Hypersensitivities

Question 1

In type 1 hypersensitivity, what are the

• triggers
• immune components
• timeframe
• examples
• method of diagnosis

Answer 1

Triggers => allergens

Immune components
-IgE, mast

Timeframe => <1hr

Examples
-anaphylaxis, allergy, asthma

Diagnosed via skinspirk, immunoassay

Question 2

In type 2 hypersensitivity, what are the

• triggers
• immune components
• timeframe
• examples

Answer 2

Triggers => antigen

Immune components
-AB (IgG, M) and cells with Fc receptor

Timeframe => hours-days

Examples

• AI haemolytic anemia
• transfusion reaction
• goodpastures

Question 3

In type 3 hypersensitivities, what are the

• triggers
• immune components
• timeframe
• examples

Answer 3

Triggers => AB-AG immune complex

Immune components
-results in activation of complement and cells with Fc receptor

Timeframe => 1-3weeks

Examples

• SLE
• serum sickness

Question 4

In type 4 hypersensitivity, what are the

• triggers
• immune components
• timeframe
• examples

Answer 4

Triggers => cell mediated

Immune components
-CD8, 4

Timeframe => days-weeks

Examples

• graft rejection
• T1D, RA
• asthma

Question 5

What are the allergic mediators in a type 1 hypersensitivity

What do they all do collectively?

Answer 5

Histamine
Tryptase
Protease
NO
IL3, 4, 8, 9, TNFa

VD
SMC
neutrophil, basophil, eosinophil, Tcell recruitment

Question 6

Describe the 4 stages of anaphylaxis

Answer 6

Stage 1 => itch, hives
Stage 2 => swelling away from source, incontinence
Stage 3 => systemic impact, SOB
Stage 4 => hypotension, LOC

Question 7

What is autoimmunity

Answer 7

Loss of tolerance to self components

Can be linked to pathology

Question 8

Describe how thymic education contributes to tolerance

Answer 8

1. functional TCR
2. positive response between TCR + MHC
3. negative response between TCR and self antigen on MHC

If all 3 stages passed, enter peripheral circulation
-cells that are unable to function correctly/respond to self antigens die by apoptosis

Question 9

Describe how restricted migration contributes to tolerance

Answer 9

Naive T cells, central memory Tcells only circulate between SLO and blood
-do not enter tissues unless activated

Question 10

Describe how anergy contributes to tolerance

Answer 10

APC with MHC specific to a self antigen will lose its constimulatory molecule

• Signal 1 => MHC=TCR
• Signal 2 not possible due to lack of costumulation => TCell also loses its costimulatory molecule

Question 11

Describe how Tregs contribute to tolerance

• actions on APC
• actions on CD4

Answer 11

APC

• decrease costimulation
• alter cytokine production

CD4
-no proliferation, cytokine production

Question 12

What are the 4 factors that you can use to define an AI disease

Answer 12

Evidence of loss of tolerance to self
Passive transfer of disease via effectors
Clinical responsiveness to immune suppression/reestablished tolerance
Genetic clusters of immune linked genes

Question 13

Describe the genetic contributors of AI disease

-Tregs

Answer 13

Defective IL2 signalling

• decreased expression, signalling
• loss of FoxP3Tregs => poor Treg function

IL2 is vital for Treg function

Question 14

Describe the environmental contributors of AI disease

-bystander activation

Answer 14

Inflammation escalated by cytokines against infection => cell damage

Self AG picked up by APC => migrate to LN => activate autoreactive Tcell => escalates inflammation further

Question 15

Describe the environmental contributors of AI disease

-molecular mimicry

Answer 15

AA seq presented on MHC common to self and pathogen

=> activation of Tcell

Question 16

Describe the environmental contributors of AI disease
-Neoepitopes

What are the consequences

Answer 16

Post translation modification due to environmental factors
-citrullination or deamination => altered AA

Mistranscription, mistranslation due to cellular stress
-alternative splicing or altered reading frame=> altered AA

Self produced protein no longer seen as self protein