Additional Notes All

7/31/2019 Additional Notes All

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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=qga3Wn76d9w


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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/Inflammation


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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


37/45

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


45/45

Done by:

BAYAN JARADAT

GOOD LUCKall in theexam :)

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