hypersensitivity disorders

Question 1

hypersensitivity (or allergy) is an ____ immune response harmul to the organism itselt

Answer 1

exaggerated

Question 2

types I, II, and III are ____ - mediated which correspond to defenses against ____ pathogens

type IV are _____ - mediated which correspond to defenses against ____ pathogens

Answer 2

anti-body extracellular

cell intracellular

Question 3

type I hypersensitivity:

• ____ reactions
• mediated by ____ and ____ Abs that activate ____ cells and ____ to release inflammatory mediators
• also utilize ____ helper cells due to class switching (to IgE)
• triggered by ____ Ags (typically allergens)
  
  • bind with extremely high affinity, even tiny amounts of Ag are able to elicit a massive and ____ rxn

Answer 3

• immediate
• allergens IgE mast eosinophils
• Th2
• environmental
  
  • rapid

Question 4

type I hypersensitivity:

• mast cells release (IgE binds to ____ on mast cells)
  
  • ____ → vasodilation and inceased vascular permeabiltiy (preformed)
  • ____ → protein degradation
  • ____ → vasodilation (denovo)
  • ____ → bronchospasm (asthma) and other smooth muscle contraction (denovo)
  • other cytokines that lead to ____ inflammation

Answer 4

• FceR1
  
  • histamine
  • proteases
  • prostaglandins
  • leukotrienes
  • local

Question 5

type I exposures:

• initial allergen encounter (primary exposure)
  
  • no ____ reaction
  • DC captures, processes, and presents Ag to ____ in LN
  • ____ are created to recognize specific Ag
  • these IgE Abs bind ____ on ____ cells to anticipate future attack
• subsequent allergen encounter (secondary exposure)
  
  • ____ cells are primed and ready to go due to primary exposure
  • Ag binds to mast cells → ____ on mast cells
  • ____ release of granules containing products of mast cells

Answer 5

• • immediate
    
    • CD4 (will differeniate to Th2)
    • IgE Abs
    • FcRe mast
• • mast
    
    • crosslink
    • immediate

Question 6

type I phases:

• immeidate
  
  • ____ after exposure and lasts about an hour
  • effects
    
    • ____ from histamine and prostaglandins
    • ____ from constricted bronchioles
    • ____ from increased vascular permeability of histamine
• late phase
  
  • ____ after exposure
  • effects
    
    • infiltrate of ____ , ____ , and ____ cells

Answer 6

• • minutes
    
    • effects
      
      • vasodilation
      • congestion
      • edema
• • hours (2-24)
    
    • effects
      
      • eosinophils, neutrophils, T

Question 7

examples of type I hypersensitivity:

• systemic anaphylaxis
  
  • allergens:
  • route of entry:
  • response:
• acute urticaria (wheal-and-flare)
  
  • allergens:
  • route of entry:
  • response:
• allergic rhinitis (hay fever)
  
  • allergens:
  • route of entry:
  • response:
• asthma
  
  • allergens:
  • route of entry:
  • response:
• food allergy
  
  • allergens
  • route of entry:
  • response:

Answer 7

• systemic anaphylaxis
  
  • drugs, serum, venoms, peanuts
  • intravenous (either directly or following oral absorption into the blood)
  • circulatory collapse, tracheal occlusion, death
• acute urticaria
  
  • insect bites, allergy testing
  • subcutaneous
  • local increase in blood flow an vascular permeability
• allergic rhinitis
  
  • pollens (ragweed, birth, etc), dust-mite feces
  • inhalation
  • edema of nasal mucosa, irritation of nasal mucosa
• asthma
  
  • danders (cat), pollens, dust-mite feces, cold, viral infections, exercise
  • inhalation
  • bronchial constriction, increased mucus production, airway inflammation
• food allergy
  
  • tree nuts, peanuts, shellfish, milk, eggs, fish
  • oral
  • vomiting, diarrhea, pruritis (itching) urticaria (hives), and anaphylaxis (rarely)

Question 8

allergen testing (type I):

based on ____ type I hypersensitivity

positive reaction shows:

____ minutes after exposure

Answer 8

local

redness, swelling, itchiness

20-30

Question 9

allergen specific immunotherapy (allergen - SIT):

• only ____ for allergic diseases available at this time
• is performed by the administration of ____ doses of the allergen
• mechanism
  
  • induce peripheral ____ cell tolerance to allergens
  • increase the ____ for mast cell and basophil activation by allergens
  • decrease ____ -mediated histamine release by mast cells and induction of ____ and ____
• the generation of induced regulatory FoxP3+, CD4+, CD25+ ____ cells is the key mechanism in. allergen-SIT increases cytokines ____ and ____
• increases ____/____ cytokine ration

Answer 9

• cure
• increasing
• • T
    
    • thresholds
    • IgE IgA IgG
• Treg IL-10 TGF-beta
• Th1/Th2

Question 10

type II hypersensitivity:

• ___ - mediated
  
  • Ab ____ binds to tissue/cellular Ag
• Ab bind to Ag
  
  • activate ____ ____ → recruit leukocytes and release inflammatory cytokines via (C3 and C5)
• ____ binds FcRs on ____ and ____
  
  • typically these Ags are too big to be engulfed by phagocytes so they will release ____ enzymes and ____ → causes bystander damage

Answer 10

• Ab
  
  • directly
• • classical compllement
• IgG macrophages neutrophils
  
  • lysosomal ROS

Question 11

2 types of effector mechanisms of type II hypersensitivity

Answer 11

complement-mediated cytotoxicity

Ab-dependent cellular cytotoxicity (ADCC)

Question 12

type II reaction to remember:

• graves disease
  
  • Ab targets ____ receptor
  • causes stimulation of ____ → resulting in ____
• myasthenia gravis
  
  • Ab targets ____ receptor
  • Acetylchoine can’t bind → ____ paralysis
• hemolytic anemia
  
  • hemolytic disease of ____
  • ____ induced hemolytic anemia
• rheumatic fever
  
  • targets myocardial Ags (from confusion with ____ Ag)
  • inflammation of ____ → myocarditis
• rheumatoid arthritis

Answer 12

• graves disease
  
  • TSH (thryoid stimulating hormone)
  • TSH → hyperthyroidism
• myasthenia gravis
  
  • ACh
  • flaccid
• hemolytic anemia
  
  • newborn
  • drug
• rheumatic fever
  
  • streppococcal
  • myocardium

Question 13

hemolytic disease of newborn (type II):

• occurs when
  
  • mom = Rh ____
  • baby = Rh ____
• 1st pregnancy the baby ____
  
  • Rh+ baby causes mother to create Rh ____
  • 1st baby is not at ____ but future pregnancies are
• 2nd and future pregnancies the baby does not ____
  
  • Rh+ baby has their blood cells ____ by mothers Abs after crossing the ____
• treatment is ____ ____ (RhoGAM) at ____ weeks

Answer 13

• • negative
    
    • positive
• survives
  
  • Ab
  • risk
• survive
  
  • lysed placenta
• anti-anti Rh 28

Question 14

myasthenia gravis and graves disease (type II):

• both: Abs bind ____
• myasthenia gravis
  
  • Abs bind ____ ____ receptor (NAchR) on ____ ____
  • ____ receptor to acetylcholine activation
  • symptoms:
• graves disease
  
  • Abs bind ____ ____ ____ receptors (TSHR)
  • ____ receptor
  • causes ____
  • symptoms:

Answer 14

• receptors
• • nicotinic acetylcholine skeletal muscles
    
    • blocks
    • muscle weakness, drooping of eyelids, impaired speech
• • thyroid stimulating hormone
    
    • activates
    • hyperthyroidism
    • anxiety, tremor, heat sensitivity, buldging of eyes (exophthalmos)

Question 15

goodpasture’s syndrome (type II)

• Abs bind to college on ____ and ____
• bind to ____ subunit of type ____ collagen and destroys it
• renal glomeruli → ____ ____
• pulmonary alveoli → ____ ____ ____ ____
• activates ____

Answer 15

• lung and kidneys
• A3 IV
• progressive glomerulonephritis
• necrotizing hemorrhagic interstitial pneumonitis
• completment

Question 16

both type II and III hypersensitivities are ____ -mediated, the difference being where the Ag is ____

Type II = Ag located in ____

type III = Ag located ____

Answer 16

Ab located

tissue

solbule/circulation

Question 17

type III hypersensitivity mechanism:

• failure/inability of immune cells to clear ____ ____ ____
• complexes can circulate and ____ in vessel walls
• these immune complexes induce vascular inflammation and subsequent ____ damage to tissues
• deposited complexes
  
  • activate classical ____ releasing ____ and ____ attracting immune cells
  • activate immune cells via ____ receptors
• activated immune cells cause ____ in tissue where complexes are deposited

Answer 17

• soluble immune complexes
• deposit
• ischemia
• • complement C3a C5a
    
    • Fc
• inflammation

Question 18

clinical presentation of type III hypersensitivity:

• in general, immune complexes will be depositing in the walls of blood vessels, causing inflammation of the vessel itself → ____
• these complexes are too large to be ____ and therefor will have a hgher likelihood of being deposited in locations that filter ____ such as
  
  • ____ can beceome inflammed → ____
  • ____ ____ filter plasma to make synovial fluid, immune complex deposition in synovial joints causes them to become inflamed and painful → ____

Answer 18

• vasculitis
• filtered plasma
  
  • kidneys nephritis
  • synovial joints arthritis

Question 19

systemic lupus erythematosus (SLE):

• type ____ hypersensitivity
• cause: ____ Abs (tested for to confirm diagnosis)
• symptoms:
  

Answer 19

• III
• anti-DNA
• • rash, frequently a Malar or butterfly rash on the face
    
    • arthritis
    • nephritis

Question 20

polyarteritis Nodosa (PAN):

• type ____ hypersensitivity
• reaction to ____ ____ Ags
• results in deposition of complexes throughout the body causing ____ of muscular ____
  
  • resulting in weak vessels, increasing the changes of ____/____
  • can be thought of a mini ____

Answer 20

• III
• hepatitis B
• necrosis arteries
  
  • rupture/hemorrhage
  • aneurysm

Question 21

acute post-streptococcal (or infectious) glomerulonephritis:

• type ____ hypersensitivity
• reaction to ____ Ags that linger in the blood following infection
• can have type ____ characteristics

Answer 21

• type III
• streptococcal Ags
• II

Question 22

serum sickness:

• type ____ hypersensitivity
• introduction of ____ Abs in the form of antiserum or antitoxins, can be used to eliminate certain toxins in the blood (antitoxin is the main treatment for venomous animal bites and some bacterial infections that produces bloodborne toxins)
• introduced Abs form complexes with the toxin and trigger complement activation and Fc receptors as discussed earlier

Answer 22

• III
• exogenous

Question 23

arthus reaction:

• type ____ hypersensitivity
• caused by ____ introduction of Ag in an individual that has already been immunized against the Ag
• immune complexes form in the site resulting in an area of ____ and local vasculitis
• can be a rare complication of some modes of immunization that require multiple administrations ( ____ and ____ )

Answer 23

• III
• subcutaneous
• necrosis
• tetanus and diphtheria

Question 24

type IV hypersensitivity is also called ____ hypersensitivity (DTH)

*if see the word “chronic” in a stem, think type IV or if see “reaction occurs several hours to over a day later” think type IV

Answer 24

delayed-type

Question 25

_type IV Hypersensitivity:_ * caused by * ____ \_\_\_\_ cells in autoimmune disease * ____ T cell response to Ag * results in * cytokine (from ____ and ____ ) stimulation of inflammation via macrophages and neutrophils or from direct ____ killing * tissue injury results from products of the recruited and activated neutrophils and macrophages such as lysomal enzymes, ____ , NO, and proinflammatory cytokines

Answer 25

* * autoreactive T * exaggerated/over dramatic * * Th1 and Th17 * CTL * ROS

Question 26

_multiple sclerosis:_ * type ____ hypersensitivity * caused by autoreactive T cells against ____ , the protein in myelin and sheaths of neurons * results in many ____ symptoms

Answer 26

* IV * myelin * neurologic

Question 27

_rheumatoid arthritis:_ * type ____ hypersensitivity * causes ____ \_\_\_\_ * presence of ____ \_\_\_\_ , autoantibodies that react to the Fc portion of IgG, is diagnostic

Answer 27

* III/**IV** * joint inflammation * rheumatoid factor

Question 28

_type I Diabetes (T1DM):_ * caused by autoreactive T cells against ____ \_\_\_\_ Ags * T cells are activated in the LN traffic to the pancreas where they ____ and accumulate resulting in organ specific inflammation * local APCs capable of presenting Ag in the context of class ____ MHC and secreting ____ play an important role in the pathogenesis of T1DM \*islet cell autoantibodies (ICA) are diagnostic but not the main mechanism\*

Answer 28

* pancreatic Beta-cells * proliferate * II IL-12

Question 29

_inflammatory bowel disease (IBS):_ * type ____ hypersensitivity * some causes are ____ some are \_\_\_\_ * immune causes can be alterations in proportion of certain ____ microflora, infection by certain pathogenic organisms, or infection with certain organiss that stimulate autoimmune reactions

Answer 29

* IV * immune non-immune * gut

Question 30

_contact dermatitis:_ * caused by ____ , an oil from poison ivy which ____ with skin proteins (pentadecacetochol alon does not elicity a T cell response - conjugation is required) * ____ to a ____ later, after T cells have been activated, a reaction occurs resulting in dermatitis * primary exposure = ____ reaction * secondary exposure = ____ reaction

Answer 30

* pentadecacatechol conjugates * hours day * no * yes

Question 31

_type IV hypersensitivity/DTH in diagnostic testing:_ * the reaction is called delayed because it typically develops ____ to ____ hours after Ag challenge * humans bay be sensitized for DTH reactions by microbial infections ( ____ ) , by contact sensitization ( ____ ), or immunization ( ____ \_\_\_\_/\_\_\_\_ ____ ) * ____ injection of T cell Ags can be used to test if an individual has been exposed to that antigen in the past * protein Ag derived from ____ \_\_\_\_ is injected into the dermis * if pt has been infected with TB, they will have T cells that are sensitized to the Ag and a ____ will occur within 24-48 hours at the site of injection * if they have not ben exposed, ____ reaction will occur

Answer 31

* 24-48 * TB poison ivy diphtheria toxin/tetanus toxin * intradermal * mycobacterium tuberculosis * reaction * no

Question 32

_advice for identifying type IV hypersensitivity questions on a test:_ * autoimmunity is a ____ condition, if you have ____ T cells, they will continue to react to self-Ag indefinitely * infections such as ____ and other granulomatous diseases, in addition to aberrant reactions to gut microflora (as occurs in ____ ) results in ____ infections \*\* if you see the word chronic or something along the lines of a day after being exposed → good change it is type IV \*\*please be careful of Ab mediated autoimmune disorders, such as Graves disease, myasthenia gravis, and SLE, as these are also chronic conidtions but are obvisouly not type IV as they are Ab dependent *

Answer 32

* chronic autoreactive * tuberculosis IBS chronic