L55 Hypersensitivity reactions Flashcards Preview

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Flashcards in L55 Hypersensitivity reactions Deck (103):
1

Name the 4 types of hypersensitivity reactions?

a) I – Immediate hypersensitivity
b) II – Antibody-mediated hypersensitivity
c) III – Immune complex mediated hypersensitivity
d) IV – Delayed (T cell-mediated) hypersensitivity

2

5 classes of antibodies>?

IgG, IgM, IgD, IgA1, IgE

3

What receptor is expressed by macrophage to recognize which antibody?

Fcγ receptor to recognize IgG

4

What are 3 outcomes of the activation of classical complement system?

 Lyse microbes
 Complement fragments (e.g. C3b receptor)
osponize microbes >> phagocytosed
 Inflammation

5

Is classical complement activation complement specific?

No

6

What are the key/ signature cytokines produced by:
Th1
Th2
Th17
Treg

Th1 = IFN-γ (does not secrete IL-4)

Th2 = IL-4 (does not secrete IFN-γ)

Th17 = IL-17

Treg = IL-10

7

What is the role of Treg?

Immune tolerance and regulation

8

What is the difference in the pathogens that activate Th1, Th2 and Th17?

Th1 = Viral and INTRAcellular bacteria

Th2 = Extracellular parasite

Th17 = Extracellular bacteria and Fungal

9

In autoimmunity, which T helper cells are expressed?

Th1
Th17

10

In Humoral immunity, which T helper is expressed?

Th2

11

What is the nature of Hypersensitivity reaction?
What is the result?

Normal antigen-driven adaptive immune process, but exaggerated in
response magnitude / inappropriate form

 Cause host tissue damage
 Can be life-threatening

12

Compare the corresponding antibody/ mediator to type of hypersensitivity reaction?

I = IgE
II = IgM/IgG + complement
III = Antigen-antibody immune complexes (IC)
IV = Th1 T helper cells

13

Compare the speed of hypersensitivity reactions?

I= Immediate
II = fast
III = slow
IV = delayed

14

What WBC detects allergen by responding to IgE in Type I hypersensitivity rxn?

Mast cells

15

What is the receptor on mast cell for Ab?

high affinity receptor for Fc portion of IgE antibody (FcεRI)

16

What are some symptoms of Rhinitis in Type I hypersensitivity?

Rhinitis: itchy nose, mouth, eyes, throat, skin

Sneezing, runny nose, nasal congestion

Tearing eyes, coughing

17

Where are mast cells located? Are they in the blood stream?

tissues exposed to environment (e.g. skin, mucosal lining of respiratory tract, digestive tract, conjunctiva)

Do not circulate in blood

18

What is contained in mast cells?

Pre-formed granules containing histamines and proteases

19

What are some allergens for Type I hyp. reaction?

Pollen
Animal dander
Mold
Faecal pellets of housemold mites (Der P1 protein from Dermatophagoides pteryonyssinus)

20

What are the 2 routes of action in Type I hyp. rxn?

1) IgE mediated mast cell degranulation

2) Th2 response - sensitization and activation for RE-EXPOSURE to allergen

21

Explain the action of IgE mediated mast cell degranulation ?

1) allergen binds to IgE on mast cell surface

2) Cross link of IgE receptor (FcεRI) >> Influx of Ca2+ intracellularly >> Initiation of intracellular signalling events

3) Induce rapid degranulation

22

What is the immediate response of mast cell after stimulation by allergen?

Exocytose pre-formed granules > release:

1) Vasoactive amines (e.g. histamine, serotonin)
2) Inflammatory mediators, heparin
3) Proteases (e.g. typtase, chymase)

23

What is the role of Vasoactive amines (e.g. histamine, serotonin) and Inflammatory mediators, heparin?

-vascular dilatation,
-smooth muscle contraction, -Increase glandular / mucus
secretion
-Increase vascular permeability
-Increase sensory neural
stimulation

24

What is the role of proteases (e.g. tryptase, chymase)?

Proteolysis of damaged tissue

25

What is the response of mast cell within hours of being stimulated by allergen?

activate enzymatic modification of arachidonic acid >> secrete lipid mediators

26

What lipid mediators are secreted by mast cells?

Prostaglandins
Leukotrienes
Bradykinin

27

What is the role of prostaglandin?

Vascular dilatation, pulmonary smooth muscle contraction, platelet
aggregation

28

What is the role of Leukotrienes?

pulmonary smooth
muscle contraction,
Increase vascular permeability

29

What is the role of BRADYKININ?

Increase vascular permeability, smooth muscle contraction

30

What is the response of mast cells within days of being stimulated by allergen?

activate transcription of cytokine genes >> secrete pro-inflammatory cytokines
(e.g. IL-8)

31

What is the role of pro-inflammatory cytokines?

Recruit inflammatory / immune cells

Induce inflammation

32

Link the following symptom of localized allergic reaction with physiological changes:
Watery eyes, Rhinitis (runny nose)?

Increased mucus secretion
Induced by vasoactive amines, proteases

33

Link the following symptom of localized allergic reaction with physiological changes: Angioedema, Hives (skin flush, itching)?

Vasodilation and increased vascular permeability

Induced by Vasoactive amines, prostaglandins, leukotrienes, bradykinins:

34

Link the following symptom of localized allergic reaction with physiological changes: Wheezing, shortness of breath, chest tightness?

Bronco-constriction due to smooth muscle contraction

Induced by: Vasoactive amines, prostaglandins, leukotrienes, bradykinins, platelet-activating factors

35

Link the following symptom of localized allergic reaction with physiological changes:
Coughing, sneezing, itchy sensation?

Sensory neural stimulation

Induced by Vasoactive amines

36

Name the two localized allergic reactions in type I hyp. rxn?

Allergic rhinitis
Asthma

37

Describe the sensitization phase in Th2 reaction in type I hyp. rxn?

Allergen binds to naive B cell receptor > recognized by CD4 on Th2

Th2 secrete IL-4,5,13 to induce B cell differentiation>> plasma cells to make allergen specific IgE

IgE binds to IgE receptors (FcεRI) on mast cells >. mast cells are sensitized

38

Describe the activation phase in Th2 reaction in Type 1 hyp rxn?

UPON RE-EXPOSURE OF ALLERGEN

IgE receptors (FcεRI) crosslink >> intracellular Ca2+ flux >> initiate intracellular signaling
events >> induce rapid mast cell degranulation

39

What type of hyp rxn is anaphlaxis? What is the difference in symptoms compared to normal type 1 HS?

Severe form of Type 1 HS

Difference: Anaphylaxis causes systemic reactions rapidly

Normal type 1 HS causes localized symptoms (rhinitis, asthma)

40

Name some allergens causing anaphylaxis?

bee stings, medication (antibiotics), food

41

compare the mast cell degranulation in anaphylaxis vs normal type 1 HS?

Anaphylaxis = IgE-mediated mast cell degranulation in MULTIPLE tissues

Normal Type 1 HS = '' in localized tissue

42

What are 4 main symptoms of anaphylaxis?

1) bronco-constriction > shortness of breath

2) Swelling of larynx > airway obstruction

3) Extensive vasodilation of blood capillaries > rapid hypotension > Shock

4) Coronary spasm > cardiac arrest

43

What is the treatment for anaphylaxis?

Injectable epinephrine

44

Apart from systemic anaphylaxis, allergic rhinitis and asthma, what are 2 other IgE mediated allergic reaction?

Food allergy (e.g. to shellfish, milk, eggs, fish, wheat) >> causes vomiting, diarrhea, pruritis, hives

Wheal and flare (e.g to insect bites or allergy testing) >> causes local vasodilation and edema

45

What blood cell works with IgE to fight blood borne helminths?

Eosinophil

46

IgE-mediated allergic reaction have different consequences depending on?

1) Dose of allergen
2) Route of entry

47

How are " high risk" people to type I allergic reaction different to low risk individuals?

High risk = Genetically susceptible to Type 1 HS >> have much high levels of IgE than low risk individuals

48

What is hygiene hypothesis?

Microbial exposure in early life has protective influence in the development of allergy and asthma

49

What allergy tests can be done for Type 1 HS?

Skin test:
a) Patch test
b) Prick/ scratch test
c) Intradermal test

Blood test> ELISA to test for allergen-specific IgE

50

How do skin tests for allergic reaction work?

Delivery tiny and controlled amount of extracts from potential allergens

Look for reaction over time:
Red, itchiness, swelling, hives

51

What are 3 treatment options for allergy?

1) Avoidance of allergens
2) Drugs
3) De-sensitization

52

What are 4 groups of drugs for treating allergy?

A C C ISE

A Cute Cat Eats Icky Shellfish *allergy*

-Anti-histamines
-Corticosteroid
-Cromolyn sodium
-B agonists: Epinephrine, Isoproterenol, Salbutamol

53

Name some antihistamines?

histamine receptor blockers (H1 and H2)

54

What is the role of corticosteroid and cromolyn sodium?

- Corticosteroid: immune suppression
- Cromolyn sodium: prevents mast cell degranulation

55

What are the effects of Salbutamol, Epinephrine, Isoproterenol?

Adrenaline-like substances: reverse effect of histamine

Epinephrine (β agonist >> potent cardiac stimulant)

Salbutamol (β2 agonist >> treat asthma)


Isoproterenol (β agonist>> increase HR, increase SBP, lower DBP)

56

How is de-sensitization done to treat allergy?

immunization of small, increasing amount of allergen over a long period of time

57

What are the 2 possible mechanisms of de-sensitization in treating allergy?

 Develop allergen-specific IgG for antigen competition (less IgE binding)


 Develop allergen-specific regulatory T cells (Treg) >> suppress effector T cell responses

58

What are the risks of de-sensitization in treating allergy?

Effectiveness not universal

Risk of triggering the hypersensitivity reaction

59

What is the mediator of Type II HS?

Antibody-mediated cytotoxicity

IgM/ IgG + Complement system

60

What is the effector of Type II Hs?

Complement mediated Cytotoxicity/ cell lysis/ dysfunction

*Not mast cells*

61

Explain the action of type II HS?

antigen -antibody immune reaction > activate complement > Complement mediated Cytotoxicity > cell lysis

62

What is a problem of type II HS?

Targets normal cells

63

Give two possible causes of Type II HS?

Incompatible blood transfusion

Haemolytic disease of newborn

64

Explain the cause and outcome of incompatible blood transfusion?

Haemolytic reaction of the donor's red cells by antibody of the recipient (e.g. Group O recepient receives Group A blood > donor's group A blood reacts with the Anti-A antibodies in recipients plasma)

>> complement - mediated lysis of RBC

65

Majority of people are Rh +ve or -ve?

If one is Rhesus -ve, what antibody does the person have?

 Majority = Rh+ve


 If Rh-ve: have anti-Rh IgG

66

What is the baby Rh if mother is Rh -ve and father is Rh +ve?

Baby = Rh +ve

like father

67

Explain how anti-Rh IgM doesn't develop during 1st pregnancy of a Rh-ve mother bearing a Rh+ve baby?

During 1st pregnancy: fetal RBCs are sheltered from maternal circulation by the placenta

68

Explain how anti-Rh IgM develops in Rh-ve mother during 1st delivery of a Rh+ve baby?

Deliver > Placenta separates from uterine wall >
**Rh antigen on fetal RBC meets with Rh-specific B cell in maternal circulation**

> Mother B cells differentiate into:
1) memory cell**
2) plasma cells which produce anti-Rh IgM**

69

What does the anti-Rh IgM do in the blood stream contaminated with Rh+ve blood?

Secreted IgM clears Rh+
from circulation

70

How come a Rh-ve mother causes haemolytic disease during her 2nd pregnancy?

Mother already acquired anti-Rh IgM plasma and memory cells from first pregnancy

Maternal blood can diffuse across placenta to attach fetal RBC during 2nd pregnancy > haemolytic disease

71

What is the name of the fetal haemolytic disease caused by Type II HS?

Erythroblastosis Fetalis

(IgG-mediated attack of fetal RBC >> ADCC, phagocytosis... etc)

72

Compare the type of immune response between the 2nd and 3rd pregnancy of a Rh-ve mother baring Rh+ve children?

2nd preg = primary immune response

3rd preg = secondary immune response

73

Explain the process of Myasthenia gravis? (type II)

anti-acetylcholine auto-antibodies cause blockage of Ach receptors >> block neurotransmitter signaling at neuromuscular junction

>> cause muscle weakness

74

What are the mediators and effectors of Type III HS?

Immune complex mediated HS

Mediator: antigen-antibody immune complexes
Effector: IC-mediated inflammatory responses

75

Explain the action of Type III HS?

antigen-antibody immune complexes (IC): form aggregates in circulation >> deposit in small vessels in tissues

>> activate complement, IC-mediated inflammatory
responses

76

What are the two immune complex mediated inflammatory responses in type III HS?

1. Complement-, Fc receptor-mediated inflammation

2. Osponization, phagocytosis

77

IC complexes circulate and deposit at which tissues?

Small vessels in joints, kidneys, skin ...

78

Explain the action of Complement- and Fc receptor-mediated inflammation?

complement by-products C5a, C3a >> attract and activate neutrophils >> chemotaxis to injured tissue > release enzymes, reactive oxygen intermediates at site

79

Explain the action of Osponization, phagocytosis?

C3b osponizes cell >> cell recognized by C3b receptor + Fc receptor on phagocyte>> phagocytosis

80

List 4 consequences of Type III HS?

Comp
Neut
Pla
Microthrom
Vascu

Complement activation

Neutrophil attraction and activation

Platelet aggregation and microthrombus formation

Systemic Vasculitis and inflammation

81

What are the results of systemic vasculitis at joints, kidneys?

Joints : arthritis
Kidneys : Glomerulonephritis

82

What is serum sickness?

Transient allergic reaction to foreign serum proteins in
anti-serum of foreign / non-human sources

(e.g. as treatment to snakebite)

83

How are foreign serum proteins resolved in the body?

 Day 5-8 after foreign serum injection: form antigen:antibody
complexes >> fever, vasculitis, arthritis, nephritis

 By Day 9: high level of antibody against foreign serum proteins >> clear

84

What is SLE? which gender predominate?

Systemic lupus erythematosus

female

85

What causes SLE?

Loss of tolerance to self-antigens >> pathogenic antinuclear autoantibodies >> IC -mediated tissue / organ inflammation

86

What are some symptoms of SLE?

Butterfly rash

Lupus nephritis

Pleural effusion

Arthritis

Heart problems

87

What are the effectors and mediators of Type IV HS?

Delayed -type hypersensitivity

Mediator = Th1

Effectors= Cell-mediated inflammatory responses (CMI), involving macrophages and CD8 T cells

88

Onset of Type IV DTH ? What is this HS against?

1-2 days after antigen exposure

Against facultative intracellular micro-organisms (e.g Mycobacterium tuberculosis)

89

Explain the sensitization phase of Type IV DTH to produce CD4+ T cells?

APC (e.g. macrophages, Langerhans cells) take up antigen / allergen >> migrate to lymph node to activate T, B cells towards site of infection

>> differentiate T cells to mostly CD4+ Th1 (sometimes CD8)

90

what cytokines and chemokines are secreted by Th1, and what are the results of the secretion?

Cytokines: IFN-γ , IL-12 , TNF-β ... etc
Chemokines: IL-8, CXCL8, MCP-1 ... etc

rapidly recruit, activate macrophages, CD8+ T cells, neutrophils

91

After macrophages are activated in Type IV DTH, what are the cell-mediated inflammatory responses of macrophages?

Increase production of:
Class II MHC
TNF receptors
Oxygen radicals
Nitric oxide

92

In type IV DTH, what is the result of re-exposure?

Rapid recruitment of macrophages that produce TNF- a + CD8+ T cells

> inflammatory infiltration, local edema and erythema

93

In contact hypersensitivity, allergens are taken up by which cells?

Skin:
Dendritic cells and APCs

>> migrate to lymph nodes for T cell activation and Th1 development

94

Explain how TB causes granulomatous hypersensitivity?

Intracellular pathogen initially infects and activates alveolar macrophages to phagocytose > but ****cannot clear the infection****

Infected macrophages
continue to present Mtb antigens to TH1 cells >>

cause endless acitvation of macrophages, migration of B, T cells

>> TB granuloma

95

What is the structure of Tb granuloma?

Center = persistent antigen

Surrounded by necrotic tissue, multinucleated giant cells / epitheloid / foamy
macrophages, lymphocytes and granulocytes

96

What is the cytokine used by Th1 to stimulate macrophages?

IFN-γ

97

What is the cytokine used by dendritic cells to stimulate Th1 differentiation?

IL-12

98

What is the role of TB granuloma formation?

Fence off infectious agents and prevent dissemination

99

Apart from TB, what are some other diseases associated with granuloma formation?

Leprosy, Shistosomiasis, Sarcoidosis, Crohn's disease

100

What is the test for TB infection?

Tuberculin skin test

Subcutaneous inject of purified protein derivative (PPD) from infectious TB strain

101

Tuberculin skin test gives positive results under which 2 situations?

response in 48-72 hours if
1) Exposed to Mtb
2) Patient is vaccinated with BCG > gives false +ve result

102

Compare the manifestations of HS?

I = Allergy, anaphylaxis
II = Cytotoxicity/ abnormalities in cell function
III = systemic immune complex deposition
IV = systemic and local inflammation, granuloma

103

Compare the diseases that cause each type of HS?
**important**

I = allergic rhinitis, asthma, anaphylaxis

II = Myasthenia gravis, blood transfusion incompatbility, Erythroblastosis fetalis

III = serum sickness, SLE

IV= TB, Crohn's, Sarcoidosis, leprosy, Shistosomiasis

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