The Immune System. Albert Urwyler University Hospital Basel, Switzerland

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1 The Immune System Albert Urwyler University Hospital Basel, Switzerland

2 Outline Invaders and Physical Barriers Innate Immune System AdapAve Immune System AnAbodies B Cells Clonal SelecAon T Cells AcAvaAon of the adapave immune System secondary lymphoid Organs Diseases of the immune System Take home message quesaons

3 Invaders and Physical Barriers Invaders Virus Bacteria Parasite Fungi Prion Physikal Barriers (first line of defense) Skin (adult body surface): m 2 Mucous membranes (adult diges1ve, respiratory, reproduc1ve tracts): 400 m 2

4 Outline Invaders and Physical Barriers Innate Immune System AdapAve Immune System AnAbodies B Cells Clonal SelecAon T Cells AcAvaAon of the adapave immune System secondary lymphoid Organs Diseases of the immune System Take home message quesaons

5 Innate Immune System Naturally present in all animals (second line of defense) Macrophages (phagocytosis of invaders) Receptors for recogniaon of danger molecules of invaders (e.g. parts of walls from bacteria) Phagosomes Lysosomes (containing chemicals and enzymes) Fusion

6 Where do Macrophages come from? Bone Marrow B Cell Helper T Cell Killer T Cell Stem Cell Self-renewing Bi-potenAal Cell Natural Killer Cell Monocyte Macrophage DendriAc Cell Neutrophil Eosinophil Mast Cell Megakaryocyte Erythrocyte

7 Life and Work of Macrophages Monocytes stay in the blood for about 3 days before entering the Assues and mature into macrophages Phagocytosis of invaders SecreAon of cytokines Cytokines are hormon-like messengers and cause inflammatory response

8 Outline Invaders and Physical Barriers Innate Immune System Adap:ve Immune System AnAbodies B Cells Clonal SelecAon T Cells AcAvaAon of the adapave immune System secondary lymphoid Organs Diseases of the immune System Take home message quesaons

9 AdapAve Immune System Bone Marrow B Cell Helper T Cell Killer T Cell Stem Cell Self-renewing Bi-potenAal Cell Natural Killer Cell Monocyte DendriAc Cell Neutrophil Eosinophil Mast Cell Megakaryocyte Erythrocyte

10 AdapAve Immune System 99% of animals have only natural barriers and the innate immune system 1% have an adapave immune system (vertebrates) ProtecAon against viruses (an/gen) B cells produce immunoglobulins (an/body): IgG (gammaglobulins): different subclasses, good opsoniser, crosses placenta IgA: main anabody class, protects mucosal surfaces, secreted in milk IgE: samulates mast cells (histamine, anaphylaxis) IgM: first acavated anabody early during infecaon, good opsoniser IgD: samulates basophil acavity in promoang both innate and adapave immunity

11 Structure of AnAbodies Light Chain Light Chain An:gen Binding Region S - S S - S Heavy Chains Fc Region - binds to Fc Receptors - determines class of Immunoglobulins

12 AnAbody Diversity B cells produce anabodies 4 gene segments for heavy chains: A, D, J, C Diversity allows producaon of 100 millions of different B cells 100 millions of different anabodies SelecAve anabodies Only a small amount of geneac informaaon is used for this producaon

13 Clonal SelecAon only about 30 B cells that produce for a given anagen in blood stream Specific B cells must be made on demand About B cell receptors (BCRs) on the surface of B cells recognise the same anagen Binding of anagen to BCR triggers proliferaaon (cell growth, 2 daughter cells within 12 hrs) in the Bone Marrow Clone of B cells aeer 1 week ProducAon of anabody molecules/sec

14 What AnAbodies do? IdenAficaAon and marking of invaders (opsonisa/on) for ingesaon and destrucaon by macrophages Macrophage AnAbody Bacterium Receptor for Fc Region of AnAbody AnAgen

15 T Cells T cells mature in the Thymus T cell proliferaaon is slower (compared to B cells), to build up a clone takes 1 week 300 billion in adults Similar to B cells with T cell receptors (TCRs) 3 main types of T cells Killer T cells (cytotoxic lymphocytes) Helper T cells Regulators T cells

16 Killer T Cells Killer T cells contact virus-infected cells trigger infected cells to commit suicide assisted suicide causes death of infected cells and viruses within this cell solve the problem of hiding virus by recognising and killing virus-infected cells

17 Helper T Cells Important part of immune system team ProducAon of cytokines Interleukin-2 (IL-2) Interferon Gamma (IFN-γ) Helper T Cell IL-2 IFN-γ IL-2 Receptor Killer T Cell IFN-γ Receptor Macrophage

18 Regulatory T Cells acavely suppress acavaaon of the immune system and prevent pathological self-reacavity, i.e. autoimmune disease involved in tolerance severe autoimmune syndrome resulang from a geneac deficiency in regulatory T cells: immune dysregulaaon, polyendocrinopathy, enteropathy, X-linked (IPEX syndrome -> FOXP3-mutaAon) TGF-beta and IL-10 have been implicated in regulatory T cell funcaon

19 AcAvaAon of the adapave immune System Major histocompaability complex proteins (MHC) present infecaon informaaon or anagen to T cells Class I MHC (8 11 amino acids, informaaon about virus infecaon in order to have a look into the cell) Class II MHC (13 25 amino acids, anagen presenang) Two-key system for acavaaon of helper T cells Presented anagen by MHC II Non-specific protein-receptor interacaon ProliferaAon of T cells to build up a clone

20 AcAvaAon of the adapave immune System AnAgen Class II MHC Molecule T Cell Receptor AcAvated Macrophage Helper T Cell AnAgen PresenAng Cell B7 CD28

21 Secondary lymphoid Organs Lymph nodes, lymphaac vessels, thoracic duct Invaders are picked up by anagen presenang cells travelling to lymph nodes B cells and T cells circulate from node to node ( daang bars ) Bringing together an:gens, B cells and T cells, ac:vates the adap:ve immune system

22 Diseases of the immune System Allergies Autoimmune Disease Immunodeficiency Cancer

23 Allergies 25% of populaaon suffers from allergies to common environmental anagens (hay fever, asthma, etc.) ConcentraAon of IgE anabodies in affected subjects is fold higher DegranulaAon of Mast Cells LiberaAon of chemicals such as histamine Environmental and geneac factors

24 Autoimmune Disease Insulin-dependant Diabetes mellitus Myasthenia gravis MulAple sclerosis Rheumatoid arthrias

25 Immunodeficiency GeneAc Effects Non-funcAonal CD40 or CD40L proteins are unable to mount a T-cell dependent anabody response DiGeorge syndrome (22q11.2 deleaon) IPEX syndrome Missing of thymic Assue (lack of funcaonal T-cells) AIDS Immunosupressive therapy (organ transplantaaon)

26 Outline Invaders and Physical Barriers Innate Immune System AdapAve Immune System AnAbodies B Cells Clonal SelecAon T Cells AcAvaAon of the adapave immune System secondary lymphoid Organs Diseases of the immune System Take home message ques:ons

27 The immune System in Anaesthesia & Intensive Care Invaders Physical Barriers Innate Immune System Adap:ve Immune System AnAbodies B Cells Clonal SelecAon T Cells AcAvaAon of the adapave immune System Role of secondary lymphoid Organs

28 The immune System in Anaesthesia & Intensive Care Effects of anaesthesia Immunosupression (Drugs, Stress, Temperature) NegaAve effects of blood transfusion Immune System related Diseases Allergies Autoimmune Diseases Immunodeficiency, AIDS InfecAons, Sepsis Cancer

29 QuesAons A Components of the innate immune system are: 1. Skin 2. Theeth 3. Receptors for danger molecules 4. Hair 5. Mucuous membranes

30 QuesAons B The adapave immune system. 1. is present in all animals 2. produces anagens 3. protects humans selecavely against bacterias 4. involves histamin secreaon 5. Is present in vertrebrates only

31 QuesAons C The following diseases are related to defects of the immune system: 1. cancer 2. rheumatoid arthrias 3. central core disease 4. AIDS 5. DiGeorgy syndrome

32 Answers QuesAons A B C 1 T F T 2 F F T 3 F F F 4 F T T 5 T T T

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