immunology remember Flashcards
how do Tregs suppress
- metabolic disruption – they out compete T cells for IL-2 as they have a high affinity alpha chain, giving them a high affinity IL-2 receptor. they also prevent CAMP from killing infected cells, disrupting normal T cell metabolism
- cytolysis – they can destroy T cells through perforin and granzyme
- suppressive cytokine production - IL-10, 35 and TGF-beta.
—– IL-10 suppresses T cell cytokine production and decrease MHC expression
—— IL-35 suppresses T cell proliferation
——- TGF-beta blocks T cell cytokine production, division, and has a killing ability - CTLA-4 binding – this is a co-inhibitory molecule. it binds with high affinity to CD80/86 on APCs, competing with T cells which express CD28 (binds to CD80 on APCs) which means these T cells are turned off. also induces DCs to produce molecules which are toxic to T cells
describe IPEX
systemic autoimmunity. patients lack the foxp3, which is necessary for Treg function and development. the patients are unable to suppress the immune function against good bacteria in the gut. this leads to a leaky gut and gut inflammation. treatment = bone marrow transplant
describe features of memory B cells
- express high affinity AB which have undergone class switching
- express high levels of MHC-II and co-stimulatory molecules
- populate the spleen and lymph nodes
- express surface Ig, but not antibody
- secrete antibody rapidly and differentiate into plasma cells when they re-encounter antigen
describe features of memory T cells
- different activation requirements and cell surface proteins from naive T cells
- cytokines IL-7 and 15 are needed for survival
- need contact with self peptide:MHC complexes to continue to proliferate
- divide more frequently than naive T cells
- proliferate at lower antigen doses
- require less co-stimulation for activation
- produce cytokines faster.
- may be strategically positioned in the tissue where they may encounter the pathogen
what is the difference between central memory T cells and effector memory T cells
central memory:
- have lymph node homing moleucles
- slower than effector cells to produce cytokines
effector memory:
- lack lymph node homing molecules
- rapidly produce cytokine upon antigenic stimulation
viral disease standard nz vaccines
hhpr mmr
h - hepatitis B
h - hpv
p - polio
r - rota virus
m - measles
m - mumps
r - rubella
bacterial disease standard nz vaccines
dtwhp
d - diphtheria
t - tetanus
w - whooping ocugh
h - haemophilus influenza type B
p - pneumococcal disease
what does INFANRIX-HEXA protect against
dtaphph
d - diphtehria
t - tetanus
a - acellular pertussis
h - hepatitis b
p - polio
h - haemophilus influenza
what is the adjuvant in INFANRIX-HEXA and why is it used
alum is the adjuvant. this stimulates PRRs through acting as a DAMP. it activates the inflammasome to increase the immune response
how does HPV cause cancer
- persistent infection
- integration of virus into host genome and increase expression of oncogenes E6 and E7
— E6: can block apoptosis through p53 degradation, resulting in the outgrowth of dysregulated cells
—- E7: inhibits RB, causing dysregulation of cellular proliferatoin and apoptosis induction
describe the HPV vaccine
this is gardasil. it contains VLPs of the recombinant major capsid protein (L1). they are produced in recombinant yeast and then self assembled into VLPs
the adjuvant is AAHS.
describe central tolerance in B cell development and negative selection processes
this is initial testing of the BCR on immature B cells.
if there is no self-reactivity, they move to the periphery and mature
if they self-react, they undergo negative selection
—– 1. anergy: unresponsiveness or paralysis of function
——2. elimination through apoptosis
——3. rescue by receptor editing – there is the continued expression of RAG which can allow BCRs to continue light chain rearrangement and alter specificity to potentially become non-reactive to self
describe central tolerance in T cell development
self reactive cells with MHC, and with self antigen are removed.
little/weak response – death by neglect
fine – positive selection
too strong – negative selection
AIRE is a TF which allows transcription to create a peripheral shadow in the thymus, which is what allows for the tolerance testing.
describe peripheral tolerance in T cell development and where each occurs
- anergy – cellular inactivation by weak signalling without a co-stimulus. happens in secondary lymphoid tissue
- Tregs – suppression by cytokines and intracellular signals. in secondary lymphoid tissue and sites of inflammation
- functional deviation – autoreactive T cells are induced to become Tregs. happens in secondary lymphoid tissue and sites of inflammation
- activation of induced cell death – through apoptosis. occurs in secondary lymphoid tissue and sites of inflammation
describe the condition resulting as a breakdown of central tolerance
APECED.
this is the failure of multiple endocrine glands and results in chronic mucucutaneous candidiasis.
this is the result of an AIRE deficiency. normally, there would be enough AIRE to express self antigen in the thymus to identify autoreactive T cells. deficiency means the auto reactive T cells can escape.
patients have autoimmunity with auto-antibodies against IL-17. Th17 cells secrete IL-17 and is important for protection against fungal infectoins. IL-17 is getting mopped up by auto reactive T cells before it can exert its function. explains chronic mucocutaneous candidiassis.
immunodeficiency to fungal infections.
