CHAPTER 7
Human Defense Mechanisms
1. Innate defenses are the first line of defense, are present at birth, and include the surface barriers skin and
mucous membranes.
2. Inflammation is the second line of defense and is activated with injury or infectious disease.
3. Adaptive (acquired) immunity is the third line of defense, is specific to particular antigens, and has
memory.
Innate Immunity
1. There are three layers of human defense: physiologic barriers, the inflammatory response, and adaptive
(acquired) immunity.
2. Physical barriers are the first lines of defense functioning to prevent damage to the individual and thwart
the entrance of pathogens. These barriers include the skin and mucous membranes.
3. Antibacterial peptides are found in mucous secretions, per- spiration, saliva, tears, and other secretions.
They provide a biochemical barrier against pathogenic microorganisms.
4. The skin, mucous membranes, and the lining of the gastrointestinal (GI) tract are colonized by commensal
or mutualistic microorganisms called the microbiome. These microorganisms provide protection by
releasing biochemical compounds which facilitate immune responses and prevent colonization by
pathogens. Within the gut, they also facilitate digestion in the GI tract.
5. The second line of defense is the inflammatory response, a rapid and nonspecific protective response to
cellular injury resulting from any cause. It can occur only in vascularized tissues.
6. Inflammation is mediated by three key plasma protein systems: the complement system, the clotting
system, and the kinin system. The components of all three systems are a series of inactive proteins which are
activated sequentially in the presence of tissue injury.
7. The complement system can be activated by antigen–anti- body reactions (through the classical pathway)
or by other products, especially bacterial polysaccharides (through the lectin pathway or the alternative
pathway). The lectin and alternative pathways do not require antibody activation to recruit phagocytes,
activate mast cells, and destroy pathogens.
Summary Review
e11
e12
Summary Review
, 8. The most biologically potent products of the complement system are C3b (opsonin), C3a
(anaphylatoxin), and C5a (anaphylatoxin, chemotactic factor).
9. The clotting system stops bleeding, localizes microorganisms, and provides a meshwork for repair
and healing.
10. Bradykinin is the most important product of the kinin system and causes vascular permeability,
smooth muscle con- traction, and pain.
11. Control of inflammation regulates inflammatory cells and enzymes and localizes the inflammatory
response to the area of injury or infection.
12. Carboxypeptidase, histaminase, kinase, and C1 inhibitor are inactivating enzymes. The fibrinolytic
system and plasmin facilitate clot degradation after bleeding is stopped.
13. Mast cells and macrophages are the most important cells for initiating the inflammatory response.
14. These cells express plasma membrane pattern recognition receptors (PRRs) which recognize
molecules produced by infectious microorganisms. These molecules include pathogen-associated
molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Toll- like
receptors (TLRs) are transmembrane receptors and nucleotide-binding-like receptors (NLR-like), and
nucleotide oligomerization domain-like (NOD-like) receptors are cytoplasmic receptors. They are
expressed by many inflammatory cells and recognize both PAMPs and DAMPs. Upon recognition,
they promote the release of cytokines and inflammatory mediators, which, in turn, eliminate
damaged cells and protect against invasion by microbes.
15. Mast cells are near epithelial surfaces and capillaries. Mast cells initiate inflammation by releasing
biochemical media- tors (histamine and chemotactic factors) from cytoplasmic granules. They also
synthesize other mediators (prostaglandins, leukotrienes, and platelet-activating factor [PAF]) in
response to stimuli. Basophils, found in blood, function in a manner that is similar to mast cells.
16. Histamine is the major vasoactive amine released from mast cells. It increases vascular
permeability through dilation of capillaries and retraction of endothelial cells lining the capillaries.
17. Tissue macrophages use PRRs to identify microorganisms and molecules from damaged tissue, and
then secrete many biochemical mediators (cytokines), which are responsible for activating other
cells and regulating the inflammatory response. These cytokines include TNF-α, interleukins,
interferons, and other molecules.
18. TNF-α is produced when PRR binding sends intracellular messengers to the nucleus of the
macrophage which activates NF-κB. TNF-α has multiple pro-inflammatory effects including vascular
effects, chemotaxis, cellular proliferation, and systemic inflammatory changes.
19. Interleukins are produced primarily by lymphocytes and macrophages. They activate the growth and
differentiation of leukocytes and contribute to systemic inflammatory changes such as fever.
20. The most important proinflammatory interleukins are interleukin-1 (IL-1) and interleukin-6.
21. Interferons are produced by cells that are infected by viruses. Once released from infected cells,
interferons can stimulate neighboring healthy cells to produce substances that prevent viral infection.
22. There are also anti-inflammatory cytokines such as TGF-β and IL-10 which downregulate the
inflammatory response. 23. The vascular responses to inflammation are vasodilation, increased capillary
permeability, and an accumulation of fluid and cells at the inflammatory site.
24. The cellular response to inflammation includes neutrophils, monocyte-derived macrophages, and other
inflammatory cells.
,25. The endothelial cells lining the circulatory system (vascular endothelium) regulate circulating
components of the inflammatory system, maintaining normal blood flow. During inflammation, the
endothelium expresses receptors that stimulate leukocytes to exit the vessel. The endothelial cell body also
retracts to allow fluid to pass into the tissues.
26. The polymorphonuclear neutrophil (PMN), the predominant phagocytic cell in the early inflammation,
exits the circulation, through retracted endothelial junctions, by diapedesis. On exiting, it moves to the
inflammatory site by chemotaxis.
27. The monocyte-derived macrophage, the predominant cell in the late inflammatory response, is highly
phagocytic. Additionally, it is responsive to cytokines, which promote wound healing.
28. Phagocytosis is a multistep cellular process, which usually results in the destruction of pathogens and
foreign debris. The steps include recognition and attachment, engulfment, formation of a phagosome,
formation of a phagolysosome, and eventual destruction of the pathogen or foreign debris. Phagocytic cells
engulf microorganisms, enclosing them within phagocytic vacuoles (phagolysosomes). The vacuoles contain
toxins (especially metabolites of oxygen) and/ or enzymes that kill and digest the microorganisms.
29. Opsonins are molecules which enhance phagocytosis by coating the antigen. This activity results in a
stronger attraction between the microorganism and the phagocyte (“marking” the organism). It also
enhances the affinity with which the phagocyte binds to the microorganism. Examples include antibodies
and the complement component C3b.
30. Eosinophils release products that control the inflammatory response, and they are the principal cells that
destroy parasitic organisms.
31. Other cells of innate immunity include dendritic cells which function as messengers between the innate
and acquired (adaptive) immune systems, NK cells which detect certain invaders and cancer cells, and
innate lymphoid cells which modulate many aspects of innate immunity.
Acute and Chronic Inflammation
1. Acute inflammation is self-limiting and usually resolves within 8 to 10 days.
Summary Review
2. Local manifestations of inflammation include the classic signs of redness, heat, swelling, pain, and
loss of function. They are the result of vascular changes associated with the inflammatory process,
including vasodilation and increased capillary permeability.
3. The principal systemic effects of inflammation are fever, leukocytosis (increased levels of circulating
leukocytes), and an increase in plasma proteins, primarily the acute-phase reactants, IL-1, and IL-6.
4. Chronic inflammation is the persistence of the inflammatory response often contributing to tissue
damage.
5. Chronic inflammation is characterized by a dense infiltration of lymphocytes and macrophages. It
can take two forms, nonspecific proliferative chronic inflammation and granulomatous chronic
inflammation.
, 6. Nonspecific proliferative chronic inflammation occurs when the acute inflammatory response fails
to eliminate the invader/injury or there is dysfunctional resolution of the acute inflammatory
response.
7. Granuloma formation is a process wherein the body walls off and isolates certain infectious
microorganisms or foreign bodies that could not be removed by acute inflammation. It serves to
protect the body from further tissue damage.
8. Both forms of chronic inflammation can contribute to tissue dysfunction and organ damage and are
the major causes of chronic disease.
Wound Healing
1. Resolution (regeneration) is the return of tissue to nearly normal structure and function. Repair is
healing by scar tis- sue formation.
2. Resolution occurs when little tissue has been lost or where the injured tissue is capable of
regeneration. This type of healing is called healing by primary intention.
3. Tissues that have sustained extensive damage or tissue types that are incapable of regeneration heal
by repair, a process which results in the formation of a scar. This process is called healing by
secondary intention.
and killing of microorganisms and limited complement activity.
2. Aging impairs the immune system due to a process called immunosenescence which causes impairment
of cellular function in both immunity and wound healing.
3. Impaired wound healing in the aging population is multi- factorial and includes changes in innate
immunity, cellular metabolism, and tissue integrity.
4. The elderly are also at risk for excessive and disordered innate immune responses called inflammaging
that contribute to many chronic diseases.
CHAPTER 8
Overview of Adaptive Immunity
1. Adaptive immunity is a state of protection, primarily against infectious agents, that differs from
inflammation by being slower to develop, being more specific, and having memory that makes it much longer
lived.
2. The adaptive immune response is most often initiated by cells of the innate system. These cells process
and present portions of invading pathogens (i.e., antigens) to lymphocytes in peripheral lymphoid tissue.
3. The adaptive immune response is mediated by two types of lymphocytes—B lymphocytes and T
lymphocytes. Each has distinct functions. B cells are responsible for humoral immunity that is mediated by
Human Defense Mechanisms
1. Innate defenses are the first line of defense, are present at birth, and include the surface barriers skin and
mucous membranes.
2. Inflammation is the second line of defense and is activated with injury or infectious disease.
3. Adaptive (acquired) immunity is the third line of defense, is specific to particular antigens, and has
memory.
Innate Immunity
1. There are three layers of human defense: physiologic barriers, the inflammatory response, and adaptive
(acquired) immunity.
2. Physical barriers are the first lines of defense functioning to prevent damage to the individual and thwart
the entrance of pathogens. These barriers include the skin and mucous membranes.
3. Antibacterial peptides are found in mucous secretions, per- spiration, saliva, tears, and other secretions.
They provide a biochemical barrier against pathogenic microorganisms.
4. The skin, mucous membranes, and the lining of the gastrointestinal (GI) tract are colonized by commensal
or mutualistic microorganisms called the microbiome. These microorganisms provide protection by
releasing biochemical compounds which facilitate immune responses and prevent colonization by
pathogens. Within the gut, they also facilitate digestion in the GI tract.
5. The second line of defense is the inflammatory response, a rapid and nonspecific protective response to
cellular injury resulting from any cause. It can occur only in vascularized tissues.
6. Inflammation is mediated by three key plasma protein systems: the complement system, the clotting
system, and the kinin system. The components of all three systems are a series of inactive proteins which are
activated sequentially in the presence of tissue injury.
7. The complement system can be activated by antigen–anti- body reactions (through the classical pathway)
or by other products, especially bacterial polysaccharides (through the lectin pathway or the alternative
pathway). The lectin and alternative pathways do not require antibody activation to recruit phagocytes,
activate mast cells, and destroy pathogens.
Summary Review
e11
e12
Summary Review
, 8. The most biologically potent products of the complement system are C3b (opsonin), C3a
(anaphylatoxin), and C5a (anaphylatoxin, chemotactic factor).
9. The clotting system stops bleeding, localizes microorganisms, and provides a meshwork for repair
and healing.
10. Bradykinin is the most important product of the kinin system and causes vascular permeability,
smooth muscle con- traction, and pain.
11. Control of inflammation regulates inflammatory cells and enzymes and localizes the inflammatory
response to the area of injury or infection.
12. Carboxypeptidase, histaminase, kinase, and C1 inhibitor are inactivating enzymes. The fibrinolytic
system and plasmin facilitate clot degradation after bleeding is stopped.
13. Mast cells and macrophages are the most important cells for initiating the inflammatory response.
14. These cells express plasma membrane pattern recognition receptors (PRRs) which recognize
molecules produced by infectious microorganisms. These molecules include pathogen-associated
molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Toll- like
receptors (TLRs) are transmembrane receptors and nucleotide-binding-like receptors (NLR-like), and
nucleotide oligomerization domain-like (NOD-like) receptors are cytoplasmic receptors. They are
expressed by many inflammatory cells and recognize both PAMPs and DAMPs. Upon recognition,
they promote the release of cytokines and inflammatory mediators, which, in turn, eliminate
damaged cells and protect against invasion by microbes.
15. Mast cells are near epithelial surfaces and capillaries. Mast cells initiate inflammation by releasing
biochemical media- tors (histamine and chemotactic factors) from cytoplasmic granules. They also
synthesize other mediators (prostaglandins, leukotrienes, and platelet-activating factor [PAF]) in
response to stimuli. Basophils, found in blood, function in a manner that is similar to mast cells.
16. Histamine is the major vasoactive amine released from mast cells. It increases vascular
permeability through dilation of capillaries and retraction of endothelial cells lining the capillaries.
17. Tissue macrophages use PRRs to identify microorganisms and molecules from damaged tissue, and
then secrete many biochemical mediators (cytokines), which are responsible for activating other
cells and regulating the inflammatory response. These cytokines include TNF-α, interleukins,
interferons, and other molecules.
18. TNF-α is produced when PRR binding sends intracellular messengers to the nucleus of the
macrophage which activates NF-κB. TNF-α has multiple pro-inflammatory effects including vascular
effects, chemotaxis, cellular proliferation, and systemic inflammatory changes.
19. Interleukins are produced primarily by lymphocytes and macrophages. They activate the growth and
differentiation of leukocytes and contribute to systemic inflammatory changes such as fever.
20. The most important proinflammatory interleukins are interleukin-1 (IL-1) and interleukin-6.
21. Interferons are produced by cells that are infected by viruses. Once released from infected cells,
interferons can stimulate neighboring healthy cells to produce substances that prevent viral infection.
22. There are also anti-inflammatory cytokines such as TGF-β and IL-10 which downregulate the
inflammatory response. 23. The vascular responses to inflammation are vasodilation, increased capillary
permeability, and an accumulation of fluid and cells at the inflammatory site.
24. The cellular response to inflammation includes neutrophils, monocyte-derived macrophages, and other
inflammatory cells.
,25. The endothelial cells lining the circulatory system (vascular endothelium) regulate circulating
components of the inflammatory system, maintaining normal blood flow. During inflammation, the
endothelium expresses receptors that stimulate leukocytes to exit the vessel. The endothelial cell body also
retracts to allow fluid to pass into the tissues.
26. The polymorphonuclear neutrophil (PMN), the predominant phagocytic cell in the early inflammation,
exits the circulation, through retracted endothelial junctions, by diapedesis. On exiting, it moves to the
inflammatory site by chemotaxis.
27. The monocyte-derived macrophage, the predominant cell in the late inflammatory response, is highly
phagocytic. Additionally, it is responsive to cytokines, which promote wound healing.
28. Phagocytosis is a multistep cellular process, which usually results in the destruction of pathogens and
foreign debris. The steps include recognition and attachment, engulfment, formation of a phagosome,
formation of a phagolysosome, and eventual destruction of the pathogen or foreign debris. Phagocytic cells
engulf microorganisms, enclosing them within phagocytic vacuoles (phagolysosomes). The vacuoles contain
toxins (especially metabolites of oxygen) and/ or enzymes that kill and digest the microorganisms.
29. Opsonins are molecules which enhance phagocytosis by coating the antigen. This activity results in a
stronger attraction between the microorganism and the phagocyte (“marking” the organism). It also
enhances the affinity with which the phagocyte binds to the microorganism. Examples include antibodies
and the complement component C3b.
30. Eosinophils release products that control the inflammatory response, and they are the principal cells that
destroy parasitic organisms.
31. Other cells of innate immunity include dendritic cells which function as messengers between the innate
and acquired (adaptive) immune systems, NK cells which detect certain invaders and cancer cells, and
innate lymphoid cells which modulate many aspects of innate immunity.
Acute and Chronic Inflammation
1. Acute inflammation is self-limiting and usually resolves within 8 to 10 days.
Summary Review
2. Local manifestations of inflammation include the classic signs of redness, heat, swelling, pain, and
loss of function. They are the result of vascular changes associated with the inflammatory process,
including vasodilation and increased capillary permeability.
3. The principal systemic effects of inflammation are fever, leukocytosis (increased levels of circulating
leukocytes), and an increase in plasma proteins, primarily the acute-phase reactants, IL-1, and IL-6.
4. Chronic inflammation is the persistence of the inflammatory response often contributing to tissue
damage.
5. Chronic inflammation is characterized by a dense infiltration of lymphocytes and macrophages. It
can take two forms, nonspecific proliferative chronic inflammation and granulomatous chronic
inflammation.
, 6. Nonspecific proliferative chronic inflammation occurs when the acute inflammatory response fails
to eliminate the invader/injury or there is dysfunctional resolution of the acute inflammatory
response.
7. Granuloma formation is a process wherein the body walls off and isolates certain infectious
microorganisms or foreign bodies that could not be removed by acute inflammation. It serves to
protect the body from further tissue damage.
8. Both forms of chronic inflammation can contribute to tissue dysfunction and organ damage and are
the major causes of chronic disease.
Wound Healing
1. Resolution (regeneration) is the return of tissue to nearly normal structure and function. Repair is
healing by scar tis- sue formation.
2. Resolution occurs when little tissue has been lost or where the injured tissue is capable of
regeneration. This type of healing is called healing by primary intention.
3. Tissues that have sustained extensive damage or tissue types that are incapable of regeneration heal
by repair, a process which results in the formation of a scar. This process is called healing by
secondary intention.
and killing of microorganisms and limited complement activity.
2. Aging impairs the immune system due to a process called immunosenescence which causes impairment
of cellular function in both immunity and wound healing.
3. Impaired wound healing in the aging population is multi- factorial and includes changes in innate
immunity, cellular metabolism, and tissue integrity.
4. The elderly are also at risk for excessive and disordered innate immune responses called inflammaging
that contribute to many chronic diseases.
CHAPTER 8
Overview of Adaptive Immunity
1. Adaptive immunity is a state of protection, primarily against infectious agents, that differs from
inflammation by being slower to develop, being more specific, and having memory that makes it much longer
lived.
2. The adaptive immune response is most often initiated by cells of the innate system. These cells process
and present portions of invading pathogens (i.e., antigens) to lymphocytes in peripheral lymphoid tissue.
3. The adaptive immune response is mediated by two types of lymphocytes—B lymphocytes and T
lymphocytes. Each has distinct functions. B cells are responsible for humoral immunity that is mediated by
