Immunology. Lecture- 8

Transcription

1 Immunology Lecture- 8

2 Immunological Disorders Immunodeficiency Autoimmune Disease Hypersensitivities

3 Immunodeficiency 1. Immunodeficiency --> abnormal production or function of immune cells, phagocytes, or complement. Can be congenital or acquired. Congenital -->most genetic errors occur on the X chromosome - thymicaplasia (born without a thymus) - Chediak-Higashi syndrome (affects neutrophil granules) - Agammaglobunlinemia (no antibody production) - C2 deficiency (missing C2 compliment protein) - Bare Lymphocyte Syndrome (no MHC class II proteins) - Selective IgA deficiency (B cells do not make IgA) Acquired Immunodeficiency--> 1. AIDS Once HIV (Human Immunodeficiency Virus) enters the body, it attaches to receptors on the surfaces of the T cells interferes with helper T cells due to destruction by the HIV virus The RNA virus can fit the CD4 receptor and invade the helper T cell and therefore will decrease cell mediated immunity. The body does produce antibodies against HIV, but HIV replicates within cells of the immune system, therefore it is likely to bind with antibodies. HIV kills off most of the helper T cells 2. Immunosuppressive drugs 3. Radiation treatments

4 Autoimmune Disease 2. Autoimmune disease --> The immune system does not distinguish between self and non self antigens The body produce antibodies and sensitized T cells that attack its own tissues When the individual's immune system ceases to tolerate self-antigens and response to that antigen to cause actual tissue destruction. Usually occurs after a microbial infection, bacterial or viral and most often in older patients due to a loss of self-tolerance Four factors influence the development of autoimmune disease: Genetic, Environmental, Endocrine, and Psychoneuroimmunological [the influence of stress and neurochemicals on the immune system]. Examples of autoimmune diseases Multiple sclerosis- white matter of brain and spinal cord are destroyed Juvenile diabetes- destroy pancreatic beta cells that production insulin Rheumatoid arthritis destroy joints Systemic lupus erythromatosus ( SLE)- affects kidney, heart, lung and skin. Glumorulonephrititis impairment of renal function rheumatic fever- caused by strep throat Causes : * Microbe antigen resembles self antigen and there is a cross reaction * Genetic background, especially changes that occur in MHC regions. The immune system will now target normal cells and creates auto-antibodies.

5 Autoimmune Disease Type I Autoimmunity Antibodies that were made in response to an infectious agent such as a virus, but these antibodies attack self due to similarities between viral and self proteins. Example: Hepatitis C causing autoimmune hepatitis Type II Autoimmunity Antibody reactions to cell surface antigen, with no cytotoxic destruction Examples: Grave's Disease : antibodies attach to thyroid gland cells. Type III Autoimmunity Immune complexes deposited in tissues, resulting in inflammation and destruction. Examples: SLE - antibodies for the basement membrane and DNA of own cells. RA - IgM binds to IgG at Fc receptors and immune complexes are deposited in the joints with inflammation leading to the destruction of bone and cartilage Type IV Autoimmunity T cells and macrophages attack normal tissue Examples: MS- myelin sheath of nerve attacked. Hashimoto's Thyroiditis - destruction of thyroid glands. Insulin dependent DM - destruction of beta cells of pancreatic islets

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7 Hypersensitivities 3. HYPERSENSITIVIES: ( allergy reactions) state of increased response to the presence of an allergic antigen leading to damage in tissues (Abnormal, vigorous immune response) Reactions can be classified as immediate or delayed. Different types of hypersensitive depending on the amount of time and the cells involved. These responses cause symptoms that range from uncomfortable (e.g., itchy, watery eyes or sneezing) to life threatening (e.g., allergic asthma, anaphylaxis, bronchoconstriction, or circulatory collapse). Hypersensitivity are classified into five types, differences in timing, mechanism, pathophysiology, and clinical manifestations. Each type may occur alone or in combination with one or more other types. Type I - Anaphylaxis Type II - Cytotoxic Type III - Immune complex mediated Type IV - Delayed type of hypersensitivity

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9 Hypersensitivities Type I: Hypersensitivities ( anaphylactic reaction) immediate, occurs within 2-30 minutes of contact with allergen involve IgE antibodies The reaction is result when allergens antigen bind to mast cells, activated mast cells release histamine (from IgE binding mast cells) which increase in blood flow and fluids to surrounding area ( sneezing, runny eyes, nose etc). These released substances have the potential to cause tissue damage (dangerous). These inflammatory mediators increase capillary permeability, vasodilation and contraction of smooth muscle. Localized ( from contact or inhaled or ingested antigen) reactions in skin --> hives, urticarial- respiratory --> Allergic reactions can create asthma, hay fever GI--> vomiting/diarrhea (food allergy) Systemic: (shock from injected antigens ) --> Anaphylactic shock, impairs smooth muscle of bronchioles and blood vessels which effect air exchange and blood pressure Atopy --> allergies to environmental antigens due to genetic causes of large amounts of IgE

10 Upon initial exposure to allergen antigen, B cells are stimulated to differentiate into plasma cells and produce specific IgE with the help of T cells. Once synthesized, IgE binds to Fc receptors on mast cells (basophils and eosinophils can also be activated) which then sensitizes these cells and leaves the two antigen binding sites free. When a second exposure occurs, the allergen cross links IgE antibody attached to mast cells or basophils and causes a degranulation and release of mediators such as histamine.

11 Anaphylaxis It is an immediate life threating system reaction that can occur on exposure to particular substances It is an immediate ( type I hypersensitivity) immunologic reaction, results from IgE antibody This reaction affects many tissues and organs Death may occur due to respiratory tract spasm and constriction or collapse. Causes: Anaphylaxis Food ( egg, milk, fish peanuts, wheat and chocolate) Medications ( penicillin, NSAD s) Insect stings ( bees, ants)

12 Hypersensitivities Subacute Hypersensitivity hours : Type II Hypersensitivity --> ( cytotoxic reaction) antibody dependent Cytotoxic reactions are mediated by IgG and IgM. The antibody reacts directly with the antigen that is bound to the cell membrane to induce cell lysis through complement activation with exposure of C-1 binding sites on IgG or IgM. called cytotoxic reactions because it results in the destruction of host cells. Examples of Diseases: Hemolytic anemia. drug reactions blood transfusion reactions

13 Hypersensitivities Subacute Hypersensitivity hours : Type III Hypersensitivities ( immune complex reaction) IgG and IgM bind antigen, forming antigen-antibody (immune) complexes. These activate complement, which results in PMN chemotaxis and activation. PMNs then release tissue damaging enzymes. Tissue damage present in autoimmune diseases immune complex that is not able to be removed by macrophages due to overaccumulation. Complement pathways activated and a variety of inflammatory processes are initiated and damage is caused, primarily in blood vessels [vasculitis], kidneys [glomerularnephritis], joints [arthritis]. Diseases resulting from Type III hypersensitivity reactions can be placed into three categories Chronic Immune complex: persistent infection [viral, bacterial, protozoal] result in a weak antibody response and complex accumulates in host tissue Prolonged Immune complex: autoimmune disease continues production of autoantibodies to self antigen and complexes are deposited in host tissue Local Immune complex: immune complexes form at body surfaces [lungs] due to repeated exposure to allergen.

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15 Hypersensitivities Type IV : Delayed Hypersensitivities ( cell mediated reaction) 1-3 days, involves activated T cells (cytotoxic & helper) initiated by T-lymphocytes and mediated by effector T-cells and macrophages. This response involves the interaction of antigens with the surface of lymphocytes. Macrophages present antigen to helper T cells, which causes them to release cytokines. Sensitized lymphocytes can produce cytokines, which are biologically active substances that affect the functions of other cells and attract more lymphocytes, macrophages, and basophils to the area. This type of reaction takes hours, or longer, after contact with the antigen to fully develop. Examples of this reactions are: dermatitis, poison ivy / oak, jewelry, cosmetics, herpes simplex, many chronic infectious diseases, including tuberculosis, fungal infections, leprosy, leishmaniasis, candidiasis.

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17 Type I: Immediate Hypersensitivity (Anaphylactic Reaction) Type II: Cytotoxic Reaction (Antibody-dependent) Type III: Immune Complex Reaction Type IV: Cell-Mediated (Delayed Hypersensitivity)

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