Immunology Flashcards
What are functions of mucosal surfaces?
Gas exchange, food absorption, sensory activities, reproduction
What are mucosal surfaces portals of entry for?
Non-pathogenic antigens
Describe the stability of mucosal surfaces?
Highly vulnerable due to fragility and permeability
What are some anatomical features of gut mucosal sites?
Intimate relationship between mucosal epithelia and lymphoid tissues, specialised antigen uptake mechanisms
What are some effector features of gut mucosal sites?
Activated/memory T cells predominate, also natural/effector T cells and secretory IgA antibodies
What are immunoregulatory features of gut mucosal sites?
Active down regulation of immune response, inhibitory macrophages and tolerising dendritic cells
Where are intestinal lymphocytes found?
Organised tissues where immune responses are induced and scattered through the intestine
What are Peyer’s patches?
Lymph nodes in the gut found under the columnar epithelium
Where do lymphatics go in Peyer’s patches?
Out but not in
Where do antigens come from in terms of the gut?
The lumen
What are Peyer’s patches covered by?
An epithelial layer containing specialised M cells
What are M cells?
Microvilli for absorption of antigens, characterised by membrane ruffles
Where does cell proliferation occur?
Germinal centre
How do M cells take up antigens?
Endocytosis or phagocytosis
Once the antigen enters the M cell it is transported across it in a vesicle. Where are these released?
The basal surface
After passing through the M cell, what is an antigen bound by and what does this do?
Bound by dendritic cells which activates T cells (if there is the right inflammatory environment)
What type of cell can extend processes across the epithelial layer to capture antigens from the lumen?
Dendritic cells
Where does the effector function of immunity take place?
Lamina propria
What cells does the lamina propria contain?
IgA producing plasma cells, memory lymphocytes, CD8 and CD4+ T cells, dendritic cells, macrophages and mast cells
Where do CD4+ T cells predominate?
Lamina propria
Where do CD8+ T cells predominate?
Epithelium
What is not present in normal lamina propria?
Neutrophils
Where do T cells enter to become primed and redistributed?
Peyer’s patches
What happens to T cells becoming primed once they enter the Peyer’s patch?
They encounter M cells and become activated by dendritic cells
Where do activated T cells drain via?
Mesenteric lymph nodes to the thoracic duct
What happens to T cells at the thoracic duct?
Return to gut via bloodstream
What is secondary immune response due to?
Increased numbers of cloned cells
What are MAdCAMs?
Molecular addressing molecules
What do MAdCAMs have integrin and chemokine receptors for?
T cells
Where is MAdCAM1 found?
Vasculature of gut and other mucosal sites
What antibody is mainly involved in intestinal response and in what form?
Dimeric IgA
Why is IgA found more in the gut than peripheries?
It is hard to digest
What other antibodies are involved in gut immunity?
Small amounts of IgM and even smaller amounts of IgG
What is the receptor for IgA and where is it found?
Poly-Ig receptor on the basolateral face of the epithelial cell
Where is IgA transcytosed to?
Apical face of the epithelial cell
What can secretory IgA on the gut surface do?
Bind and neutralise pathogens and toxins
Why is selective IgA deficiency not a huge problem?
IgM takes over its role
What are the main intra-epithelial lymphocytes?
Primarily T cells (majority CD8+ but some CD4+) and also some NKCs
What are the two types of recognition mechanisms of T cells?
Class I MHC or odd stress NKC for stress cells
What are lymphocytes in the epithelial gut lining known as?
Intra-epithelial lymphocytes
What are the functions of IELs?
Kill infected epithelial cells by perforin/granzyme and Fas dependent pathways
What can infection, damage or toxic peptides cause?
Cell stress
What do stressed cells possess?
MIC-A and MIC-B
How do stress cells get killed?
Natural killer cells bind to MIC A and B to activate IEL
How do CD4+T cells differentiate during a helminth infection?
TH1-TH2
What IL produced by TH2 cells in response to a helminth causes epithelial repair and mucus production?
IL13
What does IL5 do when produced by TH2 cells in helminth attack?
Recruits and activates eosinophils
What do TH2 cells do to B cells in helminth attack?
Drive them to produce IgE
What IL produced by TH2 cells in response to a helminth causes mast cell recruitment?
IL3 and IL9
What do TH1 cells do in response to helminths?
Activate macrophages and B cells to produce IgG
Which is better in helminth attack, TH1 or TH2?
TH2
What do mucosal immunodeficiencies usually present as?
Respiratory tract infections but some gut infections
What is important to know about selective IgA deficiency?
Sufferers are 10x more likely to have coeliac disease. They also may have an underlying immunodeficiency
What is common variable immunodeficiency a general term for?
Low immunoglobulins- failure to differentiate into Ig secreting cells
When does CVID usually present?
Adulthood
What is the problem in X-linked agammaglobulinaemia?
Mutation which stops B cells maturing
What is chronic granulomatous disease?
Commonly X-linked- failure of phagocyte respiratory burst
What does CGD present as?
Staph aureus infections or inflammatory granulomas causing pneumonia or abscesses
What treatment does CGD not respond to?
Anti-TNF
What is SCID?
Profound defect in T and B cell immunity
What are common presentations of SCID?
Oral candidiasis, chronic diarrhoea, interstitial pneumonitis, GI infections
What are type 1 hypersensitivity reactions initiated by crosslinking IgE on the surface of mast cells with an antigen?
Food allergies
What is coeliac disease?
Genetically linked, autoimmune disorder which damages the small intestine leading to malabsorption and hence malnutrition
What is coeliac disease not?
An allergy/IgE mediated
What is the immunopathology of coeliac disease mediated by?
T cells and IEL
What is the gene sequence required to have coeliac disease?
HLADQ2/8
What can severe cases of coeliac disease lead to?
Complete loss of villi
What is used to diagnose coeliac disease?
Biopsy in adults, serology and genetic screening in children
What is done before a biopsy to triage patients for coeliac disease?
Autoantibody test
What must the patient do for 2 weeks before a biopsy for Coeliac disease?
Eat gluten
Where is ulcerative colitis?
Rectum and colon- surface mucosa
What can ulcerative colitis develop?
Arthritis, uveitis, skin lesions
