPHYSIOLOGY INVOLVING THE IMMUNE SYSTEM


 Neoplasms
- Occur when mutant cells escape the normal
surveillance of the immune system and begin to
grow and multiply

 Viral invasion of cells


- Alters the cell membrane and the antigenic
presentation of the cell (the MCH)

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