Immunology Pt 2- (p123-133- Transplants, HIV and Memory) Flashcards
What is an isograft?
Transplant from a twin
What is an allograft?
From the same species
What is a xenograft?
From different species
What is a split graft?
Shared by two recipients
What can a living donor donate?
Bone marrow, kidney, liver
What are the 3 stages of transplant rejection?
Recognition -> activation -> effector function
What is the difference between T cells and B cells in terms of recognising antigen?
T cells recognise antigen with MHCs on APCs
B cells can recognise just antigen
In a transplant, what are the 2 types of recognition?
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.
What does the activation phase of the immune response to a transplant consist of?
Activation of antigen-specific lymphocytes; proliferation and maturation of B cells with Ab production
What does the effector phase of graft rejection consist of?
- Graft infiltration by alloreactive CD4+ cells
- Cytotoxic T cells- release of toxins to kill target, punch holes in target cells, apoptotic cell death
- Macrophages- phagocytosis, release of proteolytic enzymes, production of cytokines, production of oxygen and nitrogen radicals
- Abs bind to graft endothelium
How are transplants matched to donors?
Determination of donor and recipient blood group and HLA type (PCR)
Check recipients Ab against ABO and HLA- via CDC, FACS
Cross-match
What post transplantation complications are there?
Infection- conventional and opportunistic
Malignancy
Atherosclerosis
What is the pathogenesis of HIV?
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
What is the immune response to HIV?
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
How does HIV remain infectious even when coated in antobodies?
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.
How long is the median time from infection with HIV to development of AIDS?
8-10yrs
How is HIV diagnosed?
Screening Test- Detects anti-HIV Ab via ELISA
Confirmation- Detects Ab via western blot
Why is there a need to be wary when testing for HIV?
A positive test requires the pt to have seroconverted (started to produce Ab)- happens after around 10w incubation
What tests are carried out after HIV diagnosis?
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
HIV treatment?
Commence once diagnosed
HAART (Highly active anti retroviral therapy)- 2NRTIs + PI (or NNRTI) e.g. emtricitabine, tenofovir + efavirenz
HIV treatment in pregnancy?
Zidovudine
Antepartum PO; IV for delivery
PO to newborn for 6/52
Types of antiretrovirals in HIV?
Attachment inhibitors Fusion inhibitors RT inhibitors NRTI, NNRTI, NtRTI Integrase inhibitors Protease inhibitors
What is immune memory?
Feature of adaptive immune system- pool of antigen specific cells following infection with enhanced ability to a second infection
What vaccines do children receive?
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
What is herd immunity?
If enough people are immunised, it is difficult for the disease to spread amongst those that aren’t
What are the 4 features of a good vaccine?
Good protection
Single injection
No adverse effects
Easy storage
How can you ensure good response to a vaccine to generate effective memory?
Live vaccine
More persistent antigen
Assisted activation of immune response
Why doesn’t vaccination work effectively in the elderly?
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
What are the 4 different types of vaccine?
Live (attenuated)- (weakened) live bacteria
Inactivated- destroyed pathogens, not able to replicate
Subunit- antigenic proteins
Conjugated- polysaccharide and protein
What do adjuvants do?
Increase immune response without altering its specificity- e.g. slowly release antigen
What is the Mantoux test?
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
