Lecture 17: Transplant Immunology

Question 1

Autografts

Answer 1

grafts exchanged from one part of the same individual

Question 2

Isografts

Answer 2

grafts exchanged between different individuals of identical genetic constitutions (e.g. idential twins)

Question 3

Allografts (allogeneic)

Answer 3

• Grafts exchanged between nonidentical members of the same species

Question 4

Xenografts (xenogeneic)

Answer 4

• graft exchanged between members of different species
  
  • are particularly susceptible to rapid attack by naturally occuring Abs and complement
  • The insertion of human genes into the genomes of the donor animals (miniature swine) increases the chances of successful survival

Question 5

Question 6

Classs _______ HLA Ags are particularly storng barriers to transplantation

Answer 6

Class-I (HLA-A and HLA-B)

Question 7

What are the three most important Class II HLA pairs for transplation

Answer 7

• HLA-DR
• HLA-DP
• HLA-DQ

Question 8

There are hundreds of allelic forms of HLA molecules but each individual only inherits

Answer 8

10-12 alleles/person

Question 9

Are HLA Ags expressed co-dominantly

Answer 9

yes

Question 10

Types of Rejections

Answer 10

Question 11

Mechanisms of Rejections

Answer 11

Question 12

Can Chronic rejections be inhibited by immunosuppressive therapy

Answer 12

No

Question 13

Direct vs Indirect Allorecognition

Answer 13

• The direct pathway is primary response against graft:
  
  • The T cell receptors on recipient T cells directly recognize the donor MHC molecules
• The indirect response:
  
  • The recipient T cells recognize donor MHC molecules that have been processed by recipient APCs
  • The donor MHC molecules are presented as peptides in the context of recipient MHC class II molecules
  • The indirect pathway is important during chronic rejection (when the number of donor professional APCs is low to simulate a direct immune response)

Question 14

NK cells may be recruited at two points at least during the virus infection. They exhibit an innate (early in the course of infection) antiviral role following activation by epithelium derived ____. At a later stage of infections, NK cells are activated by

Answer 14

• IFN-alpha (early)
• Cytokines IFN-gamma and IL-2 produced by Th1 cells specific for the virus (Late)

Question 15

After resolution of the infection, virus-specific memory T and B cells reside long term in

Answer 15

lymph nodes, spleen, and bone marrow

Question 16

Innate immunity to intracellular bacteria

Answer 16

• is mediated by phagocytes and NK cells interactions among which are mediated by IL-12 (DCs and Macrophages) and IFN-gamma (NK cells). May control bacterial growth, but elimination of the bacteria requires adaptive immunity

Question 17

Adaptive immunity for intracellular bacteria infection

Answer 17

• adaptive immunity is cell-mediated immunity (CTLs) in which Th1 cell-produced IFN-gamma activates phagocytes to eliminate the microbes

Question 18

Activated DCs and Macrophages produce ___ and ___ which activate NK cells

Answer 18

IL-12, IL-15

Question 19

Fungi infections are recognized by _____ binding the PAMPs

Answer 19

• PRRs (TLRs and C lectin-like receptors)
• (note the detection of beta-glucan by dectin 1 is also important)

Question 20

What helper cells are the most important for fungal infections

Answer 20

Th1

Question 21

What is the major receptor involved in the non0psonic recognition of fungi

Answer 21

Mannose receptor (MR)

Question 22

____ is a specific receptor for beta-glucans expressed on macrophages

Answer 22

Dectin-1

Question 23

_____ are polysaccharide PAMPs that contain only glucose as structural components

Answer 23

beta-glucans

Question 24

DECTIN-1 binds and internalizes beta-glucans and mediates the production of reactive oxygen species (ROS), activation of _____ and subsequent secretion of proinflammatory cytokines

Answer 24

NF-kB

Question 25

Question 26

Question 27

Question 28

Question 29

Question 30