Immune system By Zoe Kopp-Weber. FOver 500 million years ago, the immune system first appeared in...
-
Upload
thomas-bryan -
Category
Documents
-
view
217 -
download
3
Transcript of Immune system By Zoe Kopp-Weber. FOver 500 million years ago, the immune system first appeared in...
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.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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.