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Y2 MECHANISMS OF DISEASE > Autoimmunity & Immunodeficiency > Flashcards

Autoimmunity & Immunodeficiency Flashcards

1
Q

Why does the immune system need to be tightly regulated?

A

It has to deal with threats from outside the body as well as internal threats

e.g. cancer cell surveillance

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2
Q

Why can severe burns make someone more susceptible to infection?

A

The skin provides a barrier to prevent pathogen entry

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3
Q

What are the main cellular components of the innate immune system?

A
  1. neutrophils
  2. complement & PRRs
  3. dendritic cells
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4
Q

What are the 3 main characteristics of the innate immune system?

A
  1. it is pre-programmed
  2. it has no memory
  3. it is triggered within seconds
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5
Q

What is the role of pattern recognition receptors (PRRs)?

A

They inform the immune system about the type of threat

e.g. bacterial, viral, etc.

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6
Q

What is the role of the dendritic cells and macrophages in the innate immune response?

A

They inform the adaptive immune system about they type of threat that is present

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7
Q

What is the role of the antigen presenting cells in the innate immune system?

Which cells are these?

A

Dendritic cells & macrophages/monocytes

They engulf debris and microorganisms, digest them and present the antigen on their cell surface

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8
Q

What are the types of phagocytes in the innate immune response?

What is their role?

A

They engulf and destroy pathogens

Macrophages and neutrophils

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9
Q

What are the granulocytes that are part of the innate immune response?

A
  1. neutrophils
  2. eosinophils
  3. mast cells
  4. basophils
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10
Q

What are the 3 types of proteins that are part of the innate immune system?

A
  1. cytokines
  2. complement
  3. acute phase proteins
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11
Q

What is the role of cytokines in the innate immune system?

A

they are chemical signals that modulate cell activity or attract cells (chemokines)

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12
Q

What is the role of acute phase proteins in the innate immune system?

A

They opsonise or present pathogens to the immune system

They coat the pathogen to make it more visible to the immune system

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13
Q

What is the most commonly measured acute phase protein?

A

CRP

It is measured as a marker of inflammation

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14
Q

What is the role of complement proteins in the innate immune system?

A

It is a cascade of proteins with multiple functions

e.g. opsonisation, killing, activation, chemoattraction

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15
Q

What are the cells of the adaptive immune system?

A

B cells, T cells and high affinity antibodies

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16
Q

What are the 3 characteristics of the adaptive immune response?

A
  1. highly tailored to infction
  2. it has memory
  3. it takes 4-6 weeks
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17
Q

What is meant by the Th1 response?

A

cytotoxic T cells directly destroy infected cells

there is less need for antibodies

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18
Q

What is meant by the Th2 response?

A

Many antibodies are produced for opsonisation of extracellular pathogens

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19
Q

What is the main difference between the Th1 and Th2 responses?

A

Th1 response targets intracellular pathogens

Th2 response targets extracellular pathogens

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20
Q

What is produced if there is no dangerous signal associated with tissue damage when the naive T cell comes into contact with an APC?

A

Regulatory T cells

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21
Q

What are the 3 categories that can influence autoimmune diseases?

A
  1. genetic background
  2. environment
  3. immune regulation
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22
Q

Why do autoimmune diseases tend to be more common in women?

A

There are a number of immune chains on the X chromosome

2 copies in a woman can lead to a higher degree of autoreactivity

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23
Q

In which locations are B and T cells generated?

A

B cells - bone marrow

T cells - thymus gland

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24
Q

How does the molecular structure of pathogens compare to that of our body?

A

Many pathogens have molecular structures that are similar to structures found in the body

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25
What is meant by negative selection of T cells?
If the MHC molecules of T cells show a high degree of engagement with self-proteins, they are destroyed
26
What is a crucial factor in deciding whether a T cell can survive or not?
The T cells must be able to engage their T cell receptors (they must be working)
27
Why do all T cells released from the thymus have some degree of autoreactivity?
The only way to check that the T cell receptor is working is to check it against self proteins All T cells may recognise some native proteins
28
How may a B or T cell develop a higher degree of autoreactivity?
Through somatic hypermutation This can lead to development of a clone with a high degree of autoreactivity
29
What happens in the periphery to ensure there are no autoreactive cells present?
If there is engagement between an APC that is NOT carrying a harmful antigen and a T cell, T cell anergy occurs The T cell becomes a peripheral regulatory T cell
30
What are the 3 categories of factors that have a causative association with autoimmunity?
1. sex hormones 2. age 3. environmental triggers
31
How does age affect development of autoimmune conditions?
autoimmunity is more common in the elderly the immune system becomes less effective with age as B and T cells shrink
32
What are the 3 main environmental triggers for autoimmune diseases?
1. infection 2. trauma tissue damage 3. smoking
33
How can infection trigger an autoimmune response?
Infection may cause a clone of a T cell to proliferate The T cell has the ability to recognise both self proteins and pathogen proteins Some pathogen proteins are very similar to self proteins and can trigger an autoimmune response
34
What is meant by the shared epitope of rheumatoid arthritis patients?
Most rheumatoid arthritis patients have a certain type of HLA molecules - HLADRB51
35
How do HLA molecules vary between individuals?
Everyone has a different HLA makeup, allowing them to respond to a variety of pathogens
36
What is the role of a HLA molecule? What does it stand for?
human leukocyte antigen it encodes cell surface molecules that present antigenic molecules to the T cell receptor
37
How can HLA molecules make someone more prone to rheumatoid arthritis?
Depending on HLA make-up, someone may be more likely to present self antigens to the immune system and initiate an autoimmune response
38
What is significant about the HLADRB51 phenotype in rheumatoid arthritis?
Having this phenotype allows you to present citrullinated peptides The body is more likely to see citrullinated peptides as foreign and start an autoimmune response against them
39
How can smoking and obesity influence rheumatoid arthritis?
You are more likely to produce citrullinated peptides
40
What is the role of the CTLA4 protein?
It moderates the amount of T cell activation through a negative feedback mechanism
41
What can go wrong with the CTLA4 protein that can lead to rheumatoid arthritis?
A variant of the molecule does not work as well The immune system cannot be suppressed and is more active Leads to autoimmune conditions
42
What is the aim of treatment to try and prevent development of rheumatoid arthritis?
Blocking certain cytokines involved in the development pathway
43
What are the 3 main things involved in the pathophysiology of autoimmune conditions?
1. autoreactive B cells and autoantibodies 2. autoreactive T cells 3. general inflammation and end organ damage
44
How can autoreactive B cells and autoantibodies affect the body?
Autoantibodies can be directly cytotoxic to cells They can interfere with normal physiological function of cells They can activate the complement system, leading to inflammation
45
How can autoreactive T cells affect the body?
They can be directly cytotoxic to cells They can produce inflammatory cytokines
46
What is the end result of having an autoimmune disease?
End organ damage This is the loss of organ function
47
What organs can be affected by autoimmune diseases? How long do they last for?
any organ can be affected it is a lifelong-chronic condition
48
What types of people are most commonly affected by autoimmune conditions?
Women and the elderly
49
What are the 2 different types of autoimmune condition?
1. organ specific | 2. systemic
50
What are the characteristics of organ specific autoimmune diseases?
They affect a single organ only Autoimmunity is restricted to autoantigens of that organ only
51
What are the characteristics of systemic autoimmune diseases?
They affect several organs simultaneously Autoimmunity is associated with autoantigens found in most cells in the body
52
What is the most common category of organ-specific autoimmune disease?
autoimmune thyroid disease
53
What is the most common category of systemic autoimmune disease?
connective tissue diseases
54
What is the process of Hashimotos thyroiditis?
Destruction of thyroid follicles by an autoimmune process This means there is no production of thyroid hormone This leads to hypothyroidism
55
What type of autoantibodies is Hashimotos thyroiditis associated with?
It is associated with autoantibodies to thyroglobulin and thyroid peroxidase
56
What is the outcome of Hashimotos thyroiditis?
Hypothyroidism
57
What is the process behind Grave's disease?
Anti-TSH autoantibodies cause inappropriate stimulation of the thyroid gland This leads to excessive thyroid hormone production
58
What is the outcome of Grave's disease?
hyperthyroidism initially eventually there is thyroid gland destruction and the patient develops secondary hypothyroidism
59
What are the typical symptoms of systemic lupus erythematosus?
1. fever 2. general tiredness 3. joint and muscle aches 4. headaches 5. butterfly rash on the face
60
How does small vessel vasculitis come about in SLE?
1. autoantibodies in the circulation recognise fragments of damaged cells 2. cell fragments and autoantibodies form complexes 3. complexes activate the complement system 4. this leads to small vessel vasculitis
61
Which organs are more likely to be affected in SLE and why?
Organs with rich capillary networks e.g. kidney, heart The blood flow is slower giving more time for the complexes to form
62
What are the 4 main connective tissue diseases?
1. systemic lupus erythematosus 2. scleroderma 3. polymyositis 4. sjogrens syndrome
63
What are the 2 different types of diagnostic tests?
1. non-specific e.g. inflammatory markers 2. disease specific e. g. autoantibody testing, HLA typing
64
When is HLA typing used?
to understand the risk factors for someone developing an autoimmune disease
65
What is meant by immunosuppression?
a natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose
66
What is meant by immunodeficiency?
the lack of an efficient immune system this makes someone susceptible to infection
67
When is immunosuppression used in treatment?
1. transplant rejection 2. autoimmune diseases 3. lymphoproliferative diseases
68
How are immunosuppression and immunodeficiency related?
Immunosuppression can induce immunodeficiency
69
What are the 2 different types of immunodeficiency?
1. Primary - caused by genetic defects in individual components of the immune system 2. Secondary - caused by the effects of external factors
70
What is the most common cause of secondary immunodeficiency?
malnutrition
71
What are other causes of secondary immunodeficiency?
1. stress 2. surgery/burns 3. cancer (especially lymphoproliferative diseases) 4. immunosuppressive drugs 5. irradiation 6. AIDS 7. other infections e.g. measles, TB
72
What does SCID stand for?
severe combined immunodeficiency syndrome
73
What causes SCID?
It is a primary immunodeficiency disease caused by defects in both B and T cells
74
What are the characteristics of SCID?
1. recurrent infection with opportunistic infections (things that do not usually cause serious symptoms) 2. presents in childhood 3. consanguinity can be related

Y2 MECHANISMS OF DISEASE (36 decks)

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