Immuno - Immune Responses To Transplants And Cancer

Front 1

Types of transplant rejection

Back 1

Types of transplant rejection
– Hyper-acute rejection: begins within hours of transplant
Pre-formed antibodies; injury via complement.
– Acute rejection: a week or more after transplant
Mixture of CD4+ and CD8+ T-cells
– Chronic rejection
Fibrosis

Front 2

Immune Responses to Transplants and Cancer - name the types of MCH1 for loading antigens

Back 2

Mostly HLA-A and HLA-B, sometimes HLA-C

Front 3

Immune Responses to Transplants and Cancer - name the types of MCH2 for loading antigens

Back 3

Mostly HLA-DR sometimes HLA-DP, and HLA-DQ

Front 4

Why do immune responses against transplants target HLA?

Back 4

Immune responses against transplants target HLA (MHC) because they are very different going from one person to another

Front 5

Bone marrow transplants (and others) that contain _______ may begin to attack the transplant recipient

Back 5

Bone marrow transplants (and others) that contain foreign T-cells may begin to attack the transplant recipient

Front 6

What is cancer?

Back 6

What is cancer?
1.Unregulated cell growth
2.Invasion of surrounding tissues
3.Potential for metastasis

Front 7

Why is cancer bad?

Back 7

Why is cancer bad?
Impinge on surrounding structures
Impair function of surrounding tissue
Impair function of distant tissue

Front 8

How does the immune system respond to cancer?

Back 8

How does the immune system respond to cancer?
Innate immune system?
Adaptive immune system?

Front 9

Leukemias and lymphomas

Back 9

Leukemias and lymphomas are immune cells that become cancerous
Growth of these abnormal clones is unregulated, suppressing the growth of
other immune cells
This results in immunosuppression
(+ suppression of red blood cells, platelets)

Front 10

Natural Killer cells

Back 10

Natural Killer cells
Activated by IL-2 and IL-12
Receptors scan cells for signs of stress
Cells with stress or without MHC-1 are killed
Induce apoptosis via Fas-L and Perforin/granzyme
Produce cytokines: IFN-γ
*Specificity is provided by IgG bound to
*Fcγ receptors resulting in antibody-dependent cellular cytotoxicity (ADCC)

Front 11

Summary of BCR and TCR diversity mechanisms

Back 11

Summary of BCR and TCR diversity mechanisms
1.Somatic recombination of V, D, J gene segments
2.RSS motifs -always directly adjacent to the coding sequence of V, D, or J
3.“12 / 23” rule (i.e. a gene flanked by 12bp spacer can be joined only to one flanked by a 23 bpspacer RSS
4.Absolutely requires lymphocyte specific recombinase, the RAG proteins and other proteins involved in DNA repair (i.e. DNA-PK, a nuclease Artemis, Ku70:Ku80, TdT, DNA ligase IV etc.)
5.Additional diversity comes from random insertion or deletion nucleotides at the ends of some gene segments
6.Further diversity from association of
7.More diversity results from somatic hypermutations in the rearranged V region

Front 12

What antigens can the adaptive immune system recognize?

Back 12

What antigens can the adaptive immune system recognize?
•Viral proteins presented via MHC2 (e.g HPV’s E6)
•Mutated human proteins (e.g. oncogene products)
•Normal human proteins only expressed in immune privileged sites (e.g. testicular proteins)

Front 13

Cancer immunology - Phase 1

Back 13

Phase 1: Tumor cells release of stress signals
–NK cells are activated, produce IFN-γ

Front 14

Cancer immunology - Phase 2

Back 14

Phase 2: Macrophage activation by danger signals and IFN-γ
–IL-12, Inflammation, suppression of blood supply→ necrosis

Front 15

Cancer immunology - Phase 3

Back 15

Phase 3: Macrophage activation of NK cells via IL-12
–Induction of apoptosis

Front 16

Cancer immunology - Phase 4

Back 16

Phase 4: Antigen presentation in lymph nodes
–Clonal expansion of TH1 and killer T-cells provide specificity to anti-tumor response
•Tumor elimination, equilibrium, or escape