6/22/202
Transplant Immunology
Maya Campara, Pharm.D., FCCP, FAST, BCPS
Clinical Associate Professor, Pharmacy Practice and Surgery
University of Illinois at Chicago
Chicago, Illinois
1
Disclosures
• The author of this presentation has no actual or potential
conflicts of interest
2
, 6/22/202
Learning Objectives
1. Differentiate between components of innate and adaptive immunity.
2. Review lymphocyte activation, differentiation and effect mechanisms.
3. Discuss pathways of allorecognition, transplant rejection and injury.
4. Assess immunologic risk of rejection.
5. Describe pathways to immunologic tolerance of allograft.
3
Immunity
Innate Adaptive
• Nonspecific, rapid • Antigen (Ag) specific, slower
– Physical barriers: skin, tissue – Ag is any molecule that can activate
– Chemical barriers: complement, pathogen adaptive immunity
associated molecular patterns, damage
associated molecular patterns (DAMPs)
• Mediated by lymphocytes and antigen
• Mediated by various cells including presenting cells
mast cell, macrophages, neutrophils,
dendritic cells, natural killer cells, etc.
• Exhibits immunological memory
• No immunological memory
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
4
, 6/22/202
Immunity
• Innate immune system (IMS) • Adaptive IMS is responsible for
causes: – Allograft recognition
– Allograft injury during reperfusion – Rejection
– Inflammation, scarring – Tolerance
– Primes/enhances activity of the
adaptive IMS
Although distinct, closely interconnected and depend
on each other for activation and attenuation.
Also, not mutually exclusive.
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
5
Ubiquitous Role of Cytokines
• Chemical messengers
– Mediate signaling and communication between cells
– Guide the behavior of cell; its response to environmental changes
• Produced on demand by various cells
– “Inter‐leukins” (IL) misnomer
– Secretion is brief, self‐limited event in response to a stimulus
• Major function
– Inflammatory responses (TNF‐alpha, IL‐1, IL‐6, IL‐17, chemochines)
– Proliferation, differentiation of cells (IL‐2, IL‐4, IL‐5, IL‐10, IL‐12, INF‐gamma, TGF‐beta)
– Neuronal, hematopoietic and embryonic development (erythropoietin, thrombopoietin, GCSF,
etc.)
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
6
, 6/22/202
Inducing stimulus
Cytokines
• Act only on cells bearing specific membrane Cytokine
receptors Cytokine
producing
cell
gene
– Cytokine binding unit
– Signal transduction unit (often shared by various
cytokines resulting in redundancy and pleiotropy) Cytokines
• Regulation of cytokine function occurs by… Cytokine receptor
Signal
– controlling quantity of cytokine produced/available
Target cell
– controlling expression of cytokine receptor components Gene
activation
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015. Biological effects
7
IL2 Receptor
• Beta/Gamma signal transduction unit exists on resting cells Cellular responses consist of changes in
• Alpha subunit, a.k.a CD25 is the cytokine binding site
• It is produced by active lymphocytes only gene expression and cell function
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
8
Transplant Immunology
Maya Campara, Pharm.D., FCCP, FAST, BCPS
Clinical Associate Professor, Pharmacy Practice and Surgery
University of Illinois at Chicago
Chicago, Illinois
1
Disclosures
• The author of this presentation has no actual or potential
conflicts of interest
2
, 6/22/202
Learning Objectives
1. Differentiate between components of innate and adaptive immunity.
2. Review lymphocyte activation, differentiation and effect mechanisms.
3. Discuss pathways of allorecognition, transplant rejection and injury.
4. Assess immunologic risk of rejection.
5. Describe pathways to immunologic tolerance of allograft.
3
Immunity
Innate Adaptive
• Nonspecific, rapid • Antigen (Ag) specific, slower
– Physical barriers: skin, tissue – Ag is any molecule that can activate
– Chemical barriers: complement, pathogen adaptive immunity
associated molecular patterns, damage
associated molecular patterns (DAMPs)
• Mediated by lymphocytes and antigen
• Mediated by various cells including presenting cells
mast cell, macrophages, neutrophils,
dendritic cells, natural killer cells, etc.
• Exhibits immunological memory
• No immunological memory
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
4
, 6/22/202
Immunity
• Innate immune system (IMS) • Adaptive IMS is responsible for
causes: – Allograft recognition
– Allograft injury during reperfusion – Rejection
– Inflammation, scarring – Tolerance
– Primes/enhances activity of the
adaptive IMS
Although distinct, closely interconnected and depend
on each other for activation and attenuation.
Also, not mutually exclusive.
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
5
Ubiquitous Role of Cytokines
• Chemical messengers
– Mediate signaling and communication between cells
– Guide the behavior of cell; its response to environmental changes
• Produced on demand by various cells
– “Inter‐leukins” (IL) misnomer
– Secretion is brief, self‐limited event in response to a stimulus
• Major function
– Inflammatory responses (TNF‐alpha, IL‐1, IL‐6, IL‐17, chemochines)
– Proliferation, differentiation of cells (IL‐2, IL‐4, IL‐5, IL‐10, IL‐12, INF‐gamma, TGF‐beta)
– Neuronal, hematopoietic and embryonic development (erythropoietin, thrombopoietin, GCSF,
etc.)
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
6
, 6/22/202
Inducing stimulus
Cytokines
• Act only on cells bearing specific membrane Cytokine
receptors Cytokine
producing
cell
gene
– Cytokine binding unit
– Signal transduction unit (often shared by various
cytokines resulting in redundancy and pleiotropy) Cytokines
• Regulation of cytokine function occurs by… Cytokine receptor
Signal
– controlling quantity of cytokine produced/available
Target cell
– controlling expression of cytokine receptor components Gene
activation
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015. Biological effects
7
IL2 Receptor
• Beta/Gamma signal transduction unit exists on resting cells Cellular responses consist of changes in
• Alpha subunit, a.k.a CD25 is the cytokine binding site
• It is produced by active lymphocytes only gene expression and cell function
Abbas AK, Lichtman AHH and Pillai S, edt. Cellular and Molecular Immunology, Philadelphia, PA: Elsevier, 9th Ed, 2018.
Coico R and Sunshine G, eds. Immunology A Short Course, Hoboken, NJ: Wiley‐Blackwell, 7th Ed, 2015.
8
