Exam 3: Dr. Pinchuk Mucosal Immunity Flashcards
What are unique features of mucosal immunity?
Combined area of the mucosal surface is much greater than that of the skin
Three quarters of the body’s lymphocytes are in secondary lymphoid tissues serving mucosal surfaces, and similar proportion of all antibodies made by the body is secreted dimeric IgA
GI tract has contiuous contacts with large populations of commensal microorganisms and substantial quantities of proteins derived from the animals and plants
What is the major challenge for mucosal immunity?
To make immune responses to eliminate pathogens, limit the growth and location of commensal microorganisms, and do not attack the food
What can be found in GALT?
Lamina propria Mesenteric lymph nodes Palatine tonsils Adenoids Lingual tonsils Peyer's patches M cells Isolated lymphoid follicles Intestinal epithelium
What is the germinal center full of?
B cells
What are M cells specialized to do?
Transport microorganisms to GALT
Are M cells antigen presenting cells?
No, but they are closely associated with DCs
How does antigen uptake and transport by M cells occur?
M cells are interspersed between enterocytes and in close contact with DCs
M cells take up antigen from the gut lumen by endocytosis
Antigens are released beneath M cells and taken up by DCs
DC dendrites also span the gut wall and engulf antigens
What can DCs do with their processes?
Extend them across the epithelial layer to capture antigen from the lumen of the gut
What are most immune system cells in the mucosal tissues?
Activated effector cells
What happens to naive lymphocytes that are activated in mucosal tissues?
The return to the tissues as effector cells
How can secretory IgA bind pathogens?
IgA can export toxins and pathogens from the lamina propria while being secreted
IgA is able to bind and neutralize antigens internalized in endosomes
Secreted IgA on the gut surface can bind and neutralize pathogens and toxins
Secreted IgA binds pathogen on M cell surface and takes it to lymphoid tissue
Secreted IgA picks up antigen in the endosomes of the M cell and takes it to lymphoid tissue
What are cytoplasmic NOD-like receptors?
Signaling PRRs
What kind of immune response to enterocytes have?
Innate
What does the binding of microbial PAMPs to their signaling PRRs promote?
The synthesis and secretion of intracellular regulatory moecules such as cytokines, chemokines, defensins that are crucial to initiating immunity and adaptive immunity
What are Th2 cells responsive to?
The host rather than helminths
What are Th2 cells?
Host protective immune responsive cells
What do Th1 cells do against helminths?
Host damage
Activate macrophages
Produce IgG2a
What are the major mechanisms of host protective immune responses against helminths with Th2 cells?
Cell repair and mucus secretion
Activate eosinophils
Produce IgE
Activation of mast cells
What do helminths-infected populations exhibit?
Lower levels of immunological diseases such as Th1 related autoimmune diseases and aberrant Th2 related diseases
What is they hypothesis for helminth-induced immune responses?
Immune system has coevolved to operate in the presence of immunomodulatory helminth infections, while in the absence or exposure to helminths, the immunoregulatory components that would normally prevent allergy and autoimmune disease become weakened
What is the unique evolutionary dialogue of helminths with their hosts due to?
Longevity within the host
Complex life cycles
Multicellular nature
What are helminth-induced immune responses like compared to other pathogens?
Very different
What is involved with the response to helminth infection and allergic reactions?
Initiation of Th2 type immunity
What are key player in helminth-induce immune responses?
DCs, CD4 Th2 cells, IL-4, 5, 9, 10, 13, IgE, chemokines leading to recruitment and infiltration of eosinophils, basophils, mast cells, and expansion of alternatively activated macrophages
What are helminths master regulators of?
Inducing a modified Th2 type response to limit a possible detrimental Th2 immunity, thus restraining the extreme symptoms: allergy or in aspects of helminth diseases such as fibrosis
What do mechanisms of helminth-induced responses lead to?
Attenuation of pathology, tolerance and ultimately persistence of the worm assuring long term survival of the parasite within the host, sustain parasite feeding, completion of the life cycle, and successful reproduction
What does a helminth infection induce?
A protective Th2 immune response
What do helminths induce?
Immunoregulation via modulation of immune cells
What may allergic inflammation be suppressed by?
A spill-over effect of immunomodulatory mechanisms of helminths infection
Look at helminth picture
Look at helminth picture
What is antibody-dependent cell-mediated cytotoxicity?
Large parasites like helmints are too big to be engulfes and killed by phagocytosis
What happens after IgE coats parasites in ADCC?
The Fc receptor of an eosinophil will then recognize IgE released by B cells and kill helminths. Subsequently, interaction between FceRI and the Fc portion of helminth-bound IgE signals to the eosinophil to degranulate
What do Th2-mediated effector mechanism act in concert with?
Other immune-mediated host responses to expel the worm from its intestinal niche
What is the first arm of the innate immune response?
Mucosal barrier and mucus
What do goblet cells with antibodies, defensins, and other antimicrobial molecules do?
Release protective agents that bombard pathogenic microorganisms to produce a hostile environment reducing their chances of reaching the host epithelium
What are mucins?
The essential anti-parasitic effector molecules over and above their importance in mucus structural integrity
How are type 2-inducing stimuli sensed?
PRRs, proteolytic cleavage of host proteins, tissue damage, and metabolic changes
Whatare the distinctive features of the mucosal immune system immunoregulatory environment?
Dominant and active downregulation of inflamamtory immune responses to food and other innocuous environmental antigens
Inhibitory macrophages and tolerance-inducing dendritic cells
What immune response is in the healthy gut?
Chronic adaptive immune response
