Module 5 Flashcards
Allergies
microorganisms that co-evolved with mammals and inhabit our body
commensal microbes
What tissues comprise MALT?
respiratory tract, GI tract, urogenital tract, salivary glands, mammary glands, lacrimal glands, conjunctiva, and pancreas
What does mucus contain that protects epithelium from damage and invasion by microbes?
secretory IgA and IgM, proteoglycans, glycoproteins, peptides, and enzymes
Tonsils and adenoids make up what?
Waldeyer’s ring (secondary lymphoid tissues in upper GALT)
What secondary lymphoid tissues are found in the lower GALT?
small intestine villi, lamina propria, isolated lymphoid follicles, peyer’s patches
What transports microbes and antigens from gut lument to GALT?
M cells (microfold cells)
Secondary lymphoid organ that underlies the gut epithelium in small intestine and have lots of T cells, B cells, and have dendritic cells and germinal centers
Peyer’s patches
What makes mucosal lymphocytes unique?
they can travel to other mucosal tissues
Mucosal B cells give rise to plasma cells that secrete what two antibodies?
IgM and dimeric IgA
Largest lymph nodes in the body and are found in the gut
Mesenteric lymph nodes
After isotype switching, what antibody acts as the B cell receptor
IgA monomer
Phenomenon where the gut is constantly exposed to foreign antigens in food and bacteria but stays totally fine
oral tolerance
Do gut macrophages produce an inflammatory response?
no
This antibody protects mucosal surfaces (namely lamina propria) form microbial invasion
secretory IgA
how do IgM and IgA in the lamina propria get secreted to the intestinal lumen?
transcytosis
Main difference between inflammation in mucosal tissues and non-mucosal tissues
non-mucosal tissues will have significant tissue damage due to inflammatory macrophages
Overreaction of the immune system to “safe” antigens
hypersensitivity
Reactions to environmental antigens are this type:
Type II-IV
Allergic disease is this type:
Type II-I
Localized ability to develop immediate hypersensitivity reactions to a variety of allergens
Atopy
What 3 things are higher in atopic patients?
Serum IgE, Th2 responses, and IL-4 production
Summarize the hygiene hypothesis
individuals raised with little to no antigen exposure show stunted immune capacity
Type of reaction caused by interaction of soluble allergens with specific IgE that cause the degranulation of mast cells
Type I
Type of reaction caused by IgG antibodies reacting to new epitopes from chemical modifications
Type II
Type of reaction caused by IgG against soluble antigens that form immune complexes, deposit in tissue, and become subject to complement fixation and phagocyte attack
Type III
Type of reaction caused by CD4 T cells responding to either epitopes of foreign proteins or to chemically modified self-proteins
Type IV
Antigens that provoke a Type I hypersensitivity response
allergens!
4 main cells involved in Type I reactions
IgE, mast cells, basophils, and eosinophils
Major effector cell during Type I reactions
mast cells
What action recruits eosinophils and basophils to tissues?
Degranulation of mast cells
2 steps of allergic reactions
sensitization and mast cell activation
What kind of cells activate B cells to secrete cytokines during allergic sensitization?
Th2 cells
Allergen specific IgE binds to which receptors on mast cells?
Fc e RI
Steps of sensitization
Th2 cells activate B cells. B cells secrete cytokines to differentiate the B cells into plasma or memory cells. The plasma cells secrete high affinity allergen-specific IgE. The memory cells will produce a strong reaction to subsequent exposures. IgE binds to FceRI receptors on mast cells. mast cells are now sensitized to the allergen
Steps of mast cell activation/reaction
Sensitized mast cells degranulate and release pre-formed mediators that initiate the allergic reaction
How long can mast cell activation take?
up to two weeks for a new allergen and a few minutes-hours for recurrent ones
What phase of allergic reaction do pre-formed mediators get released from degranulation?
immediate (early) phase
What granules are released from mast cells?
vasoactive amines (like histamine), enzymes (like proteases), and proteoglycans (like heparin)
What allergic mediator packages and stores histamine in granules?
proteoglycans
What allergic mediator causes tissue damage and activates complement?
enzymes like proteases
What allergic mediator causes mucous secretion, increases vascular permeability, and stimulates smooth muscle contraction?
vasoactive amines like histamine!
What phase of allergic reaction do newly formed mediators get released?
Late phase reaction
What are some late phase mediator molecules?
membrane phospholipids, leukotrienes, prostaglandins, platelet activating factor (PAF), and cytokines
Which allergic mediator is vasoactive, spasmodic, and a chemoattractant for neutrophils, eosinophils, and monocytes?
leukotrienes
Which allergic mediator causes bronchospasm and mucous secretion?
prostaglandin
Which allergic mediator causes platelet aggregation, histamine release, bronchospasm, increased vascular permeability and vasodilation, and attract neutrophils and eosinophils?
platelet activating factor (PAF)
Which cytokines promote leukocyte recruitment in allergic reaction?
TNF and IL-1
Which cytokine amplifies the Th2 response in allergic reaction?
IL-4
What response results from mast cell activation in the GI tract?
increased fluid secretion and peristalsis resulting in GI upset
What response results from mast cell activation in the airways?
bronchoconstriction and increased mucus secretion
What response results from mast cell activation in the vessels?
increased blood flow and permeability resulting in swelling and inflammation, and lymph movement. Systemic anaphylaxis and hives can occur with this mode as well
this reaction occurs when a stimulus other than IgE sensitization causes mast cell degranulation
anaphylactoid reactions
Which phase of allergic reaction is usually more intense?
Late phase reaction
Hemolytic anemia is an example of which type of hypersensitivity reaction?
Type II
What can induce Type II inflammatory pathways?
complement and IgG
self or foreign antigens bound to antibodies that can activate the classical complement pathway
immune complexes
Complement-recognizing receptor found on rbc’s
CR1
fever, utricaria, arthralgia, lymphadenopathy, malaise, and proteinuria are symptoms of what?
serum sickness
What happens in serum sickness?
soluble proteins are injected into the bloodstream and form immune complexes which lodge in vascular beds leading to arthritis, vasculitis, nephritis, and fever
What two situations can cause serum sickness?
passive immunization with preformed animal or non-human antibodies or transfusion with human blood products
arthus reaction is also known as
vaccine reaction
Difference between serum sickness and vaccine reaction
vaccine reaction occurs localized to the injection site whereas serum sickness is more systemic
injected soluble protein causing immune complex formation in the tissue resulting in inflammation
arthus reaction/vaccine reaction
This type of hypersensitivity is mediated by T cells
Type IV
Nickel allergy is what type of hypersensitivity reaction?
Type IV
What two T cells are recruited for Type IV reactions?
Cytotoxic T cells and T helper cells
Celiac disease (gluten-sensitive enteropathy) is what type of hypersensitivity reaction?
Type IV
Example of Type IV delayed hypersensitivity reaction?
insect bites, PPD TST
Gliadin is the antigen associated with what disease?
Celiac disaese
Contact hypersensitivity/dermatitis occurs when an antigen is exposed to what?
skin
Gluten-sensitive enteropathy occurs when antigen is exposed to what?
intestinal lumen
Delayed type hypersensitivity occurs when an antigen is what?
injected into the skin
Celiac inflammation in the small intestine is primarily mediated by what cells?
CD4 T cells and macrophages
what does tissue transaminase do?
deaminates gluten fragments
what type of cell responds to deaminated peptides presented by HLA-DQ?
naive CD4 T cells
