Leishmania

vector transmitted (sand fly bite), protazoa, zoonotic and
anthroponotic (dogs, humans and other vertebrae are reservoirs)
visceral (macrophages carry to lymph, causes
inflammation in spleen/liver, fever and anemia) often fatal
cutaneous (in skin, localized, ulcer causing) mucosal
(nose/palate mutilation) rare
no vaccine/drug
treatment: liposomal amphotericin B

Trypanosoma cruzi - chagas
"kissing bug

protozoa (eukaryote), blood parasite (hemoflagellate), heterotrophic
(gets food somewhere else)
transmission: acquired through bug feces (parental-by cut)
acute: fever/swelling. immediately after
infection. treatment- nifurtimox/benznidazole (toxic to
our cells too) chronic: heart abnormalities, dilated
esophagus or colon treatment-medication cannot cure,
diet/heart transplant, steroids
prevention: cruziguard (fake feces!!), insecticide spray,
blood donation screening, early treatment

Wucheria bancrofti

nematode, human specific, sexual dimorophism (male and female) round
white hard to remove worm
transmission:
mosquito ingests microfilariae, becomes larvae,
spreads to human (biologically), takes year to mature and have
microfilariae
pathogenesis:
asymptomatic-many microfilariae in blood, no
symptoms acute-worms in adult stage disrupt lymph system,
symptoms last 5-7 days obstructive
(chronic)-elephantiasis, swelling from scar tissue that doesnt go
down
treatment: medicine to kill larvae, food hygeine,
antiparisitic antibiotics,
prevention: avoid mosquitos, annual medicine to kill
larvae, test blood

Schistosoma

trematode (blood fluke) human=definitive, snail=intermediate
transmission: parasite reproduce in snail, hatch to larvae,
larvae infect human via direct contact with contaminated water
eggs lodge in tissues, cause immune response of swelling,
granulomas form as result of body trying to clear eggs
causes rash, headache/fever, swelling (intestine/urinary
tract)
mostly in africa; causes 200000 death/yr
treatment/prevention: drug is praziquantel, treatment lasts 1-2
days. better sanitation helps

basic t cell/b cell intra/extracellular pathogen ridance

Extracellular pathogen ingested and killed by
macrophage>>antigen presented by mhc2>> detected by cd4+ t
cells (thelper with specific antigen receptor)>> b cells told to
divide, activates macrophage
Intracellular pathogen invades cell>> it�s broken up and put
on MHC1 as antigen representor>>t cells with cd8
recognizes>>cytotoxic tcell releases perforin, granzyme and
kills host cell neatly

T cell
B cell
NK cell (natural killer cell)
M cell
superantigen

T cell=NOT PHAGOCYTE.
CD4 in adaptive and humoral, helper t cells make
cytokines CD4 t helper needed to recognize MHC II, As
stimulated, it divides and is ready to find B cells with same
antigen displayed to make antibodies or help with CD8. CD8
cytotoxic t cell Infected cell presents abnormal antigen on
MHC1, cd8 transforms to CTLymphocyte, connects to cell and induces
apoptosis
b cell=antibody producer
nk cell= in lymph and blood stream. don't need abnormal antigen to
kill. circulating looking for cells that aren�t right. can tell by
signals such as mhc 1. If virus messes up mhc1 representation so t
cells don�t attack. Natural killers will attack if missing or changed mhc1
Release perforin and granzyme causing cell suicide
m cell=covers peyers patch. Peyers patch sample environment
antigen, present antigen to (t/b cells) dendritic cell and macrophages
Bacteria goes to m cells, enters, replicates in macrophage
and travels to local lymph nodes and can travel around body
super=signals many t cells meaning excess interleukin 2 and shock-
doesn�t need antigen
staph or streptococcus don�t have to be severe to cause, just
circulating blood

COMPLEMENT
(SECOND LINE DEFENSE)
C3b causes opsonization C3a + C5a cause
inflammation C5b + C6 + C7 + C8 + C9 cause cell lysis

produced in liver, circulates in serum, heat sensitive
coat invaders to target them to be eaten (enhance
phagocytosis) = opsonization call for help, attracts
phagocytes (promote inflammation) create holes in bacteria
(cytolysis) -MAC
classical= 2 antibodies catch C1, C1 recruits c2 and c4 splitting
into a and b's for each, C4b and c2a combines to make c3 which splits
into c3a (inflammatory) and c3b (opsonizaiton and cytolysis)
alternative= b, d and p factor receptors attracted to microbe
surfaces. When c3 hits factors, c3 SPONTANEOUSLY splits into c3b and
c3a. don't need antibodies so don't need previous infection
lectin=Bacteria has surface proteins with sugar (esp mannose)(our
cells hardly ever have mannose) Immune system tells self from
everything else so if it sees mannose it targets. lectin (protein)
binds to mannose, binds to split c2 and c4 to make c4b and c2a combine
to c3

Phagocytes
(SECOND LINE DEFENSE)

Neutrophils (pmns): FIRST RESPONSE. in blood, short 24 hr life, leave
blood to fight infection in tissues/airway/tracts. Make granules,
after work may blow self up to make net
eosinophil is type, more abundant
Macrophage (from monocyte): In tissue, don't blow up/release granuoles.
Dendritic cell (from monocyte): present in tissues and lymph nodes

Phagocytosis

Chemotaxis leads phagocyte by following chemokine gradients.
attach by Fc&C3b if opsonized, TLR if not opsonized
Bring in particle in vacuole by NADPH oxidase that is
recruited to surface of phagosome that produces
superoxide/hypochlorous acid
Fusion of phagocyte+lysosome=phagolysosome that drops pH of
phagocyte and partially digests microbe
digestion & MHCII antigen display

digesion in phagocyte

O2 independent
Use acids/lactoferrin (keeps iron in phagolysosome away from
bacteria)/lysozyme (disrupts cell wall)
O2 dependent
Superoxidase: oxidative burst! NADPH oxidase-very reactive
Myleoperoxidase: catalyzes production of Hyrdrogen peroxide
(h202) plus Chlorine making hypochlorous acid (bleach!) that is very
antimicrobial that doesn�t damage our cells as much
Nitric oxide dependent makes peroxynitrite, potent
antimicrobial

Pattern recognition receptor (PRR)
Microbial-associated molecular pattern (Mamp)
(SECOND LINE DEFENSE)

When PRR detects MAMP, cytokines produced
MAMPs (shows it's not human!)
repeating unit: Lipid A, Peptidoglycan, Flagellin,
dsRNA
PRR
Toll-like receptor family (TLR) Nuclotide
oligomerization domain family (Nod) RIG-1-like RNA helicase
family (RLH)
Detect one mamp with specific PRRs; one mamp often detected
by multiple receptors

cytokine/chemokine (make inflammation!)
interferon

*Cytokines signal cells and surrounding cells to change selves by
peptides after mamp is detected
Chemokines are chemotactic (can cause immune cells to come
into area)
immune cells have receptors for cyto/chemokines to listen to
signal, may be more responsive to certain cytokines
Cytokine ex: interleukins, tumor necrosis factor, interferons
interferon: Alpha and beta signal cells to make antiviral
proteins, Gamma signals phagoctyes
Interferons detect viral RNA by PRRs. Signals
neighboring cells by interferon to produce antiviral proteins and
block protein synthesis of cell (shuts down cell for a while) so
virus cant replicate in it. First cell is dead.

inflammation
histamine

caused by cytokine response; damaged cell releases chemicals:
Histamine=common; increased blood vessel
permeability Leikotrienes=fatty acid; signal phagocytes
to ingest more bacteria/increases permeability of blood
vessels Prostaglandins=intensify histamine/kinins
make blood vessels more permeable and larger so more
macrophages and neutrophils

humoral (b cell)/cell mediated immunity (tcell)
(THIRD LINE DEFENSE)
neutrilization

Humoral: b cells produce antibodies,lymphocites make
b cell, mature in bone marrow
Antigen-Ag-causing production of antibodies hapten- too
small alone to cause antibody production, must be combined with
carrier molecules (ex: penicillin. Can be allergic to)
Antibody/ immunoglobulin (Ab/Ig)- glycoprotein binds with
antigen in response to antigen the part that binds is epitope (end
of Y shape branches)

Cell-mediated: t cells-toxic, made in bone marrow,
mature in thymus
Neutralization: toxin cant get to preferred site because
antibodies in the way (Ig A, G and M good at it)

antigens

All have same core 'Y' structure, Fc = stem of Y region
IgG, IgD, IgE (single Y)
IgG-good at opsonizing and complement, produced later in
exposure
IgA (two Y�s linked by dimer J chain) binds with mucosal
pathogen to stop from getting to epithelial
IgM (5 linked by chain) has ten binding sites so good at
clotting (AGGLUTINATION) produced early in exposure!!
Without disulfide (s-s-s-) bonds that hold lights and heavy
chains together it fall apart
Depending on variable end, antibody recognizes different antigens

Making B cells
Maor histocmompatibility complec (MHC)

{t dependent}
Have B cell with MHC 2 antigen on surface, if TH cell
matches antigen it activates B cell to make cytokines and divides
by clonal selection Antigen presented, B cell recognizes.
If antigen matches B cell receptor (antibody) it�s brought into
cell by endocytosis.Digested and put in MHC class II some
of these clones become PLASMA CELLS (secrete antibodies) or memory
b cells (long lived, quickly activated) Thelper only
recognizes B if antigen is there, has CD4 to recognize MHCII
t independent
Polysaccharides with repeating subunits T independent
activation Multiple b cell receptors so cell automatically divides
when multiple receptors activated, IGM made here Before 18 months
this doesn�t work, some vaccines not given to babies for this
reason
MHC: proteins recognizing self, present antigens

MHC I-on all cells but RBC�s
MHC II-dendritic/b cells/macrophages. Bacteria brought into
phagolysosome, broken into bits. Loaded onto MHC II, secreted to
outer membrane so MHC 2 on outer membrane to recognize

opsonization
apoptosis:

opsonization: coat invaders to target them to be eaten (enhance phagocytosis)
apoptosis: programmed cell death sends out signals to other cells
to attract macrophages
Cytotoxin releases proteins:
Perforin (perforates, riddles with holes where enzymes can pass)
Granzyme (passes through perforin holes and causes apoptosis
Granulysin targets bacteria membrane in host cell to lyse
***when it blows up it stays neat with insides contained so keeps
in bacteria/toxins/discrete doesn�t cause indogenous pyrogenes
When lots of debri, indogenous pyrogenes is released causing
fever (why you get fever after trauma/torn ligament/etc)

Naive T cells

Treg tells all to relax, its under control-I-L10 good at shutting
things down, anti-inflammatory
Th1 make Inerfeuron gamma that activaes macrophages to eat
infected cells
Th2 makes IL 4/5 activated b cells attacking outside pathogens
Th17 makes many I-L 17 that recruits neutrophils that clears
extracellular bacteria
subtypes have different rolls.
Want to tailor response to what it needs to respond to.
Na�ve cell cytokine response determined by MAMPS (peptidoglycan.
Lps. Teichoic acid. Double stranded rna. Flagellin)

What are the differences between active and passive immunization?
Natural vs artificial immunization?

IMMUNIZATION=BROAD, TYPE VACCINE
natural:
a-self recovery from infection, become immune
p-mother placenta/breastmilk
artificial: (vaccine/monoclonal antibodies)
a-vaccine
p-injection of performed antibodies

What are the main reasons for opposition to vaccination?

may also have connection to autism. don't want to
overwhelm immune system would prefer "natural
recovery" Want to �boost natural immunity� and not
vaccinate, use supplements instead reject what they believe
is infringment on freedom distrust of
outsiders/government

What impact has vaccination had on the world? How has it been measured?

protected many people from infections, sometimes for their whole
lives. has eliminated smallpox, measles and polio.

live attenuated vaccines
inactivated vaccines

live attenuated: triggers immune response (cow pox to avoid small pox)
inactivated: pathogens (killed by formaldehyde) injected hoping
they become immune
killed whole cell/virus- (whole virus vaccine is polio,
injected in arm, you may get fever while virus parts injected cause
immune response when macrophages/dendritic cells pick up take to
lymph nodes use mhc to represent antigen so helper t cells recognize
[may cause fever from making cytokines] and finds b cells with
antigen and it divides to produce antibodies)
INFLUENZA: being reproduced in eggs so all can take and many are made
subunit: acellular (not whole cell) = �Purified membrane
(bacteria), capsid or envelope (virus) proteins ex: When antibodies
cover capsule, macrophages digest, you�ll have a antibodies to this
infection. conjugated: antigen mixed with something else like
latex like fusing weak immunogen (protein/polysacc) and strong
immunogen (cholera) so both parts become immunified toxoid:
take inactivated toxin (cholera/pertussis) using heat/chemicals so
no longer enzymatic and inject in. antibodies can still recognize
and protect dna vaccine=Dna injected with virus genes like
capsid, plasmid injected into muscle cell and makes particles that
are like virus. cells take dna, show antigen & stimulate
response. Particles don�t make sick bc no viral rna!

Are inactivated or live attenuated vaccines more effective?

Live attenuated advantages: more effective, don�t need
booster bc stays in longer, safer (can immunize someone with small
deficiency). Adjuvant not required. Less cost bc no repeating, usually
oral so no nurse/needle needed
but storage harder bc need right temp

Inactivated vaccines: virulent gene taken. less effective bc
inactivated cause mostly humoral immunity response.
Dna vaccine storage cheap and easy
but Need boosters (repeated input)!
Conjugated is safest for children.

adjuvants
"dirty little secret

Addition of aluminum salts that enhance the effectiveness of the vaccine.
Adjuvants slow removal of antigen so more time to make immune
response. innate immunity stimulated by adjuvant by prrs being stimulated.
adjuvants mimmick antigen to stimulate receptors. Mostly
responsible for discomfort felt by some vaccines. Trying to find less
inflammatory/safer adjuvants
don't know exactly how they work.

Sensitivity
Specificity

Using immune system to diagnose disease.
Specific: wont detect when there is none (how often you get false
positive/high level confidence)
Sensitive: not going to miss if specimen is there
specificity: positive you can be nearly certain that they
actually have the disease. (high degree of confidence)
sensitivity: if the test is highly sensitive and the test result
is negative you can be nearly certain that they don�t have disease.
sensitivity is used to rule out disease when the result is negative.

monoclonal antibodies (hybridoma)

monoclonal means one clone of b cell to make only one antibody (with
one antigen binding site-only responds to one antigen)
Made by fusing cancerous b cell with antibody making normal b
cell, helps make immune test more accurate. Uniform, specific and
produce readily in large quantities.
Used for: Human therapy, Antigen detection
Chimeric: Genetically engineer mice so producing mice
antibody where constant region is human Humanized: only
part from mice is where antigen binds Fully: human
antibodies, expensive

Precipitation reaction
agglutination reaction

Precipitation reaction: reaction of soluble antigens with antibodies
in vile
Precipitaton made= positive test bc means antigens
present
Agglutination: insoluble antigens react with antibodies,
direct=(IGM antigens on a cell) indirect=use latex
beads coated with antigen or antibody and mix patient sample with
opposite (either antigen or antibody) and see if agglutination
happens hemagglutination=Specific type agglutination,
agglutinate rbc�s. Mix virus with rbc to see if it happens. If so,
human has virus bc antibodies would prevent this.

flourescent antibody test

direct FA=fluorescent antibodies bind directly to pathogen
indirect FA=flourescent AB binds to patient AB in serum which
attach to lab stock of pathogen.
IF IT GLOWS TEST IS + bc antibody attached

Enzyme-linked immunosrbent assay (elisa-enzyme linked to MAB (AB) is indicator)

direct=mab in well. Add patient sample that will stick if has
antigen. Add enzyme that will sandwich and add substrate that will
color change in well if antigen present and antibody with enzyme attaches
Pregnancy test detects agglutinizing hormone
indirect=antigen in well. Add patient serum that may have
antibody. Enzyme added and binds to antibody will change color if positive
*Detects antibody and sees if present

indirect and direct agglutination

agglutination: (IGM mostly) particulate or soluble antigens adhering
to particles. they are linked by antibodies to form visible
aggregates. sensitive and east to read.
indirect agglutination: detected if antigen adsorbed onto particle
with latex/cly. rapidly detects bacteria/viral diseases.
direct agglutination: detects antibodies in large antigens like
rbcs, bacteria or fungi.

How are immune reactions used to diagnose microbial diseases?

immune reactions come from stimulated antibodies.
neutralization is an antigen-antibody reaction where harmful
aeffects of a bacterial exotoxin/virus are blocked by spefic antibodies
complement-fixation is when complement binds to antigen-antibody
complex and used up or fixed.

Considering what you know about innate immunity, explain why people
who take high doses of vitamins might be at greater risk from dying
from infectious diseases or cancer.

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