Transplant Immunology Adi Alherbish

Outline Pre-sensitization: - B cells Ischemia-reperfusion injury/ innate immune response: - TLR - Complement - NK cells Afferent arm: - APC - TH cells Efferent arm: - Cytopathic T cells, T-reg - B cells, Plasma cells

Meet the Characters Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.

B cells

Sensitization Events Exposure to non- self HLA antigens

Mature B cells Memory B cells Plasma cells

Methods of Antibody Detection Clin J Am Soc Nephrol 1: 404–414, 2006

Luminex

Ischemia Reperfusion Injury

TLR HSP-70 HSP-60 TEC APCs

Immune Response to Post Ischemic Kidney Jang et al, Clinical Immunology (2009) 130, 41–50

C3 wild type mice C3 -/- deficient mice

B cell- mediated rejection IRI

NK Cells Role in Acute and Chronic Allograft Rejection IFG

HLA

MHC I: Nucleated cells

MHC II: B cells, APCs

Interferon Endothelial cells MHC I MHC I MHC II

Minor Histocombpatibility Antigens (miH) MICA MICB located in close proximity to the HLA-B locus and encode for 62 kDa cell-surface glycoproteins which share limited sequence homologies with HLA class I molecules and are not associated with b2-microglobulin

T cells

T Lymphocytes Maturation in Thymus

Direct Allorecognition

Indirect Allorecogintion

Semi-direct Allorecognition

Calcium- Calcineurin Pathway

N Engl J Med. 1998 Jun 18;338(25):1813-21.

J Am Soc Nephrol 18: 2252–2261, 2007

Belatacept (CTLA-4- Ig) N Engl J Med. 1998 Jun 18;338(25):1813-21.

+ Basiliximab MMF steroids

LFA-3–Ig, a dimeric fusion protein consisting of the CD2-binding portion of the human lymphocyte function-associated antigen-3 (LFA-3) linked to the Fc portion of human IgG1 complement-mediated lysis interruption of CD2’s interactions with LFA-3 limiting helper T cell adhesion to antigen-presenting cells disrupting the engagement of effector T cell receptor engagement with antigen and major histocompatibility complex molecules

Increased C5aR expression in TCMR infiltrating cells Protocol Bx IF/TA Increased C5aR expression in TCMR infiltrating cells

Vehicle treated recipient C5aRA Increased apoptosis in control group 1 day after transplant