Fadie Jebrail: [email protected]

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Fadie Jebrail: [email protected] Chaya Taub: [email protected] Sandra Gerges: [email protected] Androu Arsanious: [email protected] March 2 nd 2010 PHM 226, 2010 Instructor: Dr. Jeffrey Hender

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Transcript of Fadie Jebrail: [email protected]

Page 1: Fadie Jebrail: fadiejebrail@hotmail.com

Fadie Jebrail: [email protected] Taub: [email protected] Gerges: [email protected] Androu Arsanious: [email protected]

March 2nd 2010

PHM 226, 2010Instructor: Dr. Jeffrey Henderson

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Autoimmune Disease is a…

“multi-factorial processes involving dysregulation of multiple components of the immune system including the adaptive and the innate immune system” [1]

- Lang et al. Journal of Autoimmunity 2007

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Let’s talk about why it’s important first…

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Affects 5-8% of people, making it 3rd most common disease after CV disease and cancer

Rarely do people have a SINGLE autoimmune diagnosis, usually associated with chronic disease

Over 80 diseases are characterized as autoimmune disorders

Results from a failure of organism to recognize its own parts as self

This results in overactive immune response directed against body tissue

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A bit of immunology..

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Two branches: innate/ nonspecific and adaptive/specific

In the innate system: mast cells, neutrophils and macrophages (engulf cytokines inflammation)

Within adaptive, two branches: humoral-mediated (B cells) and cell-mediated (T cells)

Macrophages have a role in both branches

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When a pathogen (can be self in this case) is ingested by a macrophage, pathogen proteins attach it to class II MHC

Macrophage activated to deliver signals to T-cells which produces autocrines and stimulate their own production

Helper T cells activate B cells which produce antibodies that inhibit the pathogens

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White blood cells within tissue, having a role in innate and adaptive immunity

They engulf pathogens and debris via phagocytosis, and move around via amoeboid movement

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Results from a loss of immunological tolerance – which is the ability to ignore self-antigens

T and B lymphocytes that recognize self-antigens are usually destroyed in the Thymus and Bone marrow, respectively, preventing autoimmunity.

Infection and overstimulation of APCs can break tolerance and induce priming of T-cells

A combination of genetics and environment are responsible for autoimmune disease

Human Lymphocyte Antigen (HLA/MHC) is the best predictor as it enhances antigen presentation resulting in increased T-cell activation

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Hormones: More common in women; hormones interact with immune cells, especially steroid hormones which influence antibody production

Diet: Iodine binds to thyroglobulin making it a target for the immune system

Drugs: Hydralazine can induce autoantibodies

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Antibody-mediated (B cells) Binding of antigens on

the surfaces of B-cells produces antibodies

Autoantibodies: Bind to self-tissue, and

activates the complement cascade which targets the self-antigen to be phagocytosed (opsonized) by Macrophages

Cell-mediated (T cells)• Immune cells both kill

cells directly and indirectly via cytokines (PG, NO, etc.)

• Macrophages: – INITIATE the response

as antigen presenting cells

– PARTAKE in killing cells through antibody dependent-dependent cell-mediated cytotoxicity and by releasing cytokines (TNF and IL-1)

– PRESENT SELF-TISSUE TO T CELLS

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Immunosuppressants and anti-inflammatories

B cell depleting agents like rituximab

Anti-cytokine therapies like tocilizumab

No truly effective therapies exist

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Autoimmune disease is generally poorly understood

Many different mechanisms exist to ensure that T cells that recognize self are destroyed

Macrophages play a role in both innate and adaptive immunity via complement in the former and antigen presentation in the latter

Know slide 14 Know slide 7

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1) Rose, NR. Pathogenic Mechanisms in Autoimmune disease. Clinical Immunology and Immunopathology 53, S7-S16 1989

2) Nauta et al. A regulatory role for Complement in Innate Immunity and Autoimmunity. International Archives of Allergy and Immunology. August 2004. 134, 4 pg 310

3) Fairweather, D. Alternatively Activated Macrophages in infection and autoimmunity. Journal of Autoimmunity 33(2009) 222-230

4) Allman D, Srivastava B, Lindsley RC (February 2004). "Alternative routes to maturity: branch points and pathways for generating follicular and marginal zone B cells". Immunol. Rev. 197: 147–60.

5) http://bioweb.wku.edu/courses/biol328/Lecture11.html6) Ohashi, P. T cell signalling and autoimmunity:

molecular mechanisms of disease. Nature Reviews Immunology Vol. 2 (2002)