Hypersensitivity and Autoimmune disorders

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1 Hypersensitivity and Autoimmune disorders Dr Udani Kiriwandeniya Consultant Histopathologist/Senior lecturer

2 Learning utcomes At the end of this section the student should be able to 1.Briefly describe the types of hypersensitivity reactions giving examples 2.Define autoimmune diseases. List the types giving examples

3 Immune system To protect the body against the invasion by foreign organisms. However in certain situations the exogenous antigen or the presence of endogenous antigen mounts an unduly severe, tissue damaging inflammatory reaction.

4 Types of hypersensitivity Divided in to four types depending on the mechanism of immune recognition and the inflammatory mediator system involved. Type I hypersensitivity - Atopic or Anaphylactic reactions Type II hypersensitivity - Antibody dependent cell damage Type III hypersensitivity - Immune complex disease Type IV hypersensitivity - Cell mediated, delayed type hypersensitivity

5 Type I hypersensitivity- -Atopic or Anaphylactic Reaction -Immediate reaction -Majority of manifestations are mild -May results in life threatening reactions - Previously exposure to the antigen, IgE production(previously sensitised to an Ag) - IgE binds to the receptors in the tissue mast cells and the basophils When get exposed to the same antigen again the binding of antigen to cell bound IgE antibodies result mast cells and basophils activation and degranulation.

6 Mast cells granules contain preformed mediators- histamin, heparin, proteases. Histamin and other mediators trigger blood vessels to leak and smooth muscles to contract leads to shock and muscle spasms. The type I reaction can be localised or generalised.

7 Localised Type I reactions Ex: Urticaria Asthma Hay fever Generalised Type I reactions Binding of the Ag to IgE on circulating basophils results severe reaction with bronchospasm, peripheral vasodilatation and circulatory collapse, known as anaphylaxis. Ex: Penicillin allergy Bee sting

8 Type II hypersensitivity Antibody dependent cell damage (Cytotoxicity) Ab binds to the tissues directly. Cell damage can occur due to three main mechanisms.

9 1. Complement activation. Fixation of Ab to the cell surface produces lysis via formation of the membrane attack complex. The insertion of membrane attacking complex to the cell membrane results in cell lysis. 2. Opsonisation Cells which are coated with antibodies and complement C3b are susceptible to phagocytosis. 3. Antibody dependent cell mediated cytotoxicity NK cells, neutrophils, and macrophages attack the target cell which are coated with IgG. The mediation antibodies can be auto antibodies or alloantibodies.

10 Examples of type II hypersensitivity Autoantibody mediated Auto immune haemolytic anaemia Auto immune thrombocytopaenia (RBC are coated with auto antibodies. These antibodies promote binding of red cells to the macrophages and destruction. Usually antibody type is IgG or IgM. They also promote complement activation and red cell destruction) Alloantibody mediated Haemolytic disease of the newborn (page 67)

11 Type III hypersensitivity Immune complex disease Antibodies directly reacts with antigens forming antigen-antibody complexes. These complexes can be deposited either locally or at a distant site resulting tissue damage (systemic type) They usually deposit in vessel walls resulting tissue damage

12 Localised Immune complex disease (Arthur reaction) Refer page 67 Systemic immune complex disease - post streptococcal glomerulonephritis - systemic lupus erythematosus

13 Type IV hypersensitivity Mediated by sensitised T cells Takes time for primed T cells to react and hence there is a delay The reaction takes at least 12 hours to develop and therefore known as delayed hypersensitivity.

14 Classical example for this is the tuberculin (mantoux) test - Takes 12 hrs to show the reaction - Refer page 68

15 Autoimmune Disorders patients mount immune response to their own tissues resulting tissue and organ damage. Autoantibodies The immune system exhibits tolerance to own antigens. In autoimmune disorders there is a failure of the mechanism of self tolerance.

16 Organ specific autoimmune diseases The organ specific autoimmune diseases are characterised by chronic inflammatory cell destruction of a particular organ. The destruction is mediated by the autoantibodies which react with normal cellular components of the target organ. Non organ specific autoimmune diseases Often called the connective tissue or collagen vascular diseases. These disease are characterised by acute and chronic inflammatory lesions of many organs and by the presence of circulating antibodies.

17 Refer page 69 (5.9) Few examples for each two types Organ specific/non organ specific

1) Siderophores are bacterial proteins that compete with animal A) Antibodies. B) Red blood cells. C) Transferrin. D) White blood cells. E) Receptors.

Prof. Lester s BIOL 210 Practice Exam 4 (There is no answer key. Please do not email or ask me for answers.) Chapters 15, 16, 17, 19, HIV/AIDS, TB, Quorum Sensing 1) Siderophores are bacterial proteins