Hypersensitivity and autoimmunity

Question 1

What is autoimmune disease?

Answer 1

a failure or breakdown of immune system that maintains tolerance to self tissues

Question 2

What is cause of autoimmune disease?

Answer 2

Loss of tolerance is probably due to abnormal selection or lack of control of self-reactive lymphocytes (B and T-cells)

Damage in different autoimmune diseases may result from different effector mechanisms

Question 3

Describe a genetic risk factor for autoimmune disease?

Answer 3

susceptibility genes which render them susceptible to developing autoimmune disease (tissue type gene or gene important for controlling immune system)

gives rise to failure of self tolerance and there is a certain prevalence of self reactive lymphocytes (adaptive immune cells which are able to recognize self tissues)

following on from an infection when tissue being damaged, the self reactive lymphocytes recognize self antigens and drive autoimmune disease. Turn into chronic

Question 4

What are the ways to treat autoimmune disease?

Answer 4

-blanket immunosuppression however side effects of opportunistic infection
-Targeted selective approach – target the aberrant immune activation while leaving the rest of the immune system intact

Question 5

What is the actual damage of autoimmune diseases caused by?

Answer 5

hypersensitivity responses:

Hyper response from the immune system

Harmful immune responses that may produce tissue injury and cause serious disease

4 categories: Type I, II, III, IV (V)

Question 6

Which hypersensitivity types are antibody mediated?

Answer 6

Type I, II, III and V

Question 7

Which hypersensitivity types are T cell mediated?

Answer 7

Type IV

Question 8

What is hypersensitivity type I associated with?

Answer 8

allergy

Question 9

What antibody does hypersensitivity type 1 rely on?

Answer 9

IgE in low levels for soluble antigen
linked to mast cell (responsible for allergic response)
e.g. allergy

Question 10

What antibody does hypersensitivity type 2 rely on?

Answer 10

IgG specific for specific cell or matrix antigen

e.g.A/HA
ATP
Rheumatic fever

Question 11

What antibody does type 3 rely on?

Answer 11

IgG for soluble antigen and forming large immune complexes- predisposing them to lodging in fine capillaries and recruiting in damage

SLE
Rheumatoid arthritis

Question 12

What are type 4 responses associated with?

Answer 12

T helper cell responses
CTL (cytotoxic t lymphocyte responses)- were t cell recognizes self antigen presented by tissue type mol and driving damage

Question 13

Describe type I hypersensitivity?

Answer 13

first exposure to allergen
picked up by immune system and shown to naive T cell
that drives inflammation around meeting, drives naive t cell into type of cell that’s producing lots of IL-4
which drives B cells to produce antibody IgE
IgE mostly bound to mast cell (sedentary cell)
Once allergen shows up and antigen binds to IgE, crosslinks FcERI mols then get release of pro inflammatory mediators and induce hyper sensitivity allergic reaction.
Gr

Question 14

Type 1 effects?

Answer 14

granules released by mast cell control:
vasodilation
vascular leak
broncho constriction
intestinal hypomotility

Question 15

Describe the immediate and late phase in allergy?

Answer 15

immediate reaction:
IgE mediated effects
Vasodilation, oedema and vascular congestion

Late reaction:
eosinophil, neutrophil and T cell infiltrates

Question 16

What is atopy?

Answer 16

predisposition to allergy

Question 17

Describe type 2 hypersensitivity?

Answer 17

all about specificity, targeting a particular antigen.
Antibody deposition in extra cellular matrix
Antibody can interact via Fc receptor with a number of cells which provoke an inflammatory immune response for e.g. neutrophils and macrophages

Question 18

Describe type 3 hypersensitivity?

Answer 18

circulating immune complexes can lodge in capillaries and once lodged can interact with same proinflammatory cells as type 2 via Fc receptor. Same damage is mediated, deposition of immune complex, inflammatory lesion developing.

Question 19

Give example of abnormal physiologic responses without cell/ tissue injury?

Answer 19

antibody against thyroid stimulatory hormone receptor on thyroid epithelial cell. Stimulating production of thyroid hormones (type 5)

acetylcholine receptor targeted by antibody and preventing acetylcholine from binding and leads to profound muscle weakness (type2 )

Question 20

Describe type 4 hypersensitivity?

Answer 20

Involves either CD4 T cells (regulate immune responses) CD8 T cells (directly killing infected cells)
CD4 T cells prime CD8
either cytokine mediated: t cells producing cytokines leading to inflammatory response or direct killing of cells by CD8 T cells

Question 21

What genetically makes you more likely to get an autoimmune disease?

Answer 21

Certain HLA Alleles

Question 22

What are susceptibility factors for type 1 diabetes?

Answer 22

Slight mutations in insulin

Question 23

Where are genetic risk factors located?

Answer 23

some in genes, some around genes and part of mechanism of which regulates gene

Question 24

What are some environmental factors?

Answer 24

main one-infection
drugs, trauma and food

Question 25

What is molecular mimicry?

Answer 25

immune system makes a response against the pathogen but response is then cross reactive with a self tissue and then causes autoimmune damage
e.g. rheumatic fever

Question 26

Describe development of myocarditis? (autoimmune)

Answer 26

individual infected with streptococcus A
And within days, antibody, lots of high affinity antibody will be made against a particular protein associated with the pathogen
in some, there is a cross reactivity as these antibodies are capable of binding effectively to bacteria but also bind to cardiac myosin.

Question 27

What is immunological tolerance?

Answer 27

state of unresponsiveness to specific antigen

prevents adaptive responses that are damaging (B cells and T cells)

Question 28

Why are B cells and T cells relevant in immunological response?

Answer 28

development of B and T cells there are mechanisms to prevent cells from recognising self antigens.

But can be exploited by microbes and tumours (tumour produce substances that enhance the immune tolerance and generate an environment in which t cells are not really functional)

-how tumour can escape from immune system

Question 29

Why would we want to get rid of immune tolerance in cancer?

Answer 29

so immune system can focus on tumour and kill it

Question 30

Challenge of immunological tolerance?

Answer 30

T cell pool and there’s a specificity associated with each particular clone. You can have 10 to power 11 specificities in a normal human being. We want these T cells to make productive immune responses against pathogens (they may or may not have met before). But we do not want them to recognize self.

Question 31

B cell mechanisms?

Answer 31

Some B cells specific for a pathogen but some will be specific for an alter antigen.
Number of mechanisms which basically weed out the cell specific cells and either
make them non functional or delete completely?

Question 32

Describe systemic autoimmune disease?

Answer 32

Autoimmune process is diffuse is spread throughout the body

Affects more than one organ - not necessarily the same ones in different individuals
e.g.SLE

Question 33

Describe organ specific autoimmune disease?

Answer 33

Autoimmune process directed against one organ

Type 1 Diabetes - pancreas
Autoimmune Thyroiditis

Question 34

Summary?

Answer 34

Hypersensitivity responses can be defined as damaging responses produced during normal immune responses

Chronic activation can lead to autoimmune disease – different effector mechanisms influence the disease phenotype

Autoimmune disease - a failure or breakdown of immune system that maintains tolerance to self tissues

Loss of tolerance is probably due to abnormal selection or lack of control of self-reactive lymphocytes (B and T-cells)