Transcript Immune system - Crestwood Local Schools

Immune system
By 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.
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 defense
First, skin.
As it is the largest organ of the
vertebrate body
Provides a nearly impenetrable
barrier
Reinforces defense with chemical
weapons on the surface
Oil and sweat glands
Prevents loss of air through
evaporation
Second, cellular counterattack
Nonspecific cellular and
chemical devices respond to
infection without identifying
invaders
Central location of collection and
distribution: lymphatic system
Lymphatic 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.
Neutrophils
Kill by phagocytosis but release
chemicals that kill surrounding
bacteria and neutrophils
themselves.
Natural killer cells
Kills 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
Third defense, immune response
Best explained through
experiments of Pasteur and
Jenner
Edward Jenner studied
immunology through smallpox
Milkmaids who’d had cowpox rarely
had smallpox
Tested 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.
Pasteur studied fowl cholera
Isolated 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
response
Large, complex like proteins
Foreign to body, present on
pathogens
Different parts stimulate different
response
Different 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
antibodies
Antibody - 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 antigens
Cell-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
3 routes of entry by
virus/microorganism
Digestive tract
Microbes in food killed by saliva while
acidic stomach and digestive enzymes
kill what makes it to the intestine.
Respiratory tract
Cells 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 tract
Acidic urine washes away pathogens
from urinary tract
Vaginal secretion are also acidic and
prevent foreign invasion
If a pathogen does get by any of
these systems, the body has
other defense mechanisms
Vomiting, diarrhea, coughing,
sneezing, secreted mucous.
Complement system
20 proteins in blood plasma
Form 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
infection
Or, proteins coat microbes so
phagocytes may attach more
Interferons
Alpha and beta
Made by almost all cells
Protect normal cells near infected cells,
preventing viral replication and protein
assembly.
Gamma
Made by lymphocytes and natural killer
cells
Part of immunological defense against
infection and cancer.
Inflammatory response localized, nonspecific response
to infection
Injured cells release chemical
alarm singals
I.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 attack
Neutrophils spill chemicals
killing nearby bacteria and other
cells
Pus - dead/dying pathogens,
tissues cells, neutrophils
Monocytes engulf pathogens
and dead cells
Temperature response
Macrophages release interleukin-1
Carried by blood to brain, direct
neurons in hypothalamus to raise body
temp.
Fever
Stimulates phagocytosis
Spleen 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 system
Leukocytes - 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 cells
Helper T cells - initiate
immune response
Memory T cells - provide
quick response to angtigen
“cell poisoning” T cells - lyse
the infected cells
Suppressor T cells - terminate
immune response
B cells, however, mature in bone
marrow
Released to circulate in blood and
lymph
Recognize particular foreign
antigens
Divide 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)
MHC proteins serve as self markers
due to individuality like
fingerprints.
This allows immune system to
distinguish between foreign cells : selfversus-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
Response
Macrophages secrete interleukin-1
when processing foreign antigens
Stimulating cell division and activating
T cells, helper T cells secrete cytokines
Cytokines 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
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
Response
Unlike 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 antigencontaining 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
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
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.
Immunological Tolerance acceptance of self cells
Colonial 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
antigens
Binding 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
decades
Reason vaccines are effective
Blood type indicates the class of
antigens found on the red blood
cell surface
Tolerance 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 comon
In 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 antibodies
Modern pregnancy tests covered
with monoclonal antibodies
produced against a pregnancy
hormone.
Antigen is present, reaction
(agglutination) occurs.
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AIDS
The 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
Renders person defenseless
from infection
AZT inhibits the enzyme needed
for the virus to produce DNA
Mutation rates are high,
however, so it’s difficult to make
an effective vaccine
Antigen shifting - to mutate
frequently so the nature of
surface antigens vary
Process of evolution by natural
selection
Happens with African sleeping
sickness and influenza
New 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 antigens
Self antigen may be hidden until
exposure later occurs
Systemic 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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Allergy
Immediate 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
secreted
Excessive release causes
anaphylactic shock, a
uncontrollable fall in blood
pressure
Delayed results from secretion
of lymphokines, must be treated
with corticosteroids.