LMP299Y1 Lecture Notes - Immunoglobulin Class Switching, Transforming Growth Factor Beta, Autoimmune Disease

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3 Jun 2013
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LMP403H January 30, 2013
EXAM: Shek usually asks multiple choice questions; Ni usually asks short answer questions; M asks short
questions; multiple choice and some short answer
Tolerance = not perfect; maintain “healthy” level
Everyone has autoimmune activity ex, in Western blot lots of interaction of own leukocytes and own
antibodies
Understand SOLID UNDERSTANDING KNOW VERY WELL
Be familiar basic understanding
Immunity is defense system strong immune response needed
Malignant tumours usually occurs past forty years old young people less likely to develop tumours
typically due to stronger immune surveillance and elimination cell-mediated immune response
decreases once reach particular age, allowing tumour development
Immune tolerance if not tolerant of certain antigens, have autoimmune disease have adaptive
immune system
In short, need immunity and tolerance to be well balanced this balance in multiple layers the layers
are not perfect, but in general, it’s fine
Innate immunity “same” is not identicial but in general the same
Broad diversity T cell and B cell have large repertoire
B cell plasma mediated antibody generation humoral response
Metchnikoff experiment: thorn embedded in starfish; overnight; saw the cells congregating around the
thorn
Both humoral and cellular immunity systems need to be tolerant to avoid autoimmune disease
Innate vs acquired immunity
Platelets small cells in blood; while circulating, platelets near the vessel walls, while red blood cells,
larger, tend to be in the middle of vessels so platelets close to site of inflammation
Platelets contribute to leukocyte migration move to site of infection
Platelets can direct and destroy bacteria co-culture bacteria dn platelet, bacteria tries to survive,
platelets tries to destroy the bacteria important for certain bacterial infections
HIV patients decreased platelet numbers
Parasites attack certain parasites, like malaria transmitted by mosquitoes live in red blood cells
once proliferate to certain level, red blood cells burst open
Disease progress Science 2009 paper once malaria infected red blood cells, platelets stick to it,
releasing chemicals to induce aptoptosis of malaria-infected cell
Platelets help lymphocyte homing
CD40 ligand molecule important for Ig class switching if animal is deficient in this, difficult to switch
classes but this knockout mice, transfuse with normal platelets(contain large amount of CD40 ligand),
can help B cell class switch
Platelets contain large amount of TGF beta positively support inflammation important to immune
suppressive cytokines do platelets have immune regulatory function?
Malignant tumour Cancer Research paper TGF beta could decrease function of NK cells
Tumour infiltrated lymphocytes if see many of tehse in tumour area, prognosis is good for patient
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Usually in early stage of malignant tumour, have these cells proliferating in tumours anergy lose
certain function, cannot kill the tumour cells; able to kill in vitro but in vivo, unable to function/kill
tumour cells
Removing tumour may leave behind residual cells tumour comes back
Able to educate immune system remove tumour so platelet interaction with malignant tumour could
be new area for development of anti-tumour therapies
Semple paper in Nav Rev Imm platelets
P-selectin needed in inflammation mediate tethering of leukocyte or for T cell/B cell to come to the
site for proliferation
Animal knockouts for P selectin leukocyte cannot interact with vessel wall but later, p-selectin is
important to develop TH1 immune response, which is important for cell mediated immunity for anti-
virus, anti-TB, anti-tumour
Ni lab found fibrinogen (major protein in blood circulation) is ligand of Beta 3 integrin platelet has
no nucleus but able to de novo synthesize p-selectin platelets have remaining mRNA that can be
translated into protein p-selectin important for interacting with lymphocytes, for stem cells, etc.
Platelets affect immune control/modulate/regulate immune response, including tolerance
Platelets in immunology
Innate immunity
Direct interaction with T, B cells, etc. other cells
Express p-selectin and regulate themselves immunocompetent cells and affect adaptive immunity
Contain large amounts of TGF beta effect T regulatory cell develop, decrease immune response
Blood paper 2010 Cara C. Bertozzi et al.
Platelets regulate lymphatic vascular develppment through CLEC-2-2 SLP-76 signalling
Remove CLEC 2 from platelet surface, these animals cannot separate blood cell vessels vs lymphatic
vessels if not separated, then not good for immune system
Conglei Li Advances in Hamtology 2012
Crosstalk between platelets and the immune system
Close to site of inflammation
Interaction between innate-adaptive imunity
TGB beta important immunosuppression
Adaptive imunity immune response is process; immune reactions are once generate antibodies or
cytokines or cells, have action to target multiple layers of self-tolerance
Opsonisation antibody bind to macrophage Fc receptor
Crosstalk between the two mutually help
Emphasize multiple layers
Cells involved in cellmediated specific immune responses
APC non professional lead to tolerance; professional lead to immunity
T lymphocytes Th17 inflammatory helper cells
Significant T suppressive cells called regulatory cells could be positive or negative
Professional APC different morphology
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