immunopathology of inflammation and autoimmune disease

Question 1

what are the general principles of immune response?

Answer 1

degree of regulation
multilayer defense
network of pathogen recognition
effective intercellular communication
multiple mechanism of pathogen clearance
adaptive responses to changing pathogen
self regulation and limitation of host damage

Question 2

what is autoimmunity?

Answer 2

it is a genetically determined, inherited immune system that is a theoretical concept - the skin acts as a barrier, and some people are more susceptible than others

Question 3

what do pattern recognition receptors do in innate immunity?

Answer 3

they inform the immune system about the type of threat it is experiencing - i.e. gram negative, positive, viruses or fungi

Question 4

which cells inform the adaptive immune system about the threat?

Answer 4

dendritic cells and macrophages

Question 5

what are the characteristics of innate immunity?

Answer 5

it is pre-programmed, has no memory and is triggered quickly - within seconds - it provides the initial response to infection

Question 6

what is involved in the adaptive immunity?

Answer 6

T cells, B cells and high affinity antibodies - more targeted and powerful immune responses, is highly tailored, has memory and takes 4-6 weeks

Question 7

what is the function of cells of the innate immune system?

Answer 7

they recognise threat and engulf and destroy it

Question 8

what are APCs?

Answer 8

antigen presenting cells - macrophages, monocytes and dendritic cells - they engulf debris, digest it and then present it as an antigen on their surface

Question 9

what are phagocytes?

Answer 9

cells that engulf and destroy the cell and these are macrophages and monocytes

Question 10

what are examples of granulocytes?

Answer 10

they have slightly different effector functions - eosinophils, neutrophils, mast cells and basophils

Question 11

what are cytokines?

Answer 11

they are proteins of the innate immune system - they are chemical signals that modulate cell activity or attract cells

Question 12

what are acute phase proteins?

Answer 12

they opsonise or present pathogens to the immune system - they coat pathogens to make them more visible e.g. CRP

Question 13

what are complement proteins?

Answer 13

cascade of proteins with many functions such as opsonisation, killing, activation or chemoattraction

Question 14

what is the Th1 response?

Answer 14

it is an adaptive response that means that cytotoxic T cells will directly kill the pathogen - this is if the pathogen has infiltrated the cell and there is less need for ABs

Question 15

what is the Th2 response?

Answer 15

the adaptive response that produces lots of antibodies for opsonisation

Question 16

what happens if there is no dangerous signal associated with tissue damage?

Answer 16

production of regulatory T cells

Question 17

what do stem cells produce?

Answer 17

they produce phagocytes and APCs and lymphoid precursors which make NK, T, B and plasmacytoid dendritic cells

Question 18

what is autoimmune disease?

Answer 18

breakdown of self tolerance and clinical entities - tendency of the immune system to be self reactive

Question 19

what are the causes of AD?

Answer 19

there is a combination of factors - these are genetic (some people have different threshold for autoreactivity - some people may be genetically predisposed to have a more vigorous immune response), environmental - act on favourable genetic backgrounds and immune regulation

Question 20

why are AD more common in women?

Answer 20

autoimmune disease is more common in women because there are immune genes on the X chromosome and depending on the number of chains this can lead to higher auto reactivity (more than 2)

Question 21

why do T cells have some degree of autoreactivity?

Answer 21

to be selected for when developing T cells must engage their working receptors, and the only way to test this is through self antigens. therefore when they leave the thymus they will have some degree of autoreactivity. Those that show too much will be negatively selected (destroyed).

Question 22

What is anergy?

Answer 22

occurs when there is engagement between a T cell and a APC when it is not presenting a harmful antigen - T cell becomes a peripheral regulatory T cell

Question 23

what are other causative associations of AD?

Answer 23

sex - hormonal influence, age - elderly and environmental triggers - smoking, trauma tissue damage or infection

Question 24

what does smoking and subsequent trauma result in?

Answer 24

the immune system becoming more pro-inflammatory due to damage to epithelial lining

Question 25

what are HLA molecules?

Answer 25

they are proteins found on the surface of APCs that allow the immune system to recognise and react to pathogens - everyone has different HLAs

Question 26

what does having the HLADRN51 phenotype result in?

Answer 26

allows you to present citrullinated proteins to immune system which are triggered by environmental factors - autoimmune response

Question 27

what is the pathophysiology of AD?

Answer 27

autoreactive B cells and autoantibodies (directly cytotoxic and activation of complement - interfere with normal physiological function) and autoreactive T cells (directly cytotoxic and inflammatory cytokine production) - this results in general inflammation and end organ damage

Question 28

what is characteristic of AD?

Answer 28

exacerbation and remission

Question 29

what is organ specific AD?

Answer 29

it is affecting a single organ and is restricted to autoantigens of that organ only - it can overlap with other organ specific disease such as autoimmune thyroid disease

Question 30

what is systemic AD?

Answer 30

affects multiple organs simultaneously, and is associated with autoantigens that are found on most cells of the body. It can overlap with other systemic AD particularly connective tissue disease

Question 31

what are the two conditions in AI thyroid disease?

Answer 31

hashimotos thyroiditis and grave's disease

Question 32

what is hashimotos thyroiditis?

Answer 32

it is an AD that is to do with the destruction of thyroid follicles by autoimmune processes and is associated with autoantibodies of thyroglobulin and thyroid peroxidase - hypothyroidism

Question 33

what is grave's disease?

Answer 33

the inappropriate stimulation of the thyroid gland by anti-TSH autoantibody that leads to hyperthyroidism

Question 34

what are scleroderma, polymositis, sjogrens syndrome and SLE examples of?

Answer 34

connective tissue disease

Question 35

what are the two types of diagnostic tests and what do they test for?

Answer 35

non specific for inflammatory markers and disease specific such as autoantibody testing and HLA typing

Question 36

what is ANA?

Answer 36

antinuclear antibody testing - investigation of systemic autoimmune disease

Question 37

what is the treatment basis of AD?

Answer 37

supportive, immunosupressive and preventative

Question 38

define immunosupression and what it can result in?

Answer 38

immunosupression is the artifical or natural process that turns off the immune response either partially or completely that can be accidentally or on purpose. This results in immunodeficiency which is the lack of an efficient immune system which results in susceptibility to infection

Question 39

what are some uses of immunosupression?

Answer 39

transplant, autoimmune and lymphoproliferative

Question 40

what is the difference between secondary and primary immunodeficiency?

Answer 40

immunodeficiency is usually secondary to external factors but it may be primary - genetic defects in the individual components of the immune system - type of infection is guide to underlying cause

Question 41

what are the characteristics of secondary immunodeficiency?

Answer 41

``` transient or long lasting, minor or major trauma related cancer malnutrition radiation AD infection lymphocytes or neutrophils <1million/ml ```

Question 42

what are the characteristics of primary immunodeficiency?

Answer 42

very rare often diagnosed in early childhood but can present later in life recurrent infection

Question 43

what is SCID?

Answer 43

severe combined immunodeficiency syndromes - defects in B and T cells (more severe) - recurrent infections that are opportunistic - can used bone marrow transplantation can cure or gene therapy