Immunology Pt 2- (p123-133- Transplants, HIV and Memory)

Question 1

What is an isograft?

Answer 1

Transplant from a twin

Question 2

What is an allograft?

Answer 2

From the same species

Question 3

What is a xenograft?

Answer 3

From different species

Question 4

What is a split graft?

Answer 4

Shared by two recipients

Question 5

What can a living donor donate?

Answer 5

Bone marrow, kidney, liver

Question 6

What are the 3 stages of transplant rejection?

Answer 6

Recognition -> activation -> effector function

Question 7

What is the difference between T cells and B cells in terms of recognising antigen?

Answer 7

T cells recognise antigen with MHCs on APCs

B cells can recognise just antigen

Question 8

In a transplant, what are the 2 types of recognition?

Answer 8

Direct- Donor APC presenting antigen and/or MHC to recipient T cells. Acute rejection mainly involves direct presentation

Indirect- Recipient APC presenting donor antigen to recipient T-cells- immune system working normally as it would for infection. Chronic rejection.

Question 9

What does the activation phase of the immune response to a transplant consist of?

Answer 9

Activation of antigen-specific lymphocytes; proliferation and maturation of B cells with Ab production

Question 10

What does the effector phase of graft rejection consist of?

Answer 10

1. Graft infiltration by alloreactive CD4+ cells
2. Cytotoxic T cells- release of toxins to kill target, punch holes in target cells, apoptotic cell death
3. Macrophages- phagocytosis, release of proteolytic enzymes, production of cytokines, production of oxygen and nitrogen radicals
4. Abs bind to graft endothelium

Question 11

How are transplants matched to donors?

Answer 11

Determination of donor and recipient blood group and HLA type (PCR)
Check recipients Ab against ABO and HLA- via CDC, FACS
Cross-match

Question 12

What post transplantation complications are there?

Answer 12

Infection- conventional and opportunistic
Malignancy
Atherosclerosis

Question 13

What is the pathogenesis of HIV?

Answer 13

RNA retrovirus which targets CD4+ T helper cells as hosts

Replicates inside cells using reverse transcriptase to convert RNA into DNA which integrates into host cell’s genes

Question 14

What is the immune response to HIV?

Answer 14

Innate- non-specific activation of macrophages, NK cells and complement, stimulation of dendritic cells via TLR + release of cytokines and chemokines

Adaptive- neutralising antibodies (anti-gp120 and anti-gp41), non neutralising antibodies (anti-p24), CD8+ T cells can prevent HIV entry by producing chemokines MIP-1a,1b and RANTES

Question 15

How does HIV remain infectious even when coated in antobodies?

Answer 15

Activated infected CD4+ helper T cells are killed by CD8+ T cells, so the CD4+ are anergised and CD4 T cell memory is lost and failure to activate memory CTL.
This means monocytes and dendritic cells aren’t activated and can’t prime naive CD8 CTL. These infected monocytes and dendritic cells are killed by virus or CTL.
HIV also produces quasispecies through reverse transcriptase so can escape from immune response.

Question 16

How long is the median time from infection with HIV to development of AIDS?

Answer 16

8-10yrs

Question 17

How is HIV diagnosed?

Answer 17

Screening Test- Detects anti-HIV Ab via ELISA

Confirmation- Detects Ab via western blot

Question 18

Why is there a need to be wary when testing for HIV?

Answer 18

A positive test requires the pt to have seroconverted (started to produce Ab)- happens after around 10w incubation

Question 19

What tests are carried out after HIV diagnosis?

Answer 19

Viral load- PCR used to detect viral RNA (very sensitive)
CD4 count (flow cytometry)- to assess course of disease and onset of AIDS (<200cells/ul)
Resistance testing

Question 20

HIV treatment?

Answer 20

Commence once diagnosed

HAART (Highly active anti retroviral therapy)- 2NRTIs + PI (or NNRTI) e.g. emtricitabine, tenofovir + efavirenz

Question 21

HIV treatment in pregnancy?

Answer 21

Zidovudine
Antepartum PO; IV for delivery
PO to newborn for 6/52

Question 22

Types of antiretrovirals in HIV?

Answer 22

Attachment inhibitors
Fusion inhibitors
RT inhibitors
NRTI, NNRTI, NtRTI
Integrase inhibitors
Protease inhibitors

Question 23

What is immune memory?

Answer 23

Feature of adaptive immune system- pool of antigen specific cells following infection with enhanced ability to a second infection

Question 24

What vaccines do children receive?

Answer 24

Diptheria
Tetanus
acellular Pertussis
Inactivated Polio
Haemophilus influenza type b
Hep B 
Meningitis B + C
Men ACWY
MMR
Pneumococcal
Rotavirus gastroenteritis
HPV (girls 12-13)
Flu

Question 25

What is herd immunity?

Answer 25

If enough people are immunised, it is difficult for the disease to spread amongst those that aren’t

Question 26

What are the 4 features of a good vaccine?

Answer 26

Good protection
Single injection
No adverse effects
Easy storage

Question 27

How can you ensure good response to a vaccine to generate effective memory?

Answer 27

Live vaccine
More persistent antigen
Assisted activation of immune response

Question 28

Why doesn’t vaccination work effectively in the elderly?

Answer 28

Immune senescence- increased frequency of terminally differentiated effector memory T cells, increased expression of senescence markers and reduced production of thymic emigrants

Nutrition- insufficient energy due to poor nutrition

Question 29

What are the 4 different types of vaccine?

Answer 29

Live (attenuated)- (weakened) live bacteria
Inactivated- destroyed pathogens, not able to replicate
Subunit- antigenic proteins
Conjugated- polysaccharide and protein

Question 30

What do adjuvants do?

Answer 30

Increase immune response without altering its specificity- e.g. slowly release antigen

Question 31

What is the Mantoux test?

Answer 31

Injection of 0.1ml of tuberculin intradermally
If 48-72h later, there is induration of at least 10mm, this implies previous exposure to tuberculin protein so could represent previous BCG exposure