L11 - K Okkenhaug - Hypersensitivity

Question 1

what is hypersensitivity?

Answer 1

over reactions of the immune system - to non harmful stuff

Question 2

what are the types of hypersensitivity?

Answer 2

Question 3

describe Type 1 hypersensitivity

Answer 3

• rapid allergic reactions
• host has pre-existing IgE antibody (gerneated through Th2 response)
• MAst cells - via Fc􏰀RI cross linking degranulate histamine
• IgE is probably prebound to its receptor

Question 4

what properies to allergen have in common?

why do they stimulate a strong IgE response

Answer 4

• often proteases.
• They are generally low MW
• highly soluble, so they diffuse readily into mucus.
• They are also generally stable and can survive as a desiccated particle

Question 5

how do we determine sensitivity to allergens?

Answer 5

skin-prick test. A ‘wheal and flare’ reaction appears at the site of infection within a few minutes. The wheal is swelling (edema) and the subsequent redness (flare or erythema) is from increased blood flow.

Question 6

is type I sensitivity common/

Answer 6

very - upto 30% of some populations

Question 7

type I:

These atopic (atopy is a predisposed state) individuals have serum IgE raised 1—- times the normal level.

Answer 7

These atopic (atopy is a predisposed state) individuals have serum IgE raised 10-100 times the normal level.

Question 8

describe systemic anaphylaxis

Answer 8

allergen directly into blood - systemic anaphylaxis

increased permeability of blood vessels results in extreme drop in blood pressure and anaphylactic shock, which can be fatal.

Question 9

treatment ofr type I hypersensitivity

Answer 9

identification and avoidance of the antigen; as well as antihistamine and corticosteroids, which suppress leukocyte function.

In some cases, desensitisation may be achieved by gradual exposure to increased dose of antigen, to convert Th2 to Th1 and/or iTreg responses.

Question 10

outline asthma

Answer 10

chronic inflammation of the airways characterised by increased TH2 lymphocytes, eosinophils, neutrophils and basophils, which amplify inflammation and airway remodeling

Question 11

which genetic loci affect asthma?

Answer 11

HLA class II,

TCR and genes which affect the TH1/TH2 balance.

Other genes affect the IgE receptor and cytokines including IL-4.

In addition, are effects of non-immune genes such as those influencing smooth muscle cell behavior, bronchial physiology and tissue repair. Mice lacking the T-Bet transcription factor, which drives T cells to differentiate into TH1 cells, and suppresses the TH2 pathway, have increased levels of IL-4, IL-5 and IL-13 cytokines and have a disease similar to human asthma.

Question 12

how do you test for asthma

Answer 12

breathing exhalation rate tested after exposure to known allergen

Question 13

describe the late repsonse for asthma

Answer 13

As in the skin test, a late response follows after about 6 hours, due to leukotrienes and other inflammatory mediators. This phase is most damaging and leads to recruitment of eosinophils and TH2

lymphocytes

Question 14

why do type 1 allergies occur so fast

Answer 14

pre existing IgE

Question 15

describe type 2 hypersensitivity

Answer 15

IgM or IgG antibody binding to cells or tissue antigens

Question 16

blood transfusion is an example of what type of hypersensitivity?

Answer 16

2

Question 17

describe how blood matching works?

Answer 17

Question 18

how does the ABO blood group system work?

Answer 18

• Molecules consist of a core H antigen
• The O (null) allele is unmodified H antigen
• Sugars may be attached to this core:
• The A allele adds a terminal N-acetylgalactosamine The B allele adds a terminal galactose
• AB indicates both modifications

Question 19

describe the rhesus reaction (blood)

Answer 19

• blood incompatability
• mother is Rhesus negative and the child is Rhesus positive the mother can produce antibodies to the Rhesus antigen
• some Rh+ cells leak into the maternal circulation at birth
• IgG can cross the placenta and compromise the subsequent Rh+ baby.

Question 20

treatment for rhesus reaction?

Answer 20

giving anti-Rh antibody (RhoGam) to the mother before she reacts to her child’s red blood cells. The antibody crosslinking to FcgRIIB receptor prevents activation of naïve B cells (see lectures on antibody and tolerance).

Question 21

describe type 3 hypersensitivity

Answer 21

antigen: soluble
quantity: high - IgG response

(low quantities = IgE responses)

1. Immune complexes form and are deposited in tissues.
2. These trigger mast cells via the low affinity Fc􏰀RIII receptor.
3. Complement is activated and polymorphs are attracted to the site of deposition, causing local tissue damage and inflammation.

Question 22

examples of type 3 responses

Answer 22

arthritis and glomerulonephritis

Question 23

Other examples of T3 hypersensitisation include pigeon fancier’s lung or farmer’s lung, where the antigen is _____.

Answer 23

Other examples include pigeon fancier’s lung or farmer’s lung, where the antigen is inhaled.

Question 24

what is serum sickness

Answer 24

used to result when high doses of horse serum were used to treat pneumonia.

This classic form of type III hypersensitivity is rarely seen now although injection of serum is still used as anti-snake venom.

Question 25

describe type 4 responses

Answer 25

• t cell mediated
• release cytokines
• which recruit mononuclear cells
• 2-3 days
• required 10-100 times more antigen than other types of HyperS

Question 26

Type IV hypersensitivity reactions are orchestrated by …

Answer 26

Type IV hypersensitivity reactions are orchestrated by cytokines released by Th1 CD4 cells in response to antigen.

Question 27

the T cells responsible for the type 4 response

secrete what ?

Answer 27

chemokines

INF-gamma

TNF-alpha and LT

IL-3/GM-CSF

Question 28

damamge is usually done by what cell in type 4 hyper S?

Answer 28

macrophages (activated by T cells)

Question 29

final summary

Answer 29

Question 30

fat

Answer 30

mamba