biomed 4.2-4.4 (2)

biomed 4.2-4.4

national organ transplant act:

• no sale of human organs are legal

• medical urgency only considered for heart, liver, intestine

• no celeb status will make/ break getting a transplant

• test for HIV is positive, but asymptomatic = should still be able to get transplant

organ yes or no:

• compatibility b/w organ and recipient

• distance b/w organ and recipient

• time on a waiting list

• age of recipient (preference to children)

**Rh is negative or positive- a+, b- blood

• rh+ can recieve rh+ or rh - (d antigen)

• rh- can recieve rh- (PLASMA DOES NOT CONTAIN ANTI D AGGLUTINATS AKA ANTIBODY)

agglutinogen- ANTIGEN

agglutinin= ANTIBODY

Rh typing uses a method similar to ABO typing. When blood typing is done to see if you have Rh factor on the surface of your red blood cells, the results will be one of these:

• Rh+ (positive), if you have this cell surface protein

• Rh- (negative), if you do not have this cell surface protein

agglutination: detect certain antibodies/ antigens

antigen~ substances the body does not recognize (trigger response)

antibody~attach to the antigens on membrane, cause them to trigger response

• bc antibody has 2 arms, it can grab 2 diff rbc at once~ linking the cells together= agglutination

• EX. if blood has a antigen, anti-a antibody will bind to a antigens (bc it is not foreign) and CLUMP

**humans have several antigens located on surface of leukeocytes

• HLA~ stimulates immune response to recognize tissue as self vs non self

  • controlled by set of genes located next to each other on chromosome 6

HLA typing test/ tissue typing: which HLA antigens are present 

• similarity b/w antigens in donor and recipient

**NECESSARY BEFORE KIDNEY TRANSPLANT

HLA antigens:

• Class I Antigens (HLA-A, HLA-B, HLA-Cw)

• Class II Antigens (HLA-DR, HLA-DQ, HLA-DP) 

When performing an HLA typing test for a kidney transplant, the following HLA antigens are important:

• HLA-A

• HLA-B

• HLA-DR

MHC= HLA antigen

TEST:

6 HLA antigens (HLA-A, B, DR  x2) are examined~ each person has 2 (1 from mom one from dad)

• which of these 6 are similar b/w donor and recipient~ closeness of tissue match

• 6 is best~ occurs 25% of time b/w siblings who have same mom/dad

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• Traditional method: Blood tested with known antibodies to see which HLA antigens are present.

• Modern method: DNA is isolated → PCR amplifies → HLA genes identified precisely.

• This shows a person’s unique HLA profile, used to match them with donors.

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once theyve been matched thru hla, next step os antibody screening 

(PRA)

organ recipients serum is mixed w cells from 60 PPL- how ppl their immune system would attack

• how reactive someone 

• 0% =lots of potential donors

cross match

small amount of donors white blood cells are mixed w recipient serum

• see if the donor’s HLA will cause reaction w recipient

POSITIVE: reaction occurs- transplant not performed

NEGATIVE: no reaction- transplant can be performed

innate immunity- fast, non specific (RECOGNIZES FIRST)

• inflammation, wbc rush in

• recognizes general signs of foreignness

adaptive immunity- slower, specific

• t and b cells make non self HLA protiens on donor organ

• t cells destroy donor cells, b cells make antibodies - attack organ

Three main strategies:

• Tissue Typing (HLA Matching):

  • The closer the match between donor and recipient, the less likely the immune system will attack.

• Immunosuppressants:

  • Drugs like cyclosporine and tacrolimus.

  • Weaken the immune system to prevent rejection.

  • Must be taken for life- but increase risk of infections.

  • Risks: infections, cancer (due to weakened immune surveillance), kidney toxicity.

• Patient Monitoring:

  • Regular tests to watch for signs of rejection or infection.

  • PRA testing, blood tests, biopsies of the organ.

UNOS (united network for organ sharing)

national organ transplant act 

• no organ selling

• national waitlist/ matching systems

Ethical Considerations

• Allocation fairness:

  • Who gets priority? Based on urgency, time on list, match quality, age?

• Consent:

  • Must be informed and voluntary (opt-in vs. opt-out systems vary by country).

• Donation after brain death vs. circulatory death:

  • Raises ethical issues, especially in pediatric or vulnerable populations.

• Equity concerns:

  • Racial minorities often have less access to transplants due to HLA differences and socioeconomic disparities.

kidney transplants:

nephrectomy: donor’s kidney is removed

• long incision

• rib removal (sometimes)

ADVANCES: laparoscropic nephrectomy~ minimally invasive kidney removal

laparoscopy= small cylindrical tubes (tocars) enter abdominal cavity- camera called laparoscope views inside of abdominal cavity- remove the organ in sections through the small holes

sutures

anesthesia

donatable organs and tissues- eyes, skin, lungs, liver, heart/ heart valves, pancreas, kidneys, small intestine, bone/ bone marrow, tendons

nondonatable- brain, liver tissue, muscle tissue, hair 

xenotransplantation: transplanting organs/ tissues from ONE SPECIES to ANOTHER (usually oigs to humans)

• genetically modify pigs- make organs more compatible

• gene editing using CRISPR is used to remove/ alter genes in pigs to make their organs less likely to be rehected

RISKS:

• risk human immune system will always still reject

• pigs caryr virsuses/ bacteria

• animals rights??

BENEFITS:

• organ shortage

• no wait times

• genetic engineering= long term use

tissue engineering: artificial tissues/ organs using biological cells

• grow cells (usually from patient) on a scaffold made of collagen, synthetic polymers

• cells grow over time, form tissues that can be used in transplants + scaffold dissolves naturally 

RISKS:

• rejection if new tissue isnt recognized (ALWAYS A RISK)

• infection- not sterilized/ grown

BENEFITS:

• tissue from patients own cells- risk of rejection DOWN

• avoid need for transplant

• infinite supply- mass prodyction

bioprinting: 3d printers to print living cells layer by layer

TYPES OF STEM CELLS

embryonic

• taken from early stage embryos

• PLURIPOTENT: can become any of 200+ cell types

• removing them destroys embryo

adult stem

• tissues- bone marrow, blood, skin

• MULTIPOTENT: only become certain type of cells (blood, bone, fat, cartilage)

• limited ability

induced pluripotent stem cells

• adult cells reprogrammed to be embryonic

• PLURIPOTENT: can become any of 200+ cell types

• risk of tumors/ immune reactions

therapeutic cloning- CREATE embryo using patients own dna

• extract stem cells, guide them to become organ

CRISPR

molecular scissors 

edit genes in specific cells- remove disease causing mutations + add helpful genes

• conditions like cystic fibrosis, sickle cell anemia, cancer

• editing egg/ sperm can pass to future gen- ethical concern

💊 Immunosuppression (Anti-Rejection Drugs)

1. Induction Therapy

   • Used right after transplant

   • Strong meds to stop immediate rejection (kill or block T cells)

2. Maintenance Therapy

   • Long-term meds to keep the immune system in check

   • Prevents chronic rejection

3. Anti-Rejection Therapy

   • Used if rejection happens

   • Strong drugs to stop inflammation and immune attack