Immune Mechanisms Flashcards
In mast cell activation, which of the following is an important mediator that is newly synthesized and acts as a vasodilator and a bronchoconstrictor?
A. Histamine
B.PGD2
C.PGE2
D.Tryptase
Prostaglandin D2 is a major lipid mediator synthesized during mast cell activation that causes bronchoconstriction, tissue edema, and increased mucus secretion. Mast cells, along with basophils, and eosinophils, are one of the three major allergy effector cells activated during immediate hypersensitivity reactions.
Mast cells are present in all connective and mucosal tissues that maintain tissue homeostasis from a variety of stimuli. Mast cells secret a variety of preformed and newly synthesized mediators and cytokines during activation. Abnormal activation by allergens can lead to various allergic reactions.
Lipid mediators include prostaglandin D2 (PGD2), leukotriene (LTC4, LTD4, and LTE4), and platelet-activating factor (PAF). Lipid mediators cause bronchoconstriction, tissue edema, and mucus secretion.
Prostaglandin E2 is a lipid mediater newly synthesized by the eosinophils, not mast cells, that causes bronchodilation, suppress activation of mast cells/eosinophils, and blocks 5-lipooxygenase activation.
Which mediator is a neutrophil chemokine that promotes migration?
IL8
Neutrophils are granulocytes derived from a myeloid progenitor in the bone marrow which develop in response to cytokines such as granulocyte colony-stimulating factor (G-CSF). Cytokines such as IL-17 and IL-1 can stimulate neutrophil production by up-regulation of G-CSF. IL-6 is another cytokine that also has been shown to stimulate granulopoiesis.
Neutrophils are retained in the bone marrow via the chemokine receptors CXCR2 and CXCR4. A gain of function mutation in CXCR4 leads to WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, where patients develop peripheral neutropenia because of accumulation of mature neutrophils in the bone marrow (myelokathexis).
Exit of neutrophils from the bone marrow are mediated by cytokines such as G-CSF, which disrupts the CXCR4-CXCL12 interaction. In addition, chemokines such as CXCL8 (also known as IL-8) bind to the CXCR1 and CXCR2 chemokine receptors on neutrophils to recruit them to a site of infection or injury.
Other chemotactic factors for neutrophils include bacterial products such as N-formyl methionyl peptides, leukotriene B4, and complement split products.
Which transcription factor is most associated with T helper type 2 (TH2) cells?
STAT3
STAT4
STAT5
STAT6
Exposure to allergens and parasites promote the differentiation of T helper type 2 (TH2) cells, which are induced by alarmins from epithelial cells (IL-25, IL-33, thymic stromal lymphopoietin) and IL-4.
The key transcription factors characteristic of TH2 cells are STAT6 and GATA3, which induces the expression of the signature cytokines IL-4, IL-5, and IL-13.
GATA3 expression also prevents the differentiation of this cell to a TH1 subset.
Transcription factors
Tbet and STAT4 and STAT1 - TH1
GATA3 and STAT 6, STAT 5 - TH2
ROR gamma T and STAT3 - TH17
IRF and PU-1 - TH9
FOXP3-STAT5 - T regs
What changes are seen in airway remodeling?
The changes involved include increased goblet cells, subepithelial fibrosis and thickening of the basement membrane, goblet cell metaplasia, angiogenesis, smooth muscle hypertrophy and neovascularization. The previous changes will cause stiffer airways, diminished elastic recoil and progressive decline in FEV1 and FVC.
Although it has been assumed that remodeling contributes to airway hyperresponsiveness, some studies suggest that airway wall thickening may also be protective and reduce airway hyperreactivity. Therefore, the relationship between remodeling and the degree of airway hyperreactivity remains in question.
What is a feature of white pulp, as opposed to red pulp?
A. Contains macrophages that remove microbes and damaged or antibody-coated cells.
B. Enlarges in size during diseases of vascular engorgement such as cirrhosis.
C. Promotes adaptive immune responses to blood-borne antigens.
D. Makes up 80% of the spleen parenchyma and is the site of blood filtration
C. Promotes adaptive immune responses to blood-borne antigens.
The function of the white pulp is to promote adaptive immune responses to blood-borne antigens. The white pulp is organized around central arteries, which are branches of the splenic artery distinct from the branches that form the vascular sinusoids. The architecture of the white pulp is analogous to the organization of lymph nodes, with segregated T cell and B cell zones. Antigen presenting cells enter the white pulp, resulting in activation of the T-lymphocytes stored there. These in turn, activate the B-lymphocytes in the follicles, converting them to plasma cells which then produce of IgM antibodies initially and eventually IgG antibodies. Pathogens may also enter the follicles directly. B-lymphocytes detect this and can then present the antigen to the T-lymphocytes. This leads to a process known as co-stimulation, in which the two cell types activate each other so the B-lymphocyte is then able to become a plasma cell and produce antibodies against the pathogen. The white pulp is also important in how the body deals with encapsulated bacteria such as Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. Encapsulated bacteria tend to have a smooth surface with a negative charge which therefore reduces the ability of phagocytes to attach and engulf the bacteria. The B-lymphocytes in the white pulp help opsonize these bacteria.
Which chemokine receptor is associated with eosinophil, basophil and mast recruitment?
CHOOSE ONE
A. CCR2
B. CCR3
C. CCR4
D. CCR5
CCR3, also known as CD193, binds to a variety of chemokines, including eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). CCR3 is found on human mast cells and is associated with eosinophil and basophil recruitment and when combined with other chemokine receptors, is associated with Th2 recruitment. CCR3 may contribute to the accumulation and activation of eosinophils and is an anticipated target to block in many allergic disorders including atopic dermatitis and asthma.
CCR2 is associated with macrophage and monocyte recruitment.
CCR4 is associated with T cell recruitment.
CCR5 is associated with T cell, dendritic cell, monocyte, macrophages and NK cell recruitment. CCR5 also acts as a HIV receptor.
Bullous pemphigoid antibodies
IgG BP180 and BP230
Food dependent exercise induced anaphylaxis - most common allergen
In Japan is wheat
In the US is shellfish, followed by alcohol, tomato, cheese, celery, strawberries, wheat, peach and milk
Bird egg syndrome component
Chicken serum albumin (Gal d 5) or also known as alpha livetin
What cells present antigens in GALT (gut associatred lymphoid tissue)?
M (or microfold) cells are known as specialized epithelial cells of the follicle-associated epithelium of the gastrointestinal tract. M cells act as an antigen sampling system. The primary physiological role of M cells seems to be the rapid uptake and presentation of specific antigens and microorganisms to the immune cells of the lymphoid follicle to induce an effective immune response.
In contrast to absorptive enterocytes, M cells do not exert direct defense mechanisms to antigens and pathogens in the gut lumen.
Paneth cells are the most highly secretory of the four lineages of epithelial cells that form the intestinal mucosa. Their main function is to produce, package and export a variety of antimicrobial proteins and peptides including α-defensins, angiogenin-4, lysozyme and secretory phospholipase A2.
Formula for PPV and NPV
PPV = TP / (TP + FP
NPV = TN / (TN + FN)
Factors that increase FENO
Bronchodilator
URI (airway infection)
Allergic rhinitis
Nitrate rich diet (bacon)
Height
Factors that decrease FENO
Smoking
ICS therapy
Exercise
Spirometry maneuvers
Alcohol
Bronchoconstriction
Ciliary dyskinesia
Pulmonary hypertension
Cystic fibrosis
What is considered FREQUENT idiopathic anaphylaxis?
Frequent IA has been defined as at least two episodes in the preceding two months or at least six episodes in the preceding year.
Patients with IA who do not meet one of these criteria are categorized as having infrequent IA.
Alpha gal allergy contraindicates the use of the following medication
Cetuximab (endothelial grow factor receptor inhibitor) which cross reacts with alpha1,3 galactose (alpha gal)
