Ch 6 Immune system diseases Flashcards
What are the primary target organs of acute GVHD?
The primary targets are skin, gut epithelium, bile ducts, and lymphoid tissue.
What are the main cytokines involved in a Type 1 hypersensitivity reaction?
IL-4, IL-5, IL-13
What activates mast cell in a type 1 hypersensitivity reaction?
Cross-linking of high affinity IgE Fc receptors
Also triggered by C5a and C3a
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
Arthus reaction
Main cells involved in a Type IV hypersensitivity reaction
Th1 and Th17
Autoimmune haemolytic anaemia and Goodpasture syndrome are examples of which type of hypersensitivity reaction?
Type II
Most immediate hypersensitivity disorders are caused by excessive responses from which cell type
Th2 cells
In a type 1 hypersensitivity reaction, IgE binds to which receptor on mast cells
Fc receptors (FcER1)
What mediators are released by mast cells in a type 1 hypersensitivity reaction?
- Granule contents: Histamine, Proteases (e.g. tryptase), Proteoglycans
- Lipid mediators: Leukotrienes (B4, C4, D4), Prostaglandin D2; Platelet-activating factor (PAF)
3 mechanisms of antibody-mediated injury in type 2 hypersensitivity reactions?
- Opsonisation and phagyocytosis
- Complement and Fc receptor mediated inflammation
- Anti-receptor antibodies disturb the normal function of receptors
Cytokine that activates macrophages in type IV hypersensitivity reactions
IFN-gamma
Which complement components can activate mast cells?
C3a and C5a
What are the most potent vasoactive and spasmogenic agents released by mast cells?
Leukotrienes C4 and D4
Which mediators released by mast cells are lipid derived?
Prostaglandins and Leukotrienes (from arachidonic acid)
Platelet activating factor
Can non-antigenic stimuli cause type 1 hypersensitivity reactions?
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)
Process involved in contact dermatitis / drug reactions?
Environmental chemical binds to and structurally modifies self proteins
Modified proteins are recognised by T cells and elicit the reaction
Differences between central and peripheral immune tolerance
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
What is FOXP3 and what happens if it is defective?
A transcription factor required for the development and maintenance of functional CD4+ regulatory T cells
Mutations in FOXP3 result in severe autoimmunity
What are the patterns of nuclear staining by indirect immunofluorescence? With which diseases can each often be associated?
- 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)
What are antiphospholipid antibodies and against what can they be directed? Why are they sometimes referred to as lupus anticoagulant?
- 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)
What proportion of patients with SLE have antiphospholipid antibodies?
30-40%
What is chronic discoid lupus erythematosus? Does the antibody profile differ at all from SLE?
- 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
What are the 3 interrelated processes thought to be involved in systemic sclerosis?
- Autoimmunity
- Vascular damage
- Collagen deposition
What morphological change dominates chronic rejection of transplants?
Vascular changes - arteriosclerosis
Parenchymal fibrosis also present
What are the best known pattern recognition receptors in host defence
Toll like receptors
All TLRs signal by a common pathway that culminates in the activation of 2 sets of transcription factors
(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)
Where are TLRs located?
Plasma membrane and endosomal vesicles
What are the 3 most common forms of amyloid?
- Amyloid light chain (AL) protein
- Amyloid-associated (AA) protein
- Beta-amyloid protein (AB)
Where do fibrillar proteins deposit in amyloidosis?
Extracellularly
What is the difference between primary and secondary amyloidosis?
Primary - associated with plasma cell proliferates
Secondary - when occurs as complication as part of a chronic inflammatory process
Congo red staining shows apple-green birefringence under polarized light is diagnosis of..
Amyloidosis
Loss of function mutations in this gene involved in central tolerance can lead to autoimmune polyendocrine syndrome
AIRE (autoimmune regulator)
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
AIRE
Term for lymphocytes that recognise self antigens being rendered functionally unresponsive
Anergy
Molecule expressed on CD4+ T cells that is important for co-stimulatory signal in activation
CD28
Structurally similar molecule to CD28 but provides an inhibitory signal to CD4+ T cells that recognise self antigens
CTLA-4
Mutations in this transcription factor (normally expressed in high levels by T regulatory cells) results in severe autoimmunity
FOXP3
Term for sites such as testis, eye, brain where antigens introduced into these sites tend to elicit weak or no immune response
Immune-privileged sites
What are the two main types of HIV called and where are they distributed geographically?
HIV-1: more common in US, Europe and central Africa
HIV-2: West Africa; India
What are the 3 viral enzymes of HIV?
- Protease
- Reverse transcriptase
- Integrase
What is the major capsid protein of HIV detectable by ELISA?
p24
What is the more clinically important marker for decision making – HIV viral load or CD4+ cell count?
CD4+ cell count
Used as the primary clinical measurement of when to start antiretroviral therapy
Inherited defect in phagolysosome function
Chediak-Higashi syndrome
Congenital disorder characterised by defects in bacterial killing that render patients susceptible to recurrent bacterial infection
(defects in genes encoding phagocyte oxidase)
Chronic granulomatous disease
The most common complement protein deficiency
C2
Deficiency of this complement proteins is associated with increased risk of immune complex mediated glomerulonephritis
C3
Deficiency of this gives rise to hereditary angioedema
C1 inhibitor
What is the most common form of SCID?
X-linked
- the genetic defect in the common gamma chain subunit of cytokine receptors
- T cell development particularly affected
Inherited immune deficiency characterised by the failure of B cell precursors to develop into mature B cells
X-linked agammaglobulinemia
Syndrome where the third and fourth pharyngeal pouches (thymus) do not develop normally resulting in T cell deficiency
Deletion of chromosome 22q11
Di George syndrome
Immunodeficiency characterised by the inability to eliminate EBV, eventually leading to fulminant infectious mononucleosis and the development of B cell tumours
X-linked lymphoproliferative disease
X-linked disease characterised by thrombocytopenia, eczema, and a marked vulnerability to infection
Progressive loss of T cells in the peripheral blood
Wiskott-Aldrich syndrome
