Disorders of the Immune System

Question 1

what are the following hypersensitivity reactions mediated by?

1. Type 1
2. type 2
3. type 3
4. type 4

Answer 1

1. IgE antibodies
2. IgG antibodies
3. IgG antibodies forming immune complexes
4. T cells

Question 2

1. what is chronic granulomatous disease?
2. in what genes are mutations found?
3. what are the effects on the immune system/describe impaired functioning
4. what is this an example of?
5. name clinical signs

Answer 2

1. a genetic disorder with impairments i . the way phagocytes kill bacteria, fungi and parasites
2. phox system (phagocyte oxidase system)
3. immune cells have difficulty forming reactive oxygen compounds, in particular the superoxide radical, that is used to kill certain ingested pathogens. This leads to the formation of granulomata in many organs - a mass of granulation tissue, typically produced in response to infection, inflammation, or the presence of a foreign substance.
4. primary immunodeficiency
5. impetigo, skin and rectal abscesses, recurrent pneumonia

Question 3

1. what cells are affected by HIV?
2. how does HIV differ from AIDs?
3. what is the effect of the loss of cells mentioned in 1?
4. what does a count <200 often lead to?
5. what does a count <50 often lead to?

Answer 3

1. CD4 cells
2. HIV is the infection. It can be diagnosed regardless of the stage/CD4 count
3. reduced/loss of capacity to respond to infections
4. increased risk of pneumonia
5. increased risk of cytomegalovirus infection

Question 4

1. what is the difference between autoinflammation and autoimmunity?
2. Describe the 4 ways in which an infection can lead to the development of an autoimmune disease
   a) molecular mimickry
   b) protien changes/cryptic antigens
   c) superantigens
   d) bystander activation

Answer 4

1. autoinflammation is a prolonged, unwanted innate immune response, whereas autoimmunity is the loss/failure of self/non-self recognition
   2a) pathogens bear elements that are similar enough in amino acid sequence/structure to a self antigen. The immune system can then turn towards the self peptide, leading to the activation of auto-reactive T cells.
   2b) following tissue injury, cell death, oxidative stress, free radical production and reparative changes that occur during infection, protein changes including altered expression, post-translational modifications, denaturation/misfolding or mutations cause proteins that were recognised as self to be recognised as non-self
   2c) superantigens are proteins produced by some micro-organisms or virally infected cells that bind to TCRs, irrespective of antigen specificity. They are potent immune stimulating molecules
   2d) activation of T cells through a mechanism independent of specific TCR stimulation. This can lead to enhanced processing and presentation of self-antigens which indices the expansion of immune response towards self antigens.

Question 5

SELF RECOGNITION AND TOLERANCE

1. what is self recognition?
2. what is self tolerance?
3. Describe positive selection in the formation of self recognition
4. describe negative selection in the formation of self tolerance

Answer 5

1. the ability to recognise proteins as “self”
2. the lack of reactivity to peptide fragments from self proteins
3. some T cells will express a TCR that interacts with self MHC proteins that are expressed on thymus epithelial cells. These T cells survive. Other cells that are unable to interact with thymus epithelial cells (because they are unable to recognise self MHC proteins) undergo apoptosis
4. T cells interract with dendritic cells in the thymus. Cells that recognise self antigens/peptide fragments are eliminated.

Question 6

1. describe the cellular mechanism of an allergic response
2. describe the sensitisation process to an allergen
3. What is atopy?
4. why is an allergic response to an allergen relatively potent?
5. describe the immediate phase
6. describe the late phase
7. name 5 examples of allergic responses

Answer 6

1. IgE bind to mast cells via Fcε1 receptors. Antigen binding to IgE causes degranulation of mast cells and the release of granzyme and histamine
2. allergen is taken up by an APC and presented to a T cell. the T cell differentiates into a Th2 cell and produces cytokines. Th2 presentation of antigen to B cells, and cytokines promote class switching so that produces IgE antibodies
3. predisposition for an IgE mediated immune response. Atopic triad - asthma, eczema, hayfever. Familial link
4. because IgE antibodies are preformed and loaded onto mast cells, so a response can occur quickly.
5. cross linking of 2 IgE molecules on the surface of mast cells results in degranulation and release of inflammatory mediators.
   Histamine and leukotrienes promote smooth muscle contraction, chemotaxis and promotes oedema. Cytokines are pro-inflammatory. Tryptase activates complement. prostaglandins mediare vasodilation and increased vascular permeability.
6. migration of leukocytes, particularly eosinophils, which release peroxidase causing further tissue damage.
7. hayfever (allergic rhinitis), asthma, eczema, urticaria, anaphyalxis

Question 7

1. which antibodies are type II hypersensitivity reactions mediated by?
2. what is the effect of these responses?
3. name and describe 2 examples of type II hypersensitivity reactions
4. name 3 other examples of type II hypersensitivity reactions

Answer 7

1. IgG or IgM
2. tissue cytotoxicity (via complement or antibodies) or modifying receptors to change cellular function
3. rhesus disease/haemolytic disease of the newborn - development of anti-D antibodies which cross the placenta and mount an immune response to the Rh+ RBCs (cytotoxicity)
   drug induced haemolytic anaemia - drugs bind to cells and act as an immunological hapten; antibodies recognise the drug in combination with cells.
4. Goodpasture syndrome - IgG antibodies recognise collagen within the kidney basement membrane
   Myasthenia Gravis - antibodies block the AcHr at the NMJ
   Graves disease - antibodies bind to the thyroid hormone receptor, causing activation of the receptor and increased thyroid hormone production

Question 8

1. What are type III hypersensitivity reactions mediated by?
2. what is the role of antibody-antigen complexes normally?
3. where do these complexes normally deposit?
4. How do these complexes cause damage?
5. Name and describe 3 types of Type III hypersensitivity reactions

Answer 8

1. IgG immune complexes
2. help in the clearance of antigens. They are normally cleared by complement
3. kidneys (leading to glomerular nephritis)
   blood vessels (leading to vasculitis)
   synovial joints (leading to arthritis)
4. constant activation of complement due to a failure of immune complex clearance results in tissue damage
5. Systemic Lupus Erytheromatosus - auto-antigen is DNA. Failure of clearance of apoptotic celss
   Arthus reaction - complication of vaccination
   Serum Sickness - immune complex formation in response to a foreign protein or serum (e.g. anti-venom)

Question 9

1. what is the name given to agents that are capable of inducing an immune response?
2. What type of immune response is triggered in a Type IV reaction?
3. What do CD4 cells produce in response to secondary exposure to agent? (4)
4. name 3 examples of these reactions.

Answer 9

1. Haptens
2. Th1 response
3. IFN-gamma and TNF-alpha - tissue destruction and inflamamtion
   IL-2 to activate T helper and T cytotoxic cells
   chemokines
   IL-3 and GM-CSF - production of monocytes and macrophages
4. contact dermatitis
   metal allergies

Question 10

1. What is citrillination
2. what environmental factor can lead to citrullination?
3. Which autoimmune disease is citrullination associated with?

Answer 10

1. the conversion of arginine into citrulline; citrulline is not one of the standard 20 a.a.s encoded by DNA. Autoantibodies therefore can attack these citrullinated proteins
2. smoking
3. rheumatoid arthritis