Immunity - the basics Flashcards
What part of the immune system are inflammasomes found?
Part of the innate immune system
Outline the immune mechanism associated with gout
- multiprotein complexes in the cytosol of cells
- respond to microbes or changes associated with cell injury
- lead to activation of IL-1b and IL-18
- use the sensor NLRP3 found on PCS (macrophages/neutrophils/keratinocytes) that is stimulated by URIC ACID
- urate crystals are recognised by inflammasomes and IL-1 beta production
What is the CD4+ T cell response that IFN-gamma is associated with?
Th1 responses»_space; key cytokines - IFN-gamma + IL-2
Briefly outline the Th1 response
(a) functions
(b) cytokines
(c) clinical application examples
- key functions - production of opsonising antibodies, induction of cellular toxicity, macrophage activation (key feature)
- key cytokines: IL-2, IFN-gamma
- Clinical examples
> help in the eradication of intracellular micro-organisms such as mycobacteria
> promote cytotoxic T cell development + delayed type hypersensitivity reactions
Briefly describe the difference between classic and alternative macrophage activation
- Classically activated macrophages are known to have major roles in host defense against various microbial pathogens, including fungi
- alternatively activated macrophages are instrumental in immune-regulation and wound healing.
Briefly outline the Th2 response
(a) functions
(b) cytokines
(c) clinical application
- functions - Eosinophil + mast cell activation
- Key cytokines – IL-4, IL-5, IL-13
- Clinical applications - immune response against parasitic infections, role in development of allergy + asthma, role in collagen deposition
Dupilumab is used in the treatment of Asthma. What is it and list 2 other conditions it may be used for
- IL-4 receptor antagonist (monoclonal antibody)
- Indications
> asthma - mod-severe eosinophilic or oral glucocorticoid dependent
> atopic dermatitis
> rhinosinusitis, COPD refractory, eosiniphilic esophagitis
Briefly outline the Th17 response
(a) functions
(b) cytokines
(c) clinical application
Key functions: production of pro-inflammatory cytokines + chemokines + neutrophil recruitment
Many cytokines
Clinical application
- Early response to numerous extracellular pathogens (including bacteria + fungi)
- Important role in driving chronic inflammatory responses (e.g. chronic infection, allergy, autoimmunity) + neutrophil predominant asthma
What is the main chronic condition IL-17 antagonists are approved for
psoriasis
What is the broad role of TNF
- pro-inflammatory cytokine - many roles (induces fever, inflammation, cell death)
- thought to have dysregulation in conditions such as Alzeihmers disease, IBD, cancer
List one example of a TNF inhibitor and 3 conditions it can be used for
- etanercept (E), infliximab (I), adalimumab (A), certolizumab pegol (C), and golimumab (G), are biologic agents which are FDA-approved
- Clinical uses - Crohns disease/UC (IBD), Ankylosing spondylitis, psoriasis, uveitis
What are the principal targets of rejection in transplantation?
proteins encoded in the MHC
List the 3 types of transplant rejection
- hyperacute
- acute
- chronic
Briefly outline the features of hyperacute rejection and the mechansims associated with this
- onset: minutes to hours
- pre-existing antibodies of the RECIPIENT match foreign antigens of the donor (e.g. HLA antibodies, ABO isoaggutinnins)
- thrombosis of graft vessels + ischarmic necorosis (immune reaction activates the complement/clotting system) –> endothelial injury + thrombus formation
- Hypersensitivity Type II (completement/antibody mediated)
In a hyperacute rejection, the donots antibodies attack the graft vessels. What might be the source of how these antibodies were generated?
- previous blood transfusions (therefore importance of cross-matching)
- previous transplantations
- multiple pregnancies
*this is more a situation where there is pre-formed donor specific antibody attacking the graft tissue vs. acute rejection where there is acute cellular rejection (T-cell mediated)