Immunology Flashcards
The main cause of renal allograft loss (excluding patient death with a functioning graft) is…
Graft rejection
The most commonly transplanted solid organ is…
Kidney
Target of tacrolimus
Calcineurin
Drugs targeting calcineurin
Cyclosporine Tacrolimus
Immunosupressive drugs targeting the cell cycle
Azathioprine MMF
Anti-CD20 drug
Rituximab
Signs and symptoms of GVHD
Skin: Rash Gut: Nausea, vomiting, abdominal pain, diarrhoea, bloody stool Liver: Jaundice
Treatment of GVHD
Corticosteroids
Clinical features suggesting primary immune deficiency
Two major or one major and recurrent minor infections in one year Unusual organisms Unusual sites Unresponsive to oral antibiotics Chronic infections Early structural damage Family history Failure to thrive Skin rash (eczema) Mouth ulceration Chronic diarrhoea
List constitutive barriers to infection provided by skin
Keratin cells: tightly packed. Limit colonisation
Low oxygen tension
Low pH: due to secretions
Sebaceous glands: Produce hydrophobic oils to repel water and microorganisms
Produce lysozyme which destroys srtructural integrity of cell walls
Produce defensins: small cationic proteins that form pore like microbial membrane defects
Sweat glands: produce a watery fluid containing ammonia, and lactic acid
List constitive barriers to infection provided by mucosal surfaces
Secreted mucous:
Physical barrier to trap invading pathogens
Secretory IgA prevents bacteria and viruses attaching to and penetrating epithelial cells.
Lysozyme and antimicrobial peptides directly kill invading pathogens.
Lactoferrin acts to starve invading bacteria of iron (and has a direct antimicrobial effect)
Cilia: Cilia directly trap pathogens and contribute to removal of mucous, assisted by physical manoeuvres such as sneezing and coughing.
List the cells and soluble components of the innate immune system
Cells Polymorphonuclear cells – neutrophils, eosinophils, basophils Monocytes and macrophages Natural killer cells Dendritic cells Soluble components Complement Acute phase proteins Cytokines and chemokines
Names of specialised macrophages in different tissues: Liver Kidney Bone Spleen Lung Neural tissue Connective tissue Skin Joints
Liver Kupffer cell Kidney Mesangial cell Bone Osteoclast Spleen Sinusoidal lining cell Lung Alveolar macrophage Neural tissue Microglia Connective tissue Histiocyte Skin Langerhans cell Joints Macrophage like synoviocytes
Examples of opsonins
Antibodies Complement components Acute phase proteins such as CRP
Reactive oxygen species used in oxidative killing
Hydrogen peroxide Superoxide (O2-)
Enzyme that produces reactive oxygen species used for oxidative killing
NADPH oxidase
Types of recurrent infections caused by phagocyte defiencies
SKIN AND MOUTH Recurrent deep bacterial infections: Staphylococcus aureus
Enteric bacteria
Mycobacteria: MTB and atypical
Recurrent fungal infections: Candida albicans Aspergillus fumigatus and flavus
Primary immune deficiencies characterised by failure to produce neutrophils (Name and mutation/protein affected)
Failure of stem cells to differentiate along myeloid or lymphoid lineage Reticular dysgenesis – autosomal recessive severe SCID: mutation in mitochondrial energy metabolism enzyme adenylate kinase 2 (AK2)
Specific failure of neutrophil maturation Kostmann syndrome - autosomal recessive severe congenital neutropenia: classical form due to mutation in HCLS1-associated protein X-1 (HAX1)
Cyclic neutropenia - autosomal dominant episodic neutropenia every 4-6 weeks: mutation in neutrophil elastase (ELA-2) NOTE: ELA-2 now known as ELANE
Primary immune deficiencies characterised by failure of leukocyte migration (Name and mutation/protein affected)
Leukocyte adhesion deficiency: Deficiency in CD11a/CD18 and CD11b/CD1. In LAD1 (the more common variant) the defiency is in the Beta-2 integrin subunit (CD18) In LAD2 fucosylated carbohydrate ligands for selectins are absent. This is rarer and causes severe growth restriction and mental retardation In LAD 3 activation of all beta integrins (1, 2, and 3) is defective
Primary immune deficiencies characterised by failure of oxidative killing (Name and mutation/protein affected)
Chronic granulomatous disease Deficiency in one of the components of NADPH oxidase
Nitroblue tetrazolium (NBT) test and Dihydrorhodamine (DHR) flow cytometry test, test for the presence of… and therefore assess….
Hydrogen peroxide Ability of a cell to produce reactive oxygen species
a) Cytokines important in oxidative killing of mycobacteria b) Briefly describe the pathway
a) IFN gamma and IL12 b) Infected macrophages stimulated to produce IL12 IL12 induces T cells to secrete IFNg IFNg feeds back to macrophages & neutrophils Stimulates production of TNF Activates NADPH oxidase Stimulates oxidative pathways
Investigation of Kostmann syndrome Neutrophil count: Leukocyte adhesion markers: Nitroblue test: Pus: Deficiency: Problem:
Neutrophil count: Absent Leukocyte adhesion markers: Normal Nitroblue test: Absent Pus: No Deficiency: HCLS1-associated protein X-1 (HAX1) Problem: Maturation of neutrophils leading to congenital neutropenia
Investigation of Leukocyte adhesion deficiency Neutrophil count: Leukocyte adhesion markers: Nitroblue test: Pus: Deficiency: Problem:
Neutrophil count: Increased during infection Leukocyte adhesion markers: Absent Nitroblue test: Normal Pus: No Deficiency: deficiency in CD11a/CD18 and CD11b/CD18 Problem: Inability of leukocytes to leave the bloodstream due to lack of adhesion molecules.
