Immunology Flashcards
What is the structure in the small intestine that contains lymphoid tissue?
Peyer’s patch
Why doesn’t the Peyer’s patch have lymphatics coming IN, but going out?
Antigens come straight through the gut wall into the lymph nodes
What is the isolated lymphoid follicle for?
B cell production
What kind of cells are Peyer’s patches covered in?
M cells
at the dome of the payer’s patch
How do M cells function
They are “ruffled” - surface area for antigens
M cells take up the antigen by endocytosis and phagocytosis
Antigen is transported across the M cells in vesicles
Released at basal surface
Antigen is bound by dendritic cells, which activate T cells
What are the 2 distinct compartments of the mucosal immune system?
The epithelium and the lamina propria
Lamina propria integrins
Sense whether adhesion has occurred
What kind of cells are in the epithelium?
Intraepithelial Lymphocytes - cytotoxic T cells (CD8+)
Once activated, where do T cells travel from the payer’s patch?
Drains via mesenteric lymph nodes to the thoracic duct
Return to gut via bloodstream
What is α4:β7?
A gut homing effector
so the t cell makes its way back to the gut
What does alpha 4: beta 7 bind to?
MAdCAM-1 on specific cells in the gut
what kind of immunoglobulins does breast milk contain?
IgA
Most common Immunoglobulin in the gut?
IgA
IgA1 in particular
Is IgA monomeric or dimeric in the gut?
Dimeric
Systemically, IgA is…
monomeric
IgA in the gut…starting with an IgA secreting cell
> IgA secreting cell secretes IgA
> IgA binds to a receptor on the basolateral face of the epithelial cell.
> Via endocytosis and and transcytosis, the IgA makes its way to the apical face
> IgA is released + its secretory component
> The secreted IgA on the gut surface can bind and neutralise pathogens and toxins
> IgA is able to bind and neutralise antigens internalised in endosomes
> IgA can export toxins and pathogens from the lamina propria while being secreted itself
How are the dimers connected in dimeric IgA?
a “J chain”
Which other immunoglobin can do the same as IgA to an extent
IgM
Do intraepithelial lymphocytes need to be primed?
NO
they are already active
What can intraepithelial lymphocytes do to virally epithelial cells?
Infected cells display viral peptide to CD8 IEL via MHC class I
Activated IEL kills infected epithelial cell by PERFORIN/granzyme and Fas-dependent pathways
Prevents spreading and proliferation
Epithelial cell stress - IEL resposne
Epithelial cells undergo stress as a result of damage et al and express MIC-A and MIC-b
NKG2D on IELs binds to MIC A & B and activates the IEL
Activated IEL kills the stressed cell via the perforin/granzyme pathway
MIC-A and MIC-B are essentially flags for HELP
–
What help regulate local hypo responsiveness?
Commensal organisms
PPAR Gamma
What do bacteria do in regards to hypo responsiveness?
They mediate the generation of regulatory T cells
weak co-stimulation
Bacteria can be recognised by TLRs on epithelial cells/leukocytes
This initiates a cascade
NF Kappa B makes its way into the nucleus to transcribe an inflammatory protein
BUT
Some commensal bacteria can block this gene transcription
Some commensal bacteria can block degradation of phosphorylated IkB preventing NFkB translocation to the nucleus
What does NFϰB transcribe?
Cytokines, chemokines and defensins
Mediating an immune response
Most defences are a balance between
protection and host damage
What kills helminth infections?
IgE, mast cells and eosinophils
What Interleukin causes B cells to produce IgE?
IL-4
What cells does HIV actively infect?
Dendritic cells
These then shuttle the virus tor regional lymph nodes where they concentrate virus
Eventually infect CD4+ T cells
CVID
Common Variable Immune Deficiency
Recurrent sinopulmonary & GI infections
failure to differentiate into Ig secreting cells
Low immunoglobulins all round
Chronic Granulomatous Disease
Staph aureus/ inflammatory granulomas - pneumonia, liver abscess, perianal abscess and skin abscess.
Failure of phagocyte respiratory burst (NADPH oxidase produce ROS - this is missing)
SCID
Severe combined immune deficiency
Defect in T and B cell immunity
No functioning adaptive immune response
Opportunistic infections
Coeliac Disease
Gluten hypersensitivity
Gliadin
Both T cells and IELs destroy the gut
cytokine release leads to damage
–> Malabsorption and malnutrition
Flat mucosal surface
Diagnosing coeliac disease
Biopsy
IgA Anti TTG autoantibodies presence
Crohn’s is mediated by…
TH1 CD4+ T cells
Gamma interferon
IL-12
TNF-alpha
Treatment of Crohn’s/UC
Anti TNF alpha
