Immune systemImmune system

By Zoe Kopp-WeberBy Zoe Kopp-Weber

Over 500 million years ago, the immune system first appeared in porifera.Based on phagocytic cells only.

Lampreys, jawless fish, were the first vertebrates to have a lymphocyte based immune system.

Jawed fish evolved and B and T cells appeared.

Over 500 million years ago, the immune system first appeared in porifera.Based on phagocytic cells only.

Lampreys, jawless fish, were the first vertebrates to have a lymphocyte based immune system.

Jawed fish evolved and B and T cells appeared.

Once sharks and other cartilaginous fish evolved, the immune system of vertebrates was fully formed.

Really only one noticeable difference between shark and mammal immune systems.The antibody-encoding systems are

arranged in the genome a little differently.

Once sharks and other cartilaginous fish evolved, the immune system of vertebrates was fully formed.

Really only one noticeable difference between shark and mammal immune systems.The antibody-encoding systems are

arranged in the genome a little differently.

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3 lines of defenseFirst, skin.As it is the largest organ of the

vertebrate bodyProvides a nearly impenetrable

barrierReinforces defense with chemical

weapons on the surfaceOil and sweat glands

Prevents loss of air through evaporation

3 lines of defenseFirst, skin.As it is the largest organ of the

vertebrate bodyProvides a nearly impenetrable

barrierReinforces defense with chemical

weapons on the surfaceOil and sweat glands

Prevents loss of air through evaporation

Second, cellular counterattackNonspecific cellular and

chemical devices respond to infection without identifying invaders

Central location of collection and distribution: lymphatic systemLymphatic vessels and organs

(spleen and thymus gland), and lymph nodes

Second, cellular counterattackNonspecific cellular and

chemical devices respond to infection without identifying invaders

Central location of collection and distribution: lymphatic systemLymphatic vessels and organs

(spleen and thymus gland), and lymph nodes

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Macrophages - ingest microbes by phagocytosis.Membrane-bound vacuole

with bacterium fuses with a lysosome and oxygen free radicals kill the microbe

Supplement phagocytic cells of the liver, spleen and bone marrow.

Macrophages - ingest microbes by phagocytosis.Membrane-bound vacuole

with bacterium fuses with a lysosome and oxygen free radicals kill the microbe

Supplement phagocytic cells of the liver, spleen and bone marrow.

NeutrophilsKill by phagocytosis but release

chemicals that kill surrounding bacteria and neutrophils themselves.

Natural killer cellsKills cells infected with the viruses by

creating a hole in the plasma membrane, releasing proteins into the membrane, then sending granzymes in to initiate cell death (apoptosis)

Most potent defense against cancer.

NeutrophilsKill by phagocytosis but release

chemicals that kill surrounding bacteria and neutrophils themselves.

Natural killer cellsKills cells infected with the viruses by

creating a hole in the plasma membrane, releasing proteins into the membrane, then sending granzymes in to initiate cell death (apoptosis)

Most potent defense against cancer.

Third defense, immune responseBest explained through

experiments of Pasteur and JennerEdward Jenner studied immunology

through smallpoxMilkmaids who’d had cowpox rarely

had smallpoxTested observation by infection people

with cowpox, in turn they became immune to smallpox.

Third defense, immune responseBest explained through

experiments of Pasteur and JennerEdward Jenner studied immunology

through smallpoxMilkmaids who’d had cowpox rarely

had smallpoxTested observation by infection people

with cowpox, in turn they became immune to smallpox.

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Why?Those injected with cowpox built a

defense effective against smallpox due to the similar surfaces of the diseases.

Vaccination - injection of harmless microbe to develop resistance to a dangerous one.

Why?Those injected with cowpox built a

defense effective against smallpox due to the similar surfaces of the diseases.

Vaccination - injection of harmless microbe to develop resistance to a dangerous one.

Pasteur studied fowl choleraIsolated a culture of diseased

bacteria, forgot it for two weeks, then injected it into healthy birds.

Birds became slightly sick and recovered

Later, when injected with large amounts of live fowl cholera bacteria, the chickens wouldn’t get sick.

Pasteur studied fowl choleraIsolated a culture of diseased

bacteria, forgot it for two weeks, then injected it into healthy birds.

Birds became slightly sick and recovered

Later, when injected with large amounts of live fowl cholera bacteria, the chickens wouldn’t get sick.

Why?Bacteria can illicit imunnity if it

doesn’t kill the animal first.Antigen - a molecule that provokes

a specific immune responseLarge, complex like proteinsForeign to body, present on pathogensDifferent parts stimulate different

responseDifferent parts are antigenic determinant

sites

Why?Bacteria can illicit imunnity if it

doesn’t kill the animal first.Antigen - a molecule that provokes

a specific immune responseLarge, complex like proteinsForeign to body, present on pathogensDifferent parts stimulate different

responseDifferent parts are antigenic determinant

sites

Lymphocytes - receptor proteins on surface recognize an antigen direct a specific immune respose against the antigen/cell carrying the antigen.B cells - produce proteins called

antibodiesAntibody - protein secreted into

blood and other body fluids providing humoral immunity

“humor” as in a bodily fluid

Lymphocytes - receptor proteins on surface recognize an antigen direct a specific immune respose against the antigen/cell carrying the antigen.B cells - produce proteins called

antibodiesAntibody - protein secreted into

blood and other body fluids providing humoral immunity

“humor” as in a bodily fluid

T cells - regulate immune responses of other cells and directly attack cells carrying specific antigensCell-mediated immunity

T cells - regulate immune responses of other cells and directly attack cells carrying specific antigensCell-mediated immunity

Specific immune responses protect in 2 ways.Acquired immunity (active) -

gaining immunity by exposure, maybe be getting the disease

Ex. Chicken pox

Passive immunity - obtaining antigens from another individual

Ex. Antibodies we receive from our moms transferred across the placenta

Specific immune responses protect in 2 ways.Acquired immunity (active) -

gaining immunity by exposure, maybe be getting the disease

Ex. Chicken pox

Passive immunity - obtaining antigens from another individual

Ex. Antibodies we receive from our moms transferred across the placenta

3 routes of entry by virus/microorganismDigestive tract

Microbes in food killed by saliva while acidic stomach and digestive enzymes kill what makes it to the intestine.

Respiratory tractCells lining bronchi secrete mucus

trapping air microorganisms before reaching the lungs

Cells with cilia sweep mucous towards the glottis where it can be swallowed

3 routes of entry by virus/microorganismDigestive tract

Microbes in food killed by saliva while acidic stomach and digestive enzymes kill what makes it to the intestine.

Respiratory tractCells lining bronchi secrete mucus

trapping air microorganisms before reaching the lungs

Cells with cilia sweep mucous towards the glottis where it can be swallowed

Urogenital tractAcidic urine washes away pathogens

from urinary tractVaginal secretion are also acidic and

prevent foreign invasion

If a pathogen does get by any of these systems, the body has other defense mechanismsVomiting, diarrhea, coughing,

sneezing, secreted mucous.

Urogenital tractAcidic urine washes away pathogens

from urinary tractVaginal secretion are also acidic and

prevent foreign invasion

If a pathogen does get by any of these systems, the body has other defense mechanismsVomiting, diarrhea, coughing,

sneezing, secreted mucous.

Complement system20 proteins in blood plasmaForm membrane attack complex

Forms pore in foreign cell membrane, fluid enters and the cell swells and bursts.

Can amplify inflammatory responses, stimulating histamine responses

Or, phagocytes attracted to infectionOr, proteins coat microbes so

phagocytes may attach more readily

Complement system20 proteins in blood plasmaForm membrane attack complex

Forms pore in foreign cell membrane, fluid enters and the cell swells and bursts.

Can amplify inflammatory responses, stimulating histamine responses

Or, phagocytes attracted to infectionOr, proteins coat microbes so

phagocytes may attach more readily

InterferonsAlpha and beta

Made by almost all cellsProtect normal cells near infected cells,

preventing viral replication and protein assembly.

GammaMade by lymphocytes and natural killer

cellsPart of immunological defense against

infection and cancer.

InterferonsAlpha and beta

Made by almost all cellsProtect normal cells near infected cells,

preventing viral replication and protein assembly.

GammaMade by lymphocytes and natural killer

cellsPart of immunological defense against

infection and cancer.

Inflammatory response - localized, nonspecific response to infectionInjured cells release chemical

alarm singalsI.e., histamine which dilates local blood

vessels, increasing blood flow and making area warm.

Also increase permeability of capillaries, tissue swelling

Inflammatory response - localized, nonspecific response to infectionInjured cells release chemical

alarm singalsI.e., histamine which dilates local blood

vessels, increasing blood flow and making area warm.

Also increase permeability of capillaries, tissue swelling

Phagocytes go from blood to extracellular fluid to attackNeutrophils spill chemicals

killing nearby bacteria and other cells

Pus - dead/dying pathogens, tissues cells, neutrophils

Monocytes engulf pathogens and dead cells

Phagocytes go from blood to extracellular fluid to attackNeutrophils spill chemicals

killing nearby bacteria and other cells

Pus - dead/dying pathogens, tissues cells, neutrophils

Monocytes engulf pathogens and dead cells

Temperature responseMacrophages release interleukin-1

Carried by blood to brain, direct neurons in hypothalamus to raise body temp.

FeverStimulates phagocytosisSpleen and liver store iron, reducing

bacteria Temperatures 103 degrees F and up,

dangerous Temperatures above 105 degrees F, fatal

Denature enzymes

Temperature responseMacrophages release interleukin-1

Carried by blood to brain, direct neurons in hypothalamus to raise body temp.

FeverStimulates phagocytosisSpleen and liver store iron, reducing

bacteria Temperatures 103 degrees F and up,

dangerous Temperatures above 105 degrees F, fatal

Denature enzymes

Cells of specific immune systemLeukocytes - white blood cells

Neutrophils, monocytes (phagocytic)Lymphocytes, T cells and B cells

T cells - originate from bone marrow to thymus

Indentify pathogens by their antigens

Cells of specific immune systemLeukocytes - white blood cells

Neutrophils, monocytes (phagocytic)Lymphocytes, T cells and B cells

T cells - originate from bone marrow to thymus

Indentify pathogens by their antigens

4 principal T cellsHelper T cells - initiate

immune responseMemory T cells - provide quick

response to angtigen“cell poisoning” T cells - lyse

the infected cellsSuppressor T cells - terminate

immune response

4 principal T cellsHelper T cells - initiate

immune responseMemory T cells - provide quick

response to angtigen“cell poisoning” T cells - lyse

the infected cellsSuppressor T cells - terminate

immune response

B cells, however, mature in bone marrowReleased to circulate in blood and

lymphRecognize particular foreign

antigensDivide rapidly

Differentiate into plasma and memory cells

Plasma cells stick to antigens, flagging them for destruction

B cells, however, mature in bone marrowReleased to circulate in blood and

lymphRecognize particular foreign

antigensDivide rapidly

Differentiate into plasma and memory cells

Plasma cells stick to antigens, flagging them for destruction

Initiating immune response (example via influenza)After viruses avoid first two lines of

defense, macrophages initiate immune defense and inspect cell surfaces.

Most vertebrate cell surfaces have glyco (or MHC) proteins produced by MHC genes

Major histocompatibility proteins Genes are polymorphic (many forms)

Initiating immune response (example via influenza)After viruses avoid first two lines of

defense, macrophages initiate immune defense and inspect cell surfaces.

Most vertebrate cell surfaces have glyco (or MHC) proteins produced by MHC genes

Major histocompatibility proteins Genes are polymorphic (many forms)

MHC proteins serve as self markers due to individuality like fingerprints.

This allows immune system to distinguish between foreign cells : self-versus-nonself recognition

Antigen-presenting cells - cells that partially digest antigens, process and move them to surface of plasma membrane

Then complexed with MHC proteins so T cells can recognize them.

MHC proteins serve as self markers due to individuality like fingerprints.

This allows immune system to distinguish between foreign cells : self-versus-nonself recognition

Antigen-presenting cells - cells that partially digest antigens, process and move them to surface of plasma membrane

Then complexed with MHC proteins so T cells can recognize them.

T Cells: Cell-Mediated Immune ResponseMacrophages secrete interleukin-1

when processing foreign antigensStimulating cell division and activating T

cells, helper T cells secrete cytokinesCytokines are regulatory molecules,

lymphokines are secreted by lymphocytes

Cytokine is named according to biological activity but names can be misleading because of their different actions.

Interleukin followed by number to determine.

T Cells: Cell-Mediated Immune ResponseMacrophages secrete interleukin-1

when processing foreign antigensStimulating cell division and activating T

cells, helper T cells secrete cytokinesCytokines are regulatory molecules,

lymphokines are secreted by lymphocytes

Cytokine is named according to biological activity but names can be misleading because of their different actions.

Interleukin followed by number to determine.

Helper T cells also secrete interleukin-2, activating cytotoxic T cells and B cells

Cytotoxic T cells destroy infected cells if they display the foreign antigen with their MHC proteins

Also will attack any foreign MHC-I This causes problems like graft

rejection with transplanted tissues The closer individuals are related, the

less MHC proteins will vary, more likely tissues will be tolerated

Drug cyclosporin deactivates cytotoxic T cells

Helper T cells also secrete interleukin-2, activating cytotoxic T cells and B cells

Cytotoxic T cells destroy infected cells if they display the foreign antigen with their MHC proteins

Also will attack any foreign MHC-I This causes problems like graft

rejection with transplanted tissues The closer individuals are related, the

less MHC proteins will vary, more likely tissues will be tolerated

Drug cyclosporin deactivates cytotoxic T cells

Tumors have surface antigens that can stimulate immune destruction Initiate attack mostly by cytotoxic T

cells and natural killer cells Immunological surveillance -

proposed in 70s, described role of immune system in fighting cancer

Human interferons by genetically engineered bacteria made large amounts of substances for experimental treatment. Useful with certain cancers.

Tumors have surface antigens that can stimulate immune destruction Initiate attack mostly by cytotoxic T

cells and natural killer cells Immunological surveillance -

proposed in 70s, described role of immune system in fighting cancer

Human interferons by genetically engineered bacteria made large amounts of substances for experimental treatment. Useful with certain cancers.

B Cells: the Humoral Immune ResponseUnlike T cells, these bind to free

antigens as well.Antigen particles enter by endocytosis

and are processed by B cells

Helper T cells recognize specific antigen, bind to B cell and release interleukin-2 so the B cell divides.

B Cells: the Humoral Immune ResponseUnlike T cells, these bind to free

antigens as well.Antigen particles enter by endocytosis

and are processed by B cells

Helper T cells recognize specific antigen, bind to B cell and release interleukin-2 so the B cell divides.

This divison produces long-lived memory and short-lived plasma B cells

Plasma cells produce antibodies Antibodies are proteins called

immunoglobulins (Ig), divided into subclasses

IgM - first one secreted in primary response, allowing antigen-containing particles to stick

IgG - secreted during secondary response, major form in blood plasma

IgD - receptors for antigens on B cells IgA - major form in saliva , mucus,

breast milk IgE - promotes release of histamine

(sometimes resulting in allergies)

This divison produces long-lived memory and short-lived plasma B cells

Plasma cells produce antibodies Antibodies are proteins called

immunoglobulins (Ig), divided into subclasses

IgM - first one secreted in primary response, allowing antigen-containing particles to stick

IgG - secreted during secondary response, major form in blood plasma

IgD - receptors for antigens on B cells IgA - major form in saliva , mucus,

breast milk IgE - promotes release of histamine

(sometimes resulting in allergies)

Antibodies don’t kill pathogens directly, but activate the complement system and target the pathogen for attack by phagocytic cells.

Antibodies are made up of 2 identical short polypeptides (light chains) and 2 identical long polypeptides (heavy chains) forming a Y-shaped molecule

Antibodies don’t kill pathogens directly, but activate the complement system and target the pathogen for attack by phagocytic cells.

Antibodies are made up of 2 identical short polypeptides (light chains) and 2 identical long polypeptides (heavy chains) forming a Y-shaped molecule

Stem is formed by “constant” regions of heavy chains

Most variation occurs in the variable regions of each arm.Variable amino acid sequences

causes specificity of antibodies for antigens that reside in the arms

Stem is formed by “constant” regions of heavy chains

Most variation occurs in the variable regions of each arm.Variable amino acid sequences

causes specificity of antibodies for antigens that reside in the arms

How can B cells detect millions of foreign cells?Somatic DNA arrangement - when

an antibody is assembled, different sequences of DNA form a composite gene

More sequences generated by the shifting of the reading frame during transcription and “mistakes” during replications as lymphocytes divide.

How can B cells detect millions of foreign cells?Somatic DNA arrangement - when

an antibody is assembled, different sequences of DNA form a composite gene

More sequences generated by the shifting of the reading frame during transcription and “mistakes” during replications as lymphocytes divide.

Somatic mutation - mutations that change amino acid sequences in a somatic cell

19 million different possible antibodies without the possibility of mutations, 200 million with.

Somatic mutation - mutations that change amino acid sequences in a somatic cell

19 million different possible antibodies without the possibility of mutations, 200 million with.

Immunological Tolerance - acceptance of self cellsColonial deletion/suppression

Embryo, fetus, newborns lymphocyte clones have receptors for self antigens that are eliminated or suppressed as they mature. Cells learn to identify self antigens.

Only clones that survive are those directed against foreign cells

Sometimes B or T cells recognize their own tissues as antigens

Autoimmune disease

Immunological Tolerance - acceptance of self cellsColonial deletion/suppression

Embryo, fetus, newborns lymphocyte clones have receptors for self antigens that are eliminated or suppressed as they mature. Cells learn to identify self antigens.

Only clones that survive are those directed against foreign cells

Sometimes B or T cells recognize their own tissues as antigens

Autoimmune disease

The first time the body encounters a pathogen, few B and T cells recognize it’s antigensBinding of the antigen to its receptor

causes division and produces a clone (colonal selection)

Primary immune response - a person is sick because few cells can make an immune response so the response is weak

The first time the body encounters a pathogen, few B and T cells recognize it’s antigensBinding of the antigen to its receptor

causes division and produces a clone (colonal selection)

Primary immune response - a person is sick because few cells can make an immune response so the response is weak

Clones of memory cells develop after the primary response so should a second infection come, the response is stronger (secondary immune response)Memory cells can survive for

decadesReason vaccines are effective

Clones of memory cells develop after the primary response so should a second infection come, the response is stronger (secondary immune response)Memory cells can survive for

decadesReason vaccines are effective

Blood type indicates the class of antigens found on the red blood cell surfaceTolerance to those of own antigens

(I.e., type B to B antigens)Should they be mixed, cells clump

which can cause inflammation and organ damage.

Blood type indicates the class of antigens found on the red blood cell surfaceTolerance to those of own antigens

(I.e., type B to B antigens)Should they be mixed, cells clump

which can cause inflammation and organ damage.

Rh-positive allele is more comonIn the case of Rh-negative mothers,

they aren’t exposed to the Rh antigen of the fetus during pregnancy

During birth, exposure may occur and mother may produce antibodies against it

These can cross the placenta in future pregnancies and cause hemolysis of Rh-positive cells of the fetus

Baby is born anemic with erythrblastosis fetalis

Rh-positive allele is more comonIn the case of Rh-negative mothers,

they aren’t exposed to the Rh antigen of the fetus during pregnancy

During birth, exposure may occur and mother may produce antibodies against it

These can cross the placenta in future pregnancies and cause hemolysis of Rh-positive cells of the fetus

Baby is born anemic with erythrblastosis fetalis

Monoclonal antibodies - exhibit specificity for one antigenic determinant

Hybridoma - secretes identical, monoclonal antibodiesModern pregnancy tests covered

with monoclonal antibodies produced against a pregnancy hormone.

Antigen is present, reaction (agglutination) occurs.

Monoclonal antibodies - exhibit specificity for one antigenic determinant

Hybridoma - secretes identical, monoclonal antibodiesModern pregnancy tests covered

with monoclonal antibodies produced against a pregnancy hormone.

Antigen is present, reaction (agglutination) occurs.

AIDSThe retrovirus (HIV) mounts an attack on

CD4+ T cells (helper and inducer), leaving the immune system open to any foreign antigen

CD4+ T cells make up 60-80% of circulating T cells but HIV cells replicate before dying and infect entire population

HIV causes these cells to also secrete a suppressing factor that blocks other T cells from attacking the HIV antigen

Finally, blocks transcription of MHC genes so recognition and destruction of infected cells is hindered.

AIDSThe retrovirus (HIV) mounts an attack on

CD4+ T cells (helper and inducer), leaving the immune system open to any foreign antigen

CD4+ T cells make up 60-80% of circulating T cells but HIV cells replicate before dying and infect entire population

HIV causes these cells to also secrete a suppressing factor that blocks other T cells from attacking the HIV antigen

Finally, blocks transcription of MHC genes so recognition and destruction of infected cells is hindered.

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Renders person defenseless from infectionAZT inhibits the enzyme needed

for the virus to produce DNAMutation rates are high,

however, so it’s difficult to make an effective vaccine

Renders person defenseless from infectionAZT inhibits the enzyme needed

for the virus to produce DNAMutation rates are high,

however, so it’s difficult to make an effective vaccine

Antigen shifting - to mutate frequently so the nature of surface antigens varyProcess of evolution by natural

selectionHappens with African sleeping

sickness and influenzaNew vaccine based on DNA may help

by injecting a gene from the pathogen that doesn’t change, fragments sticking to cell membrane and marking it for destruction.

Antigen shifting - to mutate frequently so the nature of surface antigens varyProcess of evolution by natural

selectionHappens with African sleeping

sickness and influenzaNew vaccine based on DNA may help

by injecting a gene from the pathogen that doesn’t change, fragments sticking to cell membrane and marking it for destruction.

Autoimmune diseases - produced by failure of the immune system to recongize and tolerate self antigensSelf antigen may be hidden until

exposure later occursSystemic lupus erythematosus

Antibodies to nucleoproteins made Immune attack triggers inflammation

and organ damage. Must be suppressed through corticosteroids and drugs like aspirin

Autoimmune diseases - produced by failure of the immune system to recongize and tolerate self antigensSelf antigen may be hidden until

exposure later occursSystemic lupus erythematosus

Antibodies to nucleoproteins made Immune attack triggers inflammation

and organ damage. Must be suppressed through corticosteroids and drugs like aspirin

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AllergyImmediate hypersensitivity -

abnormal B cell response to allergen produces symptoms quickly

Delayed hypersensitivity - abnormal T cell response produces symptons within 48 hours after exposure

AllergyImmediate hypersensitivity -

abnormal B cell response to allergen produces symptoms quickly

Delayed hypersensitivity - abnormal T cell response produces symptons within 48 hours after exposure

Immediate results from IgE antibodies. Allergen binds to mast cells and basophils when exposed and histamine is secretedExcessive release causes

anaphylactic shock, a uncontrollable fall in blood pressure

Delayed results from secretion of lymphokines, must be treated with corticosteroids.

Immediate results from IgE antibodies. Allergen binds to mast cells and basophils when exposed and histamine is secretedExcessive release causes

anaphylactic shock, a uncontrollable fall in blood pressure

Delayed results from secretion of lymphokines, must be treated with corticosteroids.