Immunodermatology Dr. Sahu Flashcards
What is the function of MALT?
mucosa associated lymphoid tissue
mount mucosal responses to protect the body tracts
What is the function of SALT?
skin-associated lymphoid tissue
mount a cutaneous response to protect the skin
What provides the initial defense in MALT?
secretory IgA (SIgA) and innate leukocytes provide initial defense in MALT
How does MALT act to produce an immune response?
- M Cells in follicle associated epithelium of inductive site capture pathogens and convey them to mucosal APCs and T cells in domes covering B cell-containing lymphoid follicles
- DCs also capture ag via trnseptihelial dendrites
- Effector lymphocyte migrate to multiple mucosal effector site so provide coordinated protection via the common mucosal immune system
Immune responses in MALT are biased towards SIgA. Why could this be?
reduce inflammatory damage to fragile mucosae
Aggressive pathogens that that mucosal surfaces encounter may trigger responses from what immune cells
Th1/Th17 responses.
How does SALT activate immune responses?
- Keratinocytes provide an overlying physical barrier and secrete pro-inflammatory cytokines/chemokines that activate phagocytes and specialized APCs called Langerhan’s cells.
- Antigens are presented locally to activate epidermal memory T cells or are conveyed to naïve T cells in the local lymph node.
- Effector T cells generated can then home to skin sites under attack.
- While the skin is protected by Th1/Th2/Th17 responses initially, a persistent pathogen can trigger macrophage hyperactivation resulting in tissue damage.
Where are γδ T cells found and what is their function?
found in the skin
involved in skin immunosurveillance.
found in mucosal immune system
they work with activating NK receptor to recognize and kill injured enterocytes
What part of the mucosal barrier is rich in antimicrobial molecules?
the inner mucus layer
What part of the mucosal barrier is rich in antimicrobial molecules?
the inner mucus layer
What are some components of innate immunity of the mucosa? (first line of defense)
lysozyme
goblet cells
paneth cells
defenses
epithelial cells
Lysozyme has what actions?
Enzyme which hydrolyzes peptidoglycan, the main structural component of Gram positive bacterial cell walls; lysozyme can also be effective against Gram negative bacteria following damage to their outer membranes
Where is lysozyme present?
in secretions like tears sweat, saliva, sebum, gut mucosa where secreted by Paneth cells
What do goblet cells synthesize? Where do they synthesize these products?
secretory mucin and bioactive molecules in respiratory and intestinal tracts
What do Paneth cells secrete? Where are they located?
Secrete alpha defensins and bioactive molecules in the intestinal tract
What are Defensins? What do they do?
Human beta-defensins HBD
Small (35 - 40 aa) anti-microbial peptides rich in positively-charged arginine residues with 3 intra-chain disulfide bonds. Amphipathic in nature, they can penetrate microbial membranes and disrupt their integrity
HBD2 targets what?
gram -ve bacteria
HBD 3 targets what?
HBD3 gram +ve and gram -ve baceria
What does PRR stand for? What are they expressed by and what do they respond to?
Pathogen recognition receptors
Expressed by epithelial cells of enterocytes and respond to PAMPs (Pathogen-Associated Molecular Patterns)
Once PRRs recognize PAMPs they activate what to start their immune response? What do the epithelial cells in turn secrete?
activate NF-kB/other transcription factors
Epithelial cells produce chemokines, cytokines, and defensins
Where are MIC-A and MIC-B located and what do they express?
MIC-A and MIC-B— expressed on intestinal epithelial cells in response to cellular injury and stress
How do infected epithelial cells get killed through the MIC-A and MIC-B pathway?
What does GALT stand for what are its major components?
What is NALT and what are the major components?
Nasopharynx-associated lymphoid tissue.
MWhat is BALT and what are its components?
Bronchus-associated lymphoid tissue
Not generally detectable in normal lungs of adult humans
Antigens enter Peyer’s patches through what specialized cells?
M cells
What is the function of M cells?
M cells sample antigen and present them to APC
Describe the uptake and transport of ag by M cells.
- M cells take up ag by endocytosis and phagocytosis
- Ag is transported across M cells in vesicles and related at basal surface
- Ag is bound by dendritic cells, which activate T cells
Describe how lymphocytes are activated and return to tissues as effector cells?
Pathogens enter intestinal lumen through a Peyer’s Patch through an M cells > APC > Naive T and B cells activated by ag> effector T cells> mesenteric lymph nodes> through circulation> come back to mucosal tissue at site actived > kill pathogens and cytokine secretion for effect T cells, secretion of IgAa for plasma cells
Explain the priming of naive T cells and redistribution of effector T cells in the intestinal immune system.
Understand this slide on B-cell activation by helper T-cells.
Describe T-dependent ag B cell responses.
T-dependent antigensrequires receptor interactions of the B cell with the helper T cell through CD40 (on the B cell), CD40L (T cell), and the action of cytokines.
Different combinations of cytokines produced by helper T cells induce class switching.
Describe how B cells respond to T-independent ag?
complement pathway
T-independent antigenshave repetitive structures that can cross-link sufficient numbers of surface antibody to stimulate growth of the antigen-specific B cells.
Binding of the C3d component of complement to its receptor (CR2, CD21) facilitates the activation of the antibody response.
TH1 helper responses (IFN-γ) promote production of what immunoglobulins?
IgG
TH2 helper response promote production production of IgG, IgE, and IgA through what interleukin cytokine release?
IL-4, IL-5, IL-6
IgA production is promoted by what cytokines mainly?
IL-5 and TGF-B
Be able to reproduce this chart.
Reproduce chart.
Where is IgA produced in mucosa of GI and respiratory tracts?
produced by plasma cells in the lamina propria and is actively transport through epithelial cells by an IgA specific Fc receptor called the poly-Ig receptor because it recognizes IgM as well
Polymeric Ig receptor can bind to what Igs?
IgA or IgM
What are the functions of IgA in gut mucosa and epithelial surface?
In a clinical trial, polio vaccine is found to be most effective when administered orally. This oral vaccine is most likely to elicit which of the following protective immune responses?
A. Antigen gathering by dendritic cells
B. Binding of IgE to mast cells
C. CD4 cell proliferation in gut-associated lymphoid tissue
D. Increased memory B cells
E. Mucosal IgA secretion
E. mucosal IgA secretion
How does an defiency of TANK-binding kinase 1 (TBK1) inhibit IgA class switching?
TANK-binding kinase 1 (TBK1) inhibits IgA class switching.
Deficiency causes uncontrolled production of IgA and development of ‘IgA nephropathy’.
B-cell maturation antigen is also abbreviated what?
BCMA or BCM
BCMA is also known as what?
tumor necrosis factor receptor superfamily member 17
BAFF stands for what?
B-cell activating factor receptor
