W7- Lecture 34- Self-Recognition Tolerance and Hypersensitivity Flashcards
name the 7 stages of the innate immune system
1Physical barriers keep hazards outside the body
2Phagocytes engulf pathogens and cell debris
3Immunological surveillance by NK cells destroys abnormal cells
4Interferons are chemical messengers that protect against viral infection
5Complement proteins help antibodies destroy pathogens
6Inflammation limits the spread of injury or infection
7Fever accelerates tissue metabolism and cellular activity
name 4 types of Non-specific defences
in the adaptive immune system
Epithelium
Tears
Stomach acid
Urine
describe cytotoxic t cell activation
1 stimulation
Resting T cells express only a moderate-affinity IL-2 receptor
2 proliferation/ differentiation
Activated T cells express a high-affinity IL-2 receptor and secrete IL-2
Binding of IL-2 to its receptor signals the T cell to enter the cell cycle
IL-2 Induces T-cell proliferation
3 effector function
t cells lyse target cells
what is tolerance in terms of the immune system
Tolerance describes immune cell non-reactivity to antigens.
name the three types of tolerance
Self tolerance Tolerance to innate antigens
Neonatal tolerance Antigens encountered within hours after birth are tolerated
Acquired tolerance
a non reactivity to an antigen that should cause an immune response.
describe the selection of t cells in the thymus
the pre- T cells that cannot recognise self MHC (1) go through apoptosis -positive selection
then the t cells that are capable of binding and recognising to self peptides also go through apoptosis - negative selection
describe how mature t cells are activated outside of the thymus
the t cells recognise an antigen
then are co-timulated by a t helper cell
which leads to proliferation and differentiation
Describe the selection of b cells
immature b cells in the bone marrow that can recognise self MHC molecules/self antigens go through apoptosis - negative selection
when a mature b cell recognises an antigen is co-stimuated caused proliferation and differentiation into plasma cells
name three examples of Acquired tolerance
Failure of the immune system to destroy sperm and fertilised eggs
Oral tolerance. – breakdown of oral tolerance could be linked to inflammatory bowel disease.
maternal tolerance theory is the EU- FEDS theory.
what are the 4 types of Hypersensitivity
Type 1 IgE-mediated, immediate type hypersensitivity
(IgE-mediated degranulation of mast cells)
(e.g. allergic rhinitis, allergic asthma, urticaria)
Type 2 Cytotoxic reaction (complement lysis/ADCC)
(e.g. drug allergy)
Type 3 Immune complex reaction- complement activation)
(e.g. allergic vasculitis)
Type 4 T-cell mediated, delayed type hypersensitivity
(e.g. allergic contact eczema)
how long is each of the hypersensitivity types onset
1 30 mins
2 days
3 6-8 hours
4 48-72 hours
what are the general properties of allergens
Small 15-40,000 Mw proteins
Soluble
Long lasting in environment
Low dose of allergen = potent
Mucosal exposure.
Often proteases= tissue damage
Most allergens promote a Th2 immune
describe the organ manifestation of type 1 hypersensitivity distribution
skin/mucosa 45%
resp tract 25%
gastrointestinal tract 20%
cardiovascular system 10%
name an example of a Type 1 IgE mediated hypersensitivity
Dust allergens
Der p 1(protease) can cleave tight junctions (ANT-ZO1 protein )and enter the mucosa
dendritic cells take up der p 1 for antigen presenting and TH2 priming
Describe the action of a protease mediated type 1 IgE hypersensitivity
Der p 1 is example Dendritic cell present as it on cell surface (mhc2) Mhc 2 interacts with with T cell T cell differentiates to th2 T helper cell interacts with B cell Causes activation of B cell into plasma cell as which produce antibodies Code switch to Ige production Leading to over production of Ige
Describe the interaction of IgE molecules and mast cells
IgE (from plasma cells) binds of Fc receptor on mast cells
Mast cells are activated and can provide stimulation to B cells to produce more IgE molecules
describe 3 effects of mast cell activation / granule release
gastro- increase fluid secretion + increased peristasis
resp tract- decreased diameter + increased mucus secretion
cardiovascular- increased blood flow + increased permeability
what are the symptoms of upper/lower airway allergic rhinitis/ asthma
Upper airways: rhinitis nasal itch; Sneeze; Rhinorhoea; nasal obstruction.
Lower airways: asthma bronchoconstriction, mucus hypersecretion; Wheeze; Breathlessness; Cough.
what effect does allergic rhinitis/ asthma on the airways ?
+ treatment
fibrosis - damage(from lymphocytes and eosinphils) and remodeling of airway with collagen
Airway remodelling hyperplasia/
hypertrophy
what is anaphylaxis ?
+ treatment
Catastrophic lowering of blood pressure, airway constriction, swelling of epiglottis
Epinephrine relaxes bronchiole smooth muscle
what mutations in mast cells cause the following conditions ?
1Cold induced urticaria-
2phospholipid enzyme mutation
3vibrational urticaria
1Cold induced urticaria- triggered by NLP3 mutants
2Truncation of inhibitory region PLCG2 (phospholipase enzyme involved in signalling)
3Vibrational urticaria over activation of the GPCR- EMR2
what two compounds that cause Eosinophils degranulation and eventually airway remodelling
large amounts of IL5 / IL3
Why is allergy on the increase?(3)
Hygiene hypothesis
Change to a clean environment in developed countries skews the immune response to a Th2 response(not most accurate)
Th1/inflammatory immune defects are also on the rise (MS, IBD)
what is Atopic dermatitis ?
Chronic inflammation (initiated via IgE), apopotosis of keratinocytess. Leaky skin (filaggrin defect) binds keratin fibres together (leaky skin-allergens
