Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Fig. 12-CO, p. 406

• Body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells
• Immune system activities
– Defends against invading pathogens
– Removes “worn-out” cells and tissue damaged by trauma
– Identifies and destroys abnormal or mutant cells that have originated in the body
– Mounts inappropriate immune responses that lead either to allergies or to autoimmune diseases
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Major targets of immune system
– Bacteria
• Non-nucleated, single-celled microorganisms
• Primarily cause tissue damage and cause disease by releasing enzymes or toxins
– Viruses
• Consists of either DNA or RNA enclosed by a protein coat
• Cannot carry out metabolism or reproduce without invading a host cell
• Virulent forms of both bacteria and viruses can cause disease
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Effectors of the immune system
• Five types
– Neutrophils
• Highly mobile phagocytes that engulf and destroy unwanted materials
– Eosinophils
• Secrete chemicals that fight parasites
• Involved in allergic reactions
– Basophils
• Release histamine and heparin
• Involved in allergic reactions
– Monocytes
• Transformed into macrophages (tissue-bound phagocytic specialists)
– Lymphocytes
• Β lymphocytes (β cells)
– Transformed into plasma cells that secrete antibodies
• T lymphocytes (T cells)
– Responsible for cell-mediated immunity
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Mainly produced from lymphoid colonies in lymphoid tissues
• Lymphoid tissues
– Tissues that produce, store, or process lymphocytes
– Include
• Bone marrow
• Lymph nodes
• Spleen
• Thymus
• Tonsils
• Adenoids
• Appendix
• Peyer’s patches (GALT)
– Gut associated lymphatic tissue
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Table 12-1, p. 409

• Innate (nonspecific) vs. Adaptive (specific)
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Innate immune system
– Nonspecific
– Responses work immediately when body is exposed to threatening agent
– Nonselectively defend against foreign invaders
– First line of defense
– Rapid but limited responses
– Neutrophils, macrophages, several plasma proteins are important in innate defense
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Adaptive or acquired immune system
– Specifically targets foreign material to which body has already been exposed
– Body has taken time to prepare to attack
– Ultimate weapon against most pathogens
– Responses are mediated by β and T lymphocytes
– Formation of memory cells allows system to react more swiftly against specific invaders in the future
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Defenses include the following
– Inflammation
– Interferon
– Natural killer cells
– Complement system
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Inflammation
– Nonspecific response to tissue injury
– Ultimate goal is to bring phagocytes and plasma proteins to invaded or injured area
• Isolate, destroy, or inactivate the invaders
• Remove debris
• Prepare for subsequent healing and repair
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Bacterial invasion or tissue damage
Local arteriolar vasodilation
Increased blood delivery to injured tissue
Redness Heat
Increase in crucial plasma proteins, such as clotting factors, in tissue
Release of histamine by mast cells
Increased local capillary permeability
Local accumulation of fluid
Swelling Pain
Increase in phagocytes in tissue
Phagocytic secretions
Defense against foreign invader; tissue repair
Systemic responses, such as fever
Fig. 12-2, p. 411

• Inflammation
– Inflammatory response is similar no matter what the triggering event
• Defense by resident tissue macrophages
• Localized vasodilation
• Increased capillary permeability
• Localized edema
• Walling-off the inflamed area
• Emigration of leukocytes
• Leukocyte proliferation
• Marking of bacteria for destruction by opsonins
• Leukocytic destruction of bacteria
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Innate Immunity (Inflammatory Response)
Phagocyte-Secreted Chemicals
Chemical
Nitric oxide (NO)
Secreted by Function
Macrophages Toxic to nearby microorganisms
Lactoferrin
Histamine
Neutrophils
Mast cells
Protein that binds with iron, making it unavailable for use by invading bacteria
Induces local vasodilation and increases capillary permeability
Kallikrein Neutrophils Converts specific plasma proteins precursors produced by liver into activated kinins
Macrophages Induces development of fever Endogenous pyrogen
(EP)
Leukocyte endogenous mediator
(LEM)
Macrophages Decreases the plasma concentration of iron by altering iron metabolism within the liver, spleen and other tissues; also stimulates synthesis and release of neutrophils by the bone marrow
Acute phase proteins Liver upon stimulation by
LEM
Play role in inflammatory process, tissue repair, and immune cell activities
C-reactive protein Liver Specific acute phase protein that is clinically used as a blood-borne marker of inflammation
Interleukin 1 (IL-1) Macrophages Enhances proliferation and differentiation of
β and T lymphocytes
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Tissue repair can be perfect
– Cell division replaces lost cells with same kind of cells
• In nonregenerative tissue (nerve and muscle)
– Lost cells are replaced with scar tissue
• Drugs that suppress with inflammatory process
– Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Aspirin
• Ibuprofen
– Glucocorticoids
• Suppress almost all aspects of inflammatory process
• Reduce body’s ability to resist infection
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Interferon
– Transiently inhibits multiplication of viruses in most cells
– Triggers the production of virus-blocking enzymes by potential host cells
– Released nonspecifically from any cell infected by a virus
– Provides general, rapid defense until more specific but slower-responding immune mechanisms can begin
– Enhances macrophage phagocytic activity, stimulates production of antibodies, boosts the power of killer cells
– Exerts anticancer effects
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Mechanism of Action of Interferon in Preventing Viral Replication
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Natural killer (NK) cells
– Naturally occurring lymphocyte-like cells
– Nonspecifically destroy virus-infected cells and cancer cells
– Mode of action
• Directly lyse cell membranes upon first exposure to these cells
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Complement system
– Nonspecific response
– Primary mechanism activated by antibodies to kill foreign cells
– Also activated by exposure to carbohydrate chains present on surfaces of microorganisms but not on human cells
– Forms membrane attack complexes that punch holes in victim cells
– Composed of plasma proteins that are produced by the liver and circulate in inactive form
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Complement system
– Cascade sequence of events
• C1 is activated → activates C2 → activates C3 → activates C4 → activates C5
• Components C5 through C9 assemble into large, doughnut-shaped protein complex (membrane attack complex – MAC)
– Embeds itself in surface membrane of nearby microorganisms
– Resulting hole makes membrane leaky
– Victim cell swells and bursts
– Means of killing microbes without killing them
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Membrane Attack
Complex (MAC)
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Fig. 12-10, p. 420

• Several proteins in complement cascade additionally augment inflammatory process by
– Serving as chemotaxins
– Acting as opsonins
– Promoting vasodilation and increased vascular permeability
– Stimulating release of histamine from mast cells
– Activating kinins
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Two classes of adaptive immunity
– Antibody-mediated or humoral immunity
• Involves production of antibodies by β lymphocyte derivatives known as plasma cells
– Cell-mediated immunity
• Involves production of activated T lymphocytes
– Directly attack unwanted cells
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Origins of β and T Cells
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Antigen
– Large, foreign, unique molecule
– Induces an immune response against itself
– In general, the more complex a molecule is, the greater its antigenicity
• Antibody
– Complex proteins made in B and T cells that bind to an antigen in a specific
(adaptive) manner
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Each lymphocyte has surface receptors for binding with one particular type of possible antigens
• Antigens stimulate β cells to convert into plasma cells that produce antibodies
• On binding with processed and presented antigen
– Most β cells differentiate into active plasma cells
– Other β cells become dormant
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Produce antibodies that can combine with a specific kind of antigen
• All antibodies eventually enter blood where they are known as gamma globulins or immunoglobulins
• Antibody (Immunoglobulin) subclasses
– IgM
• Serves as the β cell surface receptor for antigen attachment
• Secreted in early stages of plasma cell response
– IgG
• Most abundant immunoglobulin in blood
• Produced in large amounts when body is exposed to same antigen
– IgE
• Helps protect against parasitic worms
• Antibody mediator for common allergic responses
– IgA
• Found in secretions of digestive, respiratory, and genitourinary systems; also in milk and tears
– IgD
• Present on surface of many β cells
• Function is uncertain
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Y-shaped molecules
• Composed of four interlinked polypeptide chains
– Two long, heavy chains and two short, light chains
• Properties of tail portion determine functional properties of the antibody
• Identical antigen-binding fragments (Fab) at tip of each arm (unique for each different antibody)
• Tail (constant region) regions within each subclass are identical
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Can physically hinder antigens
• By neutralization, they prevent harmful chemicals from interacting with susceptible cells
• Can bind to foreign cells by agglutination
• Enhance activity of other defense systems by
– Activating complement system
– Enhancing phagocytosis
– Stimulating killer (K) cells
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Fig. 12-10a, p. 420

Different
B cell clones
Antigens
Rough endoplasmic reticulum Plasma cells
B cell specific to antigen
Memory cells
Antibodies
Fig. 12-11, p. 421

• Activated β-cell clones multiply and differentiate into
– Plasma cells
• Produce and secrete IgG antibodies
• Antibody combines with an antigen, marking it for destruction
• During initial contact with microbial antigen, antibody response is delayed and plasma cells are formed
• Peak is reached in a couple of weeks by primary response
• After peak, antibody concentration decreases
– Memory cells
• Small percentage of β lymphocytes become memory cells
• Remain dormant
• Upon reexposure to same antigen, they are more ready for immediate action than the original lymphocytes of the clone
• Secondary response is quicker, more potent, and longerlasting
– Can be induced by disease or vaccination
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

First exposure to a pathogen’s antigens
Natural exposure to virulent, antigenic pathogen
Virulent portion Antigenic portion
Combat
Exposure to nonvirulent, antigenic pathogen through vaccination
Disease Specific B cell clone Specific B cell clone
No virulence
No disease
Plasma cells
Memory cells
(long-term immunity)
Memory cells
(long-term immunity)
Antibodies
(slow, weak primary response)
Subsequent exposure to same virulent pathogen
Plasma cells
Plasma cells
Combat
Antibodies
(swift, strong secondary response)
Combat
Antibodies
(swift, strong secondary response)
Plasma cells
Antibodies
(not needed)
No disease
Fig. 12-13, p. 423

• Active immunity
– “self-generated”
– Results from exposure to an antigen
• Passive immunity
– “borrowed immunity”
– Results from transfer of preformed antibodies
– Can provide immediate protection or bolster resistance
– Example of passive immunity is transfer of IgG antibodies from mother to fetus
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Lymphocytes respond only to antigens presented to them by antigen-presenting cells
– Macrophages can be antigen-presenting cells
• Cluster around appropriate β-cell clone
• Phagocytosis occurs, processing the raw antigen intracellularly and presenting the processed antigen, exposing it to the outer surface of the macrophage’s plasma membrane
• As macrophage engulfs and ingests microbe, it digests the microbe into antigenic peptides
• Antigenic peptides bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to passing lymphocytes
• Antigen-presenting macrophages secrete interleukin
– Enhances differentiation and proliferation of now-activated βcell clone
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Carry out cell-mediated immunity
• Do not secrete antibodies – directly bind to targets
• Killer T cells release chemicals that destroy targeted cells
• Clonal and antigen specific – acquire receptors in the thymus
• T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens
• Learn to recognize foreign antigens only in combination with a person’s own tissue antigens
• A few days are required before T cells are activated to launch a cell-mediated attack
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Two main types of T cells
– CD8 cells (cytotoxic, or killer T cells)
• Destroy host cells harboring anything foreign
– CD4 cells (mostly helper T cells)
• Modulate activities of other immune cells
• Secrete chemicals that amplify the activity of other immune cells
– Β-cell growth factor
– T-cell growth factor (interleukin 2)
– Macrophage-migration inhibition factor
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Macrophages secrete interleukin 1, which enhances B cell proliferation and antibody secretion
Invading bacteria
Interleukin 1
Macrophages “process and present” bacterial antigen to B and T lymphocyte clones specific to the antigen
Macrophage
Antibodies enhance phagocytosis by coating the bacteria and serving as opsonins
Antibodies
Helper T cell
B cell
Activated helper T cell
Helper T cells secrete B cell growth factor that enhances B cell proliferation and antibody secretion B cell growth factor
Plasma cell
Plasma cells secrete antibodies that bind with the antigenic bacteria
Fig. 12-15, p. 427

Fig. 12-17, p. 430

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Mechanism of
Killing by Killer
Cells

Fig. 12-20, p. 435

Fig. 12-23, p. 437

T cell receptor
MHC self-antigen
Cytotoxic T cell
Foreign antigen
Invaded cell
Fig. 12-19, p. 434

Innate and Adaptive Responses to Bacterial Infection
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Tolerance refers to preventing the immune system from attacking the person’s own tissues
• Mechanisms involved in tolerance
– Clonal deletion
– Clonal anergy
– Receptor editing
– Inhibition by regulatory T cells
– Immunological ignorance
– Immune privilege
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Arise from loss of tolerance to self-antigens
• Examples of causes
– Exposure of normally inaccessible self-antigens sometimes induces an immune attack against these antigens
– Normal self-antigens may be modified by factors such as drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system.
– Exposure of the immune system to a foreign antigen structurally identical to a self-antigen
– May be related to pregnancy, arising from lingering fetal cells in the mother’s body after the pregnancy
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Plasma membrane-bound glycoproteins called MHC molecules
• Synthesis is directed by group of genes called major histocompatibility complex (MHC)
• Exact pattern of MHC molecules varies from one individual to another
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Process by which T cells recognize and destroy newly arisen, potentially cancerous tumor cells
• Tumor
– Clone of cells identical to original mutated cell
• Benign tumor
– Does not infiltrate surrounding tissues
• Malignant tumor
– Invasive and cancerous
– Cells tend to metastasize
– May spread throughout body and cannot be removed surgically
• Untreated cancer is eventually fatal
• Most genetic mutations do not lead to cancer
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Due to abnormal functioning of the immune system
• Two general ways
– Immunodeficiency diseases
• Too little immune response
• Examples
– severe combined immunodeficiency
– AIDS
– Inappropriate immune attacks
• Too much or mistargeted immune response
• Categories of inappropriate attacks
– Autoimmune responses
– Immune complex diseases
– Allergies
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Acquisition of an inappropriate specific immune reactivity (hypersensitivity) to a normally harmless environmental substance
• Offending agent is known as an allergen
• Categories of allergic responses
– Immediate hypersensitivity
– Delayed hypersensitivity
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Fig. 12-24, p. 440

Comparison of Immediate and Delayed
Hypersensitivity Reactions
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Chemical mediators
– Histamine
– Slow-reactive substance of anaphylaxis (SRS-A)
– Eosinophil chemotactic factor
• Symptoms
– Vary depending on site, allergen, and mediators involved
• Hay fever
• Asthma
• Hives
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Most obvious external defense is the skin, or integument
• Consists of two layers
– Epidermis
• Outer, vascular, keratinized layer
– Dermis
• Inner, connective tissue layer
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Four cell types
– Melanocytes
• Produce melanin which protects the skin by absorbing harmful UV radiation
– Keratinocyes
• Produce keratin that forms outer protective layer of skin
• Discourages bacteria and other harmful environmental agents from entering body
• Prevents loss of water and other valuable body substances
• Secrete interleukin 1
– Langerhans cells
• Function in specific immunity by presenting antigen to helper
T cells
– Granstein cells
• Suppress skin-activated immune responses
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Contains
– Blood vessels
• Nourish the skin
• Play role in regulating body temperature
– Sensory nerve endings
• Provide information about the external environment
– Several exocrine glands and hair follicles
• Sebaceous glands
– Produce sebum
– Oily substance that softens and waterproofs the skin
• Sweat glands
– Produce sweat which helps cool the body
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Additional protective measures guard against entry of potential pathogens through internal cavities that communicate directly with the external environment
– Digestive system
• Antimicrobial salivary enzyme
• Destructive acidic gastric secretions
• Gut-associated lymphoid tissue
• Harmless resident colonic secretions
– Genitourinary system
• Destructive acidic and particle-entrapping mucus secretions
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

– Respiratory system
• Alveolar macrophage activity
• Secretion of sticky mucus that traps debris which is swept out by ciliary action
• Nasal hairs filter out large inspired particles
• Reflex cough and sneeze mechanisms expel irritant materials from trachea and nose
• Tonsils and adenoids defend immunologically
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Form of passive immunity
• ABO blood types are named for presence of antigens on surface of erythrocytes
– Type A has A antigens and anti-B antibodies
– Type B has B antigens and anti-A antibodies
– Type AB has both A and B antigens and no antibodies related to the ABO system
– Type O does not have A or B surface antigens and both anti-A and anti-B antibodies
• Transfusion reaction occurs when blood of incompatible type is given
• Blood type O is the universal donor
• Blood type AB is the universal recipient
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Transfusion Reaction
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

• Rh factor
– Rh-positive individual has Rh factor
– Rh-negative individual lacks Rh factor
– Erythroblastosis fetalis (hemolytic disease of the newborn)
• Occurs when Rh-negative mother develops antibodies against the erythrocytes of an Rh-positive fetus
• Approximately 12 other minor human erythrocyte antigen systems
Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Chapter 12 The Body Defenses
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning