Class Notes (807,938)
Canada (492,936)
Immunology (185)
IMM250H1 (158)
all (42)

01 - January 8, 2013.docx

5 Pages
Unlock Document

University of Toronto St. George

IMM430H – January 8, 2013 Presentations – 20 minutes MAX; PRIMARY IMMUNODEFICIENCIES Pre-existing diseases READ THE PAPER – TESTABLE T cell receptor - Recognize antigen using variant T cell receptors - Uses invariant CD3 chains to transduce signalling required for T cell differentiation and signalling - Defects in specific chain would interfere with maturation of specific T cell lineage o BUT these authors used two patients to demonstrate that this is not so o Selectively affect T alpha beta while sparing T gamma delta - novel phenotype of SCID  Two patients were enough to demonstrate this concept - Primary immunodeficiency emphasizes information from single patients SCID - Clinical diagnosis - Immune system is important for fighting infections and controlling itself – may have disregulation with – large spleen, large liver, large lymph nodes o Susceptible to infections AND overactivation of immune system - Additional clues to SCID o Most of the families will not reveal or do not know about consanguinity – in this paper, the authors may not have been able to determine or decided not to o Closely related o Ethnicity – certain diseases more common in certain groups o Reasons  Founder effects – especially in small communities  Family members tend to marry each other – found effects there  ADA deficiency confers some resistence to malaria – common in Somali population - Lab clues to SCID o Lab is not the best way to diagnose immunodeficiencies o Normal IgG in patient one and normal levels of other Ig o Absence of T cell DEPENDENT antibodies – usually protein antigens to vaccines and infections – o T cell independent antigens usually present – demonstrated in paper o Lymphopenia – low numbers of lymphocytes – masked by increased number of other cell lineages  Absolute number of lymphocytes would not have led to diagnosis – in both patients o Best diagnosis is absence of T cells  After excluding secondary causes of immunodeficiency like HIV, malignancy  And determine which lineage of T cells involved  Absence or presence of these different lineages help identify the specific cause of immune deficiency  Which specific lymphocyte lineage is affected helps identify the specific cause of the immunodeficiency  Ex. If both T, B, and NK cells affected – indicate defect in early hamtopoietic progenitors – could be accumutation of toxic metabolites (like AK2 deficiency)  If NK cells okay, but B and T not – suggest none of the above causes but likely something that is associated with cells expressing Ig receptor – hence defects in VDJ recombination  B cells spared, and NK affected – defect in IL2 receptor pathway or IL15 receptor pathway – since B cells not as sentive to IL2 signalling  Knowing which lymphocyte lineage is affected helps identify the cuase o Additional T cell assays  Flow cytometry for specific expression of antigens on T cells  Antibodies against alpha beta – to identify significant reduction in alpha, beta T cells while sparing gamma delta T cells o Diversity of Vbeta in peripheral T cells  Another test used by the paper  Two methods – spectrophototyping and flow cytometry against twenty four differnet variable beta chain families – nine abnormal V beta families – suggesting significant defect in T cell development and diversity - Mouse =/= humans - TBNK cells function o NK cell function by ability to lyse labelled target cells o Interested in studying response – response to various stimulation o How many cells proliferated – what these cells secreted – stimlatuion of CD3 chain o Responses of these cells to specific antigen stimulation o If these cells were exposed to that antigen previously o Common tests done in clinical labs o Can look at response of these cells to allogenic cells – mixed lymphocyte reaction o Cytotoxicity against foreign cells T cell function - T regs - Function measured in vitro by their ability to prevent expansion of other types of other stimulated T cells - A 2012 Blood paper Thymus function - Best appreciation of T cell development is getting thymus o Get the thymus before get sick, before get medications, before succumbing to the disease - In control – round shapes called _______ - Clear cortical medulla demarcation – not seen in patient - Thymus biopsy rare - Indirect measures of thymus function o Naïve versus memory T cells – not very reliable – WHAT IS THIS?? o When T cells arrange their receptors – they have
More Less

Related notes for IMM250H1

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.