Autoimmune disease Flashcards

1
Q

what attacks the body during an autoimmune disease

A

T & B cells

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2
Q

what is the humeral response of an autoimmune disease mediated by

A

B cells

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3
Q

in a humeral response, what is the target against

A

microbes which are outside of the cell & they produce antibodies against those microbes

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4
Q

what is the cellular response led my in an autoimmune disease

A

T cells & T lymphocytes

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5
Q

how does the cellular response take place by T cells in an autoimmune disease

A

T helper cells, which when detect an e.g. microorganism or detect something is wrong, will release cytokines in order to recruit neutrophils, macrophages, B cells into the area

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6
Q

what do cytotoxic T cells do when it finds the infection

A

it will induce apoptosis

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7
Q

what does an autoimmune disease cause

A

immune reactions against self antigen (the body itself becomes foreign)

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8
Q

how many % of the population has an autoimmune disease

A

1-2%

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9
Q

what three prerequisites/evidence is there that there is an autoimmune disease

A
  1. presence of an immune reaction specific for a self antigen or tissue
  2. evidence that the immune complex is the primary cause
  3. absence of any other aetiology
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10
Q

what is self tolerance

A

the lack of responsiveness to an individuals own antigens (i.e. own proteins/DNA)
our immune system can tolerate ourselves, we don’t usually attack ourselves so autoimmune is breakdown of self tolerance

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11
Q

which cells that recognise our cells as ‘the self’ that are constantly being produced, must be eliminated

A

lymphocytes - T & B cells

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12
Q

what does removal of auto reactive T & B cells result in

A

autoimmune disease

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13
Q

which cells need to be eliminated if they recognise the body as foreign

A

T & B cells

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14
Q

where are T cells produced

A

thymus

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15
Q

where are B cells produced

A

bone marrow

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16
Q

what is central tolerance

A

when T cells that recognise ‘self’ are removed in the thymus and B cells that recognise ‘self’ are removed in the bone marrow
however the process is not 100% fool proof and some T or B cells which are non tolerant/that recognise ‘self’, escape to the periphery and are auto reactive

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17
Q

when central tolerance is not 100% effective, by what other means can the T or B cells (that are non tolerant) which have escaped to the periphery be removed

A

via peripheral tolerance

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18
Q

what is peripheral tolerance

A

Anergy: prolonged or irreversible functional inactivation of lymphocytes (when cleared in peripheral part of body)

many interactions between CD28 and B7 and regulatory T cells that can induce anergy apoptosis (in periphery) in auto reactive T cells (to destroy T cells)

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19
Q

when do we induce a T cell response in relation to the peptide

A

if it is non self

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20
Q

when do we induce apoptosis in relation to the peptide

A

when it is self

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21
Q

what induces anergy

A

tissue cell or APC lacking B7

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22
Q

what causes the non up regulation of B7

A

when auto reactive T cell comes along & binds to the self peptide cell on the MHC protein, because the cell is not infected, it is not going to up regulate B7, so the cell hangs around and becomes anergic/inactive as it doesn’t get co-stimulation from B7, so lack in B7 induces anergy

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23
Q

what causes the up regulation of B7

A

bacteria inside a cell

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24
Q

what is one way of muzzling the T cell

A

by moving B7 = don’t get activation of the T cell

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25
Q

a breakdown of what mechanisms produces an autoimmune disease

A
  • central tolerance
  • peripheral tolerance
  • induction of immunity
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26
Q

what are the possible causes of an autoimmune disease

A

a combination of:

  • inheritance of susceptible gene
  • genes which may contribute to breakdown of self-tolerance
  • environmental/infective triggers that activate self-reactive lymphocytes
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27
Q

what does the inability to produce T cells cause and in return, an increase of what cell causes this

A

autoimmune disease, caused by an increase in auto reactive T cells/self reactive lymphocytes

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28
Q

what can serious trauma or stress cause

A

autoimmune disease via overload of self infecting T cells

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29
Q

what are the two possible roles in infection of autoimmune disease

A
  • induction of co-stimulators on APCs

- molecular mimicry

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30
Q

what happens during induction of co-stimulators on APCs, as a possible role in infection of autoimmune disease

A

when a microbe is picked up by an APC, it up regulates B7, but because there is a self reactive T cell, it is co-stimulated with B7/CD28 & self peptide, so we start creating more and more T cells which are reactive against itself
in other words…
it induces APC & up regulation of B7, the APC is presenting self peptide which wants to trap the T cell, making it anergic, but the bacteria up regulates B7, but to produce anergin, we use the autoimmune response = increasing number or T cells

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31
Q

what happens during molecular mimicry as a possible role in infection of autoimmune disease

A

it is the other a microbe may result in activation or T cells.
the microbial agent produces an antigen & mimics its own self antigen of tissue, so T cells rather than acquiring immunity against the microbe, they acquire immunity against ourselves so this tricks the APC to present a bit of ourselves & T cells go and attack us

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32
Q

what are the two types of clinically varied diseases of an autoimmune disease

A
  • organ specific e.g. diabetes

- systemic diseases eg SLE

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33
Q

give examples of what occurs in organ specific autoimmune diseases

A

auto reactive T cells and antibodies are specific to beta cells in diabetes
or
MS - in which auto reactive T cells target myelin in CNS

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34
Q

give examples of what occurs in systemic autoimmune diseases

A

eg in SLE (systemic lupus erythematosus), a diverse range of antibodies are directed against DNA, platelets, erythrocytes and protein phospholipid complexes

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35
Q

what is the ratio of females:males who suffer from SLE (lupus)

A

1:2500 so more common in females

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36
Q

what two types of onset can trigger SLE

A

acute or insidious (more common)

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37
Q

what is an insidious onset

A

periods of remitting and relapsing/inflammatory event in one organ then cessation
i.e. where someone may first present with a cardiac myopathy which goes away, then after have uveitis, and after have dermatitis etc, it is a sequence of inflammatory events which when all put together can be lupus

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38
Q

what are the main injuries to in SLE

A
  • skin
  • joints
  • kidney
  • serosal membranes (ie gut, pericardium, lung)
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39
Q

explain the mechanism of how UV damage + sunlight damages cells and apoptosis causes lupus

A

components found inside a cell e.g. DNA, ribosome etc don’t normally see the T cells as they’re inside the cell, so theres no reason for the T cell to be looking for stuff inside a cell, but only when a cell is damaged e.g. by apoptosis and suddenly all the components e.g. proteins come out and T cells see this as foreign as they usually only recognise the MHS cell receptors etc found on the cell surface, so the T cell makes antibodies against stuff from the inside of the cell which = lupus (a build up of antibodies against antigens inside the cell)

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40
Q

what are antinuclear antibodies (ANA)

A

immunoglobulins/antibodies, that are directed against the cell nucleus

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41
Q

what does a antinuclear antibodies (ANA) staining show

A

antibodies attaching to ribosomes, DNA, RNA, i.e. things that shouldn’t be auto reactive as they should be inside a cell & safe

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42
Q

list the main clinical manifestations and their prevalence of systemic autoimmune diseases

A

arthritis 80-90%
skin 85%
myalgia 35%
ocular 15%

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43
Q

what type of skin findings are included in the 85% of skin manifestations of a systemic autoimmune disease

A
  • malar butterfly rash (hallmark for lupus)
  • discoid lesions
  • non specific rashes (erythematous)
  • cutaneous vasculitic lesions
44
Q

what do all of the different types of skin findings which are included in the 85% of skin manifestations of an autoimmune disease all have and what does it cause

A

renal glomerular deposits - renal disease is number 1 cause of death

45
Q

which skin condition is a hallmark for SLE

A

malar butterfly rash

46
Q

what are the ophthalmic manifestations of a systemic autoimmune disease

A
keratoconjunctivitis sicca (KCS) = dry eye 
with or without xerostomia = dry mouth
47
Q

in % how common is keratoconjunctivitis sicca (KCS) with or without xerostomia/dry mouth

A

25% = most common

48
Q

what may keratoconjunctivitis sicca precede/is the onset of

A

SLE

49
Q

apart from keratoconjunctivitis sicca, what else may also precede SLE by 1-3 years

A
  • anterior uveitis
  • episcleritis
  • scleritis (inflammation of sclera)
50
Q

what eyelid condition is associated with lupus

A

discoid lesions (around the eye lid margins)

51
Q

as discoid lesions around the eyelid margins is associated with an autoimmune disease, what will they not responds to

A

antibiotics

52
Q

what is the second most common manifestation of SLE

A

retinal involvement in SLE

53
Q

what do 88% of patients with lupus have

A

active systemic disease

54
Q

what do SLE + retinopathy indicate

A

lower survival rate

55
Q

what is the cotton wool spot in lupus retinopathy a sign of

A

retinal ischemia = infarcts in the retina, indicates the retina is dying and if the retina is dying, indicates the kidneys are dying etc

56
Q

in what conditions may the cotton wool spots in lupus retinopathy be in

A
  • may be isolated
  • may be surrounded by haemorrhage
  • may be seen in regions of retinal oedema and infarction
57
Q

what does lupus retinopathy have a strong link with

A

renal nephropathy

58
Q

which layer of the retina are the cotton wool spots found in lupus retinopathy

A

RGC layer, caused by infarcts so get oedema and swelling in RGC layer causing a loss of vision

59
Q

what can cotton wool spots on the retina also be associated with, apart from lupus

A

HIV retinopathy or HIV, so not everyone with lupus will have cotton wool patches

60
Q

what does rheumatoid arthritis cause

A

chronic inflammation of joints

61
Q

what may rheumatoid arthritis also involve

A
  • skin
  • blood vessels
  • lungs
  • heart
62
Q

what is the appearance of swan sign in rheumatoid arthritis

A

folding back of thumbs, very debilitating

63
Q

how much does rheumatoid arthritis effect women

A

3:1 so women are more at risk

64
Q

what is the prevalence of rheumatoid arthritis worldwide

A

1-3%

65
Q

when does the onset of rheumatoid arthritis generally occur

A

4th - 5th generation

66
Q

what are the origins of rheumatoid arthritis

A

genetic & environmental

67
Q

what are the genetic origins of rheumatoid arthritis

A

MHC class 2 complexes - HLA-DR1, HLA-DR4 increases risk

68
Q

which other factors can also be involved in rheumatoid arthritis

A

neuroendocrine/viruses

69
Q

describe the events which take place that causes rheumatoid arthritis

A

build up of antibodies directed against self in the joints, which recruit macrophages, plasma cells, dendritic cells, lymphocytes, and get chronic inflammation in the joint, but it is mediated by the immune complexes within the cell. so antibodies directed against self cells initiate an immune reaction in the joints which results in chronic inflammation, and chronic inflammation = continuation of some stimulus to inflammation & here the stimuli are these antibodies against itself

70
Q

what is the result of chronic inflammation

A

continuous trigger/response

in case of rheumatoid arthritis = via build up of antibodies in joints

71
Q

what is visible in the sinovium of the joints in rheumatoid arthritis in high mag

A

leukocyte infiltration of T cells = scarring which changes the normal profile of the sinovium

72
Q

what does leukocyte infiltration of T cells cause to the sinovium

A

scarring which changes the normal profile of the sinovium

73
Q

what does chronic inflammation mediated by antibodies, B cell activation cause

A

a formation of antibodies inducing immune complexes

74
Q

what do cytokines recruiting macrophages to the area initiate and what does it result in

A

fibroblast, secretion of collagen, M1 macrophages etc, all resulting in a colosal mess in the joints causing scarring and it is ongoing because it is chronic

75
Q

how can you diagnose someone with rheumatoid arthritis

A

the amount of rheumatoid factor RF in their blood

76
Q

why can B lymphocytes diagnose rheumatoid arthritis

A

as it creates the antibody called rheumatoid factor

77
Q

what is rheumatoid factor

A

an immunoglobin of the IgM class

78
Q

what does rheumatoid factor bind to

A

the Fc portion of IgG

79
Q

what can rheumatoid factor + IgG + IgM lead to

A

complement activation

80
Q

what can be the ocular side effects of any autoimmune disease

A
  • keratoconjunctivitis sicca KCS (dry mouth) - most common 15-25%
  • episcleritis and scleritis
  • venous occlusions
  • cranial nerve palsies
81
Q

what are the two possible treatments of ocular side effects of any autoimmune disease

A
  • chloroquine

- steroid treatment

82
Q

what is the treatment with chloroquine associated with (side effect)

A

chloroquine retinopathy

83
Q

what is the treatment with steroids associated with (side effect)

A

subcapsular cataract

84
Q

what can steroid treatment also treat

A

rheumatoid arthritis

85
Q

what can chloroquine also treat

A

rheumatoid arthritis & malaria

86
Q

what are the symptoms of keratoconjunctivitis sicca ‘dry eye’

A
  • redness
  • dryness
  • gritty or foreign body sensation
  • burning
  • photophobia
    all get worse in windy or dry conditions
87
Q

what are the signs of keratoconjunctivitis sicca ‘dry eye’

A
  • decrease TBUT
  • positive rose bengal stain (replaced by lissamine green as less painful, both stain goblet cells/mucins which defect in causes dry eye as don’t hold onto mucins)
  • mucous strands attached to cornea and/or inferior fornix
88
Q

which autoimmune disease/systemic condition, apart from rheumatoid arthritis is keratoconjunctivitis sicca ‘dry eye’ also associated with

A

sjogren’s syndrome

89
Q

which types of keratoconjunctivitis sicca ‘dry eye’ can you get with sjogren’s syndrome

A

type 1 sjogren’s = dry eye & dry mouth
or
type 2 sjogren’s = dry eye, dry mouth and autoimmune disease e.g. rheumatoid arthritis

90
Q

what can the treatment is rheumatoid arthritis e.g. chloroquine cause to the retina

A

bulls eye maculopathy - lose central vision due to the toxicity of chloroquine

91
Q

why is steroids used to treat rheumatoid arthritis

A

it reduces inflammation by suppressing the immune system

92
Q

what can sjogren’s syndrome cause

A

widespread effects.
inflammation within the glands reduces the production of tears and saliva which causes the main symptoms e.g. dry mouth & dry eyes

93
Q

what are the two classifications of sjogren’s syndrome

A
  • primary sjogren’s syndrome - when the condition develops by itself and not as the result of another condition
  • secondary sjogren’s syndrome - when the condition develops in combination with another autoimmune condition, such as lupus, crohn’s disease or rheumatoid arthritis
94
Q

which type of keratoconjunctivitis sicca is primary sjogren’s syndrome associated with

A

type 1

95
Q

what type of keratoconjunctivitis sicca is secondary sjogren’s syndrome associated with

A

type 2

96
Q

what is ankylosing spondylitis

A

HLAB-27 positive

curvature & inflammation in the spine

97
Q

what other ocular disease is associated with ankylosing spondylitis

A

anterior uveitis develops in 25% of patients
acute & recurrent
bilateral in 85% of cases

98
Q

which gender group does ankylosing spondylitis mainly effect and at what age

A

typically males, 15-35 years

99
Q

what things is crohn’s disease associated with

A
  • acute anterior uveitis
  • psoriasis
  • inflammatory bowel disease/IBS
  • atrioventricular block or aortic valve incompetence
100
Q

what is positive in crohn’s disease

A

HLA-B27 positive

101
Q

what gender group does crohn’s disease effect more

A

females > males

102
Q

which organ specific diseases are mediated by antibodies and immune complexes type 3

A
  • myasthenia gravis (effects eye muscles)

- graves disease

103
Q

which systemic autoimmune disease is mediated by antibodies and immune complexes type 3

A

systemic lupus erythematosus (SLE)

104
Q

which organ specific diseases are mediated by T cells type 4

A
  • type 1 diabetes

- multiple sclerosis

105
Q

which systemic autoimmune diseases are mediated by T cells type 4

A
  • rheumatoid arthritis

- sjogren’s syndrome

106
Q

which autoimmune or reaction to microbe disease is mediated by T cells type 4

A

crohn’s disease