W7- Lecture 34- Self-Recognition Tolerance and Hypersensitivity

Question 1

name the 7 stages of the innate immune system

Answer 1

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

Question 2

name 4 types of Non-specific defences

in the adaptive immune system

Answer 2

Epithelium
Tears
Stomach acid
Urine

Question 3

describe cytotoxic t cell activation

Answer 3

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

Question 4

what is tolerance in terms of the immune system

Answer 4

Tolerance describes immune cell non-reactivity to antigens.

Question 5

name the three types of tolerance

Answer 5

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.

Question 6

describe the selection of t cells in the thymus

Answer 6

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

Question 7

describe how mature t cells are activated outside of the thymus

Answer 7

the t cells recognise an antigen
then are co-timulated by a t helper cell
which leads to proliferation and differentiation

Question 8

Describe the selection of b cells

Answer 8

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

Question 9

name three examples of Acquired tolerance

Answer 9

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.

Question 10

what are the 4 types of Hypersensitivity

Answer 10

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)

Question 11

how long is each of the hypersensitivity types onset

Answer 11

1 30 mins
2 days
3 6-8 hours
4 48-72 hours

Question 12

what are the general properties of allergens

Answer 12

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

Question 13

describe the organ manifestation of type 1 hypersensitivity distribution

Answer 13

skin/mucosa 45%
resp tract 25%
gastrointestinal tract 20%
cardiovascular system 10%

Question 14

name an example of a Type 1 IgE mediated hypersensitivity

Answer 14

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

Question 15

Describe the action of a protease mediated type 1 IgE hypersensitivity

Answer 15

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

Question 16

Describe the interaction of IgE molecules and mast cells

Answer 16

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

Question 17

describe 3 effects of mast cell activation / granule release

Answer 17

gastro- increase fluid secretion + increased peristasis
resp tract- decreased diameter + increased mucus secretion
cardiovascular- increased blood flow + increased permeability

Question 18

what are the symptoms of upper/lower airway allergic rhinitis/ asthma

Answer 18

Upper airways: rhinitis
nasal itch;
Sneeze;
Rhinorhoea;
nasal obstruction.

Lower airways: asthma 
bronchoconstriction, mucus hypersecretion;
Wheeze;
Breathlessness;
Cough.

Question 19

what effect does allergic rhinitis/ asthma on the airways ?

+ treatment

Answer 19

fibrosis - damage(from lymphocytes and eosinphils) and remodeling of airway with collagen

Airway remodelling hyperplasia/
hypertrophy

Question 20

what is anaphylaxis ?

+ treatment

Answer 20

Catastrophic lowering of blood pressure, airway constriction, swelling of epiglottis

Epinephrine relaxes bronchiole smooth muscle

Question 21

what mutations in mast cells cause the following conditions ?
1Cold induced urticaria-
2phospholipid enzyme mutation
3vibrational urticaria

Answer 21

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

Question 22

what two compounds that cause Eosinophils degranulation and eventually airway remodelling

Answer 22

large amounts of IL5 / IL3

Question 23

Why is allergy on the increase?(3)

Answer 23

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)

Question 24

what is Atopic dermatitis ?

Answer 24

Chronic inflammation (initiated via IgE),  apopotosis of keratinocytess.
Leaky skin (filaggrin defect) binds keratin fibres together (leaky skin-allergens

Question 25

what is Non IgE allergic diseases: Type 2 hypersensitivity ?

Answer 25

Antibodies attach to epitopes on self cells

Induces activation of compliment

Results in vasodilatation and migration of phagocytic cells to the effected tissue.

Promotes activation of membrane attack complex.

Question 26

what disorders is type two hypersensitivity often related to ?

Answer 26

destruction of blood cells/platelets-autoimmune hemolytic anemia. Hemolytic disease of the newborn Thrombocytopenia.

Question 27

describe the pathway of type 3 of hypersensitivity

Answer 27

injected antigen in an immune individual
complement is activated
C5a binds and sensitises the mast cells to respond
mast cells are activated and this induces degranulation

Question 28

what is type 3 hypersensitivity caused by ?

Answer 28

antigen antibody complexes.

Question 29

what are the 2 types of type 3 hypersensitivity ?
+ explain
+ example

Answer 29

Local form Type 3 Hypersensitivity
If an individual is immunised against an antigen, subcutaneous injection of a high concentration of that antigen induces an inflammatory response peaking within seven hours at that site.

Example - inhaled spores causing extrinsic allergic alveolitis.

Systemic form Type 3 Hypersensitivity
Antigen complexes may form systemically - promoting system wide inflammatory responses.

Example – Post infectious glomerulonephritis - antibody complexes become stuck in the glomeruli of the kidney inducing an inflammatory response. Can be caused by any bacterial infection, but most common complication with streptococcal pharyngitis

Question 30

what is the pathway of delayed hypersensitivity aka type 4

Answer 30

antigen is injected and processed by a APC
T helper cell recognises antigen and releases cytokines which act on vascular endothelium
recruitment of phagocytes+ plasma causes legion

Question 31

what is Allergic contact dermatitis ?

Answer 31

T-cell (Th1 cell) mediated (type 4)

Important cause of occupational disease

Hapten (low molecular weight agents, not immunogenic on its own - only if combined with a protein (carrier)

Poison ivy complex of urushiol-derivatives

Question 32

what allele is common with Coeliac disease?

Answer 32

95% patients have HLA-DQ2 class II MHC allele
Binds α-gliadin (derivatised by transglutaminase-enzyme)

Question 33

describe the process of Cellular destruction in Coeliac disease

Answer 33

peptides from gluten unable to bind to MHC2
enzyme tTG modifies peptides so how can bind with MCH2
this activates gluten specific CD4 T cells
the CD4 T cells destroy mucosal epithelial cells by binding Fas

Question 34

what is the immune reactant for each type of hypersensitivity ?

Answer 34

1IgE
2IgE
3IgE
4 T helper cells

Question 35

where is the antigen found or each type of hypersensitivity ?

Answer 35

1 soluble
2 cell matrix / Cell surface membrane
3 soluble
4soluble / cell associated

Question 36

what type of hypersensitivity is the following related to? 
graft rejection 
allergic constant dermatitis 
anaphylaxis 
chronic urticaria 
arthus reaction 
serum sickness

Answer 36

4graft rejection 
4allergic constant dermatitis 
1anaphylaxis 
3chronic urticaria 
2arthus reaction 
2serum sickness