Chapter 8

Biology 25: Human BiologyBiology 25: Human Biology

Prof. GonsalvesProf. Gonsalves

Los Angeles City CollegeLos Angeles City College

Loosely Based on Mader’s Loosely Based on Mader’s Human Human BiologyBiology,7,7thth edition edition

IntroductionIntroduction

Resistance: Ability to ward off disease.Resistance: Ability to ward off disease. Nonspecific Resistance:Nonspecific Resistance: Defenses that Defenses that

protect against protect against allall pathogens. pathogens. Specific Resistance:Specific Resistance: Protection against Protection against

specificspecific pathogens. pathogens.

Susceptibility: Vulnerability or lack of Susceptibility: Vulnerability or lack of resistance.resistance.

Protection Against Invading PathogensProtection Against Invading Pathogens1. First Line of Defense1. First Line of Defense: : Non-specificNon-specific natural natural

barriers which barriers which restrictrestrict entryentry of pathogen. of pathogen.

ExamplesExamples: Skin and mucous membranes.: Skin and mucous membranes.

2. Second Line of Defense2. Second Line of Defense: : Non-specificNon-specific defenses that defenses that provide rapid local response to pathogen provide rapid local response to pathogen afterafter it it has has enteredentered body. body.

ExamplesExamples: Fever, phagocytes (macrophages and : Fever, phagocytes (macrophages and neutrophils), neutrophils), inflammationinflammation, and interferon., and interferon.

3. Third line3. Third line of defense: of defense: AntigenAntigen--specificspecific immune immune responses, specifically target and attack invaders responses, specifically target and attack invaders that get past first two lines of defense. that get past first two lines of defense.

ExamplesExamples: Antibodies and lymphocytes.: Antibodies and lymphocytes.

Defenses Against Infection

First Line of Defense: Skin is an Effective Barrier Against Infection by Most Pathogens

Second Line of Defense: Interferon is Nonspecific Inhibitor of Viral Infection

Inflammation is a Nonspecific DefenseInflammation is a Nonspecific Defense

1. Damaged cells release chemical signals: Histamine and 1. Damaged cells release chemical signals: Histamine and other molecules.other molecules.

2. Local response to chemical signals:2. Local response to chemical signals: Increase in local blood flow and vascular permeabilityIncrease in local blood flow and vascular permeability RednessRedness HeatHeat SwellingSwelling PainPain

3. Phagocytic white blood cells come into area: Engulf 3. Phagocytic white blood cells come into area: Engulf bacteria, dead cell parts, and other microbes.bacteria, dead cell parts, and other microbes.

4. Tissue heals4. Tissue heals

Nonspecific Immunity

Distinguish between the kinds of carbohydrates that are Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by produced by mammalian cells and those produced by bacteria.bacteria.

Bacterial carbohydrates flag the cell for phagocytic attack.Bacterial carbohydrates flag the cell for phagocytic attack. 3 major groups of phagocytic cells:3 major groups of phagocytic cells:

Neutrophils: 1Neutrophils: 1stst to arrive at infection. to arrive at infection. Mononuclear phagocyte system:Mononuclear phagocyte system: Macrophages and monocytes.Macrophages and monocytes. Organ-specific phagocytes.Organ-specific phagocytes.

Inflammatory Response: Nonspecific Defenses

Phagocytosis

Neutrophils and Neutrophils and monocytes are monocytes are able to squeeze able to squeeze through tiny gaps through tiny gaps between adjacent between adjacent endothelial cells.endothelial cells.

Phagocytosis Phagocytes engulf particles Phagocytes engulf particles

similar to amoeba.similar to amoeba. Particle becomes Particle becomes

surrounded by surrounded by pseudopods. pseudopods.

Forms vacuole.Forms vacuole. Vacuole fuses with Vacuole fuses with

lysosomes which digest lysosomes which digest the particle.the particle.

Lysosomes can be Lysosomes can be released into the released into the infected area.infected area.

Phagocytes

Intracellular killingof microbes

Regulate inflammationExtracellular killingActivation of clotting or anti-clottingHormonal regulation

Chemical secretion

Fever

Cell wall of gram – bacteria contains endotoxin.Cell wall of gram – bacteria contains endotoxin. Endotoxin stimulate release of cytokines:Endotoxin stimulate release of cytokines:

Interleukin-1, interleukin-6 and tumor necrosis Interleukin-1, interleukin-6 and tumor necrosis factor:factor:

Produce fever, increase sleepiness, and Produce fever, increase sleepiness, and decrease plasma iron.decrease plasma iron.

May be a component of nonspecific defense May be a component of nonspecific defense system.system.

Nonspecific Immunity

Endogenous pyrogens:Endogenous pyrogens: Cell wall of gram – bacteria contains endotoxin.Cell wall of gram – bacteria contains endotoxin. Endotoxin stimulates monocytes and Endotoxin stimulates monocytes and

macrophages to release cytokines:macrophages to release cytokines: Interleukin-1, interleukin-2, TNF.Interleukin-1, interleukin-2, TNF. Increased activity of neutrophils.Increased activity of neutrophils. Increased production of interferon.Increased production of interferon. Produce fever, increase sleepiness, and Produce fever, increase sleepiness, and

decrease plasma iron.decrease plasma iron.

Nonspecific Immunity

Interferons (cytokines)Interferons (cytokines) Nonspecific, short-acting resistance to viruses.Nonspecific, short-acting resistance to viruses. Act as messengers that protect other cells in the Act as messengers that protect other cells in the

vicinity from viral infection. vicinity from viral infection. inhibit viral replication, increases NK cells, inhibit viral replication, increases NK cells,

induces MHC-I antigens.induces MHC-I antigens. inhibit viral replication, increases NK cells, inhibit viral replication, increases NK cells,

induces MHC-I antigens.induces MHC-I antigens. activates macrophages, induces MHC-II activates macrophages, induces MHC-II

antigens.antigens.

Third Line of Defense: The Immune Third Line of Defense: The Immune ResponseResponse

Immunity: “Free from burden”. Ability of Immunity: “Free from burden”. Ability of an organism to recognize and defend itself an organism to recognize and defend itself against against specificspecific pathogens or antigens. pathogens or antigens.

Immune Response: Involves production of Immune Response: Involves production of antibodies and generation of specialized antibodies and generation of specialized lymphocytes against lymphocytes against specificspecific antigens. antigens.

Antigen: Molecules from a pathogen or Antigen: Molecules from a pathogen or foreign organism that provoke a specific foreign organism that provoke a specific immune response. immune response.

Antigens

Molecules that stimulate the production of Molecules that stimulate the production of antibodies.antibodies.

Combine specifically with antibodies produced.Combine specifically with antibodies produced. Foreign to blood and other body fluids. Foreign to blood and other body fluids. Immune system can distinguish “self” molecules Immune system can distinguish “self” molecules

from nonself antigens. from nonself antigens. Large, complex molecules can have different Large, complex molecules can have different

antigenic determinant sites.antigenic determinant sites.

Lymphatic and Immune SystemLymphatic and Immune SystemComponents: Lymph, lymphatic vessels, bone marrow, thymus, spleen, and Components: Lymph, lymphatic vessels, bone marrow, thymus, spleen, and

lymph nodes.lymph nodes.Functions: Functions:

Defends against infection: bacteria, fungi, viruses, etc.Defends against infection: bacteria, fungi, viruses, etc. Destruction of cancer and foreign cells.Destruction of cancer and foreign cells. Synthesis of antibodies and other immune molecules.Synthesis of antibodies and other immune molecules. Synthesis of white blood cells.Synthesis of white blood cells.

Homeostatic Role:Homeostatic Role: Returns fluid and proteins that have leaked from blood Returns fluid and proteins that have leaked from blood

capillaries into tissues. capillaries into tissues. Up to 4 liters of fluid every day.Up to 4 liters of fluid every day. Fluid returned near heart/venae cavae.Fluid returned near heart/venae cavae.

Lymphatic System

The Immune Response Destroys Specific InvadersThe Immune Response Destroys Specific Invaders

AntigenAntigen: Molecule that elicits an immune response.: Molecule that elicits an immune response.

““Antibody generating”.Antibody generating”.

Microbial antigensMicrobial antigens: Viral capsid, bacterial call : Viral capsid, bacterial call wall, etc.wall, etc.

Nonmicrobial antigensNonmicrobial antigens: Pollen, latex, food, etc.: Pollen, latex, food, etc.

AntibodyAntibody: Protein found in blood plasma that attaches to : Protein found in blood plasma that attaches to antigen and helps counteract its effects.antigen and helps counteract its effects.

Vaccination or ImmunizationVaccination or Immunization: Process in which harmless : Process in which harmless forms of antigen or pathogen are introduced into body to forms of antigen or pathogen are introduced into body to provoke an immune response.provoke an immune response.

Lymphocytes

Derived from stem cells in the bone Derived from stem cells in the bone marrow.marrow.

Stem cells produce the specialized blood Stem cells produce the specialized blood cells.cells.

Replace themselves by cell division so the Replace themselves by cell division so the stem cell population is not depleted.stem cell population is not depleted.

Lymphocytes seed the thymus, spleen, and Lymphocytes seed the thymus, spleen, and lymph nodes.lymph nodes.

Lymphocytes

Lymphocytes that seed the thymus become T Lymphocytes that seed the thymus become T lymphocytes (T cells).lymphocytes (T cells).

Have surface characteristics and immunological Have surface characteristics and immunological function that differ from other lymphocytes.function that differ from other lymphocytes.

Do not secrete antibodies.Do not secrete antibodies. Must come in close or direct contact to destroy Must come in close or direct contact to destroy

them.them. T cells are 65 – 85% of the lymphocytes in blood T cells are 65 – 85% of the lymphocytes in blood

and most in the germinal centers of lymph nodes and most in the germinal centers of lymph nodes and spleen.and spleen.

Lymphocytes

Most of the lymphocytes that are not T cells are B Most of the lymphocytes that are not T cells are B lymphocytes (B cells).lymphocytes (B cells).

Processed in the bone marrow.Processed in the bone marrow. Function in specific immunity.Function in specific immunity. B cells combat bacterial infections as well as B cells combat bacterial infections as well as

some viral infections by secreting antibodies into some viral infections by secreting antibodies into the blood and lymph.the blood and lymph.

Provide humoral immunity (blood and lymph are Provide humoral immunity (blood and lymph are body fluids (humors).body fluids (humors).

Lymphocytes Mount a Dual Immune DefenseLymphocytes Mount a Dual Immune Defense1. Cell Mediated Immunity1. Cell Mediated Immunity Immunity that requires cell to cell contact.Immunity that requires cell to cell contact. Carried out by Carried out by T cellsT cells::

Develop in the thymus. Develop in the thymus. Only recognize antigen associated with self-protein.Only recognize antigen associated with self-protein. T cytotoxic cells:T cytotoxic cells: Important in defense against: Important in defense against:

Cancer cellsCancer cells Self cells infected with fungi, viruses, protozoans, Self cells infected with fungi, viruses, protozoans,

and bacteria.and bacteria. T helper cells:T helper cells: Play a Play a central rolecentral role in immunity. in immunity.

Act Act indirectlyindirectly by controlling the immune functions of by controlling the immune functions of other cells:other cells:

Increased antibody production by B cells.Increased antibody production by B cells. Increased phagocytosis by macrophages.Increased phagocytosis by macrophages. Increased killing of foreign and cancer cells.Increased killing of foreign and cancer cells.

Development of T and B Lymphocytes

T helper cells play a central role in immunity

Lymphokines

Interleukin-1:Interleukin-1: Secreted by macrophages and other cells.Secreted by macrophages and other cells. Activates T cells.Activates T cells.

Interleukin-2:Interleukin-2: Released by helper T cells.Released by helper T cells. Activates killer T cells. Activates killer T cells.

Interleukin-3: Interleukin-3: Serves as a growth factor.Serves as a growth factor. Activates killer T cells.Activates killer T cells.

Interleukin-4:Interleukin-4: Secreted by T cells.Secreted by T cells.

Required for proliferation and clone development of B Required for proliferation and clone development of B cells.cells.

Lymphocytes Mount a Dual Immune DefenseLymphocytes Mount a Dual Immune Defense2. Humoral (Antibody Mediated) Immunity2. Humoral (Antibody Mediated) Immunity

Antibodies are found in our body fluids:Antibodies are found in our body fluids: BloodBlood LymphLymph Interstitial fluidInterstitial fluid

Antibodies are produced by B cells.Antibodies are produced by B cells. B cells develop in bone marrow.B cells develop in bone marrow.

AntibodiesAntibodies are are specificspecific molecules that circulate through out molecules that circulate through out our body and attach to foreign our body and attach to foreign antigensantigens, marking them for , marking them for destruction.destruction.

Foreign antigen does not have to be associated with a self Foreign antigen does not have to be associated with a self antigen to be recognized.antigen to be recognized.

Antibodies can be passed from one individual to another:Antibodies can be passed from one individual to another: Mother-child:Mother-child: Mother’s antibodies cross placenta. Also Mother’s antibodies cross placenta. Also

found in breast milk.found in breast milk. Serum:Serum: Snake bite antivenom. Snake bite antivenom.

Antibodies

Antibody proteins are also known as Antibody proteins are also known as immunoglobulins.immunoglobulins.

Found in the gamma globulin class of Found in the gamma globulin class of plasma proteins.plasma proteins.

Different antibodies have different Different antibodies have different structure, as the antibodies have specific structure, as the antibodies have specific actions.actions.

Antibodies Immunoglobulin Functions

lgG Main form of antibodies in circulation: production increased after immunization; secreted during secondary response

lgA Main antibody type in external secretions, such as saliva and mother’s milk

lgE Responsible for allergic symptoms in immediate hypersensitivity reactions

lgM Function as antigen receptors on lymphocyte surface prior to immunization; secreted during primary response

lgD Function as antigen receptors on lymphocyte surface prior to immunization; other functions unknown

Active Immunity

Primary response:Primary response:First exposure to pathogen, immune First exposure to pathogen, immune

response insufficient to combat response insufficient to combat disease.disease.

Latent period of 5-10 days before Latent period of 5-10 days before measurable amounts of specific measurable amounts of specific antibodies appear in blood.antibodies appear in blood.

Active Immunity

Secondary response:Secondary response: Subsequent exposure to same antigen.Subsequent exposure to same antigen. Antibody production is much more rapid.Antibody production is much more rapid.

Maximum antibody concentration Maximum antibody concentration reached in < 2 hrs.reached in < 2 hrs.

Maintained longer period of time.Maintained longer period of time.

Clonal Selection Theory

B lymphocytes inherit the ability to B lymphocytes inherit the ability to produce a particular antibody.produce a particular antibody.

T lymphocytes inherit the ability to T lymphocytes inherit the ability to respond to particular antigens.respond to particular antigens.

Inherited specificity reflected in antigen Inherited specificity reflected in antigen receptor proteins on surface of receptor proteins on surface of lymphocytes.lymphocytes.

Clonal Selection Theory

Exposure stimulates Exposure stimulates specific lymphocytes to specific lymphocytes to divide many times until a divide many times until a large population of large population of genetically identical cells genetically identical cells (clone) is produced.(clone) is produced.

Antigens select Antigens select lymphocytes that are lymphocytes that are already able to make already able to make antibodies.antibodies.

Antibody Structure

100 million trillion 100 million trillion antibody molecules that antibody molecules that contain 4 polypeptide contain 4 polypeptide chains.chains.

FFabab regions are variable, regions are variable,

provide a specific provide a specific bonding site for antigen.bonding site for antigen.

B lymphocytes have B lymphocytes have antibodies that serve as antibodies that serve as receptors for antigensreceptors for antigens

Provides active Provides active immunity.immunity.

Antibodies are Protein Molecules that Recognize Specific Foreign Antigens

Antibodies Help Eliminate Foreign Antigens

Complement Proteins

Nonspecific defense system. Nonspecific defense system. The combination of antibodies with The combination of antibodies with

antigens does not cause destruction of the antigens does not cause destruction of the antigens or pathogen.antigens or pathogen.

Antibodies serve to identify the targets for Antibodies serve to identify the targets for immunological attack.immunological attack.

Identified antibodies activate the Identified antibodies activate the complement against specific invaders.complement against specific invaders.

Activated Complement Proteins

Direct destruction by MACVasodilationIncreased capillary permeabilityChemotaxisOpsinization

There are 11 complement proteins, designated C-1 There are 11 complement proteins, designated C-1 to C-9.to C-9.

Complement proteins can be subdivided into 3 Complement proteins can be subdivided into 3 components:components: C1: recognization.C1: recognization. C4, C2, C3: activation.C4, C2, C3: activation. C5-C9: attack (complement fixation).C5-C9: attack (complement fixation).

Complement Types

Complement Fixation

Complement proteins attach to the cell Complement proteins attach to the cell membrane and destroy it.membrane and destroy it.

Antibodies of IgG and IgM attach to Antibodies of IgG and IgM attach to antigens on invading cell membranes, bind antigens on invading cell membranes, bind to C1 activating the process.to C1 activating the process.

Activated C1 hydrolyzes C4 into C4Activated C1 hydrolyzes C4 into C4aa and and

C4C4bb..

C4C4bb binds to the cell membrane. binds to the cell membrane.

C4C4bb splits C2 into C2 splits C2 into C2aa and C2 and C2bb..

Complement Fixation

C2C2aa attaches to C4 attaches to C4bb and cleaves C3 into C3 and cleaves C3 into C3aa

and C3and C3bb. .

Fragment C3Fragment C3bb becomes attached to the becomes attached to the

complex in the cell membrane.complex in the cell membrane. C3C3bb converts C5 to C5 converts C5 to C5aa and C5 and C5bb..

C5C5bb and C6 through C9 become fixed to the and C6 through C9 become fixed to the

cell membrane.cell membrane.

Complement Fixation

Complement proteins C5 to C9 create large pores in Complement proteins C5 to C9 create large pores in membrane, causing osmotic influx of Hmembrane, causing osmotic influx of H220.0.

Complement proteins kill the cell.Complement proteins kill the cell.

Active Immunity

Primary response:Primary response:First exposure to pathogen, immune First exposure to pathogen, immune

response insufficient to combat response insufficient to combat disease.disease.

Latent period of 5-10 days before Latent period of 5-10 days before measurable amounts of specific measurable amounts of specific antibodies appear in blood.antibodies appear in blood.

Active Immunity

Secondary response:Secondary response: Subsequent exposure to same antigen.Subsequent exposure to same antigen. Antibody production is much more rapid.Antibody production is much more rapid.

Maximum antibody concentration Maximum antibody concentration reached in < 2 hrs.reached in < 2 hrs.

Maintained longer period of time.Maintained longer period of time.

Passive Immunity

Immune protection produced by the Immune protection produced by the transfer of antibodies to a recipient from a transfer of antibodies to a recipient from a donor.donor.

Donor has been actively immunized.Donor has been actively immunized. Occurs naturally in mother to fetus during Occurs naturally in mother to fetus during

pregnancy and mother to infant during pregnancy and mother to infant during nursing.nursing.

Passive Immunity

Immunological competence:Immunological competence: Ability to mount a specific immune response.Ability to mount a specific immune response. Does not develop until 1 month after birth.Does not develop until 1 month after birth. Passive immunity disappears when infant is 1 Passive immunity disappears when infant is 1

month old.month old.Infant did not itself produce lymphocyte Infant did not itself produce lymphocyte

clones.clones.

Lymphokines

Interleukin-1:Interleukin-1: Secreted by macrophages and other cells.Secreted by macrophages and other cells. Activates T cells.Activates T cells.

Interleukin-2:Interleukin-2: Released by helper T cells.Released by helper T cells. Activates killer T cells. Activates killer T cells.

Interleukin-3: Interleukin-3: Serves as a growth factor.Serves as a growth factor. Activates killer T cells.Activates killer T cells.

Interleukin-4:Interleukin-4: Secreted by T cells.Secreted by T cells.

Required for proliferation and clone development of B Required for proliferation and clone development of B cells.cells.

Major Histocompatability Complexes (MHC)

All cells except mature RBCs are genetically All cells except mature RBCs are genetically marked with histocompatability antigens on the marked with histocompatability antigens on the membrane surface.membrane surface.

Also called human leukocyte antigens (HLAs).Also called human leukocyte antigens (HLAs). The histocompatability antigens are coded for a The histocompatability antigens are coded for a

group of genes called MHC located on group of genes called MHC located on chromosome 6.chromosome 6.

MHC of genes produces 2 classes of MHC MHC of genes produces 2 classes of MHC molecules:molecules: Class-1Class-1 Class-2Class-2

Major Histocompatability Complexes

MHC-class-1:MHC-class-1: Produced by all cells but RBCs.Produced by all cells but RBCs. Picks up cytoplasmic peptides and transports Picks up cytoplasmic peptides and transports

to membrane.to membrane. Killer T cells (cytotoxic) interact with Killer T cells (cytotoxic) interact with

antigens. antigens. Coreceptor CD8 permits each type of T cell to Coreceptor CD8 permits each type of T cell to

interact only with a specific class of MHC interact only with a specific class of MHC molecules. molecules.

Major Histocompatability Complexes

MHC-class-2:MHC-class-2: Produced only on antigen-presenting cells and Produced only on antigen-presenting cells and

B cellsB cells Appear only on cell membrane when cell is Appear only on cell membrane when cell is

processing antigens.processing antigens. Activate T cells.Activate T cells. Helper T cells react with antigens.Helper T cells react with antigens. Coreceptor CD4 interact with only a specific Coreceptor CD4 interact with only a specific

class of MHC molecule.class of MHC molecule.

Monoclonal Antibodies

Commercially prepared.Commercially prepared. Exhibit specificity for one antigenic Exhibit specificity for one antigenic

determinant only.determinant only. Results in more sophisticated clinical Results in more sophisticated clinical

laboratory tests.laboratory tests. May aid in the diagnosis of cancer.May aid in the diagnosis of cancer.

Diseases Caused by the Immune System

Ability of immune system to tolerate self-Ability of immune system to tolerate self-antigens while it identifies and attacks antigens while it identifies and attacks foreign antigens that can be deranged.foreign antigens that can be deranged.

Diseases caused by the immune system can Diseases caused by the immune system can be grouped into 3 categories:be grouped into 3 categories: Autoimmune disease.Autoimmune disease. Immune complex diseases.Immune complex diseases. Allergy or hypersensitivity.Allergy or hypersensitivity.

Autoimmunity

Those produced by failure in the immune system to Those produced by failure in the immune system to recognize and tolerate self-antigens.recognize and tolerate self-antigens.

Failure due to:Failure due to: An antigen that does not normally circulate in An antigen that does not normally circulate in

the blood may be exposed to the immune the blood may be exposed to the immune system.system.

Thyroglobulin.Thyroglobulin. A self-antigen that is otherwise tolerated may be A self-antigen that is otherwise tolerated may be

altered by combining with a foreign hapten.altered by combining with a foreign hapten. Thrombocytopenia.Thrombocytopenia.

Autoimmunity

Antibodies may be produced that are directed Antibodies may be produced that are directed against other antibodies.against other antibodies. Rheumatoid arthritis.Rheumatoid arthritis.

Antibodies produced against foreign antigens may Antibodies produced against foreign antigens may cross-react with self-antigens.cross-react with self-antigens. Rheumatic fever.Rheumatic fever.

Self-antigens may be presented to the helper T Self-antigens may be presented to the helper T cells together with class-2 MHC molecules.cells together with class-2 MHC molecules. Type I diabetes.Type I diabetes.

Immediate Hypersensitivity

Production of IgE Production of IgE antibodies.antibodies.

Do not circulate in the Do not circulate in the blood.blood.

Attach to mast cells Attach to mast cells and basophils. and basophils.

When exposed again When exposed again to same allergen, to same allergen, histamine and histamine and prostaglandin D are prostaglandin D are secreted.secreted.

Produce symptoms.Produce symptoms.