Autoimmunity

Question 1

d:autoimmunity

Answer 1

the presence of immune responses against self-tissues/cells

Question 2

what is harmless autoimmunity?

Answer 2

Low titres of auto-antibodies or auto-reactive T cells

Question 3

what is harmful autoimmunity?

Answer 3

High titres of auto-antibodies or auto-reactive T cells
Significant tissue/organ damage
Chronic inflammation

Question 4

If antigen reeceptor gene rearrangement is unsuccessful what occurs in immature T+B cells?

Answer 4

No antigen-specific receptor expression  immature cells killed

Question 5

If Successful antigen receptor

gene rearrangement occurs, how does this lead to autoreactive T+B cells?

Answer 5

Surface expression of
functional antigen-specific receptors
(DO bind self-antigen)

Question 6

How does the immune system deal with the presence of autoreactive T+B cells?

Answer 6

Specific ‘tolerance’ mechanisms are required:

Deletion of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)

Inactivation of self-reactive lymphocytes in peripheral tissues that escape central tolerance (peripheral tolerance)
e.g. Regulatory T cells (TREG cells)

Question 7

d: T regulatory cells

Answer 7

role in regulating or suppressing other cells in the immune system

Question 8

f: Tregs

Answer 8

Regulatory T cells are crucial for the suppressing hyper-reactive or auto-reactive T cells

Question 9

how do Tregs carry out their function?

Answer 9

Via production of anti-inflammatory cytokines

Question 10

describe the pathogenesis of autoimmune diseases

Answer 10

Genetic susceptibility combined with an initiating event, leads to a loss of immune regulation, activating autoreactive B and T cells

Question 11

describe the pathogenesis of autoimmune diseases

Answer 11

Genetic susceptibility combined with an initiating event, leads to a loss of immune regulation, activating autoreactive B and T cells

Question 12

Name the other genes that makeup a complex genetic factor the most autoimmune diseases come from

Answer 12

HLA genes
sex determining genes
other immune response genes

Question 13

symptoms of IPEX disorder

Answer 13

Severe infections
Intractable diarrhoea
Eczema
Very early onset insulin dependent diabetes mellitus
Autoimmune manifestations

Question 14

treatment of IPEX syndrome

Answer 14

Cure: hematopoietic stem cell transplantation (HSCT)
Supportive care: immunosuppressive drugs
plus total parental nutrition

Question 15

What gene in IPEX syndrome contains the mutation? Why is this a problem?

Answer 15

Mutation in FOXP3 gene, which is essential for the normal development of regulatory T-cells

Question 16

Why are only males affected by IPEX?

Answer 16

the condition is X-linked

Question 17

How can T cells only recognise peptides antigens?

Answer 17

when their presented by Major Histocompatibility (MHC) molecules

Question 18

what are HLA genes aka and stand for?

Answer 18

MHC molecules in humans are also referred to as HLA (Human Leucocyte Antigen) molecules

Question 19

Name some class I molecules on a nucleated cell?

Answer 19

HLA-A HLA-B HLA-C

Question 20

Name some additional Class II molecules expressed by Specialised antigen-presenting cells

Answer 20

HLA-DR, HLA-DQ and HLA-DP

Question 21

How many variants of HLA molecule types does each individual possess?

Answer 21

2

Question 22

Why are HLA molecules highly polymorphic?

Answer 22

Proteins are processed into many component peptides

Different HLA molecules bind to different subsets of peptides

To maximise the net ability to bind all antigenic peptides:
Multiple different subtypes of HLA molecules
Individual HLA molecules exhibit significant allelic diversity

Question 23

What is the theory behind the influence of HLA genes in autoimmune disease?

Answer 23

if an individual has pre-disposed HLA alleles, there is a selective presentation of disease relevant self-peptides

Question 24

Name some people who are at a greater risk of autoimmune disease

Answer 24

women of childbearing age
people with a family history
people who live in a certain environment eg sunlight, chemicals etc
different races

Question 25

Name some environmental factors that can contribute to autoimmune disease

Answer 25

Infection
Cigarette smoking
Hormone levels

Question 26

d:molecular mimicry

Answer 26

is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides

Question 27

What bacteria causes toxic shock syndrome? What does the syndrome do?

Answer 27

Staphylococcal proteins
Clostridium endotoxin
These can re-activate autoreacvtive T cells that have been inactivated by regulatory T cells

Question 28

What type of antigen are the Staphylococcal proteins and

Clostridium endotoxin?

Answer 28

superantigens

Question 29

Name some autoimmune diseases that are mediated by type II hypersensitivity mechanisms in the kidneys and the endocrine system?

Answer 29

k- Goodpasture’s syndrome

E- Graves disease

Question 30

What is graves disease?

Answer 30

A leading cause ofhyperthyroidism

Auto-antibodies are generated that bind to the thyroid stimulating hormone receptor (TSHR

Question 31

Name an autoimmune disease mediated by type 3 hypersensitivity reactions?

Answer 31

Systemic lupus erythematosus (SLE)

Question 32

Symptoms of SLE

Answer 32

Skin rashes, nephritis,(inflammation of the kidney’s) alveolitis

Question 33

pathogenesis of SLE

Answer 33

apoptotic bodies aren’t cleared due to SLE, leading to Increased cell death (apoptosis)
Decreased phagocytosis of apoptotic bodies
Decreased solubilisation and clearance of immune-complexes
Loss of tolerance (no suppression of auto-reactive B cells,  production of auto-antibodies that recognise dsDNA and other nuclear self-antigens

Question 34

Name a common autoimmune disease mediated by type IV hypersensitivity mechanisms and complications of it

Answer 34

Rheumatoid arthritis (self- antigen = )
Complications:  inflammation in the lungs and heart

Question 35

what are Th17 cells?

Answer 35

are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differentiation