Immunology Flashcards
Describe the physiological function of mucosal tissues
- gas exchange
- food absorption
- sensory activities
- reproduction
Name the mucosal tissues of the human body
- lachrymal gland
- salivary gland
- gastro-intestinal gland
- kidney
- mammary gland
- uterus
- bladder
- vagina
- oral cavity
- sinus
- conjunctive
- oesophagus
- stomach
- intestine
- trachea
- lungs
Name the sections of a lymph node
- cortical sinus
- secondary lymphoid follicle (with germinal centre)
- afferent lymphatic vessel
- paracortical area (mostly T cells)
- germinal centre
- marginal sinus
- senescent germinal centre
- efferent lymphatic vessel
- artery
- vein
- medullary sinus
- medullary cords (macrophages and plasma cells)
- primary lymphoid follicle (mostly B cells)
Describe the distinctive anatomical features of gut mucosal immune system
- intimate relationship between mucosal epithelia and lymphoid tissue
- organised lymphoid structures unique to mucosal sites
- specialised antigen uptake mechanisms
Describe the distinctive effector mechanism of gut mucosal immune system
- activated / memory T cells predominate
- natural effector / regulatory T cells
Describe the distinctive immunoregulatory environment of gut mucosal immune system
- active down regulation of immune response
- inhibitory macrophages and tolerising dendritic cells
Where are intestinal lymphocytes found?
In organised tissues where immune responses are induced and scattered throughout the intestine, where they carry out effector functions
- scattered lymphoid tissues
- organised lymphoid tissues
Describe peyers patches
- covered by an epithelial layer containing specialised cells called M cells
- M cells have characteristic membrane ruffles
- antigen catchers and reaction vesicle
How do M cells take up antigens?
- endocytosis
- phagocytosis
How can dendritic cells capture antigens from the lumen of the gut?
They can extend processes across the epithelial layer
The mucosal immune system consists of which two distinct compartments?
- epithelium
- lamina propria
T cells enter peyers patches from blood vessels, directed by what?
Homing receptors
- CCR7 and L-selectin
What binds MAdCAM-1 on endothelium?
Gut homing effector T cells
Gut epithelial cells express what specific for gut homing T cells?
Chemokines
Where is MAdCAM also found?
In the vasculature of other mucosal sites
Secreted IgA on the gut surface can do what to pathogens and toxins?
Can bind and neutralise
What can export toxins and pathogens from the lamina propria while being secreted?
IgA
What is able to bind and neutralise antigens internalised in endosomes?
IgA
Describe intraepithelial lymphocytes
- special T cells in the gut
- activated appearance containing full killing machinery
- restricted antigen receptor repertoire
- expression of alpha e ; beta 7 integrin anchors them in the epithelium
- 2 types with different recognition mechanisms
- immunopathology coeliac disease
Where do intraepithelial lymphocytes lie?
Within the epithelial lining of the gut
The intraepithelial lymphocytes are what type of cell?
CD8- positive T cells
Activated IEL kills infected epithelial cells by what?
Perforin / granzyme and Fas-dependent pathways
Epithelial cells undergo stress as a result of what?
Infection, damage or toxic peptides and express MIC-A and MIC-B
What binds to MIC-A,B to activate IEL?
NKG2D
Describe some of the proposed mechanisms of mucosal hypo responsiveness
- commensal organism help regulate local hypo-responsiveness PPAR gamma
- anergy or deletion of antigen specific T cells, no costimulation
- generation of regulatory T cells particularly CD4+ TGF beta producing TH3 cells, weak costimulation
What initiates a cascade of signal that activates IKK?
Pathogen recognition by TLRs
IKK phosphorylates what?
IKB - targeting it to be degraded
What happens during the presence of commensal bacteria?
Production of PGE2, TGF-beta and TSLP inhibits dendritic cell maturation
Describe the mucosal response to infection and regulation of mucosal immune responses
- innate mechanisms eliminate most intestinal infections rapidly
- activation through ligation of pattern recognition receptors
- intracellular sensors in epithelial cells, PRR, activate the NfkB pathway
- gene transcription and production of cytokines, chemokines and defensins
- activation of underlying immune response
The outcome of infection by intestinal pathogens is determined by what?
A complex interplay between the microorganism and the host IR
Describe selective IgA deficiency
- 2/3 asymptomatic remainder recurrent sinopulmonary infections
Describe CVID
- recurrent sinopulmonary and GI infections
- failure to differentiate into Ig secreting cells
- low IgG, IgA, IgM, and IgE
- defective antigen specific antibody response
Describe XLA
- sinopulmonary and GI infection and devastating systemic manifestations of chronic enteroviral infections
- no B cell / agammaglobulinaemia
Describe CGD
- staphylococcus aureus / inflammatory granulomas-pneumona, liver abscess, perianal abscess and skin abscess
- failure of phagocyte respiratory burst
Describe SCID
- profound defect in T and B cell immunity
- oral candidiasis
- chronic diarrhoea
- interstitial pneumonitis
- GI-CMV, rotavirus, EBV
Describe food allergies
- type 1 hypersensitivity reaction initiated by crosslinking of allergen specific IgE on the surface of mast cells with the specific allergen
- memory response; immune system must be primed
Describe coeliac disease / gluten sensitive enteropathy
- genetically linked autoimmune disorder, causes damages to the small intestine leading to malnutrition
- life long, incurable
- it is not an allergy
- antigenic target gluten
- trigger unknown
- genetic susceptibility
- immunopathology T cell/ IEL mediated
- gamma interferon from gluten specific T cell activates epithelial cells which produce IL-15 which induces proliferation and activation of IEL
- both T cells and IEL can then kill epithelial cells
Describe crohns disease
- can affect any part of the GI tract from the mouth to the anus, commonly distal ileum and colon
- focal and discontinuous inflammation with deep and eroding fissures +/- granulomas
- mediated by TH1 CD4+Tcells / gamma interferon / IL-12/ TNF alpha
- multiple genetic deficiency and immunologic mechanisms - HLA
- gene identified NOD2
- intracellular PRR-muramyl dipeptide of bacterial peptidoglycan
- IL-8 (CXCL8) and neutrophil function
- IL-23/ autophagy
Describe ulcerative colitis
- restricted to rectum and colon
- starts in rectum and moves proximally and contiguously, can develop extra-intestinal manifestations
- distortion of the crypts with infiltration of monocytes / neutrophils and plasma cells
- inflammation and ulceration just in surface mucosa
- immunopathology unclear does not fit into TH1/TH2 split
- postulated may be an NK T cell mediated disease via IL-13
