The immune system gone wrong Diseases of immunity
- Slides: 44
The immune system gone wrong: Diseases of immunity
Diseases of immunity • Failure of effector mechanisms: insufficient immune response – Tolerance – Immunodeficiency • Failure of regulatory mechanisms: hyperactive immune response – Hypersensitivity – Allergy – Autoimmunity
Immunodeficiency diseases Generalized • Complete failure of adaptive immunity • Severe Combined Immunodeficiency Syndrome (SCID) • Widespread susceptibility to many agents • Generally fatal Partial • Failure of selected immune effectors • Partial susceptibility to some agents • Rarely fatal, often subclinical Tolerance to specific pathogens
X X No T cells No B cells
Severe Combined Immunodeficiency: David, the bubble boy
Partial immunodeficiencies
Tolerance to a single pathogen • Factors that promote tolerance – Young age – Large dose – Soluble antigen – Antigen in utero • Example: Bovine Virus Diarrhea
Bovine Virus Diarrhea • • Viral disease of cattle Common and widespread Most commonly subclinical: Non-cytopathic Potentially fatal: – In utero infection – Tolerance develops – Massive viral shedding – Cytopathic strains develop – Severe disease
Mild or inapparent disease IR Non-cytopathic virus Naïve adult cow Pregnant cow No specific IR Clearance Immune memory cytopathic virus Non-cytopathic Factors that promote tolerance Young age Large dose Soluble antigen Antigen in utero tolerized fetus
BVD Outcome • Tolerized calves: – Apparently healthy – Shed virus – Spread infection • Cytopathic virus – Random mutants – Disease in tolerized or non-immune animals
Immune response gone wrong: Hypersensitivity • Hypersensitivity = inappropriate/unregulated response to antigen • Foreign antigen = allergy • Self antigen = autoimmunity • Common
Classification of hypersensitvity responses • Type I: Ig. E antibody: – Immediate hypersensitivity – Allergy and Anaphylaxis • Type II: Ig. G/M antibody: Antibody – Autoimmune hemolytic anemia – Autoimmune thyroiditis • Type III: Antigen-antibody complexes – Serum sickness – Systemic Lupus Erythematosis • Type IV: Cellular immune response – Delayed-type hypersensitvity – Contact dermatitis Cells
B cells gone wrong: Ig-medated hypersensitivity Ig. E Type I hypersensitvity Ig. G Antibody-antigen complexes Type III hypersensitvity Type II hypersensitvity
Type I hypersensitivity: Ig. E and Mast Cells • Allergy: – Localized – Skin, respiratory tract • Anaphylactic shock – Systemic – Life-threatening • Requires repeated exposure to antigen
Histamine Vasoactive amines High concentration of antigen specific Ig. E
Ig. M and Ig. G-mediated hypersensitivity • Type II: Soluble antibody • Type III: Circulating immune complexes (antibody/antigen/complement)
Type II Hypersensitvity: • Circulating Ig. G/M antibodies to an inappropriate antigen • Three possible mechanisms of tissue damage: – Opsonization and phagocytosis – Complement fixation and inflammaton – Disruption of function (Neutralization)
Type II hypersensitivity: Opsonization and phagocytosis • Ig. G antibodies against cellular antigens • Antibody/complement complexes bind to cell membranes • Phagocytes bind via Fc and complement receptors • Cells are phagocytosed and destroyed
Gross photo alert
Type II hypersensitivity: Antibodymediated inflammation • Antibody directed against tissue antigens • Antibody and complement bind • Complement cascade attracts inflammatory cells • Inflammation and tissue damage
Pemphigus vulgaris: autoantibody to skin
Type II hypersensitivity: disruption of function • Neutralizing antibody • Directed against cellular receptors: – Interfere with ligand binding: prevent activation: Myasthenia gravis – Mimic ligand: activate receptor; Grave’s disease
Myasthenia Gravis • Antibody blocks acetylcholine receptors • Prevents signaling • Muscle weakness
Grave’s disease • Antibody against thyroid stimulating hormone • Antibody activates thyroid receptor • Hyperthyroidism
Type III hypersensitivity: antigenantibody complex disease • Immune-complex disease • Antibody-antigen-complement aggregates in circulation • Causes: – Persistent abnormal antigen: • Tumor immunity • Chronic infectious disease – Antibody to soluble self antigen: Systemic Lupus Erythematosus
Circulating immune complex disease Serum sickness: Circulating foreign antibody
Systemic Lupus Erythematosus • • Autoantibody to nuclear antigen Persistent antigen Complexes continue to form Systemic disease: Skin, kidney, joints, vessels affected • “Butterfly rash”
Examples of immune complex disease
Type IV hypersensitivity: T cytotoxic cells gone wrong • Cytotoxic T cells recognize self-antigen expressed on normal host cells • Cell killing and tissue damage
Type IV hypersensitivity: T helper cells gone wrong • T helper cells recognize antigen presented by antigen presenting cells • T cells produce proinflammatory cytokines • Cytokines attract neutrophils and macrophages • Release of enzymes cause tissue damage
. Examples of T Cell-Mediated (Type IV) Hypersensitivity
Induction of autoimmune disease • Failure of self-tolerance – Infectious agents – Genetic susceptibility • • • Tissue damage and inflammation Bad luck Phases of the moon Etc. “Multifactorial”
Role of infections in autoimmunity: APC activation • Infectious agent activates APC • Co-stimulatory molecules upregulated • Sufficient to overcome anergy of selfreactive T cells
Role of infections in autoimmunity: Molecular Mimicry • Microbial antigen cross-reacts with self-antigen • Presented by APC and recognized by selfreactive T cell • Anergy overcome
Induction of allergy: The Hygiene Hypothesis • Prevalence of allergic disease increasing in developed countries – – More vaccination More antibiotics Fewer infectious diseases Fewer parasite infections • Possible mechanisms: – Early infection skews T helper cell responses – Early infection activates regulatory cells – Tolerizing effects of the microbiota and/or intestinal parasites
A few diseases associated with “improved hygiene” • Atopic dermatitis • Asthma • Inflammatory bowel diseases • Autoimmune arthritis • Type 1 Diabetes mellitus • • Multiple sclerosis Helicobacter pylori Neoplasia Increased susceptibility to infectious agents
The Hygiene hypothesis
Parasitic helminths and therapy • Inverse correlation between allergy and parasite burden • Increase in allergic disease associated with anthelmintic treatment • Parasites for treatment of: – Inflammatory bowel disease – Autoimmune arthritis – Multiple sclerosis
IL-22+ CD 4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient Broadhurst, et al Sci Transl Med 2, 60 ra 88 (2010); Gross photo alert
The Microbiota Hypothesis • Microbiota enhance oral tolerance: – Germ free mice do not develop oral tolerance – Antibiotics alter the microbiota and suppress tolerance • Specific bacteria alter the Th 1/Th 2/Th 17 balance • Members of the microbial community may induce regulatory dendritic cells
Immunoregulation by enteric microorganisms APC Allergy Yang and Gao, Cellular & Molecular Immunology (2011) 8, 12– 18 No infection No allergy
- A subsequent
- Difference between acquired immunity and innate immunity
- Plastic surgery gone wrong
- Something must have gone wrong
- Plexr gone wrong
- Botox injection dubai
- You put the wrong emphasis on the wrong syllable
- What is the third line of defense in the immune system
- Flow chart
- Third line of defense immune system
- Innate immunity first line of defense
- Chapter 35 immune system and disease
- 1st 2nd and 3rd line of defense immune system
- Ap bio immune system
- Lesson 12.1 lymphatic ducts and vessels
- Lesson 12 blood and immune system
- Immune system lymph nodes
- Immunity assignment slideshare
- Overreactions of the immune system
- Lymphatic vs immune system
- Phagocitize
- Defination of immune system
- 3 lines of defence immune system
- The main function of immune system
- Tonsil histology
- Thymus
- Immune complex
- Thalassemia facies
- 1what's the purpose of the body's immune system?
- Chapter 13 lymphatic system and immunity
- Chapter 16 lymphatic system and immunity
- Lymph is composed of
- Chapter 6 musculoskeletal system diseases and disorders
- Chapter 17 reproductive system diseases and disorders
- Chapter 15 nervous system diseases and disorders
- Chapter 10 lymphatic system diseases and disorders
- Chapter 8 cardiovascular system
- Capnia medical term
- Diseases of the musculoskeletal system
- Female reproductive system diseases
- Spalding sign
- Difference between innate and learned behavior
- Chapter 55 care of the patient with an immune disorder
- Chapter 24 the immune and lymphatic systems and cancer
- Immune checkpoint inhibitors mechanism of action