Lecture 20: immunology II Flashcards
What is an example of a disease that causes immune dysfunction?
allergy
Which cells act in the allergy response?
histamine leukotriene prostaglandins mast cells and more
What is the implication of prostaglandins being part of the allergic response?
there are some uses of NSAIDs in allergy treatment
How do mast cells contribute to the allergic resposne?
release tryptases which degrade surrounding tissue
What is the allergic response?
- first exposure causes APC (tissue macrophages and dendritic cells) to take some of the allergen and present to T cells and B cells in the lymph node
- T cells which recognise the fragment become a TH2 T cell which produces key cytokines like IL4 and IL14 which work with other T cells to convert B cells into plasma cells
- plasma cells will create a population of IgE antibodies specific to the allergen (each class of B cells produces a class of antibody)
- When body is re-exposed, the IgE produced by plasma cells bind to the substance and trigger the next level of allergy reaction
- basophils (circulatory) and mast cells (residing in tissue) produce histamine which is involved in vasodilation, and activation of nerves resulting in erythema, welts, itchiness.
How can hypersensitivity be treated?
- reduce antibodies
- block receptors
- reduce T and B cell populations
What are the drug treatments for hypersensitivity?
- antihistamine
2. steroidal (creams/inhalers), avoidance of allergen, NSAIDs can provide some benefit
How is severe allergy (anaphylaxis) treated?
with immediate injection of adrenaline, particularly if bronchial spasm occurs, via IM injection into the thigh
What is omalizumab?
an anti-IgE monoclonal antibody used for severe asthma. Currently FDA, US and Europe approved
What is the basic pathophysiology of MS?
clonal autoreative T cells are present which attacks the self and destroys myelinated cells in the CNS.
What would brain tissue from an MS patient typically show?
the presence of dendritic, APC, macrophages, T cells and B cells
- normally, the brain should be free from these cells
- presence of these indicates this is what eats away at the healthy brain tissue
- the dendritic, antigen presenting cells and macrophages do most of the damage, but some B cells produce different classes of antibodies (IgG and IgM)
What is leukocyte diapedesis?
-when immune cells circulating the blood move into the tissue
What is the blood brain barrier composed of?
endothelial cells
astrocytes
pericytes and the basal membrane
What causes leukocyte diapedesis into the bbb?
- normally leukocytes would simply flow on past
- in diseases like MS, the endothelium is activated resulting in expression of molecules like VCAM-1 and ICAM-1 (family of cellular adhesion molecules)
- VCAM interacts with VLF4 on immune cells which facilitates tethering and rolling
- immune cells reach the barrier and enter.
What are potential targets to stop leukocyte diapedesis into the bbb?
- targeting the molecules involved in tethering
- targeting molecules that control the actual process
