CP5-2 autoimmune diseases Flashcards
How do the innate and adaptive immune systems interact?
Innate immune cells attract other cells via chemokines
Dendritic cells present antigens to T cells
Dendritic cells, T cells and B cells cross talk resulting in immune memory forming to determine a specific learned response within lymphoid tissues
Adaptive immune cells activate innate immune cells to direct tissue inflammation at target areas
What cells are involved in the innate immune response?
Macrophages
Dendritic cells
Mast cells
Neutrophils
Complement
What innate immune cells are activated by T cell cytokines?
Monocytes
Macrophages
What innate immune cells are activated byB cell antibodies?
active complement
What is the difference between innate and adaptive immunity?
Innate is a fast acting, shot-lasting inflammatory response to infection where as adaptive immunity is a learned response by immune organs to produce slow response, long-lasting immunity.
How do neutrophils target/attack pathogens?
By phagocytosis
How do macrophages target pathogens?
Phagocytosis and production of chemokines to attract other immune cells
How do dendritic cells target pathogens?
By phagocytosis and presentation of antigens to the adaptive immune systems i.e. to B and T cells
Which cells produce histamine? What else do they do?
Mast cells
Basophils
Eosinophils
Also lead to vasodilation and involved in allergies and anaphylaxis
What is the role of competent cells in immunity? What can they be activated by?
Directly attack pathogens via alternative and lectin pathways - activated by adaptive immune system by B-cell antibodies
What is the role of cytokines?
To signal between different immune cells
What is the role of chemokines?
To attract other immune cells to the site of inflammation
How do T cells cause inflammation?
By inflammatory cytokines release from t helper 1 cells
Help B cells make autoantibodies via t helper 2 cells
Which T cells release inflammatory cytokines?
T helper 1 cells
Which T cells help B cells make autoantibodies?
T helper 2 cells
What is autoimmunity?
When the adaptive immune system recognises and targets the body’s own molecules, cells and tissues so T cells recognise self antigens, B cells and plasma cells
What is autoinflammation?
Spontaneous attacks of systemic inflammation with no demonstrable source of infection or precipitating cause. There is an absence of autoantibodies and antigen specific auto reactive T cells and no eveicencenof auto antigenic exposure
How does autoinflammation differ from autoimmunity?
Autoinflammation = affects innate immune system, involves neutrophils and macrophages with few or no autoantibodies. Uses tissue specific factors and danger signalling with cytokine and bacterial sensing pathways which presents clinically with recurrent, unprovoked attacks e.g. Crohn’s disease. Treated with anti-cytokine therapy.
Autoimmunity = affects adaptive immune system, involves B and T cells and autoantibodies. Breaks off self-tolerance and uses MHC class II association and adaptive response genes. Presents clinically as a continuous progression e.g. polygenic rheumatoid arthritis and SLE. Treated with anti-B and T cell therapy.
What is the difference between autoimmunity and autoimmune disease?
Autoimmunity if the concept of the breakdown of self tolerance. There is an overlap with normal immune functions e.g. anti-tumour immunity
Autoimmune diseases are distinct clinical entities where autoimmunity leads to inflammation, organ dysfunction and damage
What is affected by failure of central tolerance?
T cell selection in the thymus
B cell selection in the bone marrow
What are the 3 key mechanisms of autoimmunity?
Failure of central tolerance
Genetic predisposition
Antigenic factors
What are some antigenic factors contributing to the development of autoimmunity?
Infections which trigger autoimmune response
Environmental triggers e.g. UV light, smoking
Alterations in self proteins increasing immunogenicity
What is an example of a genetic predisposition contributing to autoimmunity?
Having HLA (MHC) types selecting for certain self antigens
How does the thymus filter T cells?
Via negative selection. Tests T cells against self antigens and either deletes those that react or turns them into effector CD4 or CD8 T cells or regulatory T cells
How does the bone marrow filter B cells?
Similarly to the thymus, deleting auto reactive B cells
Which MHC class can contribute to autoimmunity?
class II MHC T cells
Which genes are known to encode MHC class II receptors?
HLA-DP, HLA-DQ, HLA-DR
What T cell binds to antigens on MHC class II molecules?
CD4+ T cells
What genes encode MHC class I?
HLA-A, HLA-B, HLA-C
What are 9 common autoimmune disease?
Type 1 diabetes
Graves’ disease and Hashimoto’s thyroiditis
MS
Systemic Lupus erythematosus
Rheumatoid arthritis
Myasthenia gravis
Perinicious anaemia
Coeliac disease
What happens as a result of FocP3 mutation?
Failure to develop regulatory T cells leading tos every autoimmunity from birth
What happens as a result of a PTPN22 mutation?
T cells are more easily activated leading to a strong immune response in general
What are risk factors for autoimmune disease?
Sex - women > men - hormones?
Age
Sequestered antigens
Environmental triggers - infection, smoking
why can infections cause autoimmunity?
because infection activate the immune system.
Can cause molecular mimicry e.g. in rheumatic fever with streptococcus infection leading to reaction against glycoproteins of the heart valves
How do autoantigens change in rheumatoid arthritis?
Citrullination of proteins make the autoantigens more immunogenic
How do autoantigens change in coeliac disease?
Tissue transglutamase alters gluten to help bind to HLA-DQ
How do autoantigens change in lupus?
Failure to clear apoptosis debris increases the availability of sequestered antigens inside the cell
What are the two sub-categories of autoimmune disease?
Organ specific vs systemic
What are properties of an organ specific autoimmune disease? What is an example?
Affects a single organ
Autoimmunity restricted to autoantigens if that organ
Overlaps with organ specific diseases
E.g. thyroid disease
What are properties of systemic autoimmune disease? What tissue is commonly affected?
Affects several organs simultaneously
Autoimmunity associated with autoantigens found in most cells of the body
Overlap with other systemic diseases
Commonly affects connective tissues
What is Hashimoto’s thyroiditis?
Destruction of thyroid follicles by an autoimmune process leading to hypothyroidism. Associated with autoantibodies to thyroglobulin and thyroid peroxidase
What is Grave’s disease?
Inappropriate stimulation of the thyroid gland by anti-TSH-autoantibodies leading to hyperthyroidism
What causes myasthenia gravis?
Autoantibodies block the acetylcholine receptor preventing normal nerve impulses
What causes pernicious anaemia?
Failure of vitamin B12 absorption as autoimmunity prevents intrinsic factor binding to B12
What are symptoms of systemic lupus erythematosus?
Photosensitive malar rash
Multiple mouth ulcers
Arthralgia (non-inflammatory joint pain)
Alopecia
Can lead to pleuritic chest pain or pleural effusion.
What causes systemic lupus erythematosus?
Autoantibodies form against multiple molecules in the cell nucleus including ddDNA, dsDNA, ribosomes and histones because nuclear antigens after apoptosis are not cleared properly so the nucleus acts as an antigen to the immune system. This leads to antibody deposition and inflammation in the skin at the dermo-epidermal junction commonly due to cell death as a result of UV light.
What is a common organ affected by lupus?
Kidneys
What are examples of “connective tissue “ autoimmune diseases?
Lupus
Scleroderma
Polymyopsitis
Sjögren’s syndrome
Ubiquitous antigens
How do innate immune cells directly detect and attack antigenic targets?
Innate immune cells directly detect and attack antigenic targets at the site of infection through phagocytosis, cytotoxicity, inflammatory mediators and attract other cells via chemokines
What causes immune cell memory to form?
Cross talk between Dendritic cells, T cells and B cells resulting in immune memory forming to determine a specific learned response within lymphoid tissues
