Ch 6 Immune system diseases

Question 1

What are the primary target organs of acute GVHD?

Answer 1

The primary targets are skin, gut epithelium, bile ducts, and lymphoid tissue.

Question 2

What are the main cytokines involved in a Type 1 hypersensitivity reaction?

Answer 2

IL-4, IL-5, IL-13

Question 3

What activates mast cell in a type 1 hypersensitivity reaction?

Answer 3

Cross-linking of high affinity IgE Fc receptors
Also triggered by C5a and C3a

Question 4

Localised area of tissue necrosis (fibrinoid necrosis) resulting from acute immune complex vasculitis usually elicited in the skin.
An example of a Type III hypersensitivity reaction

Answer 4

Arthus reaction

Question 5

Main cells involved in a Type IV hypersensitivity reaction

Answer 5

Th1 and Th17

Question 6

Autoimmune haemolytic anaemia and Goodpasture syndrome are examples of which type of hypersensitivity reaction?

Answer 6

Type II

Question 7

Most immediate hypersensitivity disorders are caused by excessive responses from which cell type

Answer 7

Th2 cells

Question 8

In a type 1 hypersensitivity reaction, IgE binds to which receptor on mast cells

Answer 8

Fc receptors (FcER1)

Question 9

What mediators are released by mast cells in a type 1 hypersensitivity reaction?

Answer 9

• Granule contents: Histamine, Proteases (e.g. tryptase), Proteoglycans
• Lipid mediators: Leukotrienes (B4, C4, D4), Prostaglandin D2; Platelet-activating factor (PAF)

Question 10

3 mechanisms of antibody-mediated injury in type 2 hypersensitivity reactions?

Answer 10

• Opsonisation and phagyocytosis
• Complement and Fc receptor mediated inflammation
• Anti-receptor antibodies disturb the normal function of receptors

Question 11

Cytokine that activates macrophages in type IV hypersensitivity reactions

Answer 11

IFN-gamma

Question 12

Which complement components can activate mast cells?

Answer 12

C3a and C5a

Question 13

What are the most potent vasoactive and spasmogenic agents released by mast cells?

Answer 13

Leukotrienes C4 and D4

Question 14

Which mediators released by mast cells are lipid derived?

Answer 14

Prostaglandins and Leukotrienes (from arachidonic acid)
Platelet activating factor

Question 15

Can non-antigenic stimuli cause type 1 hypersensitivity reactions?

Answer 15

Yes; it is estimated 20-30% of immediate hypersensitivity reactions are triggered by non-antigenic stimuli such as temperature extremes and exercise and do not involve Th2 cells or IgE (sometimes called nonatopic allergy)

Question 16

Process involved in contact dermatitis / drug reactions?

Answer 16

Environmental chemical binds to and structurally modifies self proteins
Modified proteins are recognised by T cells and elicit the reaction

Question 17

Differences between central and peripheral immune tolerance

Answer 17

Central: immature lymphocytes that recognise self antigens in the central (generative) lymphoid organs are killed by apoptosis

Peripheral: mature lymphocytes that recognise self antigens in peripheral tissues become functionally inactive, are suppressed by regulatory T cells or die by apoptosis

Question 18

What is FOXP3 and what happens if it is defective?

Answer 18

A transcription factor required for the development and maintenance of functional CD4+ regulatory T cells

Mutations in FOXP3 result in severe autoimmunity

Question 19

What are the patterns of nuclear staining by indirect immunofluorescence? With which diseases can each often be associated?

Answer 19

• Homogenous e.g. SLE
• Speckled - least specific staining. Seen with antibodies against various nuclear antigens including Sm and RNPs
• Centromeric e.g. Sjogrens syndrome, some cases of systemic sclerosis
• Nucleolar e.g. systemic sclerosis (most often)

Question 20

What are antiphospholipid antibodies and against what can they be directed? Why are they sometimes referred to as lupus anticoagulant?

Answer 20

• antibodies specific for epitopes of plasma proteins that are revealed when the proteins are in complex with phospholipids e.g. prothrombin, protein S, protein C, B2 glycoprotein
• some of these antibodies interfere with in vitro clotting tests such as partial thromboplastin time (therefore referred to as lupus anticoagulant)

Question 21

What proportion of patients with SLE have antiphospholipid antibodies?

Answer 21

30-40%

Question 22

What is chronic discoid lupus erythematosus? Does the antibody profile differ at all from SLE?

Answer 22

• Skin manifestations may mimic SLE but the systemic manifestations are rare
• Approx 35% of patients test positive for generic ANAs but antibodies to dsDNA are rarely present

Question 23

What are the 3 interrelated processes thought to be involved in systemic sclerosis?

Answer 23

• Autoimmunity
• Vascular damage
• Collagen deposition

Question 24

What morphological change dominates chronic rejection of transplants?

Answer 24

Vascular changes - arteriosclerosis

Parenchymal fibrosis also present

Question 25

What are the best known pattern recognition receptors in host defence

Answer 25

Toll like receptors

Question 26

All TLRs signal by a common pathway that culminates in the activation of 2 sets of transcription factors

Answer 26

(1) **NF-kB** (which stimulates the synthesis and secretion of cytokines and expression of adhesion molecules) (2) **Interferon regulatory factors** (stimulate production of type 1 interferons)

Question 27

Where are TLRs located?

Answer 27

Plasma membrane and endosomal vesicles

Question 28

What are the 3 most common forms of amyloid?

Answer 28

1. Amyloid light chain (AL) protein 2. Amyloid-associated (AA) protein 3. Beta-amyloid protein (AB)

Question 29

Where do fibrillar proteins deposit in amyloidosis?

Answer 29

Extracellularly

Question 30

What is the difference between primary and secondary amyloidosis?

Answer 30

Primary - associated with plasma cell proliferates Secondary - when occurs as complication as part of a chronic inflammatory process

Question 31

Congo red staining shows apple-green birefringence under polarized light is diagnosis of..

Answer 31

Amyloidosis

Question 32

Loss of function mutations in this gene involved in central tolerance can lead to autoimmune polyendocrine syndrome

Answer 32

AIRE (autoimmune regulator)

Question 33

This protein stimulates expression of some peripheral tissue-restricted self antigens in the thymus and is critical for detection of immature T cells specific for these antigens as part of central tolerance

Answer 33

AIRE

Question 34

Term for lymphocytes that recognise self antigens being rendered functionally unresponsive

Answer 34

Anergy

Question 35

Molecule expressed on CD4+ T cells that is important for co-stimulatory signal in activation

Answer 35

CD28

Question 36

Structurally similar molecule to CD28 but provides an inhibitory signal to CD4+ T cells that recognise self antigens

Answer 36

CTLA-4

Question 37

Mutations in this transcription factor (normally expressed in high levels by T regulatory cells) results in severe autoimmunity

Answer 37

FOXP3

Question 38

Term for sites such as testis, eye, brain where antigens introduced into these sites tend to elicit weak or no immune response

Answer 38

Immune-privileged sites

Question 39

What are the two main types of HIV called and where are they distributed geographically?

Answer 39

HIV-1: more common in US, Europe and central Africa HIV-2: West Africa; India

Question 40

What are the 3 viral enzymes of HIV?

Answer 40

* Protease * Reverse transcriptase * Integrase

Question 41

What is the major capsid protein of HIV detectable by ELISA?

Answer 41

p24

Question 42

What is the more clinically important marker for decision making – HIV viral load or CD4+ cell count?

Answer 42

CD4+ cell count Used as the primary clinical measurement of when to start antiretroviral therapy

Question 43

Inherited defect in phagolysosome function

Answer 43

Chediak-Higashi syndrome

Question 44

Congenital disorder characterised by defects in bacterial killing that render patients susceptible to recurrent bacterial infection (defects in genes encoding phagocyte oxidase)

Answer 44

Chronic granulomatous disease

Question 45

The most common complement protein deficiency

Answer 45

C2

Question 46

Deficiency of this complement proteins is associated with increased risk of immune complex mediated glomerulonephritis

Answer 46

C3

Question 47

Deficiency of this gives rise to hereditary angioedema

Answer 47

C1 inhibitor

Question 48

What is the most common form of SCID?

Answer 48

X-linked * the genetic defect in the common gamma chain subunit of cytokine receptors * T cell development particularly affected

Question 49

Inherited immune deficiency characterised by the failure of B cell precursors to develop into mature B cells

Answer 49

X-linked agammaglobulinemia

Question 50

Syndrome where the third and fourth pharyngeal pouches (thymus) do not develop normally resulting in T cell deficiency Deletion of chromosome 22q11

Answer 50

Di George syndrome

Question 51

Immunodeficiency characterised by the inability to eliminate EBV, eventually leading to fulminant infectious mononucleosis and the development of B cell tumours

Answer 51

X-linked lymphoproliferative disease

Question 52

X-linked disease characterised by thrombocytopenia, eczema, and a marked vulnerability to infection Progressive loss of T cells in the peripheral blood

Answer 52

Wiskott-Aldrich syndrome