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Clinical pathology > Theme 2- core clinical immunology- week 1 > Flashcards

Theme 2- core clinical immunology- week 1 Flashcards

1
Q

What is the atopic triad?

A

Triad- rhinitis, dermatitis, asthma

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2
Q

What does asthma cause?

A

Airway inflammation

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3
Q

What is rhinitis?

A

Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose.

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4
Q

What does rhinitis cause?

A

Blocked / runny / itchy nose, sneezing - often with eye symptoms (Itching / burning / watery eyes, redness)

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5
Q

What does rhinitis lead to?

A

Leads to allergic and non-allergic subdivisions

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6
Q

What does the allergic response to rhinitis lead to?

A

Allergic leads to seasonal and perennial:

Seasonal- pollen and moulds

Perennial- house dust mite, animal dander

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7
Q

What does the non-allergic response of rhinitis lead to?

A

Non-allergic leads to vasomotor, infective, structural, drugs, hormonal and polyps

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8
Q

What is the treatment of rhinitis?

A

Treatment – Antihistamines and intranasal steroids

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9
Q

What is asthma?

A

Disease of inflammation & hyper-reactivity of small airways

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10
Q

Who does asthma mostly affect?

A

In childhood - aero-allergic stimuli - house dust mite key pathogenic importance

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11
Q

What is asthma mediated by?

A

Immediate symptoms are IgE-mediated

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12
Q

What does asthma cause?

A

Damage to airways due to late phase response

Damaged airways are hyper-reactive to non-allergic stimuli e.g. Fumes

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13
Q

What is the pathogenesis of asthma?

A

Mechanism- allergen presenting by APC –> T cell proliferation and differentiation into a TH2 cell releasing cytokines- IL4, IL13 and IL5–> B cell plasma cell forming mast cells, basophils and TH2 cell forms eosinophils–>Mediator- histamines, leukotrienes, prostaglandins, cytokines and basic protein and enzymes–> Leads to asthma

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14
Q

What is dermatitis?

A

CLINICALLY - Intense itching, blistering/weeping, cracking of skin

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15
Q

What is the major trigger in atopic disease of dermatitis?

A

HOUSE DUST MITE now thought to be MAJOR TRIGGER in atopic disease

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16
Q

What is the treatment for dermatitis?

A

Topical Steroids & Moisturisers

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17
Q

What is atropy?

A

Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema).

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18
Q

What is non-atopic?

A

Some conditions are not dependent on IgE but still involve an abnormal immune response to a wide variety of external environmental agents. These conditions are known as non-atopic (non-IgE-mediated).

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19
Q

What causes an itch?

A

Filaggrin protein- main barrier function- allergic reaction leads to distruption and leads to a Th1 response then Th2 response leading to secretion of IgE. Leads to increased IL-31 causing itch.

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20
Q

How does sentisation lead to exposure?

A

IgE exposure on B cells and APC–> activates T cells- Th1 to TH2 cells via cytokines–> Th2 main allergic response–>sends to B cells to secrete IgE then differentiate into plasma cells to release IgE–> Crosslinking of mast cell and basophil cell-surface –> release of vasoactive amines–> lipid mediators, chemokines and cytokines

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21
Q

Summary of Late Phase Inflammation

A
  • Allergic inflammation (late phase of the allergic reaction).
  • Following migration to sites of allergen exposure under the influence of chemokines and other cytokines, allergen-specific T cells are reactivated and clonally expand.
  • Local IgE-facilitated antigen presentation by dendritic cells (DCs) increases T-cell activation.
  • Local IgE production is seen in allergic rhinitis and asthma but not in allergic skin inflammation (the main example of which is atopic dermatitis).
  • Eosinophils are one of the main inflammatory cells
  • TH1 cells, which produce interferon- (IFN) and tumour-necrosis factor (TNF), contribute to the activation and apoptosis of keratinocytes (in the skin), bronchial epithelial cells and pulmonary smooth-muscle cells.
  • Activation of mast cells and basophils, which release histamine, chemokines and other cytokines
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22
Q

What is specific IgE testing?

A

An allergen-specific immunoglobulin E (IgE) test measures the levels of different IgE antibodies.

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23
Q

What occurs in specific IgE testing?

A

Allergen binds to different things add patients serum, antibodies will bind then need to confirm if antibody IgE type, need to bind an antibody that binds to the IgE then need a mechanism for identification which will change colour.

Specific IgE Testing (>0.35 KuA/L)

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24
Q

What is the skin prick test?

A

Skin prick test (>2mm wheal)- prick the skin so can trigger IgE reaction- will form a wheal over 2mm of the negative control (usually 0mm) for an allergic reaction

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25
Q

What is the intra-dermal skin test?

A

Intra-dermal test- more invasive- get more allergen than in the skin prick test. Inject tiny amount into the dermis and then mark the size of the circle that has been drawn around the bleb. No control needed. Size need to increase 3mm from site of injection. Takes longer than skin prick test. Primarily done for brochoallegies.

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26
Q

What is the basophil activation test?

A

The basophil activation test (BAT) is a flow-cytometry-based functional assay that assesses the degree of cell activation after exposure to a stimuli.

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27
Q

How does the basophil activation test work?

A

Antibody binds to basophil. Then add to add allergen. This triggers the basophils, makers on the basophil increase expression.

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28
Q

What is the graded challenge test?

A

Graded challenge test- exposure to patient slowly and watch if any reactions

Gold standard test for allergy- graded challenge test

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29
Q

What are the advantages and disadvantages of specific IgE testing?

A

Specific IgE Testing

Safe

False negatives

False positives

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30
Q

What are the advantages and disadvantages of the skin prick test?

A

Skin Prick Test

Quick

Patient satisfaction

False negatives

False positives

Antihistamines

Slight risk

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31
Q

Treatment of common allergies?

A

Symptomatic

Antihistamines, Steroids, Adrenaline

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32
Q

What is specific- immunotherapy (subcutaenous or sublingual- under the tongue) used for?

A

Indications:

Life threatening reactions to Wasp & Bee sting

Severe Hay fever

Animal dander allergy

Not Helpful:

Multiple allergies

Food allergy

Eczema

Spontaneous Urticaria

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33
Q

What does allergic-specific immunotherapy allow?

A

Allergen-specific immunotherapy (SIT) improves the quality of life of treated individuals and has been shown to reduce both symptoms of allergy and medication use in controlled clinical trials.

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34
Q

What is the mechanism of SIT?

A
  • reduces mediator release
  • reduces number of cytokines in the blood, increased cytokines in tissues
  • decrease in allergen specific IgE
  • increase in ILs
  • prevention of new sensitisation and reduces symptoms of allergic reaction
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35
Q

What are major food allergens?

A
  • Water soluble glycoproteins 10 - 60 kd
  • Cow’s milk
  • Egg
  • Legumes - peanut; soybean; tree nuts
  • Fish
  • Crustaceans / molluscs
  • Cereal grains
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36
Q

What are the adverse reactions to foods?

A
  • Gastrointestinal- vomiting, diarrhoea, oral symptoms
  • Respiratory (upper & lower)- rhinitis, bronchospasm
  • Cutaneous- urticaria, angioedema, role of food in atopic dermatitis unclear
  • Anaphylaxis
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37
Q

Why does someone reaction if they have no IgE detected?

A

Different sensitivities

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38
Q

When taking someones history for a drug what should you find out?

A
  • Indication for the drug
  • Detailed description of the reaction
  • Time between drug intake and onset of symptoms
  • Number of doses taken before onset
  • Aware of pharmacological effects and non-immunological ADR
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39
Q

When managing someones drug allergy what should you do?

A

Management

  • Intradermal testing (maybe contraindicated in some situations)
  • Graded challenge
  • Desensitization
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40
Q

What cells are seen in the innate immunity?

A
  • Macrophages
  • Dendritic cells
  • Mast Cells
  • Neutrophils
  • Complement
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41
Q

What cells are seen in adaptive immunity?

A
  • T cells
  • B cells
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42
Q

What is the innate response? Recognition of what? Memory? Regulation? Response time? Duration?

A
  • Pattern recognition against broad classes of antigen
  • No memory
  • No amplification
  • Little regulation
  • Fast response (hours – days)
  • Short duration
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43
Q

What is the adaptive response? Recognition? Memory? Regulated? Response time? Duration?

A
  • Highly specific (T and B cell receptors)
  • Strong memory and amplification component (e.g. vaccines, previous infection)
  • Many regulatory mechanisms
  • Slow response (days to weeks for initial exposure)
  • Responses may last months - years
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44
Q

How does the innate response occur?

A

Innate immune cells directly detect and attack antigenic targets (e.g. microbes) Occurs at sites of infection – e.g. barrier organs

  • Phagocytosis
  • Cytotoxicity- complement sticks to cell walls and destroys them
  • Inflammatory mediators and chemokines to attract other cells
  1. Dendritic cells present antigen to T cells
  2. Cross talk between DCs, T cells and B cells
  • Immune memory to determine specific learned responses
  • Occurs in lymphoid tissues
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45
Q

How does the adaptive immune system respond?

A

Adaptive immune cells activate innate immune cells, directing tissue inflammation to specific targets

T cell cytokines activate monocytes, macrophages

B cell antibodies activate complement

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46
Q

What are phagocytic cells?

A

Phagocytic cells

Neutrophils: eat and destroy pathogens

Macrophages: also produce chemokines to attract other immune cells

Dendritic cells: also present antigen to adaptive immune system

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47
Q

What are histamine producing cells?

A

Histamine-producing cells

Mast cells, basophils, eosinophils: produce histamine and other chemokines and cytokines

Vasodilatation, attract other immune cells

Defence against parasites, wound healing but also allergy and anaphylaxis

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48
Q

What are complements in innate immune system?

A

Complement

Directly attacks pathogens via alternative and lectin pathways

May be activated by adaptive immune system via antibodies

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49
Q

What are cytokines?

A

Cytokines

Signal between different immune cells (e.g. innate to adaptive, adaptive to innate)

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50
Q

What are chemokines?

A

Chemokines

Attract other immune cells to sites of inflammation

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51
Q

How do T cells cause inflammation by inflammatory cytokines or by helping B cells make autoantibodies?

A

APC picks up antigen, goes to T cell can presents it (immune synapse- one cell talking to the other), T cells can convert naïve T helper cell to a T helper 1 cell, which makes inflammatory cytokines.

Another thing T helper 2 cells- cross talk with B cells into memory B cells which make plasma cells and produce lots of autoantibodies.

Net results of this is inflammation.

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52
Q

What do autoantibodies do?

A

Auto antibodies- Some autoantibodies directly interfere with normal physiological function rather than causing inflammation and tissue damage.

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53
Q

Definition of autoimmunity?

A

Defining characteristic: the adaptive immune system recognises and targets the body’s own molecules, cells and tissues (instead of infectious agents and malignant cells)

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54
Q

How does autoimmunity occur?

A

Main characteristics:

  • T cells that recognise self antigens
  • B cells and plasma cells that make autoantibodies
  • Inflammation in target cells, tissues and organs is secondary to actions of T cells, B cells and autoantibodies
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55
Q

What is the definition of autoinflammation?

A

The term introduced in 1999 following identification of the genetic basis of periodic fever syndromes (FMF, TRAPS, CAPS and HIDS)

To distinguish from autoimmune diseases- don’t have the adaptive immune component

56
Q

What are the main characteristics of autoinflammation?

A

Main characteristics:

  • seemingly spontaneous attacks of systemic inflammation
  • no demonstrable source of infection as precipitating cause
  • absence of high-titre autoantibodies and antigen specific autoreactive T cells
  • No evidence of auto-antigenic exposure
57
Q

Table of comparison of autoinflammation and autoimmunity

A
58
Q

What are the components of autoimmunity?

A
  • Theoretical concept
  • Breakdown of self-tolerance
  • Many cells of the immune system have capacity for autoimmune functions
  • Overlap with normal immune functions such as anti-tumour immunity
  • Some people have autoantibodies without any symptoms
59
Q

What is autoimmune disease caused by? What does it lead to?

A
  • Distinct clinical entities
  • Environmental factors acting on favorable genetic background
  • Wide variety of pathogenic mechanisms between diseases
  • Autoimmunity leading to inflammation, organ dysfunction and damage
60
Q

Where are T cells selected?

A

T cell selection in the thymus

61
Q

What are B cells produced by?

A

B cell selection in the bone marrow

62
Q

What happens when autoimmune T cells and B cells are produced?

A

When make T cells and B cells they are selected so any autoimmune ones are deleted and ones that aren’t are kept.

63
Q

What types of cells select for certain self-antigens?

A
  • Certain HLA (MHC) types select for certain self-antigens
  • Other genes that regulate immune functions
64
Q

What are antigenic factors?

A
  • Infections that trigger autoimmune responses
  • Environmental triggers: UV light, smoking
  • Alterations in self-proteins that increase their immunogenicity
65
Q

What are the causes of the autoimmune disease?

A
  • There is usually some genetic predisposition
  • The immune system has many regulatory functions to shut down immune functions – tolerance of self is a dynamic state
  • But we are not born with autoimmunity – there must be environmental triggers
66
Q

As T cells are randomly generated in the thymus they are tested against self antigens. What happens to them and what do they produce?

A

Deletion

Effector CD4 and CD8 T cells

Regulatory T cells

67
Q

What is the process in the thymus and bone marrow?

A
  • This is a process in the thymus for T cells and in the bone marrow in B cells
  • In thymus have progenitors of T cells
  • Need lots of T cells receptors that recognize any antigen that you might meet including bacteria/ viruses that doesn’t exist yet
  • This is done by when it is made they rearrange their genes
  • This variety will react to self-antigens so T cells are tested against self-antigens in the thymus and will get deleted, if doesn’t react to a self-antigen is useful and won’t harm you
  • T cells can recognize self-antigen weakly, thymus will turn that into a regulatory T cells which when instead of the attacking the antigen it will protect it and turn things off
68
Q

What is MHC Class 1 encoded by? Where are they found? What does it present to?

A
  • Encoded by genes in HLA-A, HLA-B, HLA-C
  • On all nucleated cells- if cell infected of virus it falls on that cell to report to the immune system
  • Presents antigen to CD8+ T cells- cytotoxic T cells
69
Q

What is MHC class 2 encoded by? On what cells? Presented by what cells?

A
  • Encoded by genes in HLA-DP, HLA-DQ, HLA-DR
  • On dedicated APCs
  • Presents antigen to CD4+ T cells- T helper cell which directs a whole immune response- innate
70
Q

What are causative associations other than genes for autoimmune diseases?

A

Sex (hormonal influence)- women >> men

Age- autoimmunity more common in elderly- more environmental influences as you are older

Sequestered Antigents- May be recognised as foreign by the immune system (e.g. cell nucleus, eye, testis)- antigen not seen in the immune system as it is inside a cell more likely to be recognized as foreign

Environmental triggers

  • Infection
  • Trauma-tissue damage
  • smoking
71
Q

What can cause autoimmunity as well as normal immune response?

A
  • Infections activate the immune system generally
  • Molecular mimicry-E.g. in rheumatic fever (inflammation of heart valves) antibodies against M protein of Streptococcus also react against the glycoproteins of the heart
72
Q

How can changes in amount or nature or autoantigens may cause autoimmunity?

A
  • Citrullination of proteins make them more immunogenic (leads to rheumatoid arthritis)- citrulline switches with alanine
  • Tissue transglutamase alters gluten to help it bind to HLA-DQ (leads to coeliac disease)
  • Failure to clear apoptotic debris increases availability of sequestered antigens inside the cell (leads to systemic lupus erythamatosus)
73
Q

Problems with T cell selection in the thymus and B cell selection in the bone marrow leads to what?

A

Failure of Central tolerance leads to autoimmunity

74
Q

How does autoimmunity occur from genetic predisposition?

A

Certain HLA (MHC) types select for certain self-antigens

Other genes that regulate immune functions

75
Q

How do antigenic factors lead to autoimmunity?

A

Infections that trigger autoimmune responses

Environmental triggers: UV light, smoking

Alterations in self-proteins that increase their immunogenicity

76
Q

What is organ specific autoimmunity?

A
  • Affect a single organ
  • Autoimmunity restricted to autoantigens of that organ
  • Overlap with other organ specific diseases
  • Autoimmune thyroid disease is typical- antigen specific to the thyroid, immune system attacking it so get autoimmunity
77
Q

What is systemic autoimmunity?

A
  • Affect several organs simultaneously
  • Autoimmunity associated with autoantigens found in most cells of body
  • Overlap with other non-organ specific diseases
  • Connective tissue diseases are typical
78
Q

What age of onset of autoimmunity most common?

A

More common in the elderly and women

79
Q

Cause of these symptoms?

A 28-year-old woman with recent tiredness and difficulty concentrating had experienced a decline in memory over the last several months. She also noted decreased frequency of bowel movements and an increased tendency to gain weight. She felt chilled without light sweater, even in warm weather.

Examination

She was 5’5” tall and weighed 125 lb. Her pulse rate was 58 beats per minute and her blood pressure was 138/88. She had a slightly puffy face and her eyebrows were sparse, especially at the lateral margins. The deep tendon reflexes were normally contractive, but showed delayed relaxation.

A

Diagnosis- hypothyroidism

80
Q

Cause of these symptoms?

Case 2

History

30 yrs old women presents with anxiety, weight loss, diarrhea and palpitations. Although it is winter she hardly notices cold weather. She finds it almost impossible to sleep but despite this she seems to have abundance of energy.

Examination

She had swollen red eyes, rapid pulse and sweaty hands. She has rapid reflexes.

A

Diagnosis- hyperthyroidism

81
Q

What is Hashimotos thyroiditis? What does it lead to?

A

Destruction of thyroid follicles by autoimmune process

Associated with autoantibodies to thyroglobulin and to thyroid peroxidase

Leads to hypothyroidism

82
Q

What is Grave’s disease? What does it result to?

A

Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody- mimics TSH

Leads to hyperthyrodism

83
Q

Difference between type 2 and 3 hypersensitivity?

A

Type 2 hypersensitive- antibody sticks to the cell of the organ that gets the inflammation

Type3- antibody causes inflammation in another organ that isn’t the thyroid

84
Q

What is myoasthenia gravis?

A

Myasthenia gravis-

NM disease- autoantibodies block the ACh receptor

85
Q

What is pernicious anaemia?

A

Pernicious anaemia

If have an iron deficiency- have smaller cells as less inside

Pernicious anaemia- deficiency in B12- have a problem in making the cell- lot of Hb but not enough cells so end up with MCV being large

86
Q

How do you get pernicious anaemia?

A

To absorb B12- can’t just absorb it naturally, need intrinsic factor that sticks to the B12 and allows it to be absorbed. Made by parietal cells. If have autoimmune condition that affects these cells, won’t get IF and B12 thus getting pernicious anaemia.

87
Q

What are the symptoms of SLE?

A
  • Photosensitive malar rash
  • Multiple mouth ulcers on roof of mouth
  • Arthalgia
  • Alopecia
88
Q

How does SLE occur?

A

Autoantibodies form against many different molecules in the cell nucleus

  • ddDNA
  • dsDNA
  • Ribosomes
  • Histones

Normally cell shouldn’t see things inside the cells, releasing nucleus content forming a rash i.e. sun burn damages cells

Classically antibody deposition and inflammation are seen in the skin

89
Q

How does autoimmunity occur from failed clearence of nuclear antigens?

A
  • Nuclear self-antigens are normally always intracellular, so shielded from the immune system – sequestered antigens
  • In cell death by apoptosis nuclear material is digested and cleared
  • In cell death by necrosis nuclear antigens may not be cleared and may then act as antigens to the immune system
  • UV light causes DNA damage, and cell death
  • Some people have genetic defects in mechanisms to clear cell debris
90
Q

What do antibodies against antigens form? Where do they deposit?

A

Antibodies against antigens in the nucleus combine with their targets to form IMMUNE COMPLEXES in the circulation

Immune complexes deposit in any organ – activate complement and cause inflammation

91
Q

What is lupus nephritis?

A

Normal glomerulus should be lacey and blood flows through and moves into collecting system. If have immune complex landing in there causes inflammation.

Lupus nephritis is inflammation of the kidney that is caused by systemic lupuserythematous (SLE).

92
Q

What are types of connective tissue disease?

A
  • Systemic lupus erythematosus
  • Scleroderma
  • Polymyositis
  • Sjogrens syndrome
  • Ubiquitous antigens (components of the cell nucleus) cause multisystem inflammation
93
Q

What are the two ways adaptive immune system may cause disease?

A
  • Directly (e.g. autoantibodies blocking a receptor in myaesthenia gravis)
  • By causing inflammation (e.g. autoantibodies causing inflammation and organ damage in hashimoto’s thyroiditis)
94
Q

What are the two types of autoimmune disease?

A

Organ specific (often due to an autoantigen specific to that organ, e.g. hashimoto’s thyroiditis)

Or non-organ specific (usually due to a ubiquitous antigen, e.g. anti-nuclear antibodies and widespread immune complexes)

95
Q

51 yo lady

18month history of SOB on exertion

Saw respiratory team and diagnosed with pulmonary fibrosis

Fatigue, aches and pains

Thickening of skin on hands and changes in the skin around her mouth

Examination

Sclerodactyly both hands- hardening of skin on hand

Livedo reticularis on the legs (spasms of BV- make skin mottled)

Cool feet on palpation

Diagnosis?

A

Clinical diagnosis of scleroderma (diffuse systemic sclerosis)

96
Q

What is scleroderma?

A

Scleroderma is a long-lasting disease that affects your skin, connective tissue, and internal organs. It happens when your immune system causes your body to make too much of the protein collagen, an important part of your skin.

97
Q

How to work out if a patient has an autoimmune disease?

A

To work this out we

  • take the clinical history
  • examine the patient
  • then perform some blood testing

Different autoimmune diseases can have similar symptoms

Achieve correct diagnosis

Leads to correct management

98
Q

Tests required to confirm autoimmune disease

A

ANA- antinuclear antibody

ANCA

CK- creatinine kinase

Rheumatoid Factor

Anti-CCP antibody

Complement

FBC U&Es LFTs CRP

99
Q

General principles of diagnostic testing

A

Use to answer specific questions and/or to support a clinical diagnosis,

But not as screening tools

The ability of the tests to correctly discriminate between health and disease is improved when they are used in the appropriate population

100
Q

Definition of sensitivity

A

Sensitivity [a/(a+c)]

measure of how good the test is in identifying people with the disease

a=True positive

c= False negative

101
Q

Definition of specificity

A

Specificity

[d/(b+d)]

measure of how good the test is at correctly defining people without the disease

b= False positive

d= True negative

102
Q

Positive predictive value defintion

A

Positive predictive value

[a/(a+b)]

The proportion of people with a positive test who have the target disorder

103
Q

Defintion of negative predictive value

A

Negative predictive value = d/(c+d) The proportion of people with a negative test who do not have the target disorder

104
Q

What does this diagram show?

A

ND- top diagram shows ND, if don’t have disease should test negative and vice versa, depending where we set cut off of test- want to make sure when we assign a value to the patients results that we are definitely saying they have the disease or not

Bottom diagram- can change cut off- more people testing negative when have disease vice versa

105
Q

Types of diagnostic test

A

Non specific- Inflammatory markers

Disease specific:

Autoantibody testing

HLA typing

106
Q

Non-specific markers of systemic inflammation?

A
  • ESR
  • CRP
  • Ferritin
  • Fibrinogen
  • Haptoglobin
  • Albumin
  • Complement
107
Q

What are antinuclear antibodies?

A

Antibodies in the patient’s blood that bind to the cell nucleus

We can be then more specific and identify subtypes of antibody that bind to different bits of the cell nucleus

108
Q

How Antinuclear antibody testing works?

A

1st part – put an antigen on a plate. Separate the patient’s serum (antibodies in). Put antibodies fluid over the plate. If antibody present for antigen, it should bind.

2nd part – add an antibody (with a light up label) to the antibody.

3rd part – put under fluorescent microscope to see if it’s lit. Different patterns signify different diseases.

109
Q

What do DsDNA and ENA tests do?

A

Other Techniques if positive to work out what antibodies

Immunoblots- strip of paper with specific antigens

Individual ELISA’s- add enzyme

>100 different antibodies described in SLE

110
Q

What is a microbead-based immunoassay?

A

Bead coated with antigen and then bead gives off different colours and is read my machine how much each antibody is present

111
Q

3 month history

Patchy alopecia

Painful and swollen joints of the hands

Mouth ulcers

Diagnosis?

A

SLE

112
Q

67 year old man

Presents to GP with joint stiffness and pain mainly affecting the small joints of both hands.

Stiffness worst in the morning and improves over 1-2 hours

Joint X ray- peri-articular swelling with effusion of MCP joints, osteopenia, joint space narrowing and erosions

CXR normal

Diagnosis?

A

RA

113
Q

What is rhemuatoid factor?

A

Antibody (IgM, IgG or IgA) directed against the Fc portion of IgG

Commonly found in rheumatoid arthritis but not diagnostic of the diseases (sensitivity and specificity around 70%)

Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections)

114
Q

What is another marker for RA?

A

Anti-CCP Antibody (ACPA)

ACPA more specific (95%) for RA then RF

Similar sensitivity to RF

Useful prognostic marker

ACPA positive patients tend to have more severe and erosive disease

115
Q

How to diagnose RA?

A

The diagnosis of Rheumatoid Arthritis is clinicalCombination of symptoms, Xrays, blood tests

High RhF, CCP and elevated ESR and CRP add to the probability of a definitive diagnosis

Early treatment can prevent joint damage and significant morbidity

116
Q

What is ordered when patient has vasculitis?

A

Anti neutrophil cytoplasmic antibodies (ANCA)

117
Q

53yo man

Presented to ED with 3 week history of fever fatigue muscle pain, night sweats and weight loss 6kg.

Urine dip contained blood

CXR showed evidence of lung granuloma formation

Diagnosis?

A

Diagnosis of granulomatosis with polyangitis (formally known as Wegener’s granulomatosis)

118
Q

What is granulomatosis?

A

Granulomatosis with polyangiitis is an uncommon disorder that causes inflammation of the blood vessels in your nose, sinuses, throat, lungs and kidneys. Formerly called Wegener’s granulomatosis, this condition is one of a group of blood vessel disorders called vasculitis. It slows blood flow to some of your organs.

119
Q

What identifies vasculitis?

A

Cytoplasmic (c)ANCA

Perinuclear (p)ANCA

120
Q

What antigens do cytoplasmic (c)ANCA target?

A

PR3

121
Q

What antigens does perinuclear (p)ANCA target?

A

MPO

122
Q

Cytoplasmic (c)ANCA under microscope

A
123
Q

Perinuclear (p)ANCA under a microscope

A
124
Q

What does a positive ANCA mean?

A

Positive ANCA; useful in suggesting the diagnosis in the proper clinical setting

125
Q

Does a negative ANCA assay exclude AASV?

A

Negative ANCA assays do not exclude AASV (vasculitis)

10%-50% of patients may be ANCA neg

126
Q

Reemergence of ANCA pos in a patient who was ANCA neg whilst in remission suggests what?

A

suggests a risk of disease flare.

Time to flare uncertain however

127
Q

What is organ specific autoimmune testing?

A

Theme of this testing similar to the other tests with flourescence- instead have cells on slides- tissues from rats or monkeys form stomach of liver

128
Q

How to test for autoimmune liver disease?

A

Part of non-invasive liver screen

Perform if liver tests deranged

129
Q

Autoimmune liver disease- Anti-mitochondrial Ab specific for what?

A

primary biliary sclerosis

130
Q

Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs, found in what?

A

autoimmune hepatitis

131
Q

How are antibodies detected in autoummune liver disease screening?

A

Antibodies detected by IF screening using rodent tissue block (oesophagus, liver and kidney) and antigen specific ELISA

132
Q

What are the autoantibodies in type 1 disease?

A

Several types:

  • islet cell antibodies
  • anti-GAD65 anti-GAD67
  • anti-insulinoma antigen 2 (IA-2)
  • insulin autoantibodies (IAAs)

Disappear with progression of disease and total destruction of β islet cells

Disease confirmation

to identify relatives and patients at risk of developing autoimmune diabetes

133
Q

What is Addison’s disease? Where do you detect autoantibodies?

A

Addison’s disease, also called adrenal insufficiency, is an uncommon disorder that occurs when your body doesn’t produce enough of certain hormones. In Addison’s disease, your adrenal glands, located just above your kidneys, produce too little cortisol and, often, too little aldosterone

Clinical features

Detect auto antibodies targeting the adrenal cortex

Impairs production of Cortisol

134
Q

What is pernicious anaemia? What antigen is located in the parietal cells?

A

Pernicious anemia (per-NISH-us uh-NEE-me-uh) is a condition in which the body can’t make enough healthy red blood cells because it doesn’t have enough vitamin B12.

Antigen: H+K+-ATPase located in the gastric parietal cells of rodent stomach.

Clinical Antibody present in more than 90% of patients with Pernicious anaemia.

Autoimmune gastritis leads to pernicious anaemia which is characterised by antibodies to GPC and intrinsic factor

135
Q

How do we test for anti-nuclear antibodies?

A

Indirect immunofluorescence, ELISA, microbead immunoassay, immunoblot

136
Q

What disease is associated with anti neutrophil cytoplasmic antibodies (ANCA)?

A

Vasculitis

Clinical pathology (8 decks)

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