Immunology Flashcards
Describe Bloom syndrome.
- autosomal recessive mutation BLM 15q26.1
- Disorder with increased risk of malgnancy (leukaemia, lymphoma and GI tract).
- Short stature and develop an erythematous photosensitive rash in the first 2 years.
- Mild immune deficiency with increased susceptibility to infections.
- Prevalent among the Ashkenazi Jewish population
What are the primary immunological defects of the phagocytic system?
- Neutropenia: Most forms are autosomal dominant (apart from Kostmann and Schwachman-Diamond). Bone marroe shows immature precursors.
- Leukocyte adhesion defects: defect in b chain of CD 18. Prevents migration of neutrophils to site of infection. Delayed cord detachment, high peripheral neutrophils and no pus at sit of infection.
- Chronic granulomatous disease: X-linked or autosomal dominant. Neutrophils unable to produce superoxide hampering intracellular killing.
What immunodeficiency is associated with recurrent Neisseria infection?
Complement particularly the terminal components C5-C9.
Apart from bacterial infection what are patients with complement deficiency predisposed to?
Autoimmune disorders.
Deficiency of what immunoglobulin subclass is associated with poor response to polysaccharide vaccinations and polysaccharide encapsulated bacteria?
IgG2
Describe Omenn syndrome.
- Recombinase activating gene 1 (RAG1) defect.
- Variant of SCID.
- T- B- NK+
- Recurrent infections, exudative erythroderma, lymphadenopathy, hepatosplenomegaly, chronic persistent diarrhoea and FTT.
Describe Wiskott Aldrich syndrome.
- X-linked.
- Eczema, recurrent infections and microthrombopenia.
Describe Netherton syndrome.
- Trichorrhexis invaginata also known as bamboo hair is pathognomic.
- Severe disorder of cornification.
- Caused by SPINK5 mutation.
What are the actions of IL1 and IL2?
- Produced by macrophages and polymorphs.
- Target effect on T/B/NK cells.
- Cause proliferation, differentiation and class switching.
In what conditions is ANA positive?
- Elevated in SLE.
- 40-85% of children with JIA with oligo or polyarticular involvement, less common in systemic onset.
- Associated with increase risk of chronic uveitis.
- General population.
In what conditions is ENA positive?
- SLE.
In what conditions is HLA B-27 positive?
- Enthesis related arthropathy.
- Ankylosing spondylitis.
In what conditions is rheumatoid factor positive in?
- JIA.
- Adult RA.
- SLE.
- HIV.
- Hepatitis.
- Leukaemia.
- Lymphoid malignancies.
- Pulmonary fibrosis.
- General population.
Discuss features of ankylosing spondylitis.
- Presents with SEA
- -> rheumatoid factor Seronegativity.
- -> Enthesitis - around foot and knee.
- -> oligoArthritis - legs > arms esp. hips, SI joint and axial skeleton.
- Expect elevated inflammatory markers at diagnosis in ankylosing spondylitis.
Which immune cell population is responsible for cellular rejection in organ transplantation?
- T cells - Transplant failure.
- Acute rejection is a cell mediated hypersensitivity reaction involving CD8 cell attack on graft cells whose MHC antigen has been upregulated by IFN gamma.
What is the most common genetic mutation in X-linked chronic granulomatous disease?
- gp91phox.
- Defect in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
What is the most common gastric pathogen in CVID?
- Giardiasis causes malabsorption and weight loss along with periodic abdominal pain.
- Giardia has epilsoid cysts most commonly seen in solid stool or kite shaped multiflagelate trophozoites - more commonly seen in loose stool.
Which antigen presenting cell is actively phagocytic and resides in peripheral sites?
- Dendritic cells.
- Reside in peripheral sites such as the skin, intestinal lamina propria and lungs.
What mutation is responsible for X-linked hyper IgM syndrome?
- Mutation in CD40L on surface of T cells.
- Impairs ability to interact with CD40 in B cells and allow class switching of antibodies –> only IgM produced.
What are clinical fetures of X-linked hyper IgM syndrome?
- Present with recurrent otitis media, pneumonia and sinusitis.
- Develop opportunistic infections - PCP, toxoplasmosis and chronic diarrhoea from giardia and cryptosporidium.
- Very low IgG and IgA with normal to elevated IgM.
What mutation is the cause of X-linked SCID?
- Mutation in comon gamma chain of the IL-2 receptor.
- Die in infancy without bone marrow transplant.
What are the features of Wiskott-Aldrich syndrome?
- X-linked.
- Thrombocytopenia with small platelets, combined immunodeficiency, eczema, autoimmune disease and increased risk of malignancy.
What infection are children with properdin deficiency susceptable to?
- Meningococcal infection.
What are cytokines typically expressed by TH1 cells?
- IFN gamma, IL2, IL12, GM-CSF, TNF a/b, IL18
What are cytokines typically expressed by TH2 cells?
- IL4, IL5, IL6, IL9, IL10
What are cytokines typically released by Treg cells?
- IL10, TGF b (both anti-inflammatory).
What is the most common cause of CGD?
- X-linked (65%).
- CYBB gene which codes for gp91phox.
- Inability to create reactive oxygen species from NADPH.
- Next most common mutations - p47phox, p67phox and p22phox.
What HLA type has been associated with narcolepsy with cataplexy?
- HLA-DR3
What mutation gives amgammaglobulinaemia?
- Brutins tyrosine kinase.
What mutation gives X-linked hyper Ig M?
- CD40L.
What cell lines are mission in gamma c SCID?
- T-, B+, NK-
What cell lines are missing in ADA SCID?
- T- B+, NK+/-
What cell lines are missing in RAG1/2 SCID?
- T-, B-, NK+
What cell lines are mission in IL-7R alpha SCID?
- T-. B+, NK+
What type of SCID is X-linked?
- Common cytokine receptor chain gamma.
What types of SCID are autosomal recessive?
- Jak3 and ADA.
What non-immune issues are seen in children with ADA SCID?
- Ribcage abnormalities (similar to rachitic rosary), Numerous skeletal abnormalities and chondoosseous dysplasia.
