Micro Id #1 - Hypersensitivity Reactions

Front 1

What is the Gell & Coombs Classifcation system?

Back 1

Type I- Immediate Hypersensitivity
Type II- Antibody Mediated
Type III- Immune Complex
Type IV- Delayed Hypersensitivity

Front 2

The major cytokines that influences Th cells to secrete the Th1 profile is?

The major cytokines that direct Th cells into the Th2 profile is?

Back 2

Th1 = IL-12

Th2 = IL-4

Front 3

What cytokines promote the survival of eosinophils?

Back 3

IL-3, IL-5, GM-CSF

Front 4

Where does "cross talk" between B cells and Th cells occur (be as specific as possible)

Back 4

In the secondary lymphoid tissue, such as lymph nodes. Specifically in the parafollicular cortex.

Front 5

What three processes occur in the germinal center of lymph nodes that enhance B cells killing of microbes?

Back 5

1. Somatic hypermutation
2. "testing": affinity maturation
3. Class switching

Front 6

What are the major systemic effect of re-exposure to the same antigen in a type I hypersensitivity response?

Back 6

1. Blood vessels: vasodilation, hypotension

2. Airways: broncho-constriction, increase mucous secretion

3. GI: Increased fluid secretion, peristalsis- nausea, vomitting, diarrhea

Front 7

What are the major " pre- formed" granules?

What time frame are they activated in?

Back 7

Histamine
Proteases
Chemotactic factors (ECF, NCF- eosinophil chemotactic factor,neutrophil)
TNF

1-5 minutes, immediate degranulation

Front 8

What clinical symptoms are produced by histamine release in the hypersensitivity type I response?

Back 8

1. Vasodilation
2. Increased vascular permeability
3. Bronchospasm
4. Mucous secretion

Front 9

What is the role of proteases released in granules in Type I hypersensitivity reactions?

Back 9

Generate kinin such as bradykinin
Cleave complement- increase chemotactic factor
Degrade blood vessel basement membrane

Front 10

What are the lipid mediators associated with mast cell activation? How are they produced and in what time frame are they activated?

Back 10

Leukotriene C4 and D4
Leukotriene B4
Prostaglandin D2
PAF

Produced from Platelet Activating Factor activation and Arachadonic Acid Metabolism

5-30 min

Front 11

How long does it take to make secreted cytokines (during mast cell activation)?

Back 11

Hours
This is because transcription has to occur of new cytokines.

Front 12

What is the role of leukotriene C4 and D4?

Back 12

VASOACTIVE AND SPASMOGENIC!!
increased vascular permeability, bronchial smooth muscle constriction like woah (1000x)

Front 13

What does PAF or platelet activating factor do?

Back 13

Everything
Vascular permeability, vasodilation, platelet aggregation, histamine release, bronchospasm, chemotactic

Front 14

What cytokines up regulates adhesion molecules on endothelial cells?

Back 14

TNF (there is also some stored in pre-formed granules and released initially)

It promotes influx of inflammatory cells into tissues

Front 15

What does leukotriene B4 and MIP-1a (macrophage inflammatory protein) have in common?

How do they differ?

Back 15

They both are chemotactic and attract inflammatory cells into the area.

Leukotriene B4 is a lipid mediator, also attracts neutrophils.
MIP-1a is a chemokine made in late stage reaction, only attracts monocytes.

Front 16

What a the two main phases of local type I hypersensitivity responses and what briefly happens in each?

Back 16

1. Initial response: vasodilation, smooth muscle spasm, edema (within 5-30 minutes of exposure, will subside by an hour)

2. Late phase reaction- infiltration of eosinophils and other inflammatory cell, causing tissue distruction (2- 24 hours)

Front 17

T or F
Only mast cells are capable of releasing the cytokines needed to recruit eosinophils in late phase hypersensitivity reactions.

Back 17

False
Armed mast cells can produce IL-3 and IL-5. But the main producer is Th2 cells--> IL-3, IL-5, and GM-CSF

Front 18

What is the role of Major Basic Protein and what cell is it secreted by?

Back 18

Eosinophils

Triggers histamine release but also toxic to parasites and mammalian cells

Front 19

What route of allergen administration would you expect in an anaphylactic reaction?

Back 19

Intravenous (ex: bee sting, IV antibiotic)

Front 20

What route of allergen administration could cause pulmonary findings such as upper airway allergic rhinitis or asthma?

Back 20

Inhalation

Front 21

What type of allergic route of administration would likely result in GI symptoms?

Back 21

Ingestion (ex: lactose intolerance, Gluten allergy)

Front 22

What is the clinical name for "hives"?

What are two major Anaphylatoxins that have receptors on Mast cells?

Back 22

Urticaria

C3a, C5a

Front 23

What are the Great Eight- major food allergies?

Back 23

Milk
Eggs
Peanut
Tree nut ( walnut, cashew)
Fish
Shellfish
Soy
Wheat

Front 24

What does an Epi- pen do?

Back 24

Release concentrated epinephrine which will cause vasoconstriction, smooth muscle relaxation- thus reverse bronchospasm, etc.

Front 25

What are the classic symptoms of Allergic Asthma?

In this condition is bronchoconstriction reversible or irreversible?

Back 25

Coughing
Wheezing
Shortness of Breath

Bronchoconstriction is reversible!

Front 26

What cellular/histologic changes do you expect to find in the case of a mild asthmatic?

Back 26

Goblet Cell Hyperplasia (mucous secretion)
Basement Membrane thickening with collagen deposition
Cellular infiltrate

Front 27

What is Derp-1 and how does it work?

Back 27

It is the major allergen of house dust mites. It is a cystiene protease that cleaves occludens junctions between cells and can cause mast cell degranulation.

Front 28

What route of antigen exposure causes the classic "wheal and flare" reaction?

Is this a phase I or phase II Type I hypersensitivity reaction?

Back 28

Subcutaneous, low dose exposure

Phase I, immediate response within minutes and subsides in under 1 hr.

Front 29

What causes the "wheal" and what causes the "flare" of the Wheal-and-Flare reaction?

Back 29

Vasodilation and edema results in bump or wheal

Vasodilation at edges of lesion causes flare.

Front 30

What are three ways in which you can determine what a person is allergic to?

Back 30

1. History (consider possibility of cross reactivity!)
2. Skin testing (Wheal and Flare)
3. Radioallergosorbent RAST rest (blood test that measures specific serum IgE antibodies)

Front 31

What are "atopic" individuals?

Back 31

People prone to have very strong hypersensitivity reactions, usually genetic!

Front 32

What is the "atopic triad"?

Back 32

What people who are atopic typically present with
Allergic Rhinitis - hay fever
Asthma
Atopic dermatitis- chronic eczema or urticaria

Front 33

How do allergy shots work and what are some proposed mechanisms?

Back 33

Desensitization. You administer small doeses of antigen into body at repeated intervals.

Possibly works by changing Th2 to Th1 profile. Also might cause T cell tolerance.

Front 34

What antibodies mediate Type II Hypersensitivity reactions?

What are 4 main mechanisms for this reaction?

Back 34

IgG and IgM

1. Opsonization and Phagocytosis
2. Complement & Fc Receptor Mediated Inflammation
3. ADCC
4. Antibody-Mediated Cellular Dysfunction

Front 35

What type of reaction would you expect if you gave type A blood to a person with blood type B?

Back 35

Direct Cell Lysis of RBCs can occur with major transfusion reactions.
This involves complement activation and killing of cells via MAC complexes.

Front 36

What happens physiologically during minor transfusion reactions?

Back 36

Minor = extravascular hemolysis
Opsonization via binding of C3b or Antibody and subsequent Phagocytosis.

Extravascular = in spleen, liver, bone marrow. Not in vessel or blood stream which is intravascular

Front 37

T or F
Women who are Rh+ should take rhogam after the birth of their first born Rh+ child?

Back 37

False
Only women who are Rh- will develop antibodies against Rh + fetal blood. If a woman is Rh+ she doesn't have to worry.

Front 38

What Is Erythroblastosis Fetalis and what treatment is used to prevent it?

Back 38

Aka. Hemolytic disease of newborn or Hydrops fetalis

Rh- mom produces Abs against Rh+ child and can attack child's RBCs causing severe anemia, lack of CNS developmen, and death.

Treatment= administration of Rhogam within 72 hrs post birth of first Rh+ child

Front 39

What is a "hapten"?

Back 39

Incomplete ANTIGEN that is not enough to stimulate antibody production and can only do so in combination with a particular protein (ex: certain drug induced reactions)

Front 40

What complement factors activate inflammation and how can they cause tissue damage?

Back 40

c3a and c5a are inflammatory
They can cause inflammation by recruiting leukocytes which release ROS which damages tissues.

Front 41

What type if hypersensitivity reaction causes Goodpasture Syndrome?

What is this syndrome?

Back 41

Type II Hypersensitivity
Antibodies against type IV collagen are made. Cross reaction with other basement membranes (ex: lung).

Causes rapidly progressive glomerular nephritis and if lung- Necrotizing hemorrhagic pneumonitis

Front 42

What is the characteristic appearance of Anti-GBM disease on immunofluoresence?

Back 42

Linear deposition of immune complexes

Front 43

What is meant by antibody mediated cellular dysfunction?

Back 43

When an antibody binds to target cell receptor but doesn't cause death. Rather, it causes some change in cell function (but no inflammation or cell injury)

1. Myasthenia Gravis
2. Graves Disease

Front 44

A patient comes to you who has variable muscle weakness and specifically when she is asked to blink has droopy eye lids (ptosis).

What might you find in her blood? What treatment options would you suggest based on this finding?

Back 44

Myasthenia Gravis

You might find antibodies to ACh receptors in her blood.
Treatments: AchE Inhibitors, Immunosuppression, or Thymectomy

Front 45

What is the pathology of Graves Disease (hyperthyroidism)?

What classic symptoms do these individuals have?

Back 45

Antibodies against TSH receptors counterintuitively stimulate it (they act like agonists). Thus the thyroid produces more thyroid hormones.

This causes an enlarged thyroid or goiter, and exophthalmos or bulging eyes due to cross reactivity with eye muscles.

Front 46

What two main points should you remember when it comes to Type II Hypersensitivity reactions?

Back 46

1. IgG and IgM
2. Surface proteins

Cytotoxic type reactions

Front 47

What two main points should you remember when it comes to Type I Hypersensitivity reactions?

Back 47

1. IgE
2. Immediate type

Front 48

What is the most important thing you should remember when it comes to Type III Hypersensitivity reactions?

Back 48

Circulating immune complex

(and Indirect Target or "Innocent Bystander")

Front 49

What are two main categories of immune complex disease? Provide some prototypes of each.

Back 49

1. Systemic immune complex disease (ex: Serum sickness, SLE, post-infectious glomerularnephritis)

2. Localized immune complex disease (ex: Arthus reaction)

Front 50

When von Pirquet injected children with Horse serum, what concerning symptoms did they develop and how long did it take?

Back 50

10 days after injection. This is because it takes a week to develop good antibody response and then the immune complexes (IC) formed and deposited, resulting in symptomatology.

-fever
-vasculitis, urticaria/rash
-arthritis
-nephritis

Front 51

What makes an Immune complex reaction different from a regular old Antigen-Antibody reaction?

Back 51

1. ICs are produced in excessive amounts

2. There is not efficient clearing by phagocytic system (overload or intrinsic dysfunction of the clearing system > persistence of ICs in circulation > increased tissue deposition)

Front 52

What are the three phases of a Type III hypersensitivity reaction?

Back 52

Phase 1= Abs are formed against a circulating antigen and form complexes

Phase 2= The complexes deposit into a vessel wal

Phase 3= ICs bind to inflammatory cells (Fc or C3b receptors) and trigger release of inflammatory mediators > recruit inflammatory cells > tissue injury

Front 53

Distinguish the urticaria that one gets in a Type I Hypersensitivity reaction from one in a Type III Hypersensitivity reaction?

Back 53

Type I= IgE mediated activation of mast cells which cause immediate release of histamine and this causes urticaria

Type III= C3a and C5a anaphylatoxins bind to mast cells and cause release of vasoactive amines, this is a slower response

Front 54

If a person who has a type III Hypersensitivity response is biopsied, what do you expect to see on the path slide?

Back 54

Vasculitis or destruction of vessel (pink protein deposits where dead tissue was and inflammatory cells surrounding it)

"Fibrinoid Necrosis"= pink, smudy material that replaced the necrotic vessel wall

There would be injury to the vessel wall because leukocytes would migrate in where IC were complexed and release ROS.

Front 55

What is the course of Systemic Lupus Erythematosis (SLE)?

Back 55

Chronic autoimmune disease. Relapsing & remitting course

Front 56

How would you test to see if someone has Lupus?

Back 56

Lab test for ANA (anti-nuclear Abs) specifically Abs to double stranded DNA & Anti-Smith Abs (small nuclear ribosomal antigens)

Front 57

What are some clinical manifestations of lupus?

Back 57

Malar rash "butterfly rash"
arthritis
glomerulonephritis
>> Multisystems disease

Front 58

How is Glomerulonephritis in SLE different from Goodpasture's Syndrome?

Back 58

Glomerulonephritis in SLE is a Type III Hypersensitivity reaction. The auto-antibodies are not against the GBM, it is just an innocent bystander where circulating complexes deposit. Also "lumpy bumpy" i.e. course, granular deposition of ICs on immunofluorescence microscopy.

In Goodpasture (type II) the antibodies are specifically Anti-GBM. Also linear deposition of ICs.

Front 59

T or F
In general, smaller complexes are easier for the phagocytic system to clear because they are easily broken down.

Back 59

False!
In general, larger ICs are more rapidly removed by the liver (whereas small complexes circulate for long time)

Front 60

What physicochemical properties of Ags & abs can determine the extent and location of IC deposition?

Back 60

- Charge
- Valency of Ag
- Avidity of Ab

- Hemodynamic: deposit where there is high blood pressure and turbulence

- Affinity of Ag to certain tissues (kidney, joints, etc.)

Front 61

A child comes to your clinic with blood in the urine, high fever, and a rash. His mother is very concerned. She says that he had a sore throat and maybe a strep infection over 10 days ago and that he recovered without treatment. She doesn't know if it is a virus. What do you think he might have?

Back 61

Most likely a post-infectious Glomerulonephritis. Strep cell wall Ag may initiate circulating ICs and deposit in GBM, causing classic symptomatology.

Front 62

Post infectious Hepatitis B can cause what condition that results in medium-size artery vasculitis and nephritis?

Back 62

Polyarteritis nodosa

due to IC complexes formed against Hep B antigen.

Front 63

What is a post infectious cause of Myocarditis?

Is it a Type I or Type II Hypersensitivity reaction?

Back 63

Strep (Abs to strep Ags can cross react with cardiac antigens)

Type II (because the heart is a surface!)

Front 64

How does an "Arthus Reaction" differ from a "Wheal and Flare" response?

Back 64

Wheal and Flare: IgE mediated, Type I hypersensitivity, edema, vasodilation leading to bump and surrounding erythema

Arthus reaction: IC mediated, Type III Hypersensitivity, localized area of necrosis developing over several HOURS.

Front 65

Give an example od when you might see an "Arthus Reaction".

Back 65

ex: Local reaction to Tetanus Booster.

Person has Abs to tetanus toxoid floating around. They then get a booster. Ags from booster can form ICs with previous Abs and lead to localized acute vasculitis.

Front 66

What are two main mechanisms of Type IV Hypersensitivity Reactions?

Back 66

1. Delayed-Type Hypersensitivity (ex: tuberculosis, ppd)

2. T-cell mediated cytotoxicity (resistance to intracellular pathogens, viral infections, graft rejection, tumor immunity)

Front 67

What are the 3 major cytokines that Th1 T cells produce?

Back 67

1. IL-2: autocrine loop (stimulates it to make more of itself)
2. TNF- increase adhesion molecules and that kind of thing to bring in more leukocytes
3. IFN-g: rev up macrophages!

Front 68

Are you looking at Granulomas in the skin when you are reading a ppd? why or why not?

Back 68

No
It takes a long time to make granulomas (macrophages have to get angry and wall off bacterium). You are looking at

Front 69

T or F
If a person who has just returned from an endemic country is given a ppd test and is cleared, there is no chance that they have been exposed to tb.

Back 69

False!
In order to mount a Th1 response against tb, it takes some time (macrophages get angry, then stimulate CD4 to become Th1)

Front 70

What is the classic pathological finding in a reaction against mycobacterium tuberculosi?

Back 70

Caseous necrosis and granuloma formation (macrophages transforming to epitheliod cells around the bacterium, walling it off. surrounded by lymphocytes)

Front 71

What does a "reved up macrophage" mean?

Back 71

A macrophage that has been stimulated by INF-gamma and now has more iNOS (nitric oxide, cytotoxic agent)

Front 72

what is a ppd?

Back 72

purified protein derivative of tuberculin

Front 73

What is the point of giving a two-step ppd?

Back 73

Older adults have waning Th1 responses to ppd. So the first time they are tested they may not show a response. However the first test would boost the Th1 response so that when they are re-tested, if they have previously been exposed, they will have induration of the skin.

Front 74

A cousin visits you from abroad. He has never encountered poison ivy before. One day, when you go hiking, he brushes against poison ivy. Should he get a reaction?

Several weeks later, he braves the woods again and brushed against more poison ivy? What kind of reaction will happen and how quickly?

Back 74

No, in order for reaction to happen he has to have previous exposure.

He will form blistering, pruritic skin aka "contact dermatitis". It will take only 1-2 days since memory T cells are already formed.

Front 75

T or F
Urshiol, the resin in posion ivy, is the antigen that induces a Type IV Hypersensitivity or cell-mediated response.

Back 75

False

Urshiol by itself is a hapten. When it comes into contact with the skin it becomes the antigen that participates in the hypersensitivity response.

Front 76

What two mechanisms do CTLs use to kill target cells?

Back 76

1. Perforin and Granzyme mediated
2. Fas-Fas ligand mediated apoptosis

Front 77

T or F
In viral hepatitis, the tissue damaging agent is HBV, the virus itself.

Back 77

False
The virus doesn't cause the problem. It is the CTL response to the virus that causes individual cells to die via apoptosis.