Immunology- Self recognition & Tolerance

Question 1

Define Tolerance?

Answer 1

describes immune cell non-reactivity to antigens.

Question 2

Name the 3 different tolerances and define them?

Answer 2

Self tolerance- Tolerance to innate antigens
Neonatal tolerance- Antigens encountered within hours after birth are tolerated
Acquired tolerance

Question 3

What does the breakdown of immunological tolerance leads to?

Answer 3

autoimmune disease

Question 4

What are the 2 things t -cells must undergo to function correctly?

Answer 4

To function correctly T cells have to

1) recognise self MHCs (self recognition), and
2) they must display self tolerance).

Question 5

What type of selection does pre T cells in the thymus develop self recognition?

Answer 5

+ve selection

Question 6

What is Self tolerance acquired by?

Answer 6

negative selection

Question 7

What percentage of t -cells become fully mature immunocompetent cells?

Answer 7

only 1 - 5 % will

Question 8

Define Acquired tolerance?

Answer 8

Describes a non reactivity to an antigen that should cause an immune response.

Question 9

What are some clinical examples of acquired tolerance?

Answer 9

Failure of the immune system to destroy sperm and fertilised eggs
Oral tolerance. Very important – breakdown of oral tolerance could be linked to inflammatory bowel disease.
Main theory explaining maternal tolerance is the so called EU- FEDS theory.

Question 10

Define type 1 hypersensitiivty classification?

Answer 10

IgE-mediated, immediate type hypersensitivity(IgE-mediated degranulation of mast cells)
(e.g. allergic rhinitis, allergic asthma, urticaria)

Question 11

Define type 2 hypersensitiivty classification?

Answer 11

Cytotoxic reaction (complement lysis/ADCC)
(e.g. drug allergy)

Question 12

Define type 3 hypersensitiivty classification?

Answer 12

Immune complex reaction- complement activation)

(e.g. allergic vasculitis)

Question 13

Define type 4 hypersensitiivty classification?

Answer 13

T-cell mediated, delayed type hypersensitivity (e.g. allergic contact eczema)

Question 14

Name the general properties of allergens?

Answer 14

Small 15-40,000 Mw proteins 
Soluble
Long lasting in environment
Low dose of allergen Mucosal exposure. 
Often proteases
Most allergens promote a Th2 immune

Question 15

What percentage occurs in the organ manifestations of type 1 hypersensitivity?

Answer 15

Skin / Mucosa 45 %
Respiratory tract 25 %
Gastrointestinal tract 20 %
Cardiovascular system 10 %

Question 16

What is Type 1 IgE mediated response?

Answer 16

Atopic diseases caused by individuals’ tendency to mount over zealous IgE responses

Question 17

Give an example of an Type 1 IgE mediated response?

Answer 17

Dust allergens.

Question 18

Explain the mechanism for protease mediated type 1 IgE hypersensitivity?

Answer 18

The enzyme Der p 1 cleaves occludln In tight junctions and enters mucosa
Der p 1 is taken up by dendritic cells for antigen presentation and TH2 priming
Dendritic cell primes cell In lymph node
TH2 cell induces B-cell switch to lgE production
Plasma cell travels back to mucosa and produces Der p 1- speciflc lgE antibodies
IgE binds to FcERI receptor on mast cell
Der p 1-speciflc lgE binds to mast cell; Der p 1 triggers mast-cell degranulation
Der p 1-speciflc lgE binds to mast cell; Der p 1 triggers mast-cell degranulation

Question 19

What receptors can Protease mediated type 1 IgE potentially activate?

Answer 19

Protease allergens can potentially activate PAR receptors

Question 20

What effects does Mast-cell activation have on different tissues.

Answer 20

GI Tract -
Increased fluid secretion, increased peristalsis
Expulsion of gastrointestinal tract contents (diarrhea, vomiting)

Eyes, nasal passages, and airways
Decreased diameter, increased mucus secretion
Congestion and blockage of airways (wheezing, coughing, phlegm)
Swelling and mucus secretion in nasal passages

Blood vessels
Increased blood flow, increased permeability
Increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and protein in tissues, increased effector response in tissues

Question 21

Define allergic rhinitis?

Answer 21

IgE mediated reaction to inhaled allergens

Question 22

what occurs in the upper tract when undergoing allergic rhinitis?

Answer 22

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

Question 23

what occurs in the lower tract when undergoing allergic rhinitis?

Answer 23

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

Question 24

Define Urticaria / anaphylaxis?

Answer 24

Direct/rapid route in to blood stream (sting, ingestion)

Route and dose greatly affect out come

Question 25

What effect does urticaria have on the body?

Answer 25

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

Question 26

What relaxes the symptoms of urticaria?

Answer 26

Epinephrine relaxes bronchiole smooth muscle

Question 27

What mutation causes cold induced urticaria?

Answer 27

- triggered by NLP3 mutants

Question 28

What is the role of an eosinophils?

Answer 28

mainly kill parasites via reacting towards opsonised parasites. However large amounts of IL5 / IL3 in allergy cause degranulation

Question 29

What is Atopic dermatitis?

Answer 29

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

Question 30

Define Non IgE allergic diseases: Type 2?

Answer 30

IgG mediated destruction of blood cells/platelets-autoimmune hemolytic anemia. Hemolytic disease of the newborn Thrombocytopenia. Change in signalling

Question 31

How do type 2 cells work?

Answer 31

Antibodies attach to epitopes on self cellsInduces activation of compliment Results in vasodilatation and migration of phagocytic cells to the effected tissue. Promotes activation of membrane attack complex.Used to refer to antibodies that attacked self blood cells, but now is used to describe antibodies that target other tissues.

Question 32

Define Non IgE allergic diseases: Type 3?

Answer 32

IgG immune complex deposition on vessel walls- Arthus reaction Serum Sickness, arthritis, vasculitis, nephritis, farmers’ lung

Question 33

How do type 3 cells work?

Answer 33

Caused by antigen antibody complexes. Antigen can be self antigens (i.e., nuclear material as in Lupus) or non-self antigens such as bacteria.Promotes inflammatory response.

Question 34

What are the two form types of type 3 cells?

Answer 34

Can be either :- Local form Type 3 Hypersensitivity Systemic form Type 3 Hypersensitivity

Question 35

Define local form of type 3 hypersensitivity?

Answer 35

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.

Question 36

Define systemic form of type 3 hypersensitivity?

Answer 36

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 37

What are the stages of delayed hypersensitivity in type 4 cells?

Answer 37

1. Antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells 2. ATH1 effector cell recognizes antigen and releases cytokines, which act on vascular endothelium 3. Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion.

Question 38

What is the mechanism of type 4 cells?

Answer 38

1. Contact-sensitizing agent penetrates the skin and binds to self proteins, which are taken up by Langerhans cells 2. angerhans cells present self peptldes haptenated with the contact-sensitizing agent toTH1 cells, which secrete IFN"'Y and other cytoklnes 3. Activated keratlnocytes secrete cytoklnes such as IL-1 and TNF-a and chemoklnes such as CXCLB, CXCL11, and CXCL9 4. The products of keratinocytes andTH1 cells activate macrophages to secrete mediators of Inflammation

Question 39

What are type 4 cells?

Answer 39

Related to Helper T cells interacting with activated cytotoxic T cells, NK cells or macrophages. Response is delayed and cannot be transferred in the serum.

Question 40

outline the mechanism of the Cellular destruction in Coeliac disease?

Answer 40

Peptides naturally produced from gluten do not bind to MHC class II molecules ``` An enzyme, tissue transglutaminase (tTG) modifies the peptides so they now can bind to the MHC class II molecules ``` The bound peptide activates gluten-specific CD4 T cell The activated T cells can kill mucosal epithelial cells by binding Fas. They also secrete IFN"')', which activates the epithelial cell