23 THE IMMUNE SYSTEM
Immunity refers to the immune system’s capacity to protect individuals from disease by recognizing and
eliminating potentially pathogenic (disease-generating) agents, including bacteria, bacterial toxins, viruses,
parasites, and fungi.
The presence in the body of such foreign and abnormal substances induces the immune system to develop an
immune response, a complex series of physiological events that culminates in the destruction and elimination of
Anatomy of the Immune System
Lymphoid tissues: bone marrow, thymus, spleen, lymph nodes, and tonsils, in which leukocytes develop, reside,
and come into contact with foreign materials.
The granulocytes – neutrophils, eosinophils, and basophils – have cytoplasmic granules that contain secretory
The agranulocytes – monocytes and lymphocytes – lack granules.
o Neutrophils, eosinophils, monocytes, macrophages, and dendritic cells are all phagocytes
o Neutrophils release cytokines involved in inflammation.
o Eosinophils’ primary role in the immune system is to defend against parasites by releasing toxic
o Monocytes are phagocytes in the blood, but they differentiate into macrophages in the tissue to
phagocytose tissue foreign matter. There are fixed macrophages and wandering macrophages.
o Lymphocytes are of three major types: B lymphocytes (B cells), T lymphocytes (T cells), and null cells
(lack cell membrane components that are characteristic of B cells and T cells).
o Most null cells are large, granular lymphocytes known as natural killers (NK) cells.
o When B cells contact foreign/abnormal molecules (antigens), they develop into plasma cells, which
o Antibodies (immunoglobulins) are proteins present in the plasma and interstitial fluid that target
specific antigens for destruction.
o T cells do direct damage to foreign or abnormal cells. They contact infected cells, mutant cells, and
transplanted cells and then take several days to develop into active cytotoxic T cells that destroy the
infected or abnormal cells.
o T cells secrete molecules that form pores in the target cell’s membrane. The target cell succumbs to
lysis, a process in which it fills with fluid and bursts.
o NK cells fight viral infections. They limit the production of new viruses in the body.
o NK differ from cytotoxic T cells by exhibiting immediate readiness, which enables them to respond well
before B cells and T cells as an essential part of early immune responses.
MAST CELLS AND DENDRITIC CELLS
o Precursors of mast and dendritic cells are formed in the bone marrow from hematopoietic stem cells.
Circulate freely and mature in the tissue.
o Mast cells: found in skin and mucosal epithelial tissue; secrete histamine.
o Dendritic cells: similar to macrophages in their ability to phagocytose or endocytose pathogens.
o All leukocytes develop from hematopoietic cells (blood-forming) stem cells in the bone marrow. B
lymphocytes also fully mature in the bone marrow.
o T lymphocytes must migrate to the thymus gland before they develop into maturity.
o Central lymphoid tissues: bone marrow and the thymus (as well as the fetal liver) are sites of
o Peripheral lymphoid tissue: spleen, lymph nodes, tonsils, adenoids, appendix, lymph nodules (GI tract),
and regions in the lining of the GI (Peyer’s patches); collections of B cells, T cells, and macrophages.
o Each peripheral lymphoid tissues contains a dense network of cells hat trap microorganisms and foreign
particles. 23 THE IMMUNE SYSTEM
o Spleen collects worn-out erythrocytes from the blood; it is also collecting bloodborne microorganisms
and foreign particles.
o Microorganisms and particles carried in lymph are trapped by lymph node (where lymphatic vessels
o Macrophage and lymphocyte networks of the spleen and lymph nodes filter blood and lymph,
o Tonsils and adenoids trap inhaled particles and microorganisms.
o Appendix, lymph nodules and peyer’s patches trap substances that enter the body in ingested food or
Organization of the Body’s Defenses
Nonspecific defenses: against potentially harmful substances without regard to their precise identity. Operate
before foreign material enters the body, in the form of skin and mucous membranes.
Specific immune responses: highly selective (meaning they target specific substances) and come into pla y after
nonspecific responses have already begun. Mediated by lymphocytes. This response strengthens with each
exposure to a particular offending agent.
Includes physical barriers, inflammation (a complex series of events causing accumulation of proteins, fluid, and
phagocytic cells in an area of tissue that has been injured or invaded by microorganisms), interferons (a family
of related proteins that can induce virus resistance to other cells), complement system ( a group of plasma
proteins that act to lyse foreign cells).
o Skin and mucous membrances.
o Skin consists of an outer epidermis and inner dermis. Epidermis consists of tightly packed epithelial
cells and lacks blood vessels.
o Outermost layer is composed of dead cells and keratin.
o Within the dermis are sebaceous glands, which secrete an acidic oily substance, sebum that inhibits
o Viscous mucus, which bathes the surfaces of exposed epithelia and can trap foreign matter and potential
pathogens. Have ciliated epithelial cells that line the trachea
o Microbial invasion or damage to tissue triggers a complex series of events that rapidly lead to
inflammation of the affected tissue.
o 5 major events: 1) nearby macrophages engulf debris and foreign matter 2) nearby capillaries dilate and
become more permeable to proteins and fluid 3) foreign matter is contained 4) addition leukocytes
migrate into the region 5) recruited leukocytes continue to help clear the infection, mainly by
PHAGOCYTOSIS OF PATHOGENS AND DEBRIS BY NEARBY MACROPHAGES
o Macrophages detect bacteria using receptor proteins. The resulting attachment initiates phagocytosis.
o Also stimulates the macrophages to secrete cytokines, proteins that are secreted by cells in response to
o Cytokines secreted by macrophages contribute to subsequent steps in inflammation.
DILATION AND INCREASED PERMEABILITY OF CAPILLARIES
o Nearby blood vessels dilate. The capillary walls become more permeable.
o Increased blood flow brings additional leukocytes and defensive proteins into the local circulation.
o Increased permeability allows these proteins to move into the tissues.
o Leukocytes that gather in these dilated vessels migrate from the blood into the tissue spaces.
o Vasodilation and increase capillary permeability are induced by histamine released from a variety of
cells in response to injury.
o Histamine 4 characteristic symptoms: redness, swelling, heat, and pain.
o As the capillaries become engorged with blood, the resulting increase in hydrostatic pressure plus the
increased interstitial osmotic pressure that accompanies the leakage of plasma proteins causes fluid to
filter out of the capillaries and into the tissue spaces, resulting in edema. 23 THE IMMUNE SYSTEM
o The edema exerts pressure against the surrounding tissue and skin, which contributes to pain (pain-
inducing chemical, bradykinin)
o Even though these vascular changes bring discomfort, they help gather nonspecific defenses to the site
CONTAINMENT OF FOREIGN MATTER
o Mast cells and basophils release anticoagulant heparin (suspends blood clotting and allows leukocytes
to get into injured tissues).
o Clotting factors become active and form clots around clusters of bacteria, inhibiting spread.
o Other plasma proteins and proteins released from damaged tissue aid process of clot formation.
o Portion of the clot that is at the skin’s surface dries and hardens, hence a scab which will get replaced
with new cells.
LEUKOCYTE MIGRATION AND PROLIFERATION
o After an hour neutrophils accumulate in great numbers within the affected tissue.
o Ten hours later, monocytes begin to move to the tissue, where they develop into large, active
o Signaling that tells leukocytes to move through blood vessel walls is achieved by margination,
attachment, diapedesis, and chemotaxis.
o Margination: weak interaction of leukocytes with endothelial cells lining the blood vessel near the site of
injury. Cytokines released to signal endothelial cells to express adhesion molecules (selectins); loosely
bind to leukocytes in the blood. Leukocytes also receive signals from other cytokines to get other
adhesion molecules called integrins that bind cells tightly to blood vessel wall.
o Attachment: soon followed by the cell’s transit across the wall, known as diapedesis (jump across).
Leukocyte crawls between endothelial cells of the blood vessel wall through and through the basement
o Chemotaxis: once at the point of injury, chemicals released from the bacteria and injured tissues attract
leukocytes. The phagocytic leukocytes are now at the original site of injury and bacteria invasion.
o A common sign of bacterial infection is leukocytosis, a 4-5fold increase in the number of circulating
neutrophils. Reason: cytokines secreted by macrophages eventually reach the bone marrow (stimulate
proliferation of neurotrophils to be rel