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Immunopathology 1 Flashcards

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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
what are the risk factors for the development of a food allergy?
immature mucosal immune system early introduction of solid food hereditary increase in mucosal permeability IgA deficiency or delayed IgA production
26
what do antibodies bind to in type 2 hypersensitivity?
bind to normal or altered cell surface markers recognised as non-self
27
in what situations does type 2 hypersensitivity occur?
blood transfusion reaction | haemolytic disease of the newborn
28
what is the mechanism of type 2 hypersensitivity?
binding to a target -> activates killing mechanisms -> complement -> lysis or phagocytes -> phagocytosis
29
what is haemolytic disease of the newborn?
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
30
how does a direct antiglobin test work?
no agglutination - anti-human Ig doesn't bind to RBC agglutination - anti-human Ig binds to RBC and breaks it down
31
how does type 3 hypersensitivity occur?
- antibodies react with antigens - form antibody-antigen complexes - complexes deposited locally or distant - induce inflammatory reaction: complement activation neutrophil infiltration
32
what is the mechanism of type 3 hypersensitivity?
immune complex forms randomly with tissue -> activates complement -> attracts neutrophils -> phagocyte structures damages blood vessels as phagocytes releases mediators
33
what is type 4 hypersensitivity?
delayed reaction (>12h) - involvement of T lymphocytes antibodies not involved e.g. BCG test for TB
34
what is the mechanism of type 4 hypersensitivity?
antigens -> T cell -> cytokines -> macrophage
35
what is type 5 hypersensitivity?
rare | causes cellular hyperfunction
36
what kind of conditions are caused by type 5 hypersensitivity?
Grave's disease
37
what is the mechanism of type 5 hypersensitivity?
autoantibody binds to TSH receptor -> thyroid cell stimulated -> thyroid hormone released -> thyrotoxicosis
38
what is autoimmunity?
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
what happens to a Mature T cell in lymphatic tissue with Antigen recognition with costimulation?
Activation of T cell, which proliferates and differentiates
40
what happens to a Mature T cell in lymphatic tissue with Antigen recognition without costimulation?
inactivation of T cell
41
what happens to a Mature T cell in lymphatic tissue with Deletion signal?
Death of T cell
42
what are the Hierarchy of defence mechanisms normally preventing autoimmune disease?
1. clonal deletion 2. clonal anergy 3. functional ignorance 4. active suppression 5. lack of T cell help 6. sequestered autoantigen
43
what are the two types of autoimmune disease?
organ specific | non-organ specific
44
what examples are there for organ specific autoimmune disease?
brain - multiple sclerosis thyroid - hashimoto's muscle - myasthenia gravis
45
what examples are there for non-organ specific immune disease?
muscle - dermatomyositis skin/kidney - SLE joints- arthiritis
46
what is the antigen in Grave's disease?
TSH receptor
47
what is the antigen in Pernicious anaemia?
Intrinsic factor
48
what is the antigen in Addison’s disease?
Adrenal cells
49
what is the antigen in Myasthenia gravis?
Acetylcholine receptor
50
what is the antigen in Hashimoto’s thyroiditis?
Thyroid peroxidase, thyroglobulin
51
what is the antigen in Systemic lupus erythematosus ?
DNA, nuclear antigens
52
what is the antigen in Rheumatoid arthritis?
IgG, connective tissue
53
what is the definition of rheumatoid disease?
systemic, chronic inflammation, erroneously called arthritis since blood vessels, kidneys, heart, skin, lungs affected
54
who does rheumatoid disease affect?
young to middle-aged females, 1-2% of population
55
what is the cause of rheumatoid disease?
Unknown, 80% have circulating autoantibodies (IgM) against IgG Fc region, possibly initiated by response to virus/bacterium
56
what are the Clinicopathological features of rheumatoid disease in the skin?
rheumatoid nodules, necrotic areas surrounded by macrophages
57
what are the Clinicopathological features of rheumatoid disease in the joints?
synovium targeted → destruction of cartilage/bone/tendons/ligaments
58
what are the Clinicopathological features of rheumatoid disease in the blood vessels?
vasculitis
59
what are the Clinicopathological features of rheumatoid disease in the lung/heart/kidney?
non-specific inflammation
60
what is the definition of Systemic lupus erythematosus?
Chronic illness, fluctuating, multisystem, skin, joints, kidneys, serosal surfaces
61
who does Systemic lupus erythematosus affect?
young to middle-aged females
62
what is the cause of Systemic lupus erythematosus?
spontaneous, polyclonal B cell hyperactivity, autoantibody production, immune complex formation, anti-dsDNA, type 3 hypersensitivity
63
what are the pathological processes of Systemic lupus erythematosus?
vasculitis: necrosis, rashes, muscle weakness glomerulonephritis: haematuria, proteinuria, renal failure synovitis: arthritis pleuritis: lung inflammation pericarditis/endocarditis: heart failure
64
what is the clinical course of Systemic lupus erythematosus?
varied, death from heart/renal failure, chronic illness
65
what is the "butterfly" rash characteristic of?
SLE
66
what is the mechanism of Grave's disease?
auto-antibody receptor binds to thyroid cell and overstimulates hormone synthesis to produce unregulated overproduction of thyroid hormones
67
what is the mechanism of myasthenia gravis?
autoantibody binds to ACh receptor receptor - stops ACh binding - muscle activation inhibited
68
what are the causes of breakdown in self-tolerance?
- 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
how is genetics a Contributory factor in autoimmune aetiology?
Family studies - increased susceptibility in IDDM, autoimmune thyroid disease, RA Concordance rates in identical twins HLA associations (MHC)
70
what autoimmune diseases have an altered MHC expression?
``` 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
how are hormones a Contributory factor in autoimmune aetiology?
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
how is the environment a Contributory factor in autoimmune aetiology?
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
what is the mechanism of autoimmunity in Molecular mimicry? e.g. group A streptococcus and rheumatoid heart disease
bacterial antigen -> b cell (helper T cell helps) -> plasma cell activated -> plasma cell produces cross reacting antibody -> attacks self antigen
74
what is the mechanism of autoimmunity in Provision of foreign T cell epitopes?
self antigen AND foreign antigen -> b cell (helper T cell helps) -> plasma cell activated -> plasma cell produces self reacting antibody -> attacks self antigen
75
what is the mechanism of autoimmunity in Release of sequestered or cryptic epitopes?
self antigen -> b cell infected APC cell/stress/cytokines -> b cell -> plasma cell activated -> plasma cell produces self reacting antibody (tissue usually hidden)
76
what is the mechanism of autoimmunity in Failure of suppression?
suppressive cytokines and hormones and T cell suppression that would normally suppress plasma cell are blocked. plasma cell produces self antigens
77
what is the mechanism of autoimmunity in Anti-idiotype activity?
anti-virus antibody directed against cell-binding epitope -> anti-idiotype antibody directed against anti-viral binding site -> anti-idiotype cross-reacts with viral receptor

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