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Chapter 16
IL-2 is the essential IL for growth and
differentiation; it can be autocrine or paracrine.
We have two signals in cell-cell interaction
(immunological synapse):
1. First signal: is TCR (on T-cell) binding to MHC
class II (on APC)
2.Second signal: is co-stimulatory signal provided
by interaction with accessory molecules. Which
are:
A.LFA-1 & ICAM-1 -- adhesion moleculesB.CD28 &CD80 (B7)-- t-helper activation
C.CD154 (CD40L) & CD40 -- isotype
switching (IgM---> IgH {IgA & IgE})
Not all these molecules will be available at the
initiation response, they will develop in secondarylymphoid organs, and any defect in their
development ----- immune compromised patient.
If T helper differentiated into ----- TH1 &
secreted INF (causes tissue damage & fever) ---- then it will secret inhibitory signal to TH2,
which will be turned off, and visa verse.
CD40 and CD154 (CD40L) from low affinity IgM
to high affinity IgG.
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IL-2 is the maestro. The most important
interleukin that can be produced from T cells. Its
the one that is targeted by immune suppressant
drugs.
When the cell is activated it will produce an IL-2
receptor and introduces IL-2. IL-2 acts on the
receptor on the same cell (autocrine) or can act on
other cells that have the receptor.
Mycobacterium in general induces cell mediated
immunity.
In tuberculoid leprosy, TH1 are activated and
INF-gamma will be produced and this is needed to
get rid of M.Leprae. Macrophages will be
activated.
When you do skin testing, in the tuberculoidleprosy it will be positive. Because it is the
delayed type of hypersensitivity, macrophages are
involved. While if you do that in the lepromatus
leprosy it will be negative, although we have a
massive infection going on.Why the switch doesnt take place in the latter
type? We dont know.
TH1 cells are involved in multiple sclerosis
If I have lots of immunoglobulins produced in my
body in an autoimmune disease, the treatment of
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that is to give lots of immunoglobulins. (Didn't get
what he meant)
H.influenzae and S.pnuemoniae are encapsulatedbacteria. The capsule induces thymus independent
antigens. They produce only IgM antibodies with
low affinity and low isotype switching is going to
take place. So the first time is like the second
time and no memory. If you are infected with an
encapsulated strain of H.influenzae you can be
infected again because the capsule is thymus
independent.
How do we make the capsule thymus dependent?We vaccinate with conjugated vaccines. Box 16.4
Chapter 17
The most important regulatory mechanism to keep
memory cells in our body is cytokines. They
nurture the cells and keep them alive.
Memory cells give better high affinity specific
antibodies.
The longer the antigen is present a better memory
will be present.
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As you know, we have "inactivated vaccines "and"
live attenuated vaccines". In the live attenuated
vaccines, the antigen is kept for long periods of
time in the body because it resembles natural
injection (by reducing the virulence of a pathogen,
but still keeping it viable or "live". From Wiki).
Or when we do the "adjuvant" (like an oil deposit),
it makes the antigen stays in the body for longer
time to maintain memory cells.
Chapter 19
When we are exposed to an infection, we have 1st
line of defense (skin, mucus membranes), 2nd line
of defense (the complement, interferons, Creactive protein (acute phase proteins because
there are many)), and 3rd line of defense.
Skin: sweat glands, sebaceous glands and fatty
acids all can interfere with the survival of manymicroorganisms.
We have type 1 interferons (IFN alpha and IFN
beta) with cells usually infected with viruses, and
type 2 (IFN gamma). Interferons are species
specific.
Double stranded RNA is going to activate protein
kinases and DNAses then the messenger RNA of
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the virus is going to be destroyed. (type 1 IFN
action)
Type 2 IFN (IFN gamma) has a differentmechanism of action in comparison to Type 1 IFNs;
it increases the expression of MHC class 1.
- No additional information for chapter 18.
Done by: Diala AlawnehZainab
bataineh
Rinad Al-ali
Rand
Rawashdeh
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Chapter 19
- Complement can help in the opsonization / phagocytosis process by
deposition of C3d into C3d receptors on phagocytic cells.
- C3a and C5a can act as chemotactic factors, and stimulate mast
cells and basophils at the same time.
- Deficiency in complements can lead to infection with pyogenic
microbes like Neisseria meningitidis especially if one has problems
in the lower part of the triggering cascade.
- Having problems with the upper part of the complement cascade
can lead to autoimmune diseases like SLE.
- Complement is fixed, this phrase means that the complement is
bound to the CH-2 domain.
[The doctor started reviewing the classicalpathway! Make sure you study the
previous lecture carefully from the additional notes and the book.]
- The C1qrs complex is kept together by calcium [Generation of C1qrs
complex is calcium dependent].
- C4b2a3b is C5-convertase [it acts on C5 splitting it into C5a and
C5b].
- C5b starts the attack membrane complex.
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-C1-inhibitor is a protease inhibitor.C1-inhibitor irreversibly binds
to and inactivates C1r and C1s proteases in the C1 complex of
classical pathway of complement. [Wiki]
- Decay activating factor splits C4b from C2a, thus inhibiting the
formation of C3.
Note: I didnt find the Decayactivatingfactor on the internet; instead,
it was Decay-acceleratingfactor.
- Decay-accelerating factor also known as CD55 is a protein that, in
humans, is encoded by the CD55 gene. It prevents the assembly of
the C3bBb complex (the C3-convertase of the alternative pathway)
or accelerates the disassembly of preformed convertase, thus
blocking the formation of the membrane attack complex. [Wiki]
- The alternative pathway is also known as the
properdin pathway.
- The triggering point of the alternative
pathway is the binding to lipopolysaccharides of
the gram -ve bacteria, and this is going to act
directly on C3 [We dont have here C1, C4 or
C2]. Now, C3 will split into C3a and C3b. C3a will
have the same function as in the classical pathway. C3b will bind to
the surface of the cell. If C3b binds to a foreign cell, the reaction
will continue, but if it binds to a self-cell, the reaction will stop.
Another factor is going to bind to C3b, its the B factor. Then, the
D factor will hit to the B factor [the D factor wont hit the B
factor unless the latter was bound to the C3b]. The B now will split
into Ba and Bb. This complex (C3bBb) is called C3-convertase. A loop
will happen which is called the amplification loop and we will have
more C3a and C3b. Another protein will bind to the C3bBb and its
called the properdin (P) protein. The function of the P protein is to
increase the half-life of the C3-convertase. When another
fragment of C3b is bound to C3bBbP, then this complex will be
I highly recommend watching
these 2 videos:ww.youtube.com/watch?v=http://w
qga3Wn76d9w
http://www.youtube.com/watch?v=RwJlj0OULns
http://www.youtube.com/watch?v=qga3Wn76d9whttp://www.youtube.com/watch?v=qga3Wn76d9whttp://www.youtube.com/watch?v=qga3Wn76d9whttp://www.youtube.com/watch?v=RwJlj0OULnshttp://www.youtube.com/watch?v=RwJlj0OULnshttp://www.youtube.com/watch?v=RwJlj0OULnshttp://www.youtube.com/watch?v=RwJlj0OULnshttp://www.youtube.com/watch?v=qga3Wn76d9whttp://www.youtube.com/watch?v=qga3Wn76d9w7/31/2019 Additional Notes All
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converted to C5-convertase. So, the C5-convertase is (C3b)nBbP,
where n is the number of C3b molecules. Now, C5-convertase will
act on C5 and it will split into C5a and C5b, and the reaction will
continue the same as the classical pathway.
- The half-life of C3bBb is less than 5 minutes.
- C5a is more efficient and a stronger chemotactic factor than C3a.
- When C3b binds to a self-surface, a protein called the H factor is
going to bind immediately to C3b. C3bH is a target to another
protein called I (inhibitor) factor. The I factor will immediately
destroy C3bH into inactive C3b. The inactive C3b will be split to
C3b and C3bG and the reaction will stop.
- TheMannose-binding lectin is also the same. Its simply that the
MBL protein binds to the surface of bacteria and then activates C4
and C2 [we dont have C1 here]. The reaction will continue like the
classical pathway.
- Complement Receptor 1 (also known as CD35) is the C3b receptor.
- Complement Receptor 2 (CD21) activates B-cells.
- CR 3 and CR 4 play a role in adhesion of inflammatory cells.
- We can assay for these complement components by an antigen-
antibody reaction. We bring sheep RBCs and inject them into arabbit so it would make anti-sheep RBCs antibodies. We take these
anti-bodies and put them on the sheeps RBCs so we would have
sensitized sheep RBCs. Now we add complement to those RBCs and
the complement will be fixed, then lysis is going to take place. So,
lysis of the RBCs means that complement is fixed.
- Complement fixation test: Here, we look for an antigen or an
antibody. If were looking for the antigen, its antibody has to be
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known and vice versa. Lets assume we want to look for a specific
antibody antibodies against hepatitis B surface antigen (HBsAg)
for example. We get a tube and put the patients serum in it. Then
we heat it up to around 56 C to inactivate the complement. Now, weadd the antigen to the patients serum. If there are antibodies
against HBsAg in the patients serum, a reaction will take place
between the Ab& Ag. We then add complement, if there was a
reaction between the Ab& Ag, then complement will be fixed. If the
complement was fixed, this means that there is no free complement
in the patients serum. To be sure that the complement was fixed,
we add sensitized sheep RBCs. Since fixation happened and there isno free complement present in the serum, nothing will happen! But if
there were no antibodies against HBsAg, there will be no reaction
between Abs &Ags, fixation of complement wont take place and
when we add the sensitized sheep RBCs, lysis is going to to take
place so this is a negative test.
- In the acute phase response, complement components (especially
C3) will be consumed in reactions. Therefore, C3 and othercomplement concentrations in serum are going to be low.
- C reactive protein is part of the collectins group (theyre produced
in response to inflammation).
- In inflammation, both C reactive protein and ESR (Erythrocyte
Sedimentation Rate) levels increase.
- The normal body temperature is not 37 its around 37. Its a
range from 36.6 to 37.7. Fever occurs when your body temperature
goes beyond 37.7 C.
- The use of Antipyretics is not recommended. Theyre used only
when the temperature goes beyond 39 C, and failure of normal
methods (like using cold compresses) in reducing the temperature.
- Fever up to 38.5 C is good for our body.
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Chapter 20
- Neutrophilia indicates acute pyogenic infection.
- Lots of macrophages and no pus indicate a chronic inflammation.
- Name of macrophages in different sites of the body:
Name of cell Location
Dust cells/Alveolar macrophages pulmonary alveolus of lungs
Histiocytes connective tissue
Kupffer cells liver
Microglia neural tissue
Epithelioid cells granulomas
Osteoclasts bone
Sinusoidal lining cells spleen
Giant cells Connective Tissue
Peritoneal macrophages Peritoneal cavity
Monocytes blood
- We could have normal numbers of neutrophils, but their function
is not normal and the patient will be immunocompromised.
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-Fixed macrophages are present in spleen and liver, and they
phagocytose awhole cell.
Additional notes Chapter #19
Phagocytosis and the complement proteins are the 2nd line
defense
Acute phase proteins defend us against invading
microorganisms
We can measure the inflammation by the acute phase
response proteins.
pH of the stomach is around 2.
Smoking wipes out the cilia and deprives the smoker from
very important defense mechanisms.
Cigarette smoke contains more than 5000 toxiccompounds that can stimulate not only the mucus, but also
the macrophages, and these macrophages release their
hydrolytic enzymes causing obstructive lung diseases like
chronic bronchitis.
Alveolar macrophages are part of the lower respiratory
tract barriers to infection.
Natural killer cells are activated by IFNs and they can
produce IFNs.
Interferons are non-specific in that they act against any
virally infected cell, but they are interspecies specific;
IFNs of humans act only on human cells.
IFN- can help in the expression of MHC class I
molecules, and macrophage activation.
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Antiviral effect is mostly in IFN- and IFN-.
IFN- is used in the treatment of Multiple Sclerosis
(MS)
Activators of the classical pathway are either IgM or
IgG (1 IgM pentamer or 2 IgGs), and the other Igs do not
activate the classical pathway.
The alternative pathway (Properdin pathway) is mainly
activated by the LPS of the gram ve bacteria, and it
starts at C3 directly.
Ultimate result (goal) of compliment activation is the
destruction of the cell.
C1q looks like a floret
Small fragment C2a
activates the killing
pathway, so you see lots of inflammation. Bradykinin is
going to be produced, then vasodilatation and
inflammation is going to occur.
C3a and C5a act as chemotactic factors and
anaphylatoxins. They are inflammatory mediators that
activate basophils and mast cells.
C3b initiates the membrane attack complex.
C3b will bind to Complement Receptor 1 (CR-1) on the
surface of phagocytic cells and will help in the process of
phagocytosis by opsonization.
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C3b and IgG are the main opsonins, and if they work
together they will cause a double effect.
CR-3 and CR-4 have adhesion functions. Deficiency of complement components leads to
immuncompromise disease.
We have regulatory mechanisms at every pathway, and
they are mediated by regulatory proteins. Any deficiency
of these regulatory proteins leads to excessive
inflammation where its not needed.
Angioedema (angioneurotic edema):
o Activation of mast cells and basophils
o Inflammatory reaction
o Puffy eyes
o Edema
o Could cause suffocation due to smooth musclecontraction leading to death.
If C3 binds to a self antigen or self surface, inhibitory
components will act on the C3 and destroy it.
Complement control proteins:
o Decay accelerating factor (the doctor said
activating but on wiki its accelerating)o C4b binding protein (C4BP)
o Protein S which is an inhibitor for C5b67
which binds to it and forms an inactive
complex called vitronectin(C5b67S)
o Homologous restriction factors that bind
to complement protein 8 and stop
complement protein 9s activation
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o C1 inhibitor. A deficiency in the C1
inhibitor results in angioneurotic edema.
Cobra venom activates C3b by the alternative pathway
resulting in massive inflammation and death.
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Done by: Khaulah Momani
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Special thanks to Zaid Imam for the notes and the Classic
pathway drawing
Chapter 20 Additional notes
Macrophages : based on their location in our body : mesinchymal cells in the kidney
, monocytes in the circulation and langerhan cells in the skin .
When they are activated they can produce acute phase response
IL-1, IL-6, IL-8, TNF all of these are needed in the activation and
production of Normally they are present in tissues. Call thesemacrophages the complement and raising body temperature .
IL-8 activates the bone marrow here to start calling neutrophiles
to call upon into the area and so on.
Macrophages they perform the killing process less efficiently
compared to neutrophiles because neutrophiles are so many and
macrophages presented in tissues and have to be activated .
I want to activate macrophages I can also inject antigens of
Mycobacterium tuberculosis (MTB) , we use the BCG vaccine(Bacillus Calmette-Gurin ) that we use to vaccinated against MTB ,
we inject that in the urinary bladder for the treatment of bladder
cancer.
Some pathogens are evasive means when we phagocytose organisms we
supposed to kill them. but if we failed to do that then the microorganism
has more protection mechanism :
like MTB which has specialized mycolic acid that resist
phagocytosis , they require more action ,like interferons to
activate more macrophages to kill MTB
some they have a capsule for example , the function of capsule is
for antiphagocytic , so what the body has to do to encounter this
?? to produce antibody against the capsule so antibody bind to the
capsule then macrophages come bind to the antibody through the
Fc receptors as opsonin and then help in the phagocytosis process.
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Some bacteria can produce catalase enzyme that counter the
bacteriocidal molecules that result from respiratory burst.
One of the drugs that we use to suppress the immune system is the
anabolic steroids ( corticosteroids ,cortisol , hydrocortisone).Steroid :
affect sexual functions .
increase muscle building
interferes with the metabolism of fat we can see the moon face
appearance , "buffalo neck" .
steroids also cause osteoporosis.
if you inject somebody with corticosteroids chemotactic factor will
not be produce , there will be no longer acute phase response .
septic shock :
If the patient has septic shock then he/she is dead until prove
otherwise
To reverse the septic shock :
blocking the NO production by macrophages, endothelium and smooth
muscle but it' s effective in animals not in human (not that much we cando ,may be the only thing sometimes that we give "catecholamines " toincrease the blood pressure and the tone of the blood vessels and so on
,but blocking the production of NO is successful in animals not in humans .Also we can block the TNF with monoclonal antibody , his process isineffective because it's given too late , recombinant
bacteriocidal/permeability increasing protein (BPI) binding to endotoxin
and preventing it from activating macrophages could be useful .
Chapter 21 additional notes
The NK cells : those are innate cells , non-specific, they
dont have T-cell receptor.
The T-helper 2 will give the isotype switching into the IgE
antibodies which are going to bind to the MAST cells, so the
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bound MAST cells for the first time we call them
sensitized Mast cells.
Mast cells can be stimulated by other factors like: Drugs
(such as morphine), opiates, physical exercise in certain
people, changing of temperature and some other factors
that could stimulate the mast cells & may cause what we call
urticaria.
Those mediators -especially thromboxanes- are inhibited by
the action of Aspirin (salicylic acid) which can interfere with
their processes, and thats why the salicylic acid is
considered as an anti-inflammatory drug.
Charcot-leyden crystals : Which are simply Killed
eosinophils. They are indicative of a disease involving
eosinophilic inflammation or proliferation, such as is found in
allergic reactions and parasitic infections. They are often
seen pathologically in patients with bronchial asthma.
From robbins : charcot-leyden crystals collections ofcrystalloids made up of eosinophils proteins .
Response according to location:
and eosinophilsLeukotrienes: mainly respond byMucosal Mast cells-
which of course will be produced, activating TH2 cells but not TH1
cells.
. And thisHistamine: they have moreConnective Tissue mast cells-
is the difference between connective tissue mast cells and mucosal
mast cells, the 1st one has a rapid effect on the connective tissue
while the mucosal is mainly delayed, but after all, the effect will be
the same.
Treatment methods for hypersensitivity:
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1- Receptors for Leukotrienes or histamines can be blocked in a tissue
(such as bronchial smooth muscles) by anti-histamines. Sometimes
anti-histamines are not enough, so more blockage of other
mediators is needed and that is difficult.
2- By stabilizing mast cells which will prevent mast cells from
producing its mediators, which can be done by corticosteroids, and
thats why we use them in emergency.
3- Catecholamines, they stimulate and receptors.
Drugs that are given in emergencies are given in large doses, so ifanybody comes to the clinic that has an anaphylactic shock caused by a
sting of a bee or a wasp, or major allergies against anything, the drugs
of choice that are given are: Catecholamine, adrenalin, high dose
hydrocortisone to stabilize the mast cells, and corticosteroids to
inhibit the synthesis of the mast cell mediators. Cromoglycate can also
be given which may stabilize mast cells, and the cromoglycate is a drug
that sometimes you can use for prophylaxis (like in bronchial asthma
and hay fever), and this will block the receptors on the surface of themast cells, so it stabilizes the mast cells. but the action of
corticosteroid is so effective in suppressing the immune system.
A patch test is a method used to determine if a specific substance
causes allergic inflammationof the skin. It is intended to produce a
http://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Skinhttp://en.wikipedia.org/wiki/Skinhttp://en.wikipedia.org/wiki/Skinhttp://en.wikipedia.org/wiki/Inflammation7/31/2019 Additional Notes All
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local allergic reaction on a small area of your back where the diluted
chemicals were planted.
NK cells function when we have evasive viruses like: HSV, or in tumorsfor example sometime mutation could take place and will mutate the
cell not to produce MHC antigens. we have so many viruses like: HSVs
which are so many like Type 1 and 2, CMV (cytomegalovirus), and EBV
(Epstein-Barr virus), so all of those can be killed by the NK cells.
FasL: It is not usually expressed unless the Killer cell is
activated.
When Natural killers bind to Non-classical MHC, they can't
bind to classical ones. This is exactly what the dr said .
Done by : Saif Adnan Massadeh
Additional Notes Chapter 21
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-The killer cells involved in case of worms( parasistic infection) are
eosinophils in particular
-Now parasites produce soluble Ag's that stimulate B cells because they
are going ti be presented to T cells ( TH2) and Th2 produce IL4 and
IL5(LATER)
-IL4 stimulates B cells to switch to IgE(binds mast cells and sensitize
them)
-Immune system uses mast cell in defense because of their role in induction
of inflammation
-The specificity will be determined by the variable region of each of the
IgE's bound on mast cells.
-mast cell stimulation(degranulation):
1- cytokines ..( tryptase and chemotripsin)
2- inflammatory mediatiors or vasoactiveamines
a.preformed(histamine)
(actually process of degranulation means substances already preformed in
granules )
b.formed later( arachidonic acid metabolism)
***slow reactive substance of anaphylaxis is considered from the
lipooxygenase(delayed.. hours) pathway)) )
3.other cytokines after stimulation like IL3.IL4.IL5
IL3 stimulates B.M
IL4 ..stimulates TH2 ..which will produce more IL4 and will suppress TH1 .
IL5 eosinophil production and activation
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-Mast cells has fcRI and we have type 2 as well ( fcRII)!
-Precursor cells of mast cells are unknown but the differentiating facortsor stimulating could be IL3,,IL5
-Mast cells activated also by opiates (like morphine)
-Stimulation of mast cells appear immediately
-Within seconds of degranulation we will have inflammation
-Then the Arachidonic acid metabolism products will be produced and other
mediators will be formed
-When we are exposed to pollens for example.. this will develop immediate
type hypersensitivity or bronchial asthma within secondsof exposure
-So chemotrypsin and tryptase will activate the driving force of parasites
to come out by their production of mucus and other things mentioned in book
-Histamine also produces signals that tells that there is parasitic infection
in particular area and leads to vasodilatation of course.
-Thromboxane action(figure21.6) exactly the same of histamine
-Signs of inflammation include redness ,hotness, tenderness-Redness and hotness due to vasodilatation
-And tenderness due to smooth muscle contraction
-Later-phase inflammation (chronic inflammation) from mediators produced
later
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-Mucosal mast cell has more leukotriens than other mast cells
-Musical mast cells and connective tissue mast cells have plenty of
histamine so the response is very rapid
-Eosinophils .. . 2-4 % pf leukocytes in blood
-If more than that then ( parasitic infection or allergy)
-Neutrophils about 66%.. the most
-There are three mediatiors present in eosinophil granules and not in mast
cells such as major basic protein and cationic protein that lead to rupture of
cytoplasmic membrane .
-Their precursor cells(eosinophils) produced under the effect of IL3 and
then IL5 leads to their differentiation into eosinophils
-IL8 ..C5A.. C3A are chemotactic factors mainly for neutrophils
-Peroxidase generates hypochlorite anion.. very strong oxidizing agent (in
eosinophils)
-In immediate hypersensitivity when you look for eosinophils in patient's
mucus you will find parts of eosinophils(by products) resulted from damaging of
eosinphils called charcot leyden crystals ,, u can do this by simple test to check
for eosinophilia as part of immediate hypersensitivity
-Now other role played by eosinophils in neutralizing the effect ofinflammation mediated by IgE RESPONSE but mainly their presence in the
damage they inflect was not supposed to this part of the reaction but
supposed in case of parasitic infection but the unlucky ones that have history of
atopy ( genetic susceptibility to induce IgE respone when we are exposed to
allergen . Inherited from parents to pollens for example .. 20 % of population
by the way have atopy history or hypersensitivity history and sometimes having
a history of atopy could be good .. why because u will have excessive
inflammation and something that doesn't kill you make you stronger !
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-How we can control inflammatory reaction by mast cells
-Corticosteroids will suppress mast calls synthesis of mediators and inhibit
inflammatory reaction
-And we have chromoglycate ( I think) to stabilize mast cell
-And we could block the receptors for histamine and leukotriens when we
get antihistamine for example and this what we use in treatment of
hypersensitivity and we use of course other substances that block the action of
other mediators as well ..desensitization or hypo sensitization-And u cannot have anti-leukotriens or anti-prostaglandins !!!
-NK called large granular lymphocytes
-They are larger than lymphocytes
-NK cells response to any virally infected cells or tumor cells under only one
condition in case that antigen was not presented to T cytotoxic cells by MHC 1
because if we have presentation the MHC will give INHIBITORY signal to
inhibit NK not to come closer ans NK cells have receptora on surface that sense
the presence of MHC-Ag's ..we call the KIR or NGK2/CD94 ..those NGK2
recognizes other minor not the major MHC .. ( HLA-E for example )
-NK cells form almost 5-15% of lymphocytes in thoracic duct and u don't
differentiate them by shape as I said !
-Nk has CD16/ Fc16RIII for IgG ,, and this is a way included in killing
mechanism of NK ( ADCC) .
-In tumor cells, part of the tumor mechanism is to produce mediators that
suppress the immunological responses (suppress the expression of MHC antigens
) .
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-NK cells are part of the innate system , not specific ( don't have
receptors for any antigen ) Also have no memory .
-Herpes simplex , cytomegalovirus , Epstein- bar virus all suppress the
expression of MHC class I molecules .
-INF-alfa , INF-beta and IL-12 stimulate NK cells
- We have 2 types of TNF : ones that are secreted from the cell and ones
that are already present and stable on the surface of the NK, CTL and
macrophages .
-FAS and FAS ligand interaction are used by the body to shape the immune
system .
- Lymphokine activated killer cells : taking the NK cells from a patien and
activating them by cytokines ( INF-) and then returning them back into the
cells .
- Fas ligand is not normally present but it has to be activated so that it will
express FAS ligand .
- Apoptosis is very important to shape up our immune system .
- IL-2 can activate Bcl2 genes .Bcl2 will suppress the caspases so that it
will not destroy DNA .
- In lymphorpilferative disorders , we have over expression of Bcl2 genes .
** Done by : Haya Alrawabdeh , Bara' Alzubi
Chapter 22 Inflammation will cause hotness a, redness (because of vasodilatation )
and tenderness (because of edema )
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Parasitic infection :
-acute : activation of mast cells , chemotrypsin and other mediators that
stimulate the production of mucus
-chronic : activation of eosinophiles
The viral infection the damage is because of IFN gamma
Tissue damage in the granuloma is because of activate d macrophages or
the microorganism itself
The main problem of schistomiasis is entrapment of its eggs in tissue and
induce schitomosomal couples that goes to superior and inferior
mesenteric veins and lay down its eggs then it goes to urinary bladder or
the GIT so entrapped eggs in the wall of the intestine ( GIT ) many willbe washed back by the flow of the blood to the liver so activation of
chronic response massive eosinophilia responsible of the most of the
damage that is going to takes place
Influenza it should be cleared out withen 7-10 days through NK , T
cytotoxic cells
(influenza virus rarely develops into chronic inflammation )
Tuberculosis (usually develops into chronic inflammation)
reemerging of TB is due to poverty, immune suppression and HIV
the TB disease is on the top of the list of WHO hopefully to clear it out
from the surface of this planet
primary tuberculosis in the lung we call it ghon focus
lymphokines from infected macrophages will activate other macrophages
and altering T helper cell to produce IFN gama
reactivation of primary TB will cause secondary TB and that because of
taking immunesuprtion drugs like when the patient is under stress
pulmonary TB is the most dangerous because it is transmited through the
air and can stay for a long time in the air the infectivity of this organism
is very high , and these patient should be in isolation (air isolation )
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in primary TB organism form tubercles or granuloma in the upper part of
the lung where the oxygen concentration is the highest
reactivation of tuberculosis usually happens in the apices of the lungs
sever immunodeficiency like in AIDS there would be more diffuse
infection that is beyond the lung (miliary TB ) which could go anywhere
through the blood
skin test for TB :
5 international injection units so activation of skin macrophages
(langrhans cell) where they take up the microorganism and form a
thicker part (granuloma) this reaction could take 48-72 hours thats why
we call it delayed type hypersensitivity and then we measure thediameter of the circle (the thickening) not the inflammation
interpretation of the test (-ve or +ve )will be affected by the age of patient and whether he is taking drugs or
notin the past response
10 ml or more positive
5 ml or less negative.more than 5 and less than 10 intermediate
but this criteria has been changed to depends on the clinical condition ofthe patient
hepatitis B virus(oncogenic virus )70-80 % develops acute response(IFN alpha and beta induce its clearance
) while 20% develops into chronic (we call it chronic active hepatitis
massive damage in the liver liver failure
there could be a mutation which could develops a hepatocellular
carcinoma
abd el halim hafeth died of liver failureuses reverse transcriptase (like HIV virus ) for their replication so we
can use reverse transcriptase inhibitors to treat it such as lambdin
in chronic response of the virus there will be an inflammation that cause
tissue destruction and massive damage caused by CD8+ cell with the help
of IFN gamma and thats why we never trate patients with hepatitis B
virus with IFN gamma we treat them with IFN alpha ,IFN beta but
mostly IFN alpha (we give IFN alpha because it has fewer inflammation
effects than IFN gamma )IFN alpha and gamma works reverse to each other
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-IFN alpha inhibits the viral replication by destroying its mRNA
- active vaccination of hepatitis B is 3 doses that we give you when you
when you enter the hospital , between the 1st and the 2nd doses there is
one month and 4-6 months between the 2ndand the 3rd doses and thats
to increase number of memory cells
chapter 23 : cytokines are molecules that can be secreted by any type of cells. If its
from lymphocytes we call it lymphokines
up regulation cytokines activation ,down regulation cytokines suppressing
such as IL-10 / TGF-B
the cytokines will binds to its receptor but if the receptor is missing thereaction wont takes place those receptors are developed in response to
activation
you should know the function of each cytokine in the context of their
presence
we use IFN beta to treat Multiple sclerosis
Memory cells require cytokines , if they are not present the memory
cells is going to die
IFN gamma induce the production of MHC class one
Done by: Razan Salah and Sara Turki
Add. Notes for Immunology Lecture 8th July 2012
Chapter 23 Cytokine in Immune System
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1) Specific chemokine receptor used as co receptor for HIV:
CXCR4 & CCR5
2)CD40L and FasL not present in normal situation, produced
during activation
3)Pro-inflammatory cytokines: IL-1, IL-6 & TNF
4)IL-6: can be measured during septic shock
5)IL-2: produced specifically but acts non-specifically. (can
act on T-cell of different specificity)
6)Priming: activation of virgin T-cell
7)TGF-: oral tolerance (our body doesnt react with foods
that we eat)
Chapter 24 Infections & Vaccines
1) Vaccine comes from word vacca(Latin) cow cowpox.
Edward Jenner is the first to discover working vaccine of
smallpox using cowpox. Earlier, Chinese people discovered
too but it was not successful because they use smallpox type
which is deadly. Cowpox is milder and doesnt cause death.
2)Now we use Vacciniavaccine against smallpox which is live-
attenuated type.
Immunity
Active
Natural Artificial
Passive
Natural Artificial
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1) Examples:
a. Natural active: when we get infected naturally
b. Artificial active: given live vaccine
c. Natural passive: colostrums in breast milk given tobabies
d. Artificial passive: antibody cultured in horse used for
human
2)When given antibodies from other species, human develop
serum sickness. So, we changed to human antibodies.
Vaccine
Killed Live-attenuated
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1) For rule of thumb: live-attenuated is better than killed
because it resembles natural active immunity
2)Purpose of adjuvant: keep immunity for longer period
3)Problem with live-attenuated vaccine:
a. Cant be used in immunodeficient and pregnant patient
b. Reverse mutation to wild strain (e.g. DPT vaccine.
Pertussis strain reversed in some people. So weve
changed to aDPT vaccine acellular Pertussis)
4)Examples of live-attenuated vaccine:
a. Poliomyelitis ( )
b. MMR measles, mumps and rubella. In Jordan we used
measles only.
c. BCG (M. bovis) used in developing countries
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Chapter 26
Desensitization or hyposensitization By changing the route of administration of
the allergen, for example from cutaneous to subcutaneous. here we can change
the immune mechanism by shifting the IgE antibodies to IgG antibodies. IgG
antibodies are called blocking antibodies.
This process is effective if the patient has just one type of allergy ,but if
more its so difficult !
Chapter 27
There are many factors help in immune disease development :
genetic factors : run in families ,like HLA type .
Infections and cross immunity. Like Group A hemolytic streptococcus which
cause acute Rheumatics fever and Rheumatic heart disease and post strep.
glomerulonephritis .
In the Treatment of Rheumatic fever we use anti-inflammatory drugs.
Environmental factors.
B1 cells are not specialized and non professional cells .
B1 cells may form isohemagglutinins by binding to proteins of RBCs and
production of natural Ab anti-A & anti-B ABisohemagglutinins . Those natural
Abs may develop in response to normal flora in our GIT.
Autoimmune disease either localized or systemic.
About the evidence that T-cells initiate the autoimmune diseases by providinga cytokine network . those cytokines lead to the production of Igs or CD8+.
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Immune privileged sites :testicles, BBB and cornea.
in poly- endocrine syndrome patients have failure in the presentation of self
antigens in the thymus.
Restriction phenomena : MHC alleles less efficient in presenting antigens to T-
cells .
Diagnostic tests :
In direct immunoflourescence the antibody in known and the antigen is
unknown , so we can detect the presence of an antigen.
usually we detect auto antibodies by indirect immunoflourescence. The
antigen in the tissue is known , we want to see if the patient has antibodies
against that particular antigen in the tissue so We add the patient serum to the
tissue then incubate and wash. then add a secondary Abs which are
flourescenated this secondary Abs bind to the patient antigen, then incubate
and wash. Then examine the specimen under the fluorescent microscope. the
intensity of the light depends on how much Abs do we have.
in ELISA we detect any type of Abs .the antigen is known ,add the patient
serum which supposed to have antibodies against an auto-antigen , add the
secondary Abs which have the HRP horse radish peroxidase enzyme .
Infections predispose to IDDM by molecular mimicry process like coxsackie B
viruses.
In celiac disease the presence of tissue transglutaminase Abs is an indirect
indication that we do have autoimmunity against gliadin.
No Abs against tissue transglutaminase unless they bind to gliadin-indirect
measure-.
When we talk about tissue transglutaminase Abs we mean anti- endomysial Abs.
Butterfly appearance seen in SLE disease ; rashes on the face.
In SLE disease immune complexes may precipitate in the kidney.
In pernicious anemia , patients have anti -parietal cells antibodies against
parietal cells in the stomach , where they are very important in secretion of
transporter factor to transfer vitamin B12,so here Vitamin B12 will not going to
be absorbed then patient will have megaloblastic anemia.
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In SLE disease we use antinuclear antibodies in indirect immunoflourescence
to detect the presence of these antibodies that patients may have .
In pregnancy because of suppression of T -cell mediated immunity , humeral
immune response is going to be produced. so there will be plenty of Abs inpregnancy and that make sense cause there are IgG antibodies cross the
placenta to the baby and IgA antibodies go the colostrums.
Chapter 28
Hashimotos thyroditis patients have Abs against thyroglobulin, the outcome is
hypothyrodisim.
Addison disease against suprarenal gland.
Graves disease Against thyroglobulin receptors,the outcome is thyrotoxicosis
,cause there will be stimlulation of thyroid hormones .
Myasthenia graves antibodies against acetylcholine receptors,no acetylcholine
is going to be produced the outcome is paralysis.
Blood groups are carbohydrate antigens on the surface of RBCs called H
antigens.
We have more than 600 antigens on the surface of RBCs .we have majors and
minors .
If the father is A and the mother is A ,The possibilities are A and O children.
Rh is extremely antigenic.if you are Rh- and exposed to Rh+ cells ,anti- D
antibodies are going to be produced.
In figure 28.8 the mother is going to be primed, sensitized against Rh+ cellsafter her first baby delivery.
In hemolytic disease of the newborn the baby is going to complain about anemia ,
jaundice .immediately we do exchange transfusion .
Mainly those antibodies are IgM antibodies isohemagglutinins-, what is the
significance to know that? In many few rare case it could be IgG .that means if
the mother has blood goup O ,she has anti-a and anti-b Abs those usually dont
cross placenta since they are IgM. Some cases if they are IgG can cross theplacenta and cause hemolysis and complement system will be activated.
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Forgive me for any mistake, Good luck
Done By : Dua alkhader .
Immuno additional notesdone by : Bayan Jaradat
lecture : 20 Chapter : 28
- In type II hypersensitivity Igs(Ab) simplyIgM and IgG are going to bind to the
surface of the cell and the complement is
going to be activated and the surface is
going to be destroyed
- Complement activation is the key of
damage in this type
(Figure 28.1) This is the Coombs test.
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(A) If you have normal RBCs as such andyou have antibodies that dont react,
you will see the RBCs free.(B) But if you have sensitized RBCs (anti
D antibody bound to the D antigen on
the surface of RBCs) and you add the
anti-globulin reagent against the RBCs,
clumping will take place (positive test).
When you do that to the baby, this means
that the baby is sensitized, and then we
have to do exchange transfusion; we have
to change ALL the blood of the baby withO negative blood; we get rid of those so
they dont cause complement activation
and damage to RBCs.
- Hemolytic disease of the newborn(also
called hydrops fetalis which leads to
massive edema and death) develops in the
second pregnancy if the mother was Rh-
and her first baby was Rh+ ,so that
during labor fetal red cells leak into the
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mother and will survive long enough to
elicit an IgG response ,then in the second
pregnancy the maternal anti-D antibodiescross the placenta and attack fetal red
cells , to avoid this from happening women
with such like case should have anti-D
anti-bodies (Rogan) injection within the
first 72 hrs after the delivery of Rh+baby , so these anti-D anti-Abs will
neutralize RBCs that got access to the
mother
- Sometimes, hemolytic diseases could happen
because of incompatible blood groups. For
example, if the mother has blood group B
(having anti-A antibodies) and the baby is
blood group A, and these anti-A antibodies
by coincidence are IgG (not IgM), they could
cross the placenta and cause hemolytic
disease for the newborn!
- In case of emergency, we dont have to do
blood matching; we can give O negative
blood immediately since it doesnt have any
antigens.
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- Sometimes, the autoimmune hemolysis could
occur because of infections (they cross
react with the I antigen, for example) ordrugs (they bind to the surface as haptens
and antibodies will develop against them).
- Auto-antibodies can also be produced by
malignant clones of B cells; such as in chronic
lymphocytic leukemia or lymphoma.- Sometimes, they notice that immunoglobulins
at normal body temperature (37 C) dont
react, but at a temperature less than 37 C
they could react; we call these cold
agglutinins; they cause agglutination in the
cold.
- There is two auto-immune diseases for
the thyroid gland ,one is called haiku
thyro-toxicosis (hypothyroidism) ;
suppression of the effect of the thyroid
of the thyroxin ,here the Abs will bind to
the thyroid and the complement will be
activated and the thyroid cells are going
to be destroyed , so there will be
deficiency in the thyroxin and the patient
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will have hypothyroidism or nixie deem
disease (not sure about the name !)
The other disease is called graves diseasewhich is an over-stimulation of the thyroid
gland (hyper production of thyroxin) where
the stimulation happens by an auto-
antibody that binds onto the thyroid
stimulating hormone (TSH) receptor- Plasmapheresis is used to get rid from
cytotoxic antibodies that are in serum by
filtering the blood through pushing the
serum of the patient against the semi-
permeable membrane where these Igs willpass through and clear the serum from
these Igs
- Goodpastures syndrome : where are
antibodies that are going to react againstthe basement membrane of the kidney as
well as the alveolar cytoplasmic membrane
; so there are two Abs in goodpastures
syndrome one will react to the kidney and
the other to the lung at the same time ,
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so complements will be activated and
kidneys as well as the lungs will be
destroyed
- In another disease called Pemphigus,
antibodies develop against the desmoglein in
the skin causing inflammation.
-
In myasthenia gravis, patients feel veryweak. One year ago, we had a patient with
myasthenia gravis who couldnt even blink his
eyes! Here, antibodies develop against the
acetylcholine receptors, so acetylcholine
doesnt pass through the neuromuscular
junction, so the patient is going to have
muscle paralysis.
- Diagnosis: ALL these diseases can be
diagnosed by detecting antibodies in blood
samples.
- we have a common antigen called the I
antigen which is non-allelic. The I
antigen is normally present on the
surface of RBCs and you dont have anti
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I antibodies in your circulation unless
you have an autoimmune phenomena.
When anti I antibodies develop, weregoing to get hemolytic diseases.
- Remember : Blood groups are
glycoproteins present on the surface
of RBCs. If you have blood group A,
then you have anti-B antibodies. If
you have blood group B, then you have
anti-A antibodies. If you have blood
group AB, then you dont have anyantibodies. If you have blood group
then you have anti-A and anti-B
antibodies
- These antibodies are called
isohemagglutinins; which are natural
antibodies of the IgM type [rarely could
be IgG and could cross the placenta and
cause ABO incompatibility between the
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baby and the mother]. Those
isohemagglutinins develop in response to
normal flora (bacteria) in the intestineand their way of development is a little
bit complicated; they start with our
growth as natural antibodies .
- If you have incompatible blood; for
example, blood group A with anti-A
antibodies, then agglutination is going to
develop and complement will be
activated destroying RBCs. Almost 90%of incompatible blood transfusions are
mainly because of what we call clerical
error; somebody made a mistake in
patient's identification and gave the
wrong blood to the wrong patient! So wehave very strict rules regarding blood
transfusion.
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- If the antibodies are of the IgG type,
they dont cause agglutination; so what
do they do when they bind to the Iantigen, for example? Those will be
taken to macrophages in the spleen and
the whole antibodies and RBCs are going
to be phagocytosed easily, so theyre
going to be destroyed as well.
- So, if you have sensitization to RBCs
by IgGantibodies, theyre going to be
destroyed by macrophages in the
spleen. If RBCs are sensitized by IgM
antibodies, theyre going to be
agglutinated and destroyed by
complement and maybe by
phagocytosis as well.
How can we prevent type II hypersensitivity?
- Proper cross-matching to prevent anyincompatible blood transfusion.
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- Giving anti D antibodies after labor: theminute the baby is born, we do the anti-
globulin test; if the bay has sensitized RBCs,then you take these sensitized RBCs and you
put a drop of the anti-globulin reagent; we
call that direct Coombs test. So, the anti-
globulin will react against the human globulin
making coagulation or clumping; this ispositive Coombs test.
- Using immune-suppressive drugs tosuppress the auto-antibodies.
- We can do plasmapheresis; getting rid ofthe auto-antibodies.
Winning doesnt always mean
being first ,winning means that
you are doing better than you
have done before
BONNIE BLAIR
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Done by:
BAYAN JARADAT
GOOD LUCKall in theexam :)