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Immunity > Lecture 1 - Hypersensitivity > Flashcards

Lecture 1 - Hypersensitivity Flashcards

1
Q

What is haemolytic anaemia??

A

When the body destroys more RBC than normal often due to a structural defect in the RBC like hereditary Spherocytosis, DIC

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2
Q

What is good pastures syndrome?

A

Type of nephritic syndrome

Antibodies to type IV collagen in the glomerular basement membrane leading to inflammation within the kidney

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3
Q

What is myasthenia gravis?

A

Neuromuscular junction disorder where anti bodies to the ACh receptors on the skeletal muscle are blocked or destroyed

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4
Q

What is Graves’ disease?

A

Where autoantibodies that are like TSH bind to TSH receptors

Immune system produces proteins that mimic thyroid stimulating hormone leading to hyperthyroidism

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5
Q

What are some non organ specific autoimmune conditions/

A

Systemic lupus eryhtrematous

Rheumatoid arthritis

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6
Q

What is the definition of hypersensitivity?

A

The antigen specific immune responses that are either inappropriate or excessive and result in harm to the host

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7
Q

What is an antigen?

A

Any substance that triggers an immune repsonse as form of effector T/B cells and antibodies

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8
Q

What are some exogenous antigens that can trigger hypersensitivity?

A

Non infectious substances
Infectious microbes
Drugs

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9
Q

What are some intrinsic antigens that may trigger hypersensitivity?

A

Infectious microbes (mimicry)
Self antigens

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10
Q

What are type of hypersensitivity reactions?

A

Type I (A)
Type II (B)
Type III (C)
Type IV (D)

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11
Q

Broadly what are Type I hypersensitivity reactions?

A

Immediate / Allergy reaction (Environmental non infectious antigens)

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12
Q

Broadly what are Type II hypersensitivity reactions?

A

AntiBody - dependant cytotoxicity

Antibodies to membrane bound antigens

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13
Q

Broadly what are type III hypersensitivity reactions?

A

Immune Complex mediated to soluble antigens

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14
Q

Broadly what are type IV hypersensitivity reactions?

A

Delayed or cell mediated to environmental infectious agents and self antigens

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15
Q

What are the 2 phases to hypersensitivity reactions?

A

Sensitisation phase

Effector phase

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16
Q

What is the sensitisation phase of hypersensitivity reactions?

A

The first encounter with the antigen leading to activation of APCs and memory effector cells

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17
Q

What is the effector phase of hypersensitivity reactions?

A

The pathological reaction upon re-exposure to the same antigen and activation of the memory cells of tthe adaptive immunity

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18
Q

What antibodies drive Type II hypersensitivity reactions?

A

IgG or IgM antibodies

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19
Q

How long does it take for a Type II hypersensititvy reaction to develop?

A

5-12hrs after re encountering the antigen

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20
Q

What are some examples of cell bound antigens that type II hypersensitivity reactions can be set up against?

Exogenous:
Endogenous:

A

Exogenous = blood group antigens, Rhesus D antigens

Endogenous = self antigens (auto immune)

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21
Q

What are the 2 immune mechanisms by which Type II hypersensitivity can cause tissue damage?

A

Complement activation

Antibody-dependant cell toxicity

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22
Q

What can be activated in complement activation causing tissue damage in Type II hypersensitivity?

A

Cell lysis
Neutrophil recruitment by C3a/C5a
Opsonisation (C3b)

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23
Q

What are some clinical examples of Type II hypersensitivity which causes tissue damage via complement activation?

A

Haemolytic disease of newborn

Transfusion reactions

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24
Q

What are some clinical examples of Type II hypersensitivity reactions that involve antibody dependent cell cytotoxicity?

A

Autoimmune haemolytic anaemia

Immune thrombocytopenic purpura

Good pastures syndrome

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25
Q

What is the antigen in Haemolytic disease of newborn?

A

Rhesus D

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26
Q

What is the antigen in transfusion reactions?

A

ABO system

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27
Q

What is the antigen in Autoimmune Haemolytic anaemia?

A

RBCs

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28
Q

What is the antigen in immune thrombocytopenic purpura?

A

Platelets

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29
Q

What is the antigen in good pastures syndrome?

A

Collagen IV in basement membrane of kidney

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30
Q

What antibody drives Type II hypersensitivity reactions in a haemolytic transfusion reaction?

A

IgM

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31
Q

What is a haemolytic transfusion reaction?

A

When the wrong type of blood is transfused into a patient either due to:
-error in identifying
-testing error
-improper labelling

Leading to an immune response being set up

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32
Q

What are the antigens and what are the antibodies involved in haemolytic transfusion reactions?

Describe the mechanism

A

When there’s incompatibility in the ABO antigens from the donor blood on the RBCs so donor lysis is induced by the IgM from the recipient in a Type II hypersensitivity reaction

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33
Q

What is the clincal outcome for haemolytic transfusion reactions? (Type II hypersensitivity)

A

Shock
Respiratory distress
Kidney failure
Death

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34
Q

What are the 4 different blood groups?

A

A
B
AB
O

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35
Q

What are the antibodies and antigens in blood Group A?

A

Antibodies in plasma: Anti-B

Antigens on RBC: A antigen

36
Q

What are the antibodies and antigens in blood Group B?

A

Antibodies in plasma= anti A

Antigens on RBC= B antigen

37
Q

What are the antibodies and antigens in blood Group AB?

A

Antibodies in plasma= NONE

Antigens on RBC= A and B antigen

38
Q

What are the antibodies and antigens in blood Group O?

A

Antibodies in plasma = Anti A and Anti B

Antigens on RBC = none

39
Q

What makes blood group O the universal donor group?

A

Has no antigens on the red blood cell so no anti antibodies will attach to them

40
Q

What is the main Type II hypersensitivity disease that’s driven by IgG?

A

Haemolytic disease of the newborn

41
Q

What is pathological process of haemolytic disease of the new born?

(Type II hypersensitivity)

A

Mother is Rhesus D -ve but fetus/baby is Rhesus D +ve

During delivery Fetal Rhesus D antigens enter into maternal circulation, mother then produces rhesus D antibodies (This is the Sensitisation stage)

If mother gets pregnant again with another rhesus D +ve baby, the rhesus D antibodies will cross the placenta and cause damage to fetal red blood cells

42
Q

What are the complications of Haemolytic disease of the new born?

A

Hydrops fetalis
Liver/splenomegaly
Severe hyperbilirubinemia
Kernicterus

43
Q

What is the antigen for Haemolyitc disease of the newborn?

A

Rhesus factor D

44
Q

How does haemolytic disease of the new born cause severe hyperbilirubinaemia?

A

Increased amount of haemolysis leads to prehepatic jaundice

45
Q

How does haemolytic disease of the new born cause hydrops fetalis, liver/splenomegaly?

A

The high levels of bilirubin cause hepatic damage
This leads to impaired ability to produce albumin leading to hydrops fetalis
Leading to liver and splenomegaly

46
Q

What is kernicterus?

A

When the high levels of bilirubin in the blood due to haemolytic disease of newborn damages the brain

47
Q

What is the treatment for the Type II hypersensitivity reaction for Haemolytic disease of the newborn?

A

RhoGAM

48
Q

When is RhoGAM administered?

A

3days after delivery or miscarriage of a rhesus Postive infant

49
Q

How does RhoGAM treat haemolytic disease of newborn?

A

RhoGAM binds to the rhesus D antigens preventing maternal circulation from detecting it preventing the production of Rhesus D antibodies to prevent the formation of the Type II hypersensitivity reaction

50
Q

What are some examples of Type II hypersensitivity reactions associated with physiological changes?

Where an immune response is raised against a receptor

A

Graves’ disease
Myasthenia gravis
Pernicious anaemia

51
Q

What is the immune mechanism of Graves’ disease?

A

IgG antibodies (TSH like protein) that bind to TSH receptors (antigen) leading to Hyperthyroidism

52
Q

What is the immune mechanism of myasthenia gravis?

A

IgG antibodies produced to block/destroy ACh receptors (antigen) on the muscle at neuromuscular junctions

53
Q

What is the immune mechanism behind pernicious anaemia?

A

IgG prevents the production of intrinsic facotr in gastric parietal cells leading to lack of uptake of B12

54
Q

How do we treat type II hypersensitivity reactions?

A

Treat the tissue/cell damage

Physiological change

55
Q

How do you treat the tissue /cell damage in Type II hypersensitivity?

A

Corticosteroids (anti-inflammatories)

Plasmapheresis (removes circulating antibodies and infammaotry mediators)

Splenectomy (reduce opsonisation adn phagocytosis)

Intravenous immunoglobulin (block Fc receptor)

56
Q

How do you treat the physiological changes seen in Graves’ disease type II hypersensitivity reactions?

A

Antit thyroid drugs
Thyroidectomy

57
Q

What drug is used to treat myasthenia gravis?

How does it work?

A

Pyridostigmine

Reduces/inhibits acetylcholinesterase so increases levels of ACh at neuromuscular junctions

58
Q

How do you treat pernicious anaemia?

A

Vitamins B12

59
Q

What type II hypersensitivity reactions does plasmapheresis treat?

A

Myasthenia. Gravis
Goodpastures syndrome
Graves’ disease

60
Q

How does plasmapheresis therapy work to treat type II hypersensitivity reactions?

A

Removes inflammatory mediators and auto-antibodies

Only short term relief, allows healing of damaged tissue (since body still making autoantibodies)

61
Q

What type of reaction are Type III hypersensitivity reactions?

A

Immune complexes between IgG or IgM and antigens

62
Q

What type of antigens are involved in Type III hypersensitivity reactions?

A

Soluble antigens tthat form immune complexes

63
Q

What are immune complexes?

A

A multi-molecular complex of antibodies and bound antigen

Tissue damage caused by deposition of immmune complexes in blood vessels

64
Q

What are some factors affecting immune complex pathogenesis?

A

Intermediate size immune complexes

Chronic infections

Low affinty antibodies

65
Q

What is the pathological mechanism for Type III hypersensitivity reactions?

A

Intermediate sized immune complexes in the tissue

Comeplement activated (C5a) leading to neurotrophic chemotaxis

Neutrophil adherence and degranulation of mast cells attacking self membranes causing dysregualted inflammation

66
Q

What are some examples of Type III hypersensitivity reactions?

A

Rheumatoid arthritis

Infectious glomerulonephritis (post streptococcal glomerulonephritis)

Systemic lupus erythematosus

67
Q

What is the antigen of rheumatoid arthritis?

A

The Fc portion of IgG (self-antigen)

68
Q

What is the timing of how rheumatoid Arthritis presents?

A

Episodes of inflammation and then remission

69
Q

When does rheumatoid arthritis have a poor prognosis?

A

<30 yr old
High titre of rheumatoid arthirits antibodies
Female
Joint erosions
DR4 allele

70
Q

What is the antigen to Systemic lupus Erythematosus?

A

Double stranded DNA

71
Q

What is the most complex Type III (C) hypersensitivity reaction?

A

Systemic lupus erythematosus

72
Q

What is the pathological mechanism of Type IV hypersensitivity reactions?

A

Not antibody mediated

Involves lymphocytes and macrophages becoming sensitised to an antigen which then activates T cells to evoke a response

73
Q

What triggers Type IV hypersensitivity reactions?

A

Environmental factors
Infectious microbes
Drugs

74
Q

What are the 3 different subtypes of Type IV hypersensitivity reactions (delayed)?

A

Contact hypersensitivity
Tuberculin hypersensitivity
Granulomatous hypersensitivity

75
Q

What is a granuloma?

A

Local immune repsonse composed of macrophages and lymphocytes in response to foreign antigens that can’t be removed or destroyed from the host

76
Q

How long does it take for Type IV hypersensitivity reactions to take place?

A

24-72hr

77
Q

How does pathogenesis of type Iv hypersensitivty occur?

A

Sensitisation activates TH1 cells

Th1 cells make interferon gamma and TNF beta activating macrophages

78
Q

What is contact hypersensitivty?

A

Epidermal reaction (type IV hypersensitivity)
Occurs 48-72hrs post exposure

79
Q

How do you diagnose contact hypersensitivty?

A

Patch testing

80
Q

What is granulomatous hypersensitivity?

A

Type IV hypersensitivty

Occurs 21-48 days after exposure leading to tissue damage

81
Q

What are some causees of granulomatous hypersensitivty?

A

Tuberculosis
Leprosy
Schistosomiasis
Sarcoidosis

82
Q

What are some Type IV hypersensitivity reactions caused by endogenous antigens?

A

Insulin-dependant diabetes Mellitus

Hashimotos Thyroiditis

83
Q

What is the pathology of insulin dependant diabetes Mellitus?

A

Antigen is pancreatic islet cells

84
Q

What is the difference in n type of hypersensitivty reaction for Graves’ disease and Hashimoto’s disease?

A

Graves’ disease = Type II hypersensitivty

Hashimoto’s disease = Type IV hypersensitivty

85
Q

What is the pathology of Hashimotos thyroiditis?

A

Antibodies destroy thyroid tissue

86
Q

What are some corticosteroids that can treat type III and IV hypersensitivty?

A

Oral Prednisolone

Immunity (9 decks)

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