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immunology y2 RDT > Immunology 2 > Flashcards

Immunology 2 Flashcards

1
Q

When are organs transplanted?

A

Organs are transplanted when they are failing or have failed, or for reconstruction.

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2
Q

What are the 2 types of transplants? (with respect to effects on life)

A

Life saving or life-enhancing

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3
Q

What are life-saving transplants?

A

• Done when other life support methods have reached end of their use • Done when other methods that have been used can no longer be used E.g. liver, heart (left ventricular assist device) and small bowel (TPN- total parenteral nutrition)

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4
Q

What are life enhancing transplants?

A

• Done when other life support methods are less beneficial/ sustainable e.g. kidney dialysis. • Another organ is not vital for these patients but it will enhance their lives- e.g. cornea transplant or reconstructive surgery

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5
Q

What are autografts and give some example

A

Autografts- within the same individual (this can include stem cell therapy as well as more obvious ones like coronary bypass)

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6
Q

What are isografts?

A

Between genetically indentical individuals of the same species

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7
Q

What are allografts?

A

Between different individuals of the same species

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8
Q

What are xenografts?

A

Between individuals of different species (e.g. skin or heart valves)

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9
Q

What are prosthetic grafts?

A

Using plastic or metal.

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10
Q

What sort of organs can be allograft transplanted?

A
  • Solid organs (kidney, liver, heart, lung, pancreas)
  • Small bowel
  • Free cells (bone marrow, pancreas islets)
  • Temporary: blood, skin (burns)
  • Privileged sites: cornea
  • Framework: bone, cartilage, tendons, nerves
  • Composite: hands, face, larynx
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11
Q

Give some examples of organs and their reasons for failure

A
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12
Q

What are the 2 types of allograft donors?

A

Deceased donor or living donor

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13
Q

What can living donors donate?

A

Bone marrow, kidney, liver. Can be genetically related or unrelated (e.g. spouse)

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14
Q

What are the 2 types of deceased donors? and what is the main difference between them

A
  1. DBD- deceased-brain death (heart beating- brain dead but circulation is reestablished)
  2. DCD- deceased- cardiac death (heart not beating)
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15
Q

What is deceased brain death?- when does it occur

A

Brain injury/ damage has caused death before terminal apnoea has resulted in cardiac arrest- e.g. intracranial haemorrhage or road traffic accidents.

The apnoeic coma is not due to depressant drugs, hypothermia, NM-blockers, metabolic or endocrine disturbances

Circulation is established through resuscitation and death is confirmed through neurological criteria-i.e. demonstrate that there is lack of brain stem function (no cranial nerve reflexes like pupillary reflex, gag reflex, motor response to cranial nerves, no respiratory movements on disconnection from ventilator)

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16
Q

What is DCD and when does it occur?

A
  • Death is confirmed using the cardio-respiratory criteria
  • Controlled- patients with injuries or conditions so severe to justify withdrawal of life-sustaining cardiorespiratory treatments on the grounds of best interests.
  • Uncontrolled- no successful resuscitation
  • Long period of warm ischaemia time
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17
Q

What do you need to exclude the possibility of with deceased donors?

A

Malignancy

Drug abuse/ overdose/ poison

Disease of the transplanted organ

Viral infection

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18
Q

What are the things you have to take into account when thinking about organ allocation

A
  • Waiting time
  • HLA match and age combined
  • Donor-recipient age difference
  • Location of patient relative to donor
  • HLA-DR homozygosity
  • HLA-B homozygosity
  • Blood group match
19
Q

What are some strategies to increase transplantation?

A
  • Increased deceased donation- marginal donors – i.e. elderly with several comorbidities
  • Increased living donation- transplantation across tissue compatibility barriers and potentially thinking about organ swaps for better tissue matching
  • Thinking about new methods- xenotransplantation or stem cell research
20
Q

What are the 2 main protein variations that can stimulate immune responses to transplantation?

A

ABO groups

HLA- coded on chromosome 6 codes for MHCs

21
Q

What are ABO blood groups?

A

A and B proteins (with carbohydrate chains) are found on the surface of RBCs and they are also found in the endothelial lining of blood vessels in the transplanted organ.

People who do not have A and/or B antibodies have naturally occurring AB antibodies

22
Q

What are ABO’s expressed?

A

They are expressed on the surface of blood cells and on the lining of the endothelial cells.

23
Q

What happens if you donate an organ to someone from different blood groups

A

A heart donation from a blood group B donor will have cells expressing blood group B carbohydrate complexes. If it is donated to someone who is group A (with anti-B antibodies), the anti-B antibodies will bind to the B blood group antigens on donor endothelium.

This is antibody-mediated rejection.

24
Q

When are ABO-incompatible transplantations done?

A

Antibodies in the recipient are removed

There will be a good outcome

It is done for kidneys, liver and heart

25
Q

What are HLA’s?

A

They are cell-surface proteins which are highly variable throughout the population.

Foreign proteins are presented to immune cells by antigen-presenting cells in the context of HLA molecules. The HLA lets the immune system know that it is “self” cells.

They are cell-surface proteins.

26
Q

What are the 2 different classes of HLA molecules?

A

Class I- A, B, C expressed on all cells

Class II- (DR, DQ, DP)- expressed on antigen-presenting cells

HLA molecules are highly polymorphic, and each person has most often 2 types for each HLA molecule (mum and dad).

27
Q

What is rejection of transplant?

A

The immune reaction can cause immune graft damage and failure- i.e. rejection of the transplant.

28
Q

How is organ rejection confirmed?

A

When rejection occurs, a diagnosis is confirmed by taking a graft biopsy and treatment is immunosuppressive drugs.

29
Q

What are the 2 types of rejection?

A
  • T cell mediated rejection
  • Antibody mediated rejection
30
Q

What is t cell mediated rejection?

A

APCs meet t cells in circulation. APCs are carrying fragments of the donor’s HLAs. T cells become activated.

Lymphocytes rupture the tubular basement membrane (by the tether, roll, arrest and diapedesis). T cells accumulate in the interstitial area (causing inflammation), tubulitis and local organ damage.

Graft is infiltrated by allo-reactive CD4+ cells.

31
Q

What role do CD8+ t cells do in t- cell mediated rejection?

A
  • kill the target (granzyme B)
  • punch holes in the target cells (perforin)
  • Induce apoptotic cell death (Fas-L)
32
Q

what do macrophages do in t-cell mediated rejection?

A

Phagocytose

Release proteases

Produce cytokines

Oxygen/ nitrogen radicals

33
Q

What is antibody mediated rejection?

A

This is when antibodies are made against the graft HLA and AB antigen.

34
Q

What are the 2 ways antibodies can arise?

A
  • Pre-transplantation (sensitised)- patient has already been exposed to that HLA before either via pregnancy or previous transplants
  • Post-transplant (de novo)
35
Q

What do antibodies do?

A

Recruit complement and activate the complement pathway.

They recruit inflammatory cells (Fc receptors)

After this macrophages are ready to go and start their function.

36
Q

How are kidneys monitored for post-transplant rejection?

A

rise in creatinine, fluid retention, hypertension

37
Q

How are liver transplants checked for rejection?

A

rise in LFT stats (bloods to measure enzymes released from the liver if damage), coagulopathy and biopsies

38
Q

How are heart transplants checked for rejection?

A

breathlessness and pulmonary infiltrate

39
Q

What are the 2 types of immunosuppressive drugs and what are some examples?

A

Target T cell activation and proliferation- anti CD4 Abs, JAK3 inhibitors, azathioprine, cyclosporine

Target B cell activation and proliferation, and antibody production- splenectomy, anti CD20 antibodies, Bortezomib (proteasome inhibitor), anti-C5, IV immunoglobin plasma exchange (IVIG).

40
Q

When are immunosuppressives given?

A
  1. Pre-implantation- induction agent causing T-cell depletion or cytokine blockade
  2. Base-line immunosuppression- signal transduction blockade (CNI inhibitors like cyclosporine), antiproliferative agents (azathioprine) and corticosteroids.
  3. If needed- treatment of episodes of acute rejection- t-cell mediated (steroids, anti-t agents) and antibody mediated- IVIG, plasma exchange, anti CD20 anti-complement
41
Q

What are the problems associated with immunosuppression?

A

Infections, tumours and drug toxicity

42
Q

What sort of infections are you at risk of post-transplant

A
  1. Conventional infections- bacterial, viral and fungal
  2. Opportunistic infections- Cytomegalovirus, BK virus, Pneumocytis carinii. These are normally harmless infections but are severe if immunosuppressed.
43
Q

What are some malignancies you can get post-transplant?

A
  • Skin cancer
  • Post-transplant lymphoproliferative disorder – Epstein Barr virus driven
  • Kaposi’s sarcoma

immunology y2 RDT (2 decks)

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