transcript
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- The Immune System CAMPBELL and REECE Chapter 43
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- Innate Immunity nonspecific defense that is active immediately
upon infection found in all animals & plants includes: outer
covering skin or shell chemical secretions @ openings to interior
of body
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- Immune System must be able to identify nonself from self
detection determined by molecular recognition of receptor
molecules
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- Adaptive Immunity found only in vertebrates very specific aka
acquired immune response activated after innate responses &
develops more slowly
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- Innate Immunity of Insects only have innate immunity 1 st line
of defense (barrier defenses) Exoskeletons: effective against most
pathogens: made of polysaccharide, chitin
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- Innate Immunity in Insects: Barrier Defenses lining of
intestine: has chitin where it blocks infection by pathogens
ingested in food secretes lysozyme, enzyme that breaks down
bacterial cell walls
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- Insects Internal Immune Responses if pathogen gets by barrier
defenses: 1. hemocytes: immune cells in hemolymph some can
phagocytose others secrete chemicals that kill pathogens & help
entrap large parasites (like Plasmodium) interaction with pathogens
some secrete antimicrobial peptides circulate in hemolymph
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- Phagocytosis
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- Insect Immune Cells bind to molecules unique to outer layers of
fungi, or bacteria fungal cells: polysaccharides bacteria:
combinations of sugars & a.a. not found in animal cells
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- Innate Responses unique for different classes of pathogens
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- Innate Immunity in Vertebrates coexists with adaptive immunity
mechanisms 2 are strongly interdependent basis same as innate
immunity in invertebrates but there are additions most research
done on mammals
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- Barrier Defenses epithelial tissues block entry of many
pathogens skin mucous membranes line organs that have opening to
outside of body mucus: viscous fluid that blocks microbes &
other particles saliva, tears have washing action keeping microbes
from colonizing
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- Barrier Defenses cellular secretions lysozyme kills by breaking
down cell walls saliva, tears dilute & prevent colonization
sweat pH 3 4 stomach pH 2
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- s Internal Innate Defenses 1. phagocytes cells that can detect
fungi & bacteria use several types of receptors: Toll-like
receptor (TLR) binds to fragments of molecules characteristic of
set of pathogens similar mechanism used in insects
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- TLR Signaling Pathway
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- TLR TLR3 sensor for dsRNA (viral) TLR4 recognizes
lipopolysaccharide (surface of many bacteria) TLR5 recognizes
flagellin (bacterial flagella protein)
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- Types of Phagocytic Cells 1. Neutrophils circulate in blood
attracted by signals sent from infected cells 2. Macrophages larger
cells migrate thru tissues or reside permanently in organs/tissues
likely to have invaders
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- Types of Phagocytic Cells 3. Dendritic cells mainly found in
tissues that contact outside (skin) stimulate adaptive immunity
after engulfing pathogen 4. Eosinophils found beneath mucous
membranes low phagocytic activity speciality: able to defend
against parasitic worms secrete enzymes
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- Natural Killer Cells circulate thru body detecting abnl surface
proteins of cells infected with virus or cancer cells on detection
secrete chemicals that kill affected cell
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- Lymphatic System network of vessels that connect lymphatic
tissues thru out body ICF lymph vessels venous drainage some
macrophages in lymph nodes
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- Lymphatic System dendritic cells migrate to lymph node after
interacting with pathogen interact with other immune cells
stimulating adaptive immunity attack aka APCs: Antigen-Presenting
Cells
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- Lymphatic System
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- Pathogen Recognition Triggers: release of peptides &
proteins attack pathogens or impede their reproduction
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- Interferons proteins released in response to viral infection
vertebrates only now used in early treatment
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- Complement System ~30 proteins in plasma circulate in inactive
state activated by substances on surfaces of some microbes
activation starts cascade of reactions lysis of invading cells
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- Inflammatory Response innate immune defense triggered by
physical injury or infection of tissue involving the release of
substances that promote swelling, enhance the infiltration of WBCs,
& aid in tissue repair & destruction of invading
pathogens
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- Histamine 1 of inflammatory signaling molecules stored in
granules of mast cells (in CT)
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- Cytokines group of small protein secreted by # of cell types:
macrophages helper T cells regulate function of other cells to
enhance immune response promote increased blood flow to injured
area causes redness & increased skin temp engorged capillaries
leak fluid localized swelling
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- Inflammatory Response
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- Some Pathogens Evade Innate Immunity Bacteria: some have outer
capsule that interferes with recognition & phagocytosis
Streptococcus pneumoniae
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- Adaptive Immunity unique to vertebrates relies on
lymphocytes
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- Thymus organ in thoracic cavity some new lymphocytes travel
from bone marrow thymus & are taught how to respond in immune
attack mature into T cells
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- B Cells lymphocytes that stay in bone marrow to mature become
effector cells for humoral immune response
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- Antigen (agn) substance that elicits an immune response by
binding to receptors of B cells, antibodies, or of T cells example:
bacterial or viral protein agn receptor: general term for a surface
protein, on B or T cells, that binds to agns, initiating adaptive
immune responses
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- agn receptors specific enough to bind to just one part of 1
molecule from particular pathogen 1 B cell or 1 T cell makes only 1
specific receptor ~ 100,000 agn receptors on 1 B or T cell
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- B Cell or T Cell Receptors
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- agns usually large foreign molecules (proteins or
polysaccharides most often) stick out surface of foreign cells or
virus molecule of toxin secreted by bacteria
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- Epitopes small, accesible region of agn to which an agn
receptor or antibody (aby) binds aka: agn determinant
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- Epitopes single agn typically has several different epitopes
each will bind to receptor with different specificity agn receptors
of B & T cells encounter agns differently
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- Recognition of agn by B Cells B cell agn receptors Y shaped
made of 4 polypeptide chains 2 identical heavy chains 2 identical
light chains disulfide bridges link them
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- B Cell Antigen Receptor heavy chains extend into cytoplasm
anchor receptor light & heavy chains have constant(C) region
(nearly same on all B cells) & variable (V) regions (great amt
variation from 1 B cell to another) includes tail (heavy chain
only)that extends thru membrane & into cytoplasm and all
disulfide bridges
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- B Cell Activation starts when agn binds to a B cell agn
receptor ends with B cell secreting soluble form of its agn
receptor = antibody (aby) or immunoglobulin (Ig) abys have same Y
shaped organization as the B cell agn receptor
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- B Cell recognition of agn
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- T Cell Recognition of agn agn receptors made of 2 chains: chain
& a chain linked by disulfide bridges both chains pass thru
plasma membrane & into cytoplasm both have C regions & V
regions
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- T Cell Antigen Receptors fundamentally different from B Cell
these bind only to fragments of agns displayed or presented on
surface of host cells host protein that displays the fragment
called MHC (major histocampatibility) molecule
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- T Cell Recognition of agns begins when pathogen or part of one
either infects or is taken in by a host cell enzymes in host cell
break pathogen smaller peptides (each 1 called agn fragment) which
bind to MHC molecule combination moves to cell membrane outer
surface = agn presentation
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- agn presentation advertises fact that this cell has been
invaded by foreign substance when presenting cell meets T cell with
compatible agn receptor it will bind to the agn fragment & the
MHC molecule
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- 4 Major Characteristics of Adaptive Immunity 1. immense
diversity of lymphocytes & receptors enables immune system to
detect pathogens never before encountered 2. adaptive immunity
normally has self tolerance arises as B cell matures
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- 4 Major Characteristics of Adaptive Immunity 3. cell
proliferation triggered by activation greatly increases the # of B
and T cells 4. there is a stronger & more rapid response to agn
previously encountered immunological memory occurs after mature
lymphocyte encounters & binds to a specific agn
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- B & T Cell Diversity everyone has ~ 20,000 protein-coding
genes but has ~1 million different B cell agn receptors & ~ 10
million T cell agn receptors manage this by making different
combinations
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- B Cell Diversity 3 genes code for light chain 1.V segment 2.J
segment (joins) 3.C segment V + J = variable region light chain
gene contains 1 C segment, 40 different V segments & 5
different J segments: these pieces can be combined in 200 different
ways heavy chain segments have even more combinations possible
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- Enzyme complex called recombinase links 1 light chain gene
segment to 1 J gene segment forming single exon that is part V
& part J
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- Recombinase acts randomly linking any 1 of 40 V gene segments
with any 1 of 5 J segments same random connections made in heavy
chains once rearrangements complete agn receptors can be built
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- Origin of Self - Tolerance because combinations are random
sometimes receptors will be made that are specific for epitopes on
own cells/molecules as lymphocytes mature in bone marrow or thymus
their agn receptors are tested for self reactivity when discovered
are destroyed by apoptosis or rendered nonfunctional
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- Proliferation of B & T Cells successful match between
epitope with an agn receptor triggers a # of changes in cell #
& activity changes activate the lymphocyte # of cell divisions
producing a clone population some become effector cells Helper T
Cells Cytotoxic T Cells rest become memory cells long-lived cells
effector cells should same agn be encountered any time in animals
life
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- Immunological Memory gives individual long term protection from
an infection or vaccination Primary Immune Response produces
effector cells from a clone of lymphocytes peaks 10 -17 days after
initial exposure
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- Immunological Memory Secondary Immune Response if individual
exposed again to same agn there is a faster, larger & longer
response peaks 2- 7 days after exposure is hallmark of adaptive
(acquired) immunity
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- Humoral Immune Response occurs in blood & lymph abys
neutralize or eliminate toxins & pathogen in blood or lymph
includes a primary & secondary immune response
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- Cell-Mediated Immune Response specialized T cells destroy
infected host cells includes primary & secondary immune
responses
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- Helper T Cells triggers both humoral & cell-mediated immune
responses but does not directly carry out these responses signals
from helper Ts initiate production of abys that neutralize
pathogens activate T killers
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- T Helper Cells need 2 things to activate adaptive immune
responses 1. foreign molecule must bind to agn receptor of T cell
2. agn must be displayed on surface of an Agn-Presenting Cell (APC)
APC must be a dendritic cell, macrophage, or B cell
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- APCs have a 2 nd class of MHC molecules most body cells have
Class I MHC molecules APCs also have Class II MHC molecules
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- Class II MHC Molecules provide molecular signature by which APC
is recognized complex interaction between T cell & APC
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- T Cell Proliferation follows agn presentation by dendritic cell
or macrophage forms clone of helper Ts
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- B cells present agn to activated helper T cells these T cells
then stimulate activate B cells & cytotoxic T cells
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- Cytotoxic T Cells in cell-mediated immune response role:
effector cells synthesize toxic gene products that kill infected
cells activated by signaling molecules from helper T cells +
interaction with APC
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- Activation of B Cells when stimulated by both an agn &
cytokines secreted from helper Ts B cell differentiates into an
aby- secreting plasma cell
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- Activation of B Cells
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- Activated B Cells give rise to thousands of plasma cells 1
plasma cell secretes ~2,000 aby/s plasma cell lives 4 5 days
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- Antibody Function do not kill pathogens bind to agns
inactivation or destruction
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- Antibody-Mediated Mechanisms of Antigen Disposal
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- Active Immunity defenses that arise when a pathogen infects the
body & prompts a primary or secondary immune response
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- Passive Immunity pregnant moms IgG abys cross placenta &
protect fetus last few wks few mos newborn receives IgA abys in
breast milk give boost to babys immune system until it fully
develops Adults: IgA in tears, saliva, mucus
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- Artificial Active Immunity Immunizations: introduce agns to
body abys develop giving immunity to person receiving vaccination
Jenner: took cowpox virus to induce adaptive immunity against small
pox (closely related viruses)
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- Small Pox Vaccination
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- Antibodies as Tools Monoclonal Antibodies: made by clone of B
cells in reaction to single epitope used in medical diagnosis &
treatment: Home pregnancy tests genetically engineered to use as
immunotherapy
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- Blood Groups
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- Tissue & Organ Transplants MHC molecules stimulate the
immune response that rejection MHC molecules have many alleles and
any 1 individual has many that vary in shape & charge for most
transplant recipients there will be some MHC molecules seen as
foreign
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- Tissue & Organ Transplants to decrease the chance of
rejection the donor & recipient are matched = MHC molecules
same is both as much as possible also, recipient takes meds to
suppress immune response makes recipient more vulnerable to
infections
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- Moon Face
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- Graft Versus Host Rejection seen in bone marrow transplants
recipients bone marrow radiated b/4 to get rid of abnl cells also
wipes out their immune system lymphocytes in donors marrow react to
foreign recipients tissues and cells
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- Allergies exaggerated hypersensitivity reactions to allergens:
agn that triggers exaggerated immune response most involve aby of
IgE class example: hayfever agn on surface of pollen grains
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- Allergic Response agn attaches to IgE abys on mast cells when
cross linked release of histamine typical allergic symptoms of
itchy eyes, sneezing, runny nose, teary eyes, smooth muscle
contraction constriction of airways
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- Anaphylactic Shock whole-body, life-threatening reaction in
response to allergen due to widespread release of histamine by mast
cells: abrupt dilation of peripheral blood vessels quick drop in BP
& constriction of bronchioles (smaller airways) death can occur
w/in minutes due to decreased blood flow and inability to
breathe
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- Autoimmune Diseases Immune system reacts to some molecules of
self
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- Autoimmune Diseases
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- Exercise & the Immune System moderate exercise boosts the
immune system & significantly reduces susceptibility to colds
& other URTI exercise to pt. of exhaustion more frequent
infections psychological stress disrupts immune system by altering
interplay of
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- Stress & the Immune System psychological stress disrupts
immune system by altering interplay of the nervous system endocrine
system & immune system rest important for immunity adults with
< 7 hrs sleep/nite : 3x more likely to get sick when exposed to
cold virus as those who average 8 hrs sleep/nite
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- Immunodeficiency Diseases immune response to agns deficient or
absent frequent infections & increased risk of certain cancers
Inborn Immunodeficiency: genetic or developmental defect in immune
system Acquired Immunodeficiency: follows exposure to chemical or
biological agents
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- SCID Severe Combines ImmunoDeficiency: missing one or more
immune cells freq. die in infancy due to infections treatment: bone
marrow transplant stem cell transplantation gene therapy
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- Immundeficiency Disease Caused by Drugs drugs used to fight
against autoimmune diseases or prevent transplant rejection
suppress immune system immunodeficiency state
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- Immunodeficiency Disease Caused by Cancer Hodgkins Lymphoma
best known for this possible genetic predisposition
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- AIDS Acquired ImmunoDeficiency Syndrome caused by HIV (Human
Immunodeficiency Virus)
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- HIV escapes & attacks adaptive immune response infects
helper Ts virus binds specifically to the CD4 accessory
protein
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- HIV also infects cells with low levels of CD4: macrophages
brain cells
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- HIV RNA Genome reverse transcribed product DNA inserted into
host genome directs production of new virus
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- Immune Response to HIV immune system does respond to HIV attack
but some escape: 1. the virus has high rate of mutation during its
replication so has high agn variation (each infected individuals
population of the virus is evolving w/in that individual) 2.viral
DNA w/in host genome it is protected from immune system (some
latent for period of time then activate)
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- Latent HIV also protected from any anti-virals used to treat
patient
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- HIV over time avoids adaptive immune system & destroys it
viral reproduction (lytic cycle) & cell death loss of helper T
cells loss of humoral & cell-mediated immune responses
progresses to AIDS
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- 2 Infections Pneumocystis carinii fungal pneumonia Kaposis
Sarcoma herpesvirus rare cancer except in AIDS Candida fungal
infection rare except in babies
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- Progress of Untreated HIV
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- Treatment Strategy use combinations of anti-virals since each
round of HIV has mutations still get drug-resistant strains
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- Transmission of HIV virus particles or infected cells person to
person in any body fluid semen blood breatmilk most infections from
unprotected sex or tainted needles having another STD or some break
in mucous membranes increases likelihood of HIV
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- Transmission of HIV newly infected person can pass it on even
b/4 their blood test (+) for HIV blood test measures HIV abys 10
50% new cases got it from another newly infected person
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- Evolutionary Adaptations of Pathogens that Avoid Immune
Responses 1. antigenic variation immunologic memory is a record of
previous epitopes encountered pathogen may no longer express those
agns viruses parasites
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- Antigenic Variation in Trypanosoma bruceii
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- Influenza Virus mutates as spreads person to person exchanges
genes with pigs, chickens Influenza outbreak 1918-1919: >20
million died worldwide
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- Latency 2 nd way pathogens can change to avoid immune system a
largely inactive state dormant viruses quit making most viral
proteins and no free virus particles so do not trigger adaptive
immune response viral genome still in host nuclei
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- Latency typically persists until conditions arise that are
favorable for viral transmission or unfavorable for host survival
or defense (currently fighting another infection
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- Herpes Simplex Viruses establish home in sensory neurons after
initial infection Type I: mostly oral herpes infections Type II:
mostly genital herpes stimuli likely to cause recurrences: fever
emotional stress menstruation
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- Cancer & Immunity when adaptive immunity inactive,
incidence of certain cancers increases 15 20% of human cancers
involve viruses
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- 6 Viruses Known to Cause Cancer 1. Herpesvirus 2. Hepatitis B
3. Human Papilloma Virus (HPV) 4. Hepatits C 5. Human T cell
lymphotropic virus 6. Epstein-Barr virus
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- Vaccinations Hepatitis B HPV
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