Unit 5-Chapter 37 Immunity
Immunity- an organisms cap a city to resist and combat
infection.
 Humans constantly come across a huge number of
viruses, bacteria, fungi, parasitic worms and other
pathogens
 However humans coevolved with many of these
pathogens so you have defenses that protect you from
them
 It is very important to be able to detect self from nonself
 All modern multi-cellular eukaryotes bear a set of
receptors that collectively recognize around 1000
different nonself cures called pathogen- associated
molecular patterns (PAMP’s)
 PAMP’s may include bacterial cell wall components,
flagellum, pilus proteins, and double stranded RNA.
 PAMP is an antigen which means it helps recognize
nonself molecules or cell components
 Binding of cell receptors to antigen trigger activation
of a complements
 A compliment is a set of proteins that circulate
through the body when activated they can destroy
invading cells or mark them for uptake by phagocytic
cells
http://www.youtube.com/watch?v=z3M0vU3Dv8E
Bozeman Immune System
2 types of immunity
Innate immunity- fast general defenses against infection,
pattern receptors and responses we are born with.
Adaptive immunity- immune defenses to vast array of
specific pathogens that an individual may encounter in their
lifetime.
Immunity is a 3 step defense system.
1st- physical, chemical, and mechanical barriers usually
keep pathogens outside of the body.
2nd- Imnate immunity issues a general response after tissue
is damaged or after antigen is detected.
3rd- adaptive immunity is initiated as leukocytes (WBC’s)
divide to form huge populations that a specific antigen and
destroy anything bearing it.
 Some of the WBC’s remain after the infection so if the
same antigen returns these “memory cells” mount a
secondary response.
Surface barriers
 Your skin teems with about 200 different kinds of
yeast protists and bacteria especially moist areas and
cavities on a daily basis.
 These microorganisms called your normal flora are
part of your first line of defense against negative
invaders.
HOWEVER! When these external Flora get inside they
wreak havoc. Some common culprits include…
Pneumonia, ulcers, colitis, whooping cough, meningitis,
cancers o fcolon, stomach, intestines and more.
 Overuse of antibiotics has helped turn some of our
natural flora against us.
ORAL flora –
 There are about 400 species but causes dental plaque
which is just a thick biofilm of bacterial and archae
colonies.
Problems arise – due to some of their extracellular
products such as lactic acid
→ weakening connections between teeth and gums
allow for pockets to form as we age. Bacteria
accumulate and secrete destructive enzymes and acids,
this is called Peridontis.
→ Worst yet a contributor to periodontist (also called
periodontal disease) is a species called Pgingivitalis
which is associated with a atherosclerotic plaque or
coronary artery disease.
SO TAKE CARE OF YOUR TEETH PEOPLE!
 Thinner barriers such as in the sinuses, mouth and
urethra have their own way of dealing with intruders.
 Many secrete mucus containing lysozyme which may
trap microorganisms and kill them. Others produce
other enzymes low in pH which the organisms cannot
withstand.
Triggering innate defensesthese defenses do not change over the lifetime they are
carried out by complements and phagocytic white blood
cells.
COMPLEMENTS
There are about 30 different complement proteins
circulating through the blood and interstitial fluid at all
times, most are in activated.
When they complement detects antibodies clustered on the
surface of an antigen they initiate a series of reactions.
C-3 is an extremely abundant complement which will coat
an area marking it for destruction.
Some complements can target pathogens even without an
anti-body response.
One such complement combined to six different pathogens
yeast, HIV, flu, salmonella, strep, and leishmania.
Normal body cells continually make protein that inactivate
complements so they do not spread too far into healthy
tissue.
Phagocytic (WBC’s) leukocytes
phagocytic leukocytes use chemotaxis to detect their target
3 main types include… Neutrophils, macrophages,
dendritic cells
INFLAMMATION and FEVER
Inflammation is a fast multiple response which destroys
active tissue and jump starts the healing process.
Inflammation begins when cells degranulate into affected
tissue in response to pattern receptor binding to an antigen.
Fragments of see three complement trigger de granulation.
Among the substances released by Degranulating
leukocytes are prostaglandins as histamines. This causes
nearby arterioles to widen, blood flow to the area increases,
more phagocytes arrive attracted to cytokines. Phagocytes
migrate out a blood vessel into interstitial fluid. Swelling
and pain occur because prostaglandins and histamines
widen the spaces between cells in capillary walls so they
make capillaries in the affected tissue leakier to plasma
proteins. This makes interstitial fluid hypertonic water
follows by osmosis, tissue swells. Once these stimuli
subside macrophages begin to produce compounds that
suppress inflammation and promote tissue repair. Chronic
inflammation is not a normal condition.
file:///F:/Media/PowerPoint_Lectures/chapter37/videos_animations/inflamation_mhtml
FEVER
fever occurs in response to infection, cytokeines
stimulate brain cells to release prostaglandins acting
on the hypothalamus to raise bodies internal
temperature. Fever enhances immune defenses by
increasing the rate of enzyme activity, speeding up
metabolism, tissue repair, and formation and activity
of phagocytes. Pathogens multiply slower at high
temperatures.
Fever signifies the body is fighting something and
should not be ignored HOWEVER brain damage or
death can occur if core temperature reaches 107.6°F.
Antigen receptors
if innate immune mechanisms do not rid the body of
invading pathogens and infection may become
established.
Innate immune responses are triggered by leukocytes
that detect antigen by antigen receptors. Several
antigen receptors exist plasma membrane proteins
that recognize PAMPs are one type T cells they are
another type called T cell receptors or TCRs for
short.
Another part recognizes certain proteins in the
plasma membrane of body cells as being part of
themselves these are called MHC markers.
Antibodies are another type of antigen receptor.
Antibodies are Y-shaped protein made only by B
cells and can bind to an antigen. They activate
complement and facilitate phagocytosis, neutralize
toxic molecules, prevent pathogens from attaching to
body cells.
Antibody molecules consist of four polypeptide
chains to light chains to heavy chains each chain has
a theory of and constant region the variable region
form 2 antigen binding sites which are antigen
receptors.
Each antibody having constant region that determines
its structural identity or class, there are five antibody
classes – IgG, IgA, IgE, IgM, and IgD – [IGE stands
for immunoglobulin]
most of antibodies circulating in the bloodstream and
tissue fluids are IgG which bind pathogens, neutralize
toxins, and activates complements. It is the only
antibody that can cross the placenta to protect a fetus.
IGA – is the main antibody in mucus and other
exocrine gland secretions.
IGE made by B cells is incorporated into plasma
membrane of mast cells, Basophils, and some
dendritic cells. It triggers the anchoring cell to release
its granules.
Humans can make billions of unique antigen
receptors.
Genes that code for the receptors do not occur in a
continuous stretch one chromosome, they occur in
several segments on different chromosomes. Several
versions exist and segments are spliced together
during B and T cell differentiation. This results in
2.5 billion different combinations of gene segments.
Before a new be cell leaves the bone marrow is
already making antigen receptors. In time that the cell
has more than 100,000 antigen receptors they mature
after encountering hormones in the thymus gland
stimulating them to make T cell receptors.
file:///F:/Media/PowerPoint_Lectures/chapter37/vide
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ADAPTIVE IMMUNITY
Lymphocytes and phagocytes interact to effect the 4
defining characteristics of adaptive immunity, which
are self/nonself recognition, specificity, diversity, and
memory.
 Self/nonself recognition- t cell recepotors have
the ability to recognize self by MHC markers.
TCRs, and other antigen receptors recognize
nonself in the form of antigens
 Specificity- tailored to combat specific antigens.
 Diversity- antigen receptors on a bodys
collection of B and T cells
 Memory- It takes about a week for B and T cells
to respond in force the first time they encounter
an antigen.
Two Arms of Adaptive Immunity-The antibodymediated and cell-mediated immune response.
 Antibody-mediated immune response- Bcells
produce antibodies targeting a specific invader.
 Cell-mediated immune response-targets
intracellular pathogens where cytotoxic Tcells
and NK cells detect and destroy infected body
cells or cancers.
Antigen Processing
Both types of adaptive immunity are initiated by
recognition of antigen by Tcell receptors.
Intercepting and clearing out antigen
Self notes went here
The Antibody-Mediated Immune Response
B cells are triggered to make antibodies specific to a
particular pathogen or toxin in extracellular fluid.
The secreted antibodies bind to the pathogen causing
uptake by phagocytic WBCs, and keep pathogens
from infecting other cells and neutralize toxins, and
help eliminate both from body.
http://www.cengage.com/biology/book_content/9781
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ctures/chapter37/videos_animations/antibody_mediat
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The Cell-Mediated Immune Response
A cell mediated immune response involves the
production of cytotoxic T cells and other
lymphocytes that recodgnize specific intracellular
pathogens. (does not involve antibodies)
Cytotoxic Tcells kill ailing body cells that may be
missed by an antibody-mediated response. These
cells would display certain antigens, altered proteins
and polypeptides. (responsible for transplant
rejections)
http://www.cengage.com/biology/book_content/9781
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NK Cells
Natural Killer cells will kill body cells that lack MHC
markers or have altered markers. Cytokines secreted
by helper T cells stimulate NK cell division. The
new effector NK cells attack body cells tagged by
antibodies for destruction.
When Immunity Goes Wrong
 When Exposure to harmless substances
stimulates an immune response than you have an
allergy
 Allergens are often drugs, foods pollen, dust
mites, fungal spores, poison ivy, venom from
bees and other insects
 Some people are genetically predisposed to
allergies, however infections, stress and changes
in air and temp can also trigger reactions
 1st exposure to allergens stimulates B cells to
secrete IgE which anchors to mast cells and
basophils
 Later, exposure causes antigens to bind to IgE
the anchoring cells (mast cells and basophils)
then degranulate and inflammation occurs
 Reactions can include swelling, itching, redness,
and mucus formation
 Antihistamines relieve symptoms by acting on
histamine receptors other meds can prevent
degranulation
A Balance of Immune Response is Really Important
 Immune defenses that kill pathogens can also kill
body tissues So-C3 compliment is activated
continuously to inhibit proteins that deactivate
fragments or else compliment cascades would
occur at all times.
 Anaphylactic Shock may occur if immune
responses are too extreme and not kept in check
o Shock occurs when cytokines and
histamines are released in all parts of the
body causing everything to swell including
airways
 Severe asthma or septic shock may occur when
too many neutrophils degranulate at once.
o “cytokine storms”- when leukocytes release
too many cytokines at the same time and
widespread inflammation can result in organ
failure (H5N1) flu is known for this
Auto Immune Disorders
 Usually people do not make antibodies to
molecules which occur on their own healthy
body cells (normal MHC markers) BUT
sometimes things go wrong
 Usually the Thymus “weeds out” defective T cell
receptors if this mechanism fails mature
lymphocytes that do not discriminate between
self and non self are produced and these
lymphocytes mount an Auto Immune Response.
 Examples:
o Graves Disease occurs when antibodies bind
to stimulatory receptors on thyroid gland
causing excess production of thyroid
hormone
 Quickens metabolic rate, uncontrollable
weight loss, rapid irregular heart best,
sleeplessness, mood swings, bulging
eyes
o Multiple Sclerosis- self reactive T cells
attack myelin sheaths of axons
 Weakness and loss of balance paralysis
and blindness
 Specific alleles on MHC markers, bacterial and
viral infections are often underlying causes of
autoimmune disorders
Immune Deficiency
 Impaired immune function is dangerous and
sometimes lethal
 Primary immune deficiencies present at Birth are
the outcomes of mutations
o Ex. SCID’s
 Secondary immune deficiency is caused by
exposure to an outside agent usually a virus
o Ex. Aids
HIV and AIDS
AIDS is a collection of disorders which results from
infection with HIV virus that cripples the immune
system. 33.3 million individuals have HIV it’s
considered a pandemic.
There is no cure for HIV
→ at first people appear to be in good health possibly
fighting a cold or flu
→ eventually fever, enlarged lymph nodes, fatigue,
and weight loss with night sweats occur.
→ Then yeast infections of the mouth, esophagus,
and vagina often occur. Pneumonia, gastrointestinal
inflammation and diarrhea appear. Colored lesions
from Kaposi’s sarcoma erupt over the body. Other
cancers are also common.
HIV – is a retrovirus with a lipid envelope consisting
of small pieces of plasma membrane. Proteins jut
from the envelope, span it, and line its inner surface.
Beneath the envelope viral proteins enclose two RNA
strands and reverse transcriptase enzyme. When a
retrovirus particle infects a cell, reverse transcriptase
copies the viral RNA into DNA integrating it into the
hosts cell’s DNA. Now the host begins to produce
viral proteins.
HIV mainly infects macrophages, dendritic cells, and
helper T cells. Viral particles enter the body,
dendritic cells engulf antigen to naïve T cells army
of HIV neutralizing IgG antibodies and HIV specific
cytotoxic T cells form.
HIV and AIDS
 The initial response rids the body of most-but not
all- of the virus
 HIV infects a few helper Tcells in a few lymph
nodes
 Years or even decades-the level of HIV remains
low
 Patients are contagious at this stage, though
symptoms are not apparent
 Eventually-level of virus-neutralizing IgG
plummets, production of Tcells slows
 Adaptive immune system becomes less and less
effective at fighting the virus
 Transmission-mostly by unprotected sex with an
infected partner
o Infected mothers may pass virus during
pregnancy, labor, delivery or breast feeding
o Contact with blood
 Ex. Iv drug users, hospital patients in
less developed nations and blood
transfusion
 Testing done through blood, saliva or urine
 Treatments-No cure-but slow the progression.
Drugs target retroviral replication
 Historyo HIV-1 evolved to infect humans from a SIV
(simian immune deficiency virus) that
effects chimpanzees in west central Africa
o Earliest known evidence was blood from a
man in 1959 and a lymph node removed
from a woman in 1960 (in west central
Africa)
o The gene sequences were a little different
suggesting the virus had been around for a
while and had mutated
o Mutation rates of HIV suggest that it may
have been around since the early 1900s
Vaccines
 Immunization-process designed to induce
immunity
o Active immunization is preparation that
contains antigen ( a vaccine )
 1st immunization elicits a primary
immune response
 2nd booster elicits a secondary immune
response for enhanced immunity
o Passive immunization-made from antibodies
purified from another persons blood
 Has an immediate benefit when exposed
to potentially lethal agents
 Ex. Tetanus, rabies, Ebola, venom
or toxin
 Only lasts as long as the original
antigens do (no memory cells are made)
 1st vaccination developed in late 1700s against
small pox by using pus from cowpox sores!
Yuck!