Immuno week 9

Question 1

B cell differentiation in Plasma Cells & Memory
Plasma Cells
The Ig production of B cells will change from membrane form-> ?
caused by?

Answer 1

Plasma Cells
○ The Ig production of B cells will change from membrane form-> to the secreted form
■ Caused by alternative RNA processing of the heavy chain messenger RNA

Question 2

B cell differentiation in Plasma Cells & Memory
● Memory B Cells
When are they generated?
what are they capable of?
what sort(s) of IR? what is most common?what is the sort of survival rate of a memory cell? why?

Answer 2

● Memory B Cells
○ Generated during germinal center rxns and are capable of making rapid responses
to subsequent introduction of AG! (T-dependent IR)
○ They can also be created in the T-independent IR but it is not as common
○ Memory cells survive long a long time even if they are not AG stimulated due to inc levels
of anti-apoptotic protein BCL-2

Question 3

T independent
Also called what?

Answer 3

T independent AKA: Thymus independent

Question 4

T independent
T independent AG= ?

Answer 4

T independent AG= do not need the help of helper t cells

Question 5

T independent

IgM -what is the relationship?
isotope switching?
long or short lived Plasma cells?
protein or non-protein AG?

Answer 5

T independent AG= do not need the help of helper t cells
○ Mainly IgM (low affinity & repeated AG epitopes
○ Typically no or low isotope switching to IgG & IgA
○ Short lived plasma cells
○ Typically nonprotein AG

Question 6

T independent
what relationship with marginal zone and B-1 subsets?
Marginal zone =?
B-1=?

can they be processed and presented?
what result with BacT cells?
what relevance for the generation of natural AB?

Answer 6

○ Marginal zone and B-1 subsets are important for TI AG
■ Marginal zone= typically responds to polysaccharides
■ **B-1= **mainly respond to AG in the peritoneum and mucosal sites
○ These AG cannot be processed and presented in MHC molecules so they cannot be
recognized by CD4 cells
○ Many BacT cell walls are made up of polysaccharides therefore they commonly undergo
this type of IR
○ This IR is also important for the generation of natural AB

Question 7

T independent

what 5 things are important to remember about T DEPENDENT AG?

Answer 7

● Reminder:
● T dependent AG= rxn occurs in the FOLLICLES
○ Isotype switching
○ High affinity
○ Memory B cells
○ Long lived plasma cells

Question 8

Antibody Feedback

explain the downregulation of AB production

Hint: secreted by ?
How does this affect B cell activation?

Answer 8

The downregulation of AB production by secreted IgG AB
Basically what happens is: IgG AB’s will block continued B cell activation
through the formation of Ag- AB complexes that will bind to inhibitory
receptors on the AG specific B cells

Question 9

Antibody Feedback
More detailed version:
IgG AB inhibit B cell activation by what
what do they bind with
what is relevent about the tail of the receptor?
what does it allow for?

Answer 9

More detailed version:
○ IgG AB inhibit B cell activation by making AG-AB complexes.
○ These complexes will bind to the BCR for the FC portion of the IgG antibody (CD32
Fcgamma receptor 2)
○ The tail of this receptor has immunoreceptor tyrosine-based inhibition motif (ITIM)
○ This allows for an inhibitory signaling cascade to be activated which will stop B cells from
continued activation

Question 10

What is Immunotolerance?

Answer 10

Whenever your IS is unresponsive to an AG that it has been exposed to.
○ The AG may induce an IR or tolerance depending on the conditions of exposure and the presence or absence of other factors.

Question 11

What is Immunotolerance?
what are tolergens?

Answer 11

Tolerogens- AG that induce tolerance

Question 12

What is Immunotolerance?
what is self-tolerance and why is it important?

Answer 12

Self-tolerance- tolerance to SELF AG! Is soooo freaking important
○ This is a fundamental part of the normal IS

Question 13

What is Immunotolerance?
what is the result of failure to self-tolerate?

(think your mother and your brother Mikey)

Answer 13

Failure of self- tolerance-> IR against self -> autoimmunity

Question 14

What is Immunotolerance?

what is Self-non-self discrimination-

Answer 14

Self-non-self discrimination- is the ability of the IS to recognize and respond to foreign AG but not the self
AG

Question 15

What is Immunotolerance?
what are the mechanics of tolerence?

Answer 15

Mech of tolerance: will eliminate and inactivate lymphocytes that express high affinity receptors for self
AG

Question 16

What is Immunotolerance?
Is tolerance AG specific?
would chemo be an example?

Answer 16

Tolerance is AG specific!!!
○ Different from therapeutic immunosuppression (think chemo)
● Pop quiz: what did we say was important to prevent autoimmunity at the level of the thymus????

Question 17

Central vs. Peripheral tolerance
What is central tolerance?
mature or immature?
what is the primary location?
when does it occur?
what does it result in?
which lymphocyes get a “second chance”?
how effective is it?

Answer 17

● Central tolerance- think immature and primary lymphoid organs
○ Occurs when lymphocytes encounter and AG which will either result in cell death or
replacement of the receptor with one that is not self reactive
■ Which of the lymphocytes did we talk about that gets a “second chance?”
■ This is not 100% effective which is why peripheral tolerance is NB!

Question 18

Central vs. Peripheral tolerance
mature or immature?
where does it occur?
what happens?
why is M8 involved?
Why is Treg relevant?

Answer 18

● Peripheral sites- mature lymphocytes in secondary/ peripheral sites
○ Mature lymphocytes that are self reactive will become incapable of activation by
re-exposure to that AG or will be destroyed via apoptosis.
○ MB for maintaining unresponsiveness to self AG
○ Maintained by Treg that actively suppress the activation of lymphocytes specific for self
AG

Question 19

More Details about Central T cell Tolerance (review)
Remember negative selection?
how is apoptosis involved?
what about Treg?

Answer 19

● Remember negative selection?
○ T cells that recognize and bind too strongly to self AG will die via apoptosis
○ Some turn into Treg cells

Question 20

More Details about Central T cell Tolerance (review)
when does this occur? class specific or inspecific?
what does it affect? what relevance does this have for tolerance? why?
Negavite selection relates to T cells how? where are they presented?

Answer 20

Remember this is occurring before they are class specific (double pos)!
○ So it affects both MHC1 and 2 and the tolerance of CD4 and CD8 cells
○ Negative selection is the reason that most mature T cells are unresponsive to self AG that
are presented in the thymus- THE FREAKIN’ AIRE GENE

Question 21

More Details about Central T cell Tolerance (review)
Medullary thymic epithelial cellsproduce what? are controlled how? what result?
What is the role of autoimmunity? examples would include what?

Answer 21

Medullary thymic epithelial cells (MTECs) produce peripheral tissue AG
and are under control via the AIRE gene to prevent autoimmunity
○ Autoimmunity- group of dzz that AB and lymphocyte mediated injury to multiple
endocrine organs EX: parathyroid, adrenals, skin, etc
○ (will have lectures about specific dz to come :))
○ I would suggest looking back over my old slides just to give yourself a refresher about this

Question 22

More Details about Peripheral T cell ToleranceMOA
What is Anergy?
why does it occur? what is missing?
what relevance is costumilatory signals?

Answer 22

MOA
○ Anergy- this is whenever the cell is unresponsive
■ Absence of costim signal or the innate IS may make the cells incapable of
responding
■ Do you remember the costimulatory signals??

Question 23

More Details about Peripheral T cell Tolerance
● MOA
what are the mechanics that cause anergy?
Hint:
TCR induced cignal–> ?
SelF AG recognition w/e costimulation—>?
How is Ubiquitin involved?
T cells recognize self AG w/o innate IR–> ?

What happens to Tregs?
What about deletion? apoptosis?

Answer 23

■ Diff Mechs that can occur to cause anergy include:
● TCR induced signal transduction is blocked
● Self AG recognition w/o costimulation-> ubiquitin ligase activation-> TCR
proteins are targeted for proteolytic degradation in proteasomes or lysosomes
○** Do you remember whenever else we talked about ubiquitin?**
● T cells recognize self AG w/o innate IR-> inhibitory receptors of the CD28->
terminate T cell response

○ Suppression by Tregs
○ Deletion- when the cells are destroyed (apoptosis)

Question 24

More Details about Peripheral T cell Tolerance
● MOA
○ Anergy- this is whenever the cell is unresponsive
○ Suppression by Tregs
What is the role of Tregs?
they express high levels of what?
what do they depend upon? what do some require?
where are they located? how do they get there?
can they develop after inflammatory rxn?
again, what is deletion/apoptosis?

Answer 24

● MOA
○ Anergy- this is whenever the cell is unresponsive
○ Suppression by Tregs
■ Tregs job in life is to suppress the IS
■ They express high levels of IL-2a (CD25) and the transcription factor FOXP3
● THEY ARE DEPENDENT ON IL-2 FOR SURVIVAL AND FUNCTION & some require
TGF-B to be generated

■ Tregs in lymphoid tissue-> derived from the thymus due to self AG expression
■ They can also develop after an inflammatory rxn
○ Deletion- when the cells are destroyed (apoptosis)

Question 25

More Details about Peripheral T cell Tolerance MOA ○ Anergy- this is whenever the cell is unresponsive ○ Suppression by Tregs ○ Deletion- when the cells are destroyed (apoptosis) explain thr role of t cells? what are the 2 major pathways?

Answer 25

MOA ○ Anergy- this is whenever the cell is unresponsive ○ Suppression by Tregs ○ Deletion- when the cells are destroyed (apoptosis) ■ T cells that recognize self AG w/ high affinity or are repeatedly stimulated by AG die via apoptosis ■ The 2 major pathways ● Mitochondrial (intrinsic) pathway ● Death receptor (extrinsic) pathway

Question 26

● MOA ○ Anergy- this is whenever the cell is unresponsive ○ Suppression by Tregs ○ Deletion- when the cells are destroyed (apoptosis) ■ T cells that recognize self AG w/ high affinity or are repeatedly stimulated by AG die via apoptosis ■ The 2 major pathways ● Mitochondrial (intrinsic) pathway How are they regulated? How are they initiated? what is the process starting with BAX and BAK which results in cell death?

Answer 26

● MOA ○ Anergy- this is whenever the cell is unresponsive ○ Suppression by Tregs ○ Deletion- when the cells are destroyed (apoptosis) ■ T cells that recognize self AG w/ high affinity or are repeatedly stimulated by AG die via apoptosis ■ The 2 major pathways ● **Mitochondrial (intrinsic) pathway** ○ Regulated by **BCL-2** family proteins ○ Initiated when these cytoplasmic proteins are **induced**/ activated ○ **BAX and BAK** proteins then insert of the outer mitochondrial membrane-> mitochondrial permeability-> inc c**ytochrome** c to leak out and activate **caspase 9**-> cell death

Question 27

● MOA ○ Anergy- this is whenever the cell is unresponsive ○ Suppression by Tregs ○ Deletion- when the cells are destroyed (apoptosis) ■ T cells that recognize self AG w/ high affinity or are repeatedly stimulated by AG die via apoptosis ■ The 2 major pathways ● Death receptor (extrinsic) pathway what about FAS/FASL? What role caspace 8 Soooo intrinsic= ? that results in caspace 8?

Answer 27

● Death receptor (extrinsic) pathway ○ Remember FAS/ FASL??? ○ Activated caspase 8 will cleave other caspases-> apoptosis **● SOOOOOO intrinsic=mitochondria= caspase 9/ extrinsic=FAS/FASL= caspase 8**

Question 28

Central and Peripheral B Cell Tolerance CENTRAL explain the process from NB to protein AG? are protein AG t-dependent? What happens in the Bone Marrow? how does a self AG w/high affinity affect this? *Remember when I told you B cells are the ones that get the “second chance at life”?

Answer 28

CENTRAL ● NB to maintain unresponsiveness to **T-INDEPENDENT** self AG and aids in preventing AB responses to protein AG ○ (remember protein AG are typically T-dependent) ● In the Bone marrow->immature B cells express IgM ○ If they recognize self AG w/ high affinity they either change their **specificity (receptor editing) or they are deleted!** ■ Remember when I told you B cells are the ones that get the “second chance at life”?

Question 29

Central and Peripheral B Cell Tolerance PERIPHERAL what happens if they recognize self AG w/o specific helper T cells? MOA? (4 facts)

Answer 29

PERIPHERAL ● Recognize self AG w/o specific helper T cells can become anergic or die via apoptosis **● MOA** ○ Anergy ○ Deletion ○ Signaling by inhibitory receptors CD22 ○ Regulation of B cells by Treg subset **(follicular regulatory Tfr cells)**

Question 30

Hypersensitivity RXNs!!!! Intro to hypersensitivity is the mechanism the same or different than normal IR? How is it direted against AG? what about location? How many types of hypersensitivity rxns? can more than on hypersensitivity rxn occur at a time? is this a good thing? what sort of host is required?

Answer 30

Intro to hypersensitivity ● **Same mechanism as the normal IR** ○ Too intense & directed against AG that pose no threat at inappropriate locations ● For this class-> 4 types of hypersensitivity rxns ○ **More than 1 hypersensitivity rxn can occur at a time** ● **Basically just excessive and undesirable ● Can only occur in a pre-sensitized host!!!** ok freaking funny picture attached : When u realize you are acting like a brat but you are already in too deep and can't stop=lolololol. funny TA

Question 31

The different Types of Hypersensitivity Type 1 (broad definition--specific cards to follow) what is a basic example? when does it occur? releases what? resulting in immediate what?

Answer 31

Type 1 ○ THINK ALLERGEN! ○ Immediate hypersensitivity which involved IgE mediated release of histamine ○ immediate/ anaphylactic

Question 32

The different Types of Hypersensitivity ● Type 2 (broad definition--specific cards to follow) what is it? what is bound to a cell surface?

Answer 32

● Type 2 ○ AB dependent Cytotoxic ○ IgG or IgM AB bound to cell surface AG w/ complement fixation

Question 33

The different Types of Hypersensitivity ● Type 3 (broad definition--specific cards to follow) what are they? treatment? where do they deposit?

Answer 33

● Type 3 ○ AG-AB complexes (immune-complex rxns) ○ Deposit in postcapillary venules w/ complement fixation

Question 34

The different Types of Hypersensitivity ● Type 4 (broad definition--specific cards to follow) Are they T cell mediated? what sort of hypersensitivity to rxn?

Answer 34

● Type 4 ○ T cell mediated!!!! ○ Delayed hypersensitivity rxn

Question 35

Type 1 Hypersensitivity Acute inflammation--> ? -->resulting in what? Ag binds to what? where?

Answer 35

Type 1 Hypersensitivity ● Acute inflammation-> due to explosive release of mast cell granule contents-> vasodilation factors are released (histamine & serotonin) ○ AG bind to IgE on mast cells

Question 36

Type 1 Hypersensitivity ENV AG in food/ inhaled air-> ? Is there a consequence? what if the response is IgE all the time? What about heredity? what effect? which breeds are predisposed?

Answer 36

ENV AG in food/ inhaled air-> produce IgG or IgA-> no obvious consequence ○ But if they respond by producing lots of IgE all the time-> atopy and these patients are atopic ○ Hereditary: both parents atopic-> atopic offspring w/ allergies ■ Breed predisposition: terriers, dalmatians, irish setters

Question 37

Type 1 Hypersensitivity what role Eosinophils? are they attracted to mast cells? if so what relationship to helminthic infetions?

Answer 37

Eosinophils also play an important role (remember from our chart?) ○ They are attracted to sites of mast cell degranulation and then release their own molecules ■ Their ability to kill parasites increases which makes sense b/c IgE= important for helminthic infections!

Question 38

Type 1 Hypersensitivity So what are the NB cells of a type 1 hypersensitivity??

Question 39

Type 1 Hypersensitivity CS of T1H: what happens, what result?

Answer 39

CS of T1H: excessive release of inflammatory mediators (mast, eosin, baso), can lead to acute anaphylaxis & death :(, smooth muscle contraction (why ppl can’t breathe)

Question 40

Type 1 hypersensitivity specific types of rxns ● Acute anaphylaxis ○ Cattle, pigs, sheep, & cats=major organ affected is ? horses= ? dogs=?

Answer 40

● Acute anaphylaxis ○ Cattle, pigs, sheep, & cats=major organ affected is the lung ○ horses= lung and intestines (makes sense b/c horses colic ALLLLLL the freakin’ time ○ dogs= liver especially the hepatic veins

Question 41

Type 1 hypersensitivity specific types of rxns ● Inhaled AG ○ Inflammation in the URT-> ? ○ Aerosolized AG contact with the eyes-> ?

Answer 41

Inhaled AG ○ Inflammation in the URT-> fl. Exudation from the nasal mucosa and tracheobronchial constriction ○ Aerosolized AG contact with the eyes-> conjunctivitis & lacrimation

Question 42

Type 1 hypersensitivity specific types of rxns Food Allergies-> ? what % of skin DZZ are to to allergic dermatitis? GI issues? ingested protiens recognized as foreign? what about CS? what happens and what result?

Answer 42

Food Allergies-> typically due to protein rich foods ○ 30% of skin dzz are due to allergic dermatitis ○ 10-15% GI issues ○ 2% ingested protein are recognized as foreign ○ CS: typically papules and erythematous, highly pruritic w/ poor response to corticosteroids ■ Chronic cases: hyperpigmentation, lichenification, pyoderma

Question 43

Type 1: Atopic Dermatitis Chronic multifactorial syndrome-> ? Is it common in dogs? is there a breed predilection? Is it a pure TIH? CS? TX?

Answer 43

● Chronic multifactorial syndrome->& is very itchy :’( ○ House dust, mites, pollens, molds, yeast ● Common in dogs (2⁄3 of my freaking litter ) ● Breed predilection: retrievers, setters, terriers, beagles, cocker spaniels, boxers, bulldogs, & shar-peis ● Probably not a pure TIH (remember multifactorial and chronic) ○ Not all dogs will have an elevated IgE ● CS: itchy asf, excessive licking, skin lesions typically on the vent. Abdomen, otitis externa ● Avoid the allergen (obvi) but not always practical, topical tx= emollient shampoos, antihistamines, glucocorticoids ● LILO IS THE MF POSTER CHILD FOR THIS!!!!

Question 44

Type 1 continued Vaccines & drugs ● Vax w/ ? ● Severe w/ ? ● Drugs: ?

Answer 44

Vaccines & drugs ● Vax w/ aluminum adjuvants ● Severe w/ killed FMD vax, rabies vax ● Drugs: most are too small to be antigenic but can be haptens

Question 45

Type 1 continued ● Drugs: most are too small to be antigenic but can be haptens ○ What is a hapten?? ○ Penicillin allergy- how is it enduced? what is the process? ○ Sensitized animals-> ? ○ Contaminated milk-> ?

Answer 45

● Drugs: most are too small to be antigenic but can be haptens ○ What is a hapten?? ○ Penicillin allergy- may be induced by therapeutic exposure or by ingestion of penicillin-contaminated milk ■ Molecule is degraded in vivo which binds to proteins and provokes an IR ○ Sensitized animals-> acute systemic anaphylaxis or can be mild ○ Contaminated milk-> severe diarrhea

Question 46

Type 1 continued Helminths ● IgE responses-> ? ● Tapeworm infections-> ? ● Anaphylaxis can be stimulated... ? ● Other factors: ?

Answer 46

Helminths ● IgE responses-> allergy and anaphylaxis ● Tapeworm infections-> resp. Distress or urticaria ● Anaphylaxis can be stimulated if a hydatid cyst rupture or blood transfusion from a heartworm positive dog ● Other factors: Arthropod AG, venom, warble fly, saliva, mange

Question 47

RBC AG what happens with Transfusion from 1 patient to another genetically different individual? what response? what happens to transfused RBC? intravascular hemolysis? extravascular hemolysis? what leads to type 2?

Answer 47

Transfusion from 1 patient to another genetically different individual ○ -> AB response ○ -> rapid elimination of transfused RBC ○ -> **intravascular hemolysis **via the complement system (hemoglobinemia and hemoglobinuria) ○ OR **extravascular hemolysis** via opsonization (macrophages) ● **CELL DESTRUCTION BY AB-> TYPE 2**

Question 48

RBC AG what blood groups? what if patients have the same blood group? what if patient has IgM AB to the doner--> ? this will lead to what? what should you test for and why? what relevance Donor RBC mixed with recipient serum?

Answer 48

● Blood Groups: ○ A, B, O= human ● If patiens have the same blood group-> transfusion is easy and successful ● If patient has IgM AB to the donor-> RBC are attacked immediately ○ This can lead to a type 2 hypersensitivity ○ mild-> death depending on how much incompatible blood is transfused ● TEST RECIPIENT FOR AB AGAINST DONORS RBC BEFORE TRANSFUSION ○ Donor RBC are mixed w/ recipient serum (major crossmatch) ■ Lysis or agglutination= don’t do it!!

Question 49

Type 3 hypersensitivity LOCAL Local rxt.... where? What Ex: SQ injection of an AG w/ a patient that has IgG AB-> ? what happens when Arthus rxn-> ? what about Neutrophils adhere to the vascular endothelium-> ? Mast cells-> ? neutrophils-> ? what should you remember about Arthus rxn?

Answer 49

LOCAL ● Local rxn w/ immune complexes w/n tissues!!! ● Ex: SQ injection of an AG w/ a patient that has IgG AB-> acute inflammation will develop at the site ○ Arthus rxn-> red, edematous, & can cause tissue destruction ○ Neutrophils adhere to the vascular endothelium-> mononuclear cells will become the predominant cell type ○ **Mast cells**-> release vasoactive amides and neutrophil chemotactic factor-> complement activation C5a production ○ **neutrophils->** cause mast cells to degranulate ● Plssss remember that arthus rxn is local

Question 50

Type 3 hypersensitivity SYSTEMIC/ GENERALIZED immune compleses are where? what is an ex?

Answer 50

SYSTEMIC/ GENERALIZED ● Immune complexes w/n Blood Vessels! ● EX: IV injection of an AG

Question 51

Type 3 hypersensitivity Staphylococcal hypersensitivity what role in dogs? what types involved, which type most common? why?

Answer 51

Staphylococcal hypersensitivity ● Pruritic & pustular dermatitis of dogs ● Type 1,3,4 are all involved but type 3 seems to be the main player due to neutrophilic dermal vasculitis

Question 52

T cell mediated (type 4) AG injected into the skin can sensitized the animals-> ?

Answer 52

AG injected into the skin can sensitized the animals-> SLOW development of inflammation at the j=injection site

Question 53

T cell mediated (type 4) ● Sensitivity results from interaction among ? what is an example?

Answer 53

● Sensitivity results from interaction among the injected AG, APC, & T Cells ● EX: tuberculin response

Question 54

T cell mediated (type 4) ● EX: tuberculin response is this common? how do you test? the most NB-->

Answer 54

● EX: tuberculin response ○ We all had to get the tuberculin skin test to come here ○ From extracts of mycobacterium tuberculosis to test to see if the patient has tuberculosis ○ The most NB-> purified protein derivative PPD tuberculin which is a poorly defined complex AG mixture

Question 55

T cell mediated (type 4) How does a TB test work? how long does it take? when is the greatest intensity? severe rxn---> ? Histo?

Answer 55

How the TB test works: ○ Tuberculin is injected in a normal healthy patient-> no rxn ○ Patient infected with the mycobacterium-> type 4 which is why you had to go back to the dr like 2-3 days post injection ■ Starts to develop at 12-24 hrs ■ Greatest intensity 24-72 hrs ■ Severe rxn: tissue necrosis ■ Histo: lots of lymphocytes and macrophages

Question 56

Tuberculin skin test continued Natural infection: M. tuberculosis is phagocytosed by ? Will stimulate a T cell mediated response and...? Memory cells then do what? Tuberculin that is injected how? what happens next? what result?? what about B cells? what is attracted to the lesion? what is released? what is th response? is there tissue damage? what happens? How are MACS involved?

Answer 56

Tuberculin skin test continued Natural infection: ● M. tuberculosis is phagocytosed by macs ● Will stimulate a T cell mediated response & the production of memory cells ● Memory cells then can respond to the bacT for many years to come no matter the route of exposure ● Tuberculin that is injected intradermally-> taken up by langerhans cells-> which go to the draining lymph node where they present to the memory cells-> T cell response ● THERE ARE NO B CELLS IN THE LESION ● T cells, macs, basophils are attracted in the lesion due to release of INFy, IL2, Il6-> local inflammatory response ● Tissue damage can occur due to release of proteases & oxidants from activated macs ● Macs then will destroy the injected AG there is a diagram on slide 26

Question 57

My notes from previous semesters on hypersensitivies Type 1 where do you find the most incidents of allergies?

Answer 57

● Allergy/ atopy ○ rxn= against an allergen ○ Developed countries have a higher incidence of allergies

Question 58

My notes from previous semesters on hypersensitivies Type 1 ● Pathway of rxn exaggerated Th2 response leads to an overproduction of what? an excessive production of what? IgE--> binding where? contact with what? resulting in what in the Mast cells?

Answer 58

● Pathway of rxn ○ Exaggerated th2 response ○ Overproduction of IL4 ○ Excessive production of IgE ■ What do you know about IgE???? ○ IgE-> binds to mast cells ○ Contact w/ allergen ○ Mast cell degranulation (histamine and serotonin-> inflammation)

Question 59

My notes from previous semesters on hypersensitivies Type 1 ● FceRI- on mast cells High or low affinity? is it reversible? Excessive IgE--> what?

Answer 59

● FceRI- on mast cells ○ High affinity receptor ( irreversible) ○ Excessive IgE-> generate a Th2 response ■ IL4, IL5, IL13 ○ Allergic anaphylaxis-> life-threatening systemic **graph on slide 28

Question 60

My notes from previous semesters on hypersensitivies Type 1 Resp. tract-> ? where what result in dogs? what about hystamine--? Atopic derm is most commonly associated with what? where is it most common? what animal? more specifically..... what about pruritus? when does it occur? where? what is the dx? what is the downdisde of this DX? what does it tell you?

Answer 60

● Resp. tract-> main organ responding in most spp. ○ (dog= hepatic veins) ● histamine-> major mediator ○ ruminants-> serotonin ● Atopic derm ○ Most commonly associated with IgE AB to ENV allergens ○ Common in the pups ○ Esp indoor dogs, less than 3 yrs old, pruritus= responsive to glucocorticoids, pruritus- before lesions, front feet, pinna, ear margins, then dorsolumbar ■ Any of the 5=DX for AD ■ Increase in IL31-> causes the itches so block Il31-> TX but its $$$$$$ ● DX ○ Classic method- intradermal testing ○ Measurement of IgE- kinda dumb ○ Doesn’t tell you a lot

Question 61

Type 2 AB dependent cytotoxicity or cytotoxic hypersensitivity where is AB recognized? how is it mediated? what "system"? what is an example? what happens to the recipient? how does Rxn treatment work? what is the Rxn to infection Dz?

Answer 61

● AB dependent cytotoxicity or cytotoxic hypersensitivity ○ AB recognized AG of cell surface ○ Mediated by IgG and IgM ○ Complement system ● EX: incompatible blood transfusions ○ Recipient has AB against donor blood group AG -> RBC destroyed ○ Rxn to drugs ■ Can be adsorbed onto cell surface glycoproteins ○ RXn to infectious dz ■ Bacterial LPS ■ Equine infectious anemia virus ■ Babesia ■ Anaplasma ■ Hemotropic mycoplasmas slide on p 30

Question 62

Blood Groups ● Canines DEA--> ? DEA1 and 4= ? 1= ? 4=? so what sort of donor do you want? what about the 1st trans? what about the 2nd trans?

Answer 62

● Canines ○ DEA-> main one also have dal ■ DEA1 and 4= majority of the population ■ 1= highly immunogenic ■ 4= non-immunogenic ■ So you want a donor that is DEA1 NEGATIVE!!!! ○ 1st trans-> not an issue (no AB) 2nd-> can be a problem especially with DEA1

Question 63

Blood Groups ● Felines what are the 2 relelvent groups?

Answer 63

● Felines ○ AB group ○ MIK group

Question 64

Blood Groups ● Type A- where? (geographical location) what result isoAB?

Answer 64

● Type A- N. America ○ Weak isoAB against type B

Question 65

Blood Groups Type B- where? (geographical location) what result isoAB? what happens? explain neonatal isoerythrolysis: type AB= what? can they donate blood?

Answer 65

Type B- british breeds ○ Strong isoAB against type A ○ Severe and lethal ○ Neonatal isoerythrolysis ■ Type b queen + type A or AB tom-> type A or AB kittens ○ Type AB= universal recipients but they cannot donate blood!

Question 66

Blood Groups ● Equine blood groups ○ Aa and Qa- are what? ■ Neonatal isoerythrolysis? most common in what equines? what is relevant about the mare? EAA is the .... EAQ is the....

Answer 66

● Equine blood groups ○ Aa and Qa- highly immunogenic ■ Neonatal isoerythrolysis ■ Common in foals ■ mare= sensitized against fetal RBC AG ■ EAA= most severe ■ EAQ= slower onset diagram slide 32

Question 67

Blood Groups ● Bovine neonatal pancytopenia VAX induced what? adjuvanted what? what relevence in calves? how does this affect calf celss? how does it work?

Answer 67

● Bovine neonatal pancytopenia ○ Vax induced alloimmune dz ○ Adjuvanted BVDV ■ Calf- half MHC from mom and half from dad ■ So the calf cells= targeted ■ Vax inducing rxn from MHC mol. From the bovine kidney to the calf via *diagram slide 32

Question 68

Type 3 ● Immune complex is what? local treatments is found where (in the body) where is it never found (in the body) systemic rxn is within what? is it local or does it travel? what relevance to blood vessels what relevence to glomerus?

Answer 68

Type 3 ● Immune complex-mediated ○ IgG & IgM ● Local rxn ○ Within tissues ○ NEVER IN THE BLOOD ● Systemic rxn ○ Within the bloodstream ○ Can go pretty much anywhere, yo ■ Joining, blood vessels, g ■ glomerus= common places

Question 69

Type 3 ● Immune complexes- stim what resulting in what? What is Arthus rxn? where does it happen, what causes it? what is important to remember about hypersensitivity rxns?

Answer 69

● Immune complexes- stim complement system and severe inflammation ● Maurice Arthus rxn!! ○ LOCALIZED- caused by the SQ injection of an AG on an already sensitized animal **REMEMBER: hypersensitivity rxns are normal IR/ pathways just over reacting** *diagram slide 33

Question 70

Type 3 continued Canine adenovirus type 1 can cause what? what is it? how does it take place? what is the process?

Answer 70

Canine adenovirus type 1 can cause blue eye in dog during the recovery phase! ○ (nat infection or CAV-1 vax) ○ cornea= infiltrated with immune complexes-> damage to corneal endothelium-> aq humor-> enters -> edema-> blue eyes

Question 71

Type 3 continued ● Hypersensitivity pneumonitis how does it occur? what is an example? what result? what is the equine respitory dz? can you have more than one hypersendisitivity rxn at the same time? what is staph hpersensitivity? what is pruritic pustular derm? what animaL? what types, what is most commmon type?

Answer 71

● Hypersensitivity pneumonitis ○ Sensitized animals inhale AG ○ Ex: actinomycetes in hay ○ Results in edema in the alveolar spaces ○ Equine respiratory dz ■ Th2 response?? ■ No IgE so its not horsey asthma ● Remember you can have more than 1 hypersensitivity rxn happening at the same time! ○ Staph hypersensitivity ■ Pruritic pustular derm of dogs ■ Types 1,3,4 all involved but type 3= main

Question 72

Type 3 continued ● Serum sickness what is it? who gets it? what result? what is it due to? and what does this lead to? what is an example what organ is attacked?

Answer 72

Type 3 continued ● Serum sickness ○ Basically gave individuals hyperimmune horse serum and it caused arthritis, fever, & rash ○ Due to AB- AG complexes. If AG doesn’t go away then leads to chronic process ○ Ex: chronic e. canis-> renal dz ○ It's really common for a lot of these paths to attack the kidney * graph slide 35

Question 73

Type 4 ● Delayed hypersensitivity what sort of cells? why does this make sense? how is it different from type 1? what is an example? what relevance cytokine? what is the role of CD8?

Answer 73

● Delayed hypersensitivity ○ T CELLS!!!! ○ Makes sense that it is going to be delayed b/c t cells-> adaptive immunity and needs days to build a response ● Very different from type 1 which happens really fast! ● EX: TB test we all had to get to come to this beautiful place ○ Cytokine mediated ○ CD8 killing of host cells *diagram on slide 36

Question 74

Type 4 continued ● Granuloma what happens with mycobac t? what result? what 3 things surroung the bact? what result to the bacT? what is the adequate response? what is the inadequate response? what role allercic contact dermatitis? how does it happen an what are some examples? is it an immediate process? where is it usually located on the animal?

Answer 74

Type 4 continued ● Granuloma ○ mycobacT= mycolic acid which makes it resistant to phagocytosis so the macs will eat the bacT but can’t digest it ○ Results in caseous necrosis (looks like cheese) ○ Fibroblasts, lymphocytes, and macs all surround the bacT ■ bacT= won’t die but it can’t continue to proliferate due to low pH and anaerobic conditions ○ Adequate response Th1 ○ Inadequate response Th2 ■ why???? ● Allergic contact dermatitis ○ Highly reactive molecules will bind with skin proteins and act as haptens (dyes, paints, acid, etc) ○ Delayed process (duh its a type 4) ○ Usually located on hairless areas of skin in contact regions