Immunopathology 1 Flashcards

1
Q

what is hypersensitivity?

A

host tissue injured during immune response to a foreign antigen

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2
Q

how many types of hypersensitivity are there and how are they classified?

A

4 types

coombs and gell classification

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3
Q

what is the immune reactant of type 1 hypersensitivity?

A

IgE

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4
Q

what is the immune reactant of type 2 hypersensitivity?

A

IgG

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5
Q

what is the immune reactant of type 3 hypersensitivity?

A

IgG

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6
Q

what is the immune reactant of type 4 hypersensitivity?

A

TH1 cells/TH2 cells/CTL

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7
Q

what is the antigen of type 1 hypersensitivity?

A

soluble antigen

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8
Q

what is the antigen of type 2 hypersensitivity?

A

cell/matrix-associated antigen

or

cell-surface receptor

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9
Q

what is the antigen of type 3 hypersensitivity?

A

soluble antigen

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10
Q

what is the antigen of type 4 hypersensitivity?

A

soluble / cell-associated antigen

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11
Q

what is the effector mechanism of type 1 hypersensitivity?

A

mast cell activation

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12
Q

what is the effector mechanism of type 2 hypersensitivity?

A

Complement FcR+ cells (phagocytes/ NK cells)
(cell/matrix-associated antigen)

antibody alters signalling (cell-surface receptor)

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13
Q

what is the effector mechanism of type 3 hypersensitivity?

A

complement, phagocytes

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14
Q

what is the effector mechanism of type 4 hypersensitivity?

A

macrophage activation (TH1 cells)

IgE production, eosinophil activation (TH2 cells)

cytotoxicity (CTL)

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15
Q

what is an example of a hypersensitivity reaction of type 1 hypersensitivity?

A

allergic rhinitis, asthma, systemic anaphylaxis

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16
Q

what is an example of a hypersensitivity reaction of type 2 hypersensitivity?

A

drug allergies e.g. penicillin (cell/matrix-associated antigen)

or

chronic urticaria (cell-surface receptor)

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17
Q

what is an example of a hypersensitivity reaction of type 3 hypersensitivity?

A

serum sickness/arthus reaction

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18
Q

what is an example of a hypersensitivity reaction of type 4 hypersensitivity?

A

contact dermatitis (TH1 cells)

chronic asthma (TH2 cells)

graft rejection (CTL)

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19
Q

what is localised type 1 hypersensitivity?

A

hay fever, asthma

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20
Q

what is generalised type 1 hypersensitivity?

A

anaphylaxis

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21
Q

what is the mechanism of type 1 hypersensitivity?

A

allergen binds to IgE on mast cell (containing heparin and histamine) -> crosslinks 2 receptors -> activates cell -> degranulation

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22
Q

when mast cells are activated and degranulate, what is the effect on the gastrointestinal tract?

A

increased fluid secretion
increased peristalsis
diarrhoea/vomitting

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23
Q

when mast cells are activated and degranulate, what is the effect on the airways?

A
increased diameter
increased mucus secretion
congestion of airways
coughing/phlegm
swelling and mucus in nasal passages
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24
Q

when mast cells are activated and degranulate, what is the effect on the blood vessels?

A

increased blood flow
increased permeability

increased fluid in tissues -> increased lymph to lymph nodes -> increased cells and protein in tissues, increased effector response in tissues

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25
Q

what are the risk factors for the development of a food allergy?

A

immature mucosal immune system
early introduction of solid food
hereditary increase in mucosal permeability
IgA deficiency or delayed IgA production

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26
Q

what do antibodies bind to in type 2 hypersensitivity?

A

bind to normal or altered cell surface markers recognised as non-self

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27
Q

in what situations does type 2 hypersensitivity occur?

A

blood transfusion reaction

haemolytic disease of the newborn

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28
Q

what is the mechanism of type 2 hypersensitivity?

A

binding to a target -> activates killing mechanisms ->

complement -> lysis
or
phagocytes -> phagocytosis

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29
Q

what is haemolytic disease of the newborn?

A

RhD- mother
RhD+ baby

baby makes RhD+ cells

mother makes anti-RhD- by B cells

next pregnancy these antibodies attack the foetus and lyse foetus red blood cells

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30
Q

how does a direct antiglobin test work?

A

no agglutination - anti-human Ig doesn’t bind to RBC

agglutination - anti-human Ig binds to RBC and breaks it down

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31
Q

how does type 3 hypersensitivity occur?

A
  • antibodies react with antigens
  • form antibody-antigen complexes
  • complexes deposited locally or distant
  • induce inflammatory reaction:
    complement activation
    neutrophil infiltration
32
Q

what is the mechanism of type 3 hypersensitivity?

A

immune complex forms randomly with tissue -> activates complement -> attracts neutrophils -> phagocyte structures

damages blood vessels as phagocytes releases mediators

33
Q

what is type 4 hypersensitivity?

A

delayed reaction (>12h) - involvement of T lymphocytes
antibodies not involved
e.g. BCG test for TB

34
Q

what is the mechanism of type 4 hypersensitivity?

A

antigens -> T cell -> cytokines -> macrophage

35
Q

what is type 5 hypersensitivity?

A

rare

causes cellular hyperfunction

36
Q

what kind of conditions are caused by type 5 hypersensitivity?

A

Grave’s disease

37
Q

what is the mechanism of type 5 hypersensitivity?

A

autoantibody binds to TSH receptor -> thyroid cell stimulated -> thyroid hormone released -> thyrotoxicosis

38
Q

what is autoimmunity?

A

breakdown of self-tolerance

tolerance - clonal deletion:

predominantly at T cell level in thymus

induced apoptosis

peripheral tolerance for T cells that escape elimination in the thymus

39
Q

what happens to a Mature T cell in lymphatic tissue with Antigen recognition with costimulation?

A

Activation of T cell, which proliferates and differentiates

40
Q

what happens to a Mature T cell in lymphatic tissue with Antigen recognition without costimulation?

A

inactivation of T cell

41
Q

what happens to a Mature T cell in lymphatic tissue with Deletion signal?

A

Death of T cell

42
Q

what are the Hierarchy of defence mechanisms normally preventing autoimmune disease?

A
  1. clonal deletion
  2. clonal anergy
  3. functional ignorance
  4. active suppression
  5. lack of T cell help
  6. sequestered autoantigen
43
Q

what are the two types of autoimmune disease?

A

organ specific

non-organ specific

44
Q

what examples are there for organ specific autoimmune disease?

A

brain - multiple sclerosis
thyroid - hashimoto’s
muscle - myasthenia gravis

45
Q

what examples are there for non-organ specific immune disease?

A

muscle - dermatomyositis
skin/kidney - SLE
joints- arthiritis

46
Q

what is the antigen in Grave’s disease?

A

TSH receptor

47
Q

what is the antigen in Pernicious anaemia?

A

Intrinsic factor

48
Q

what is the antigen in Addison’s disease?

A

Adrenal cells

49
Q

what is the antigen in Myasthenia gravis?

A

Acetylcholine receptor

50
Q

what is the antigen in Hashimoto’s thyroiditis?

A

Thyroid peroxidase, thyroglobulin

51
Q

what is the antigen in Systemic lupus erythematosus ?

A

DNA, nuclear antigens

52
Q

what is the antigen in Rheumatoid arthritis?

A

IgG, connective tissue

53
Q

what is the definition of rheumatoid disease?

A

systemic, chronic inflammation, erroneously called arthritis since blood vessels, kidneys, heart, skin, lungs affected

54
Q

who does rheumatoid disease affect?

A

young to middle-aged females, 1-2% of population

55
Q

what is the cause of rheumatoid disease?

A

Unknown, 80% have circulating autoantibodies (IgM) against IgG Fc region, possibly initiated by response to virus/bacterium

56
Q

what are the Clinicopathological features of rheumatoid disease in the skin?

A

rheumatoid nodules, necrotic areas surrounded by macrophages

57
Q

what are the Clinicopathological features of rheumatoid disease in the joints?

A

synovium targeted → destruction of cartilage/bone/tendons/ligaments

58
Q

what are the Clinicopathological features of rheumatoid disease in the blood vessels?

A

vasculitis

59
Q

what are the Clinicopathological features of rheumatoid disease in the lung/heart/kidney?

A

non-specific inflammation

60
Q

what is the definition of Systemic lupus erythematosus?

A

Chronic illness, fluctuating, multisystem, skin, joints, kidneys, serosal surfaces

61
Q

who does Systemic lupus erythematosus affect?

A

young to middle-aged females

62
Q

what is the cause of Systemic lupus erythematosus?

A

spontaneous, polyclonal B cell hyperactivity, autoantibody production, immune complex formation, anti-dsDNA, type 3 hypersensitivity

63
Q

what are the pathological processes of Systemic lupus erythematosus?

A

vasculitis: necrosis, rashes, muscle weakness
glomerulonephritis: haematuria, proteinuria, renal failure
synovitis: arthritis
pleuritis: lung inflammation
pericarditis/endocarditis: heart failure

64
Q

what is the clinical course of Systemic lupus erythematosus?

A

varied, death from heart/renal failure, chronic illness

65
Q

what is the “butterfly” rash characteristic of?

A

SLE

66
Q

what is the mechanism of Grave’s disease?

A

auto-antibody receptor binds to thyroid cell and overstimulates hormone synthesis to produce unregulated overproduction of thyroid hormones

67
Q

what is the mechanism of myasthenia gravis?

A

autoantibody binds to ACh receptor receptor - stops ACh binding - muscle activation inhibited

68
Q

what are the causes of breakdown in self-tolerance?

A
  • polyclonal activation: dominant autoreactive cell switches on when exposed to disease e.g. epstein-barr virus
  • cross reactive agents - bacterium epitope close enough to self epitope. cross reaction
  • aberrant antigen presentation - structures not shown to T cells effectively. change in macrophage activity - presented oddly reaction
  • regulatory abnormalities - stop signal constantly - dominant - over time breaks down
  • release of sequestered antigens - parts of tissues/cells that immune system doesn’t reach - these cells released (damaged) = autoimmune response
69
Q

how is genetics a Contributory factor in autoimmune aetiology?

A

Family studies - increased susceptibility in IDDM, autoimmune thyroid disease, RA

Concordance rates in identical twins

HLA associations (MHC)

70
Q

what autoimmune diseases have an altered MHC expression?

A
grave's disease - thyroid epithelium
type 1 diabetes - pancreatic B cells
IBD - gut epithelium
alopecia areata - hair follicle cells
primary biliary cirrhosis - bile duct epithelium
Sjogren’s syndrome - salivary ducts
71
Q

how are hormones a Contributory factor in autoimmune aetiology?

A

autoimmune diseases generally more common in females

oestrogens accelerate animal model of SLE

oestrogens can increase antibody production by inhibiting T cell suppressor activity

72
Q

how is the environment a Contributory factor in autoimmune aetiology?

A

Infectious agents, e.g. rheumatic heart disease following group A streptococci, rheumatoid factors following TB or leprosy

Drugs and chemicals, e.g. L-dopa and SLE

penicillamine and pemphigus vulgaris

silicon/vinyl chloride and scleroderma

cigarettes/hydrocarbon solvents and Goodpasture’s syndrome

73
Q

what is the mechanism of autoimmunity in Molecular mimicry?

e.g. group A streptococcus and rheumatoid heart disease

A

bacterial antigen -> b cell (helper T cell helps) -> plasma cell activated -> plasma cell produces cross reacting antibody -> attacks self antigen

74
Q

what is the mechanism of autoimmunity in Provision of foreign T cell epitopes?

A

self antigen AND foreign antigen -> b cell (helper T cell helps) -> plasma cell activated -> plasma cell produces self reacting antibody -> attacks self antigen

75
Q

what is the mechanism of autoimmunity in Release of sequestered or cryptic epitopes?

A

self antigen -> b cell
infected APC cell/stress/cytokines -> b cell

-> plasma cell activated -> plasma cell produces self reacting antibody

(tissue usually hidden)

76
Q

what is the mechanism of autoimmunity in Failure of suppression?

A

suppressive cytokines and hormones and T cell suppression that would normally suppress plasma cell are blocked. plasma cell produces self antigens

77
Q

what is the mechanism of autoimmunity in Anti-idiotype activity?

A

anti-virus antibody directed against cell-binding epitope -> anti-idiotype antibody directed against anti-viral binding site -> anti-idiotype cross-reacts with viral receptor