A-III Immunodeficiency, transplantation Flashcards
What is immunodeficiency?
Immunodeficiency is a condition where the immune defense is impaired, for example, by genetic defects, leading to repeated infections and enhanced susceptibility to malignancies. It can be caused by defects in the innate or adaptive immune systems
What are the two main categories of causes of immunodeficiency?
The two main categories are primary causes (genetics, developmental defect, often inherited, affecting either adaptive or innate immunity) and secondary causes (malnutrition, infection, drugs, irradiation, spleen removal, tumors, HIV).
What are the primary causes of immunodeficiency?
genetics, developmental defect
What are the secondary causes of immunodeficiency?
malnutrition, infection, drugs, irradiation, spleen removal, tumors, HIV
What is SCID and what broad aspect of the immune response does it affect?
SCID stands for severe combined immune deficiency and causes individual to not have adaptive immune system. Lacking MHC Class II often causes SCID-like immunodeficiency or SCID
What immune cell type is primarily affected in X-linked agammaglobulinemia (XLA)?
B-cells are primarily affected in XLA, leading to arrested development in B-cell development due to the inability to signal from pre-BCR to further develop the BCR.
What are the primary defects in Hyper IgM syndrome and what is a key consequence?
The primary defects in Hyper IgM syndrome are CD40L or CD40 deficiency or B-cell intrinsic AID deficiency, leading to no isotype switching. This results in susceptibility to extracellular bacteria and no germinal centers.
What are some examples of defects in the innate immune system and their consequences?
◦ Defects in phagocytes leads to susceptibility to extracellular bacteria and fungi
◦ Defects in complement activation pathways:
▪ Classical pathway (C1, 2, 4) can lead to immune-complex disease (e.g., lupus).
▪Lectin pathway (C2, 4, MBL, MASP1, 2) can lead to bacterial infection.
▪ Alternative pathway (Factor D, P) can lead to severe infection because bacteria.
▪ Defects in C3b deposition (C3) can lead to infection with bacteria, sometimes immune-complex disease.
▪ Defects in MAC (C5-9) can lead to infection with Neisseria spp. only.
What are the main treatment options for immunodeficiencies?
The main treatment options mentioned are gene therapy and stem cell transplantation.
What is a crucial factor to consider in stem cell transplantation to avoid rejection?
The MHC (Major Histocompatibility Complex) needs to match to avoid reaction to the transplant
How does HIV lead to immunosuppression?
HIV infects CD4+ cells via CD4+ and chemokine receptors, leading to a drop in CD4+ cells in the blood below a certain threshold, which is defined as AIDS
What is HAART and how does it treat HIV infection?
HAART (Highly Active Antiretroviral Therapy) blocks virus replication in CD4+ cells
What are some consequences of AIDS besides infections?
People with AIDS are also more likely to develop tumors, indicating that the immune response normally helps in controlling cancer cells
What is an autograft and give an example?
An autograft is when the donor and recipient are the same person. Example: moving skin from one place to another
What is an isograft?
An isograft is a graft between identical twins, which typically has few problem as they share HLA alleles
What is an allograft and how common is it?
An allograft is when the donor and recipient are the same species but different people, and it is the most common type of graft
What is a xenograft and at what level is it primarily used?
A xenograft is when the donor and recipient are not the same species, and it is primarily used at the research level
What is the primary reason for graft rejection in allo- and xenografts?
Allo- and xenografts are always rejected if there is no matching antigens (alloantigens, xenoantigens) that serve as targets for recognition by the recipient’s immune system
What are the two main pathways of alloantigen recognition by the recipient’s T-cells?
Direct recognition: Recipient’s TCR recognizes MHC molecule on the graft as something foreign.
Indirect recognition: Recipient’s DC takes up peptide from allogenic MHC, processes it, and presents it to recipient T-cells.
How do effector T-cells contribute to graft rejection?
Effector T-cells move to the allograft and kill the cells directly (CD8+ T-cells) or secrete cytokines (CD4+ T-cells) leading to macrophage activation and inflammation
Describe hyperacute graft rejection: its timing and mediators.
Hyperacute rejection happens within minutes and is mediated by natural antibodies and the complement system (e.g., reactions to foreign blood types)
Describe acute graft rejection: its timing and mediators.
Acute rejection takes days and is triggered by lymphocytes and antibodies, leading to inflammation of the endothelium
Describe chronic graft rejection: its timing and mediators.
Chronic rejection takes months and involves a chronic inflammatory reaction in the graft vessel wall (like scar tissue), mediated by CD4+ cells.
What is a mixed lymphocyte reaction (MLR) used for?
MLR is used to check if a graft will work or not by mixing blood mononuclear cells from the donor and recipient and seeing if there is a reaction
Why is HLA matching important in transplantation?
MHC (HLA) needs to match between the donor and recipient because there is a lot of variation between MHC molecules, and the immune system will only recognize the ones they are “trained on” as self-MHC. The more alleles that match, the more likely graft survival is.
What is Graft vs Host Disease (GVHD) and when does it occur?
GVHD occurs when transplanting hematopoietic stem cells. T-cells from the graft tissue attack the host, causing inflammation in several places
What factors make finding a “perfect match” for organ transplantation very hard?
The recipient often doesn’t have much time, and blood group and HLA need to match. For some organs, the donor has to be dead and the tissue needs to be transplanted quickly before it degrades
Name an immunosuppressive drug and its mechanism of action
Cyclosporine is an immunosuppressive drug that inhibits IL-2 genes
True or False: Immunodeficiency always affects both the innate and adaptive immune systems
False
True or False: Primary immunodeficiencies are often inherited
True
True or False: SCID primarily affects the innate immune response
False
True or False: X-linked agammaglobulinemia (XLA) affects T-cells
False
True or False: Hyper IgM syndrome can be caused by a deficiency in CD40L or CD40, leading to impaired isotype switching
True
True or False: Defects in the classical pathway of complement activation (C1, 2, 4) can lead to increased susceptibility to Neisseria infections
False
True or False: HAART treatment for HIV works by killing infected CD4+ cells
False
True or False: In an autograft, the donor and recipient are different species
False
True or False: Graft rejection is primarily a concern in autografts and isografts
False
True or False: Direct recognition in graft rejection involves the recipient’s T-cells recognizing processed peptides from the donor’s MHC presented by the recipient’s dendritic cells
False
True or False: Hyperacute graft rejection is mediated by T-cells
False
True or False: Chronic graft rejection can take months to develop and is mediated by CD4+ cells
True
A mixed lymphocyte reaction (MLR) is performed to encourage a strong immune response against a potential graft
False
True or False: Matching more HLA alleles between a donor and recipient increases the likelihood of graft survival
True
True or False: Graft vs Host Disease (GVHD) occurs when the recipient’s immune cells attack the graft tissue
False; its the graft tissue that attack host tissue
True or False: Inbred mice are heterozygous at every genetic locus
False; its the other way around
True or False: For a successful blood transfusion, only the ABO blood group needs to match
False; the rhesus antigen also need to match
True or False: Recipients of organ transplants typically only need immunosuppression immediately after the transplant surgery
False; they need immunosuppression the rest of their life
True or False: Cyclosporine, an immunosuppressive drug, inhibits the production of antibodies.
False; it inhibits IL-2 genes
