IMD course Lectl for Triploi University.ppt

Immunologically mediated diseases course ‫ا ألمراضذاتا لطبيع ة ا لمناعية‬ Immunology II Prof. Salem Mohamed Salem Elghmati Tripoli University Faculty of Pharmacy Department of microbiology and immunology Lecture 1 &2 ‫مراجع...

Immunologically mediated diseases course ‫ا ألمراضذاتا لطبيع ة ا لمناعية‬ Immunology II Prof. Salem Mohamed Salem Elghmati Tripoli University Faculty of Pharmacy Department of microbiology and immunology Lecture 1 &2 ‫مراجع للمنهج‬ ‫‪2‬‬  Immunologically mediated diseases course Introduction  Definition of immunologically mediated diseases?  Immunologically mediated diseases (IMD): is a term used to describe the diseases where their underling cause is an immune response to an invading agents such as microorganisms or the auto immune reactions of the immune cells & its immunological products to host own tissues or organs resulting in either halting their functions or their destruction. :‫ تعريف اإلمراض ذات الطبيعة المناعية‬ ‫ هو مصطلح يستعمل لوصف اإلمراض التي سبب نشأتها هو الرد‬ ‫المناعي لجسم اإلنسان نتيجة تعرضه لغزو خارجي من الجراثيم‬ ‫او المواد الطبيعة المحيطة به او الناتج من نواتج الجهاز المناعي‬ ‫أو الخاليا المناعية الموجهة لذات الجسم والتي تؤدي إلى‬ ‫تعطيل عمل أعضاء الجسم او تدميرها و فقدان الجسم لوظائف‬.‫تلك األعضاء‬ 3  Definitions‫ت[[[ع[ري[فات‬  1 -What is an immune response?  Immune response (IR) It is made up of a complex sequence of events, it is triggered by the introduction of stimulus (immunogen or antigen) and usually culminates in the elimination of the provoking agent. :‫الرد المناعي‬  ‫ه[و عبارة ع[ن مجموع[ة م[ن إحداث متتابع[ة يقوم به[ا‬  ‫ بس[[بب دخول مثي[[ر ام امينوجي[[ن او‬،‫الجهاز المناع[[ي‬.‫انتيجين‬ ‫هذا الرد المناع[[ي اعتيادي[[ا يخل[[ص الجس[[م م[[ن ذل[[ك‬ .‫الجسم الغازي المسبب له‬ 4  Immunologically mediated diseases course  2- Immunogen : It is a molecule that can induce an immune response..‫ هو جزئي يستطيع أن يسبب بشكل مباشر الرد المناعي‬  3 - Antigen :It is a molecule that is able to react with the product of the immune system particularly the antibody it may or may not induce an immune response. ‫ه[[و جزئ[[ي يس[[تطيع ان يتفاع[[ل م[[ع نوات[[ج الرد المناع[[ي و‬  ‫بالذات مضاد األجس[ام و يمكن[ه أ[و ال يمكن[ه التس[بب ف[ي الرد‬.‫المناعي‬ 5  ‫أنواع الرد المناعي‬  Our bodies do produce specific and non-specific immune response. The latter is a function of innate immune system which is responsible for the natural immunity while the former is function of the adaptive immune system and responsible for the acquired immunity. ‫ أجس[امنا تنت[ج نوعان م[ن الرد المناع[ي أ[م رد مناع[ي عام أ[و‬.‫رد مناعي خاص‬ ‫ الرد المناع[ي العام مس[ئول عل[ى المناع[ة الطبيعي[ة بينم[ا الرد‬.‫المناعي الخاص مسئول على المناعة المكتسبة‬  Table (1) summarizes the main difference between the two systems. ‫ ي[[بين الفرق بي[[ن جهاز المناع[[ة الطبيعي[[ة و‬1 ‫ جدول رق[[م‬.‫المناعة المكتسبة‬ 6  Table (1) the differences between Innate and adaptive immune system Property ‫ا لخاصية‬ Innate immune system Adaptive immune system ‫جهاز المناعة المكتسبة جهاز المناعة الطبيعية‬ Type of immunity Natural Acquired ‫نوع المناعة‬ ‫طبيعية‬ ‫مكتسبة‬ Physical barriers Skin and mucous membrane None ‫ال ت وجد‬ ‫الحواجز الطبيعية‬ ‫الجلد و االغشياء المخاطية‬ Enzymes e.g. lysozyme Soluble factors Antibodies & lymphokines acute phase proteins ‫مواد ذائبة‬ e.g. C.R.P interferon. Macrophages, neutrophiles T cells B cells and Cells ‫ا لخاليا‬ and NK cells monocytes. Self-non-self discrimination Yes Yes ‫التميز الذاتي للجسم‬ Specificity No Yes ‫خصوصية التفاعل‬ Memory Yes No ‫تذكر الجسم الغريب‬ 7  Immunologically mediated diseases course For third year pharmacy student  Prof. Salem Mohamed Salem Elghmati Tripoli University  Faculty of Pharmacy  Department of microbiology and immunology  Lecture 3 &4 8 ‫عالقة الجهاز المناعي الطبيعي و الجهاز‬ ‫المناعي المكتسب‬ ‫المناعية‬  With respect ‫باإلمراض‬ to IMD diseases, both the elements of the innate immune system and the elements of the adaptive immune system are responsible for these diseases. ‫ باإلشارة إل[ى اإلمراض المناعي[ة فأ[ن ك[ل م[ن جهاز المناع[ة‬ ‫الطبيعي[ة و جهاز المناع[ة المكتس[بة مس[ئولين ع[ن نشأ[ة هذه‬.‫اإلمراض‬  They cooperate to manifest these diseases. A typical examples of this cooperation is the lysis action of the complement (an element of the innate system) to the invading foreign body when the its specific antibody (an element of the adaptive immune response) is combining to it. ‫ فعندم[ا‬،‫ الجهازي[ن يتعاونون ف[ي اس[تكمال نشأ[ة هذه اإلمراض‬ ‫يتكون مضاد أجس[ام م[ن الجهاز المناع[ي المكتس[ب تس[تخدمه‬ ‫خالي[[ا الجهاز المناع[[ي الط[[بيعي او المكم[[ل لتحلي[[ل الخالي[[ا‬.‫المصابة او الضارة بالجسم‬ 9 ‫منافذ دخول الجسم الغازي لجسم اإلنسان‬ ‫‪ The‬‬ ‫‪immunogen may encountering our bodies via three main‬‬ ‫‪routes.‬‬ ‫‪ ‬هناك ثالث مناف[[ذ ه[[ي الدم و الجل[[د و مخاط الجهاز التنفس[[ي او‬ ‫الهضمي‪.‬‬ ‫‪ Via the blood stream to the spleen, which will act as the principle‬‬ ‫‪site of immune response.‬‬ ‫‪ ‬إ[[ن كان دخول الجس[[م الغازي ع[[ن طري[[ق الدم يص[[بح الطحال ه[[و‬ ‫الساحة الرئيسية للرد المناعي‪.‬‬ ‫‪ Localized Via the skin, the immunogen is transferred through the‬‬ ‫‪afferent lymphatic to the nearest lymph node which will act as the‬‬ ‫‪principle site of immune response.‬‬ ‫‪ ‬إ[ن كان دخول الجس[م الغازي ع[ن طري[ق الجل[د ينتق[ل هذا الجس[م‬ ‫الغازي ع[[ن طري[[ق األوعي[[ة اللمفاوي[[ة الداخ[[ل ال[[ى اقرب عقدة‬ ‫لمفاوية و تصبح العقدة هي الساحة الرئيسية للرد المناعي‪.‬‬ ‫‪10‬‬ ‫منافذ دخول الجسم الغازي لجسم اإلنسان‬  Via the mucosa of respiratory tract or the gastrointestinal tract where the tonsils or peyer’s patches will be the principle site of immune response. ‫ إ[ن كان دخول الجس[م الغازي ع[ن طري[ق المخاط ف[ي الجهاز‬ ‫التنفس[[ي او الهضم[[ي تص[[بح اللوزتي[[ن او عق د باي ر ه[[ي‬.‫الساحة الرئيسية للرد المناعي‬  The immune response took place in either the spleen or in the lymph nodes depending on the route of entrance of the immunogen into our bodies. ‫بالتالي فأن الرد المناعي سيحدث ام الطحال او العقد اللمفاوية‬.‫حسب دخول الجسم الغازي ألجسامنا‬ 11 ‫الجهاز اللمفاوي‬ ‫‪12‬‬  ‫آلية عمل الجهاز المناعي‬ Reaction of our bodies to the antigen  In our bodies, Our immune system discriminates self from non-self antigen and reacts against non-self antigens. ‫ ف[[ي أجس[[امنا الجهاز المناع[[ي يفرق بي[[ن أجس[[ام الجس[[م و‬.‫األجسام الغريبة‬  Following a primary contact with antigen (Ag), there are weak adaptive, and non adaptive response, but if the same Ag persists or is encountered a second time there is a much enhanced specific response to that Ag. ‫ بع[[د التعرض األول للجس[[م الغري[[ب يحدث رد مناع[[ي خاص و‬ ‫ضعي[ف و رد مناع[ي عام و عن[د التعرض الثان[ي للجس[م الغري[ب‬ ‫تتضاع[[ف قوة الرد المناع[[ة الخاص وتبق[[ى قوة الرد المناع[[ي‬.‫العام كما هو‬ 13  ‫خصائص الجهاز المناعي المكتسب‬  Un-like the non-adaptive immune response, the characteristics of the adaptive immune response is the specificity and the memory. ‫ بخالف الجهاز المناع[ي العام الط[بيعي إ[ن م[ن خص[ائص الجهاز‬.‫المناعي المكتسب هي الخصوصية و التذكر للجسم الغازي‬  The element of the adaptive immune system are three major cell types namely monocytes, thymus-derived T lymphocytes i.e. T cells and bone marrow derived lymphocytes i.e. B cells. These cells interact with each other either directly or via interleukins (substances produced by these cells). ‫ خاليا الجهاز المناعي المكتسب هم‬ Monocytes , T lymphocytes and B lymphocytes  ‫ هذه الخاليا تتواصل مع بعضها البعض ام بشكل مباشر او‬.‫ بواسطة سوائل مناعية تنتج منها تسمى انترلوكين‬14  ‫أنواع الرد المناعي المكتسب‬  The response of these cells to the immunogen either require Ag presenting cells i.e. monocytes or macrophages and this type of immune response is called T cell dependent Ag. ‫ الرد المناع[ي الذي يحتاج تقدي[م الجس[م الغازي إل[ى خالي[ا‬. T cell dependent Ag ‫ت اللمفاوية يسمى‬  and that who do not require Ag presenting cells is called as T cell independent Ag e.g. trigger of B lymphocytes with pokeweed mitogen (PWM) may stimulate it directly to produce antibodies. ‫ الرد المناع[[ي الذي ال يحتاج تقدي[[م الجس[[م الغازي إل[[ى خالي[[ا ت‬ ‫اللمفاوية يسمى‬. T cell independent Ag  Figure 1 show T cell dependent Ag response for virus infection and fig. 18-24 for tumor..‫ توضح الرد المناعي المعتمد لغزو فيروسي‬1 ‫ صورة‬ 15  Immunologically mediated diseases course  Prof. Salem Mohamed Salem Elghmati Tripoli University  Faculty of Pharmacy  Department of microbiology and immunology  Lecture 5 &6 16 ‫وات الرد المناعي المكتسب‬ ‫‪17‬‬  ‫مصادر اإلمراض‬ There are three main origins for diseases initiation:.‫ ثالث مصادر أساسية لإلصابة باإلمراض‬ Infectious mediated diseases; due to infection with microorganisms and parasites..‫ نتيجة اإلصابة بالعدوى من الجراثيم‬ Organ disorder mediated diseases; such as peptic ulcer, cancer, atrophied heart, hypertension, accidental injury …. etc..‫ نتيجة لتدمر العضو لخلل في نفس المريض‬ Immunological mediated diseases ‫ نتيجة الرد المناعي العكسي للجسم (( اإلمراض‬.))‫المناعية‬ . 18  Introduction to IMDs Not all immune system responses produce a desirable result, such as immunity to disease. Occasionally the reactions of the immune system are harmful. Hay fever, transplant rejection, and autoimmunity are examples of harmful immune reactions. Infection and immunosuppression are examples of failure of the immune system. Superantigens activate many T-cell receptors, resulting in the release of excessive amounts of cytokines that can cause adverse host 19  ‫اإلمراض المناعية ثالث أنواع‬ According to the cause the immunological mediated diseases can be classified into three main types. ‫ حسب أسباب نشؤ المرض يمكن تقسيم‬ :‫األمراض المناعية إلى ثالثة أنواع‬ 1 -Immunodeficiency diseases..‫ أمراض العوز المناعي‬-1  2-Allergy diseases or hypersensitivity diseases..‫ أمراض الحساسية‬-2  3-Disordered immune regulation or autoimmune diseases..‫ أمراض المناعة الذاتية‬-3  20 1-Immunodeficiency diseases: 1-‫أمراضا لع وز ا لمناعي‬  Collectively we may say that the main four components of the immune system consists of: ‫ م[[ن المعروف أ[[ن المكونات األرب[[ع للجهاز المناع[[ي الط[[بيعي او‬ :‫المكتسب هي‬  Antibody mediated immunity (B cell function). B ‫ المناع[ة م[ن خالل مضادات األجس[ام وه[ي تعن[ي وظيف[ة خالي[ا‬-1 .‫المناعية‬  Cell mediated immunity (T cell function)..‫ المناعية‬T ‫ المناعة الخلوية وهي تعني وظيفة خاليا‬-2   Phagocytosis (macrophage and neutrophiles function)..‫ البلعمة بواسطة خاليا الماكروفاج و خاليا البيضاء المتعادلة‬- 3   Complement (C1 – C9 complement components) responsible for cell lysis.. C1 – C9 ‫عمليات المتمم لتفتيت الخاليا بواسطة مكوناته من‬-4  21  1-Immunodeficiency diseases: 1-‫أمراض‬ ‫ا لع وز ا لمناعي‬ Any deficiency in these main components may result immunodeficiency diseases which in turn will lead to destruction to our bodies and death. ‫أي نقص في تلك المكونات او خالل في‬ ‫عملها سيؤدي إلى أمراض العوز المناعي‬ ‫التي بدورها ستدمر الجسم و تتسبب في‬.‫الوفاة‬ 22  ‫‪1-Immunodeficiency diseases:‬‬ ‫أمراضا لع وز ‪1-‬‬ ‫ا لمناعي‬ ‫‪ The‬‬ ‫‪deficiency in these main components may result from:‬‬ ‫‪ ‬العوز المناعي في األربع مكونات قد ينتج من‪:‬‬ ‫‪ Congenital: e.g. gene deletion and rearrangement.‬‬ ‫‪ ‬م[ن الع[ام[ل الوراث[ي كم[ا ه[و الحال ف[ي فقدان جي[ن (مورث) او‬ ‫حصول إعادة ترتيب للجين‪.‬‬ ‫‪ Acquired: e.g. post viral infection or drug abuse.‬‬ ‫‪ ‬مكتسب عقب اإلصابة لعدوى فيروسية او سوء استمال دواء‪.‬‬ ‫‪ Vitamin deficiency : e.g. B12.‬‬ ‫‪ ‬فقدان او نقص فيتامينات مثل ‪. B12‬‬ ‫‪ Autoantibody: e.g. antibody to T cells.‬‬ ‫‪ ‬تكون مضاد أجسام ذاتية مثل مضاد لخاليا ‪ T‬المناعية‪.‬‬ ‫‪23‬‬  Clinical features associated with immunodeficiency disease These can be classified into three categories:.‫وهي ثالثة درجات من العالمات‬ a) Highly suspicious features when the patient suffer from chronic infection or recurrent infections or unusual infecting agents or in case of incomplete response to treatment. ‫عالمات عالي[[ة التأكي[[د مث[[ل عندم[[ا يعان[[ي المري[[ض‬ ‫عدوى مزمن[ة او يعان[ي م[ن توال[ي العدوى م[ن حي[ن‬ ‫إل[ى آخ[ر او م[ن اإلص[ابة عدوى غي[ر معتاد اإلص[ابة‬.‫بها او عدم وجود استجابة للعالج‬ 24  Clinical features associated with immunodeficiency disease b) Moderate suspicious features: when there is skin rash or chronic diarrhea hepatosplenomegaly or growth failure. ‫عالمات متوس[طة التأكي[د مث[ل عندم[ا حدوث طف[ح‬ ‫عل[[ى الجل[[د او وجود إس[[هال مزم[[ن او تضخ[[م ف[[ي‬.‫الطحال و الكبد او فشل في نمو المريض‬ c) Specific features when here is case of ataxia, thrombocytopenia or eczema. ‫عالمات خاص[[ة بإمراض معين[[ة مث[[ل تكس[[ر ف[[ي‬.‫الصفائح او ظهور الصدفية‬ 25 ‫بارات تشخيص العوز المناعي‬ ‫‪26‬‬  Evaluation depends on the deficient component  For antibody deficiency can be evaluated by:  Determination of immunoglobulin levels.  Suchick `s test i.e. IgG antibody response.  IgM antibody function.  For cell mediated immunity can be evaluated by:  Total and differential leukocyte count.  Total lymphocyte population and its subsets.  Skin test delayed hypersensitivity test Tuberculin test.  Response of T cell to antigens lymphocyte stimulation test. 27  For phagocytosis can be evaluated by:  Determination of total polymorphnucealar cell count PMN  Determination of PMN metabolic function.  Phagocyte assays.  For complement deficiency it is evaluated by : 1- the determination of its serum levels by immunodiffusion or ELISA assays. 2- Complement fixation test. 28  The principal function of the immune system is to prevent microbial infection.  Therefore, disorders resulting in impaired function of the immune system (immunodeficiency) result in increased susceptibility to infection.  Immunodeficiency can arise from an intrinsic defect (Innate) of a component of the immune system [primary immunodeficiency (PID)]. 29 Alternatively,immunodeficiency may be secondary (Acquired) to another pathological condition, which adversely affects immune function, as a result of other diseases or conditions such as: » HIV infection » Malnutrition » Immunosuppression Both primary and secondary immunodeficiencies result in increased susceptibility to infection. 30  Classification Primary Secondary Immunodeficiency Immunodeficiency Most are genetically May arise as determined complications of cancers, infestations, malnutrition, or side effects of immunosuppression, Irradiation and Less common chemotherapy. More common 31  From a clinical perspective, immunodeficiencies can be classified into eight categories: 32 Primary Immunodeficiency Diseases occur when there is a defect in any one of the many steps during lymphocyte development 33  Primary Immunodeficiency Diseases Manifestations: Disorders are manifested at different levels including : ◦ B cell, T cell, phagocytic cells and complement system. ◦ Most prominent manifestations: dermatological conditions such as eczema and cutaneous infections. 34  Symptom s: Recurrent respiratory infections. Persistent bacterial infections →sinusitis, otitis and bronchitis. Increased susceptibility to opportunistic infections (OIs) and recurrent fungal yeast infections. Skin and mucous membrane infections. Resistant thrush, oral ulcers and conjunctivitis. Diarrhoea and malabsorption. Failure to thrive and delayed or incomplete recovery from illness. 35  Etiology Aetiology associated with Genetic defects of missing enzymes. Specific development impairment (pre-B-cell failure). Infections Malnutrition Drugs 36  Classification of Primary IDDs 1. Primary B cell immunodeficiency: I. X-linked A gammaglobulinaemia (Burton's disease) II. Selective IgA deficiency 2. Primary T cell immunodeficiency: I. Di George syndrome II. Ataxia – telangiectasia III. Wiskott – Aldrich syndrome IV. Acquired immunodeficiency V. Chemotaxis deficiency VI. Chronic granulomatous disease VII. Chediak – Higashi syndrome VIII. Leukocyte adhesion deficiency 3. Complement system deficiency 37  1. Primary B Cell Immunodeficiency Common variable immunodeficiency associated with – Mature B cells failure to differentiation into mature plasma secreting cells (antibody forming cells). I. X-linked A gammaglobulinaemia (XLA)/Bruton’s Disease: Deficiency of B cell tyrosine kinase causing failure in the development of pre-B cell maturation to B cells. Majority of XLA patients show: – Profound hypogammaglobulinaemia involving all immunoglobulin classes with