The document summarizes the process of reductive adaptation that occurs in the body when a child's nutrient intake is insufficient to meet daily needs. It involves physiological and metabolic changes that conserve energy and prolong life by mobilizing fat stores, then protein stores, and reducing the body's activity and functions. This leads to important consequences like increased risk of hypoglycemia, fluid overload, impaired immune function, and cell damage. The goal of these changes is to allow the child to survive as long as possible in a state of malnutrition.
This document discusses peripheral neuropathy, including:
1. Peripheral neuropathy is inflammation and degeneration of the peripheral nerves or cranial nerves, impairing their conductivity. Common causes include diseases like diabetes, medications, trauma, toxins, and genetic factors.
2. Peripheral neuropathies can be classified based on the type of nerve affected (motor, sensory, autonomic), number of nerves (mononeuropathy, mononeuritis multiplex, polyneuropathy), or the pathological process (inflammation, compression, toxicity).
3. Clinical examination helps classify the neuropathy based on features like distribution of symptoms, timing, associated findings, and results of electrodiagnosis and lab tests
Everything you should know about Osteoporosis?
What is Osteoporosis?
Osteoporosis is a disorder of bones characterized by low bone density and a deterioration of bone micro- architecture that enhances bone fragility and increases the risk of fracture
Osteoporosis becomes a serious health threat for aging men & postmenopausal women by predisposing them to an increased risk of fracture
Do you know that?
Osteoporosis is responsible for >1.5 million vertebral and non-vertebral fractures per year
Spine, hip, and wrist fractures are most common.
Wilson's disease is caused by a genetic defect resulting in excessive copper deposition in tissues. It impairs the liver's ability to excrete copper into bile. Clinical features vary widely and include hepatic, neurological or psychiatric symptoms. Diagnosis involves low serum ceruloplasmin, high urinary copper, and Kayser-Fleisher rings on eye exam. Treatment includes copper-restricting agents like penicillamine or trientine to increase copper excretion, or zinc to reduce copper absorption. Liver transplantation may be considered for severe liver disease. With lifelong treatment, prognosis is good if Wilson's disease is diagnosed and managed early.
The ketogenic diet was initially developed in the 1920s to mimic the metabolic effects of fasting for treating epilepsy. It has since shown benefits for a variety of metabolic, oncologic, neurodegenerative, and psychiatric disorders through mechanisms like improving mitochondrial function and ATP production. Common indications for the ketogenic diet include epilepsy, Parkinson's disease, Alzheimer's disease, cancer, traumatic brain injury, autism, and depression. Side effects can include low-level acidosis, constipation, and nutrient deficiencies.
Osteoporosis is a disease characterized by low bone mass and deterioration of bone tissue, leading to fragile bones and increased risk of fractures. It is defined by the World Health Organization as a bone mineral density score of -2.5 or below. Those at highest risk include older adults, especially post-menopausal women, and those with low calcium/vitamin D intake or other risk factors such as smoking. Symptoms include back pain from fractured or collapsed vertebrae. Diagnosis involves bone mineral density tests and other lab tests. Treatment focuses on calcium, vitamin D, bisphosphonates, and lifestyle changes to build strong bones early in life and prevent bone loss later in life.
A ketogenic diet is a low-carb, high-fat diet that shifts the body's metabolism away from glucose and towards ketone bodies. It has been used to treat epilepsy, cancer, Alzheimer's, and other diseases. The diet forces the body to burn fats rather than carbohydrates. This makes it an effective treatment for cancer since cancer cells cannot use ketones for energy. In addition to weight loss, the ketogenic diet provides more energy and fewer side effects than chemotherapy or radiation. It is becoming a popular alternative treatment option.
Body composition analysis provides information about percentages of body fat, fat distribution, and body measurements that are useful for athletic performance and health. There are direct and indirect methods of analyzing body composition, with indirect methods including hydrostatic weighing, bioelectrical impedance, air displacement plethysmography, and skin fold measurements. Each method has advantages and limitations regarding accuracy, reliability, required equipment and cost.
The document summarizes the process of reductive adaptation that occurs in the body when a child's nutrient intake is insufficient to meet daily needs. It involves physiological and metabolic changes that conserve energy and prolong life by mobilizing fat stores, then protein stores, and reducing the body's activity and functions. This leads to important consequences like increased risk of hypoglycemia, fluid overload, impaired immune function, and cell damage. The goal of these changes is to allow the child to survive as long as possible in a state of malnutrition.
This document discusses peripheral neuropathy, including:
1. Peripheral neuropathy is inflammation and degeneration of the peripheral nerves or cranial nerves, impairing their conductivity. Common causes include diseases like diabetes, medications, trauma, toxins, and genetic factors.
2. Peripheral neuropathies can be classified based on the type of nerve affected (motor, sensory, autonomic), number of nerves (mononeuropathy, mononeuritis multiplex, polyneuropathy), or the pathological process (inflammation, compression, toxicity).
3. Clinical examination helps classify the neuropathy based on features like distribution of symptoms, timing, associated findings, and results of electrodiagnosis and lab tests
Everything you should know about Osteoporosis?
What is Osteoporosis?
Osteoporosis is a disorder of bones characterized by low bone density and a deterioration of bone micro- architecture that enhances bone fragility and increases the risk of fracture
Osteoporosis becomes a serious health threat for aging men & postmenopausal women by predisposing them to an increased risk of fracture
Do you know that?
Osteoporosis is responsible for >1.5 million vertebral and non-vertebral fractures per year
Spine, hip, and wrist fractures are most common.
Wilson's disease is caused by a genetic defect resulting in excessive copper deposition in tissues. It impairs the liver's ability to excrete copper into bile. Clinical features vary widely and include hepatic, neurological or psychiatric symptoms. Diagnosis involves low serum ceruloplasmin, high urinary copper, and Kayser-Fleisher rings on eye exam. Treatment includes copper-restricting agents like penicillamine or trientine to increase copper excretion, or zinc to reduce copper absorption. Liver transplantation may be considered for severe liver disease. With lifelong treatment, prognosis is good if Wilson's disease is diagnosed and managed early.
The ketogenic diet was initially developed in the 1920s to mimic the metabolic effects of fasting for treating epilepsy. It has since shown benefits for a variety of metabolic, oncologic, neurodegenerative, and psychiatric disorders through mechanisms like improving mitochondrial function and ATP production. Common indications for the ketogenic diet include epilepsy, Parkinson's disease, Alzheimer's disease, cancer, traumatic brain injury, autism, and depression. Side effects can include low-level acidosis, constipation, and nutrient deficiencies.
Osteoporosis is a disease characterized by low bone mass and deterioration of bone tissue, leading to fragile bones and increased risk of fractures. It is defined by the World Health Organization as a bone mineral density score of -2.5 or below. Those at highest risk include older adults, especially post-menopausal women, and those with low calcium/vitamin D intake or other risk factors such as smoking. Symptoms include back pain from fractured or collapsed vertebrae. Diagnosis involves bone mineral density tests and other lab tests. Treatment focuses on calcium, vitamin D, bisphosphonates, and lifestyle changes to build strong bones early in life and prevent bone loss later in life.
A ketogenic diet is a low-carb, high-fat diet that shifts the body's metabolism away from glucose and towards ketone bodies. It has been used to treat epilepsy, cancer, Alzheimer's, and other diseases. The diet forces the body to burn fats rather than carbohydrates. This makes it an effective treatment for cancer since cancer cells cannot use ketones for energy. In addition to weight loss, the ketogenic diet provides more energy and fewer side effects than chemotherapy or radiation. It is becoming a popular alternative treatment option.
Body composition analysis provides information about percentages of body fat, fat distribution, and body measurements that are useful for athletic performance and health. There are direct and indirect methods of analyzing body composition, with indirect methods including hydrostatic weighing, bioelectrical impedance, air displacement plethysmography, and skin fold measurements. Each method has advantages and limitations regarding accuracy, reliability, required equipment and cost.
Neurological Complications of Vitamin and Mineral DeficienciesAde Wijaya
This document discusses the neurological complications that can arise from deficiencies or excesses of various vitamins and minerals. It covers several B vitamins including thiamine (beriberi, Wernicke's encephalopathy), niacin (pellagra), vitamin B6, B12, and folate. It also discusses neurological effects of deficiencies in vitamins A, C, D, E, biotin, and vitamin K. Regarding minerals, it summarizes complications of calcium, magnesium, iodine, zinc, copper, iron, selenium, and manganese deficiencies or toxicities. Common neurological presentations include encephalopathy, myelopathy, peripheral neuropathy, seizures, developmental delays, and movement disorders.
Dr. Sharanya Rajan's document defines obesity and discusses its epidemiology. Key points include:
- Obesity is defined as a BMI ≥ 30 and is caused by an imbalance between energy intake and expenditure.
- Over 1.6 billion adults are overweight globally, with 400 million obese. Obesity is more common in women and increasingly affects poorer populations.
- Hypothalamic and genetic factors contribute to obesity development. Conditions like Prader-Willi syndrome, leptin/leptin receptor deficiencies, and POMC/MC4R mutations can cause monogenic obesity.
- Adipokines like leptin and resistin, as well as gut and pancreatic hormones, help regulate
Obesity - Pathophysiology, Etiology and management Aneesh Bhandary
Obesity is a state of excess adipose tissue mass. A massive psychosocial, pathophysiological problem that results in a high rate of mortality as well as morbidity. The basic mechanisms of the illness and its management as of 2017 are described in this presentation
Beriberi is a disease caused by vitamin B1 (thiamine) deficiency that can affect the heart and circulatory system (wet beriberi) or the nerves (dry beriberi). Symptoms of wet beriberi include shortness of breath and leg swelling, while dry beriberi causes muscle weakness and paralysis. Beriberi is treated with thiamine supplementation and is more common in those with alcohol use disorder or those eating diets lacking thiamine-rich foods like whole grains.
Essential tremor is a common condition characterized by bilateral, fast, low amplitude tremors mainly in the upper limbs that are often inherited and worsened by anxiety. It causes postural tremors when holding objects. Huntington's disease is a cause of chorea that presents in middle life with initial subtle movements and later psychiatric and cognitive symptoms due to a CAG trinucleotide repeat expansion. Tourette's syndrome is the most common cause of tics, characterized by multiple motor and at least one vocal tic starting in childhood and persisting over a year, affecting boys more than girls and associated with behavioral problems and disorders like ADHD and OCD.
Amyotrophic lateral sclerosis (ALS), AKA "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
This document discusses peripheral neuropathy, which refers to diseases that affect nerves outside the brain and spinal cord. It covers the types of peripheral nerves and classifications of neuropathies. Some key causes of peripheral neuropathy discussed include diabetes, nutritional deficiencies like B1/B12 deficiency, alcoholism, infections like HIV and leprosy, and certain drugs. Symptoms, clinical presentations, investigations, and treatment approaches for different types of peripheral neuropathies are also summarized.
1. Life expectancy has increased significantly over the past century from 47 years to over 76 years due to control of infectious diseases and medical innovations.
2. Gerontology is the comprehensive study of aging while geriatrics focuses on diseases and problems of older adults.
3. Many body systems are impacted by aging including decreased function of the cardiovascular, respiratory, musculoskeletal and nervous systems.
4. Promoting healthy behaviors such as exercise, nutrition, social engagement and annual health screenings can help optimize health and functioning in older adults.
Rett syndrome is a neurodevelopmental disorder that affects girls almost exclusively.
It is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.
This document summarizes the management of morbid obesity. It defines obesity as an energy imbalance, classifies obesity by BMI, examines the genetic and environmental origins of obesity, discusses current treatment options including diet, pharmaceuticals, and bariatric surgery, and explores the effects and prevalence of obesity.
This document discusses gait disorders and their causes. It defines normal gait and describes the gait cycle. It then discusses various types of abnormal gaits such as sensory ataxia caused by disturbances in sensory input, cerebellar ataxia presenting with wide-based staggering gait, and spastic gait caused by lesions interrupting the corticospinal pathway. It also covers parkinsonian gait, multisystem atrophy presenting with features of both parkinsonism and cerebellar ataxia, and spinocerebellar ataxia which is an inherited condition. Various causes of acquired and inherited ataxias are described.
Gerontology & Geriatrics: Research is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Gerontology.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all the areas of Gerontology. Gerontology & Geriatrics: Research accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of gerontology.
Gerontology & Geriatrics: Research strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
The document discusses energy expenditure and basal metabolic rate (BMR). It defines energy expenditure as the amount of energy needed for bodily functions like breathing and circulation, while BMR is the minimum energy required for essential physiological processes when at rest. The document outlines several factors that affect BMR, such as age, gender, weight, and thyroid function. Maintaining caloric balance between intake and expenditure through diet and exercise can prevent weight gain.
This document discusses peripheral neuropathy, including:
- The clinical effects of motor, sensory, and autonomic nerve injury, including weakness, loss of sensation, and autonomic dysfunction.
- The two main types of peripheral neuropathies - axonopathies which affect nerve fibers, and myelinopathies which affect the myelin sheath.
- The many potential causes of peripheral neuropathy both inherited and acquired, such as diabetes, toxins, infections, inflammation and genetic disorders. A thorough history and examination is needed to determine the underlying cause.
Osteoporosis is a disease where bone density and bone mass are reduced, leading to fragile bones that are more prone to fractures. It occurs when the balance between bone resorption and formation is disrupted, causing more old bone to be removed than new bone formed. Key signs are fractures of the wrist, spine, and hip. Risk factors include older age, female sex, smoking, excessive alcohol, family history, and certain medical conditions. Treatment focuses on lifestyle changes like exercise and nutrition to build bone mass, as well as medications to reduce bone loss.
An overview of the gastrointestinal tract, changes as a result of aging, and a description of how nutrition may prevent or improve common GI problems in the older adult. Note: this presentation is intended for a health/medical literate audience.
Cervical spondylosis is a degenerative condition affecting the bones and discs in the neck. It usually appears in people over age 40 and progresses with age. Common symptoms include neck pain and stiffness that worsens over time and may radiate to the shoulders and arms. Treatment focuses on relieving pain and preventing injury, and may include neck braces, exercises, medication, injections, or surgery for severe cases. Risk factors include aging and previous neck injuries.
The document discusses paraplegia, which is an impairment of motor or sensory function in the lower extremities. It describes the different types as spastic or flaccid paraplegia. The causes of spastic paraplegia are then outlined, including both cerebral and spinal causes such as cerebral diplegia, parasagittal meningioma, compressive spinal disorders like disc prolapse, and non-compressive disorders like motor neuron disease. The causes of flaccid paraplegia are also listed, including lesions of the anterior horn cells, peripheral nerves, or myoneural junction disorders.
This document provides an overview of the approach to evaluating and diagnosing ataxia. It defines ataxia and describes how it can be caused by lesions in the cerebellum, posterior column, or vestibular system. It then discusses the clinical features, investigations, and treatment of various causes of ataxia, including cerebellar lesions, hereditary ataxias like Friedreich's ataxia and ataxia telangiectasia, metabolic disorders, and more. The document emphasizes taking a thorough history and examination to identify features that can help determine the underlying cause of ataxia in each patient.
Neurological Complications of Vitamin and Mineral DeficienciesAde Wijaya
This document discusses the neurological complications that can arise from deficiencies or excesses of various vitamins and minerals. It covers several B vitamins including thiamine (beriberi, Wernicke's encephalopathy), niacin (pellagra), vitamin B6, B12, and folate. It also discusses neurological effects of deficiencies in vitamins A, C, D, E, biotin, and vitamin K. Regarding minerals, it summarizes complications of calcium, magnesium, iodine, zinc, copper, iron, selenium, and manganese deficiencies or toxicities. Common neurological presentations include encephalopathy, myelopathy, peripheral neuropathy, seizures, developmental delays, and movement disorders.
Dr. Sharanya Rajan's document defines obesity and discusses its epidemiology. Key points include:
- Obesity is defined as a BMI ≥ 30 and is caused by an imbalance between energy intake and expenditure.
- Over 1.6 billion adults are overweight globally, with 400 million obese. Obesity is more common in women and increasingly affects poorer populations.
- Hypothalamic and genetic factors contribute to obesity development. Conditions like Prader-Willi syndrome, leptin/leptin receptor deficiencies, and POMC/MC4R mutations can cause monogenic obesity.
- Adipokines like leptin and resistin, as well as gut and pancreatic hormones, help regulate
Obesity - Pathophysiology, Etiology and management Aneesh Bhandary
Obesity is a state of excess adipose tissue mass. A massive psychosocial, pathophysiological problem that results in a high rate of mortality as well as morbidity. The basic mechanisms of the illness and its management as of 2017 are described in this presentation
Beriberi is a disease caused by vitamin B1 (thiamine) deficiency that can affect the heart and circulatory system (wet beriberi) or the nerves (dry beriberi). Symptoms of wet beriberi include shortness of breath and leg swelling, while dry beriberi causes muscle weakness and paralysis. Beriberi is treated with thiamine supplementation and is more common in those with alcohol use disorder or those eating diets lacking thiamine-rich foods like whole grains.
Essential tremor is a common condition characterized by bilateral, fast, low amplitude tremors mainly in the upper limbs that are often inherited and worsened by anxiety. It causes postural tremors when holding objects. Huntington's disease is a cause of chorea that presents in middle life with initial subtle movements and later psychiatric and cognitive symptoms due to a CAG trinucleotide repeat expansion. Tourette's syndrome is the most common cause of tics, characterized by multiple motor and at least one vocal tic starting in childhood and persisting over a year, affecting boys more than girls and associated with behavioral problems and disorders like ADHD and OCD.
Amyotrophic lateral sclerosis (ALS), AKA "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
This document discusses peripheral neuropathy, which refers to diseases that affect nerves outside the brain and spinal cord. It covers the types of peripheral nerves and classifications of neuropathies. Some key causes of peripheral neuropathy discussed include diabetes, nutritional deficiencies like B1/B12 deficiency, alcoholism, infections like HIV and leprosy, and certain drugs. Symptoms, clinical presentations, investigations, and treatment approaches for different types of peripheral neuropathies are also summarized.
1. Life expectancy has increased significantly over the past century from 47 years to over 76 years due to control of infectious diseases and medical innovations.
2. Gerontology is the comprehensive study of aging while geriatrics focuses on diseases and problems of older adults.
3. Many body systems are impacted by aging including decreased function of the cardiovascular, respiratory, musculoskeletal and nervous systems.
4. Promoting healthy behaviors such as exercise, nutrition, social engagement and annual health screenings can help optimize health and functioning in older adults.
Rett syndrome is a neurodevelopmental disorder that affects girls almost exclusively.
It is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.
This document summarizes the management of morbid obesity. It defines obesity as an energy imbalance, classifies obesity by BMI, examines the genetic and environmental origins of obesity, discusses current treatment options including diet, pharmaceuticals, and bariatric surgery, and explores the effects and prevalence of obesity.
This document discusses gait disorders and their causes. It defines normal gait and describes the gait cycle. It then discusses various types of abnormal gaits such as sensory ataxia caused by disturbances in sensory input, cerebellar ataxia presenting with wide-based staggering gait, and spastic gait caused by lesions interrupting the corticospinal pathway. It also covers parkinsonian gait, multisystem atrophy presenting with features of both parkinsonism and cerebellar ataxia, and spinocerebellar ataxia which is an inherited condition. Various causes of acquired and inherited ataxias are described.
Gerontology & Geriatrics: Research is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Gerontology.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all the areas of Gerontology. Gerontology & Geriatrics: Research accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of gerontology.
Gerontology & Geriatrics: Research strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
The document discusses energy expenditure and basal metabolic rate (BMR). It defines energy expenditure as the amount of energy needed for bodily functions like breathing and circulation, while BMR is the minimum energy required for essential physiological processes when at rest. The document outlines several factors that affect BMR, such as age, gender, weight, and thyroid function. Maintaining caloric balance between intake and expenditure through diet and exercise can prevent weight gain.
This document discusses peripheral neuropathy, including:
- The clinical effects of motor, sensory, and autonomic nerve injury, including weakness, loss of sensation, and autonomic dysfunction.
- The two main types of peripheral neuropathies - axonopathies which affect nerve fibers, and myelinopathies which affect the myelin sheath.
- The many potential causes of peripheral neuropathy both inherited and acquired, such as diabetes, toxins, infections, inflammation and genetic disorders. A thorough history and examination is needed to determine the underlying cause.
Osteoporosis is a disease where bone density and bone mass are reduced, leading to fragile bones that are more prone to fractures. It occurs when the balance between bone resorption and formation is disrupted, causing more old bone to be removed than new bone formed. Key signs are fractures of the wrist, spine, and hip. Risk factors include older age, female sex, smoking, excessive alcohol, family history, and certain medical conditions. Treatment focuses on lifestyle changes like exercise and nutrition to build bone mass, as well as medications to reduce bone loss.
An overview of the gastrointestinal tract, changes as a result of aging, and a description of how nutrition may prevent or improve common GI problems in the older adult. Note: this presentation is intended for a health/medical literate audience.
Cervical spondylosis is a degenerative condition affecting the bones and discs in the neck. It usually appears in people over age 40 and progresses with age. Common symptoms include neck pain and stiffness that worsens over time and may radiate to the shoulders and arms. Treatment focuses on relieving pain and preventing injury, and may include neck braces, exercises, medication, injections, or surgery for severe cases. Risk factors include aging and previous neck injuries.
The document discusses paraplegia, which is an impairment of motor or sensory function in the lower extremities. It describes the different types as spastic or flaccid paraplegia. The causes of spastic paraplegia are then outlined, including both cerebral and spinal causes such as cerebral diplegia, parasagittal meningioma, compressive spinal disorders like disc prolapse, and non-compressive disorders like motor neuron disease. The causes of flaccid paraplegia are also listed, including lesions of the anterior horn cells, peripheral nerves, or myoneural junction disorders.
This document provides an overview of the approach to evaluating and diagnosing ataxia. It defines ataxia and describes how it can be caused by lesions in the cerebellum, posterior column, or vestibular system. It then discusses the clinical features, investigations, and treatment of various causes of ataxia, including cerebellar lesions, hereditary ataxias like Friedreich's ataxia and ataxia telangiectasia, metabolic disorders, and more. The document emphasizes taking a thorough history and examination to identify features that can help determine the underlying cause of ataxia in each patient.
1) The document discusses energy use and metabolism in animals. It shows graphs comparing the basal metabolic rate (BMR) of different animals in relation to their body size and mass. Smaller animals tend to have higher BMRs per kg of body mass.
2) The document then discusses digestion in animals. It describes the different digestive compartments and pathways for ingestion, digestion, absorption and elimination in various animal groups. Enzymatic breakdown of nutrients occurs inside or outside cells.
3) The stages of digestion - ingestion, digestion, absorption and elimination - are examined for different digestive system structures in animals like earthworms, birds and humans. Absorption of breakdown products like glucose, amino acids
2. Lastig bij afweer:
• Veel (nieuwe) woorden: moet je echt (uit je hoofd) kennen!
-ook synoniemen: denk aan antistoffen
• Veel verbanden: alles heeft invloed op alles
3. AANGEBOREN IMMUNITEIT (INNATE IMMUNITY)
- snel
- Aspecifiek/algemeen
- “Alle organismen”
1ste linie: Externe verdediging:
Barrieres
2de linie: Niet-specifieke
interne verdediging
Huid
Slijmvlies
Uitscheidingen
Fagocytotische cellen
Antibacteriele eiwitten
Inflamatie
Natural killer cellen (NK)
Aanvallende
microorganismen
(pathogenen)
Aangeboren immuniteit
niveaus immuniteit
Wat voor pathogenen bestaan er eigenlijk? En hoe verschillen ze? Welke verschillen zijn belangrijk voor afweer?
4. Vertebraten / gewervelden
Verschillende verdedigingsmechanismen:
- Barrières
- Immuniteit:
- Aspecifieke - Aangeboren (Innate) alle dieren
- Specifieke - Verworven (Adaptive) alleen vertebraten
5. Barrières
Een pathogeen moet eerst door een externe
verdediging van de cel breken.
1. Huid- en slijmlaag vormt de fysiologische barrière.
2. Sommige membranen (slijmcellen) produceren slijm, een viscose
vloeistof waarin pathogenen in blijven vastzitten.
• In de luchtpijp zorgen cilia-bevattende epitheel cellen voor
het omhoog brengen van slijm.
3. Uitscheiding van stoffen vanuit de huid/slijmlaag vormen vaak een
vijandige omgeving voor microben (chemische barrière)
• Huid heeft pH tussen 3 en 5
• Excretie van lysozym, een enzym welke de celwand van veel
bacterien afbreekt
10 m
7. Aangeboren interne immuniteit
wat als de barrière doorbroken wordt?
Interne immuniteit van evertebraten en vertebraten. Wat hebben ze
gemeen?
‘Zelf’ van ‘niet zelf’ onderscheiding
=Moleculaire herkenning! Van wat?
(foute) antigenen
8. Interne verdediging
voornamelijk door fagocytose
door fagocyten
Macrofaag (=een soort
fagocyt) geeft ontstekings-
cytokine af; hierdoor start van
ontstekingsrespons
Optie 1 aangeboren immuniteit:
fagocytose
Pseudopodia
surround
microbes.
1 Pseudopodia
surround
microbes.
1 Pseudopodia
surround
microbes.
1
Microbes
are engulfed
into cell.
2 Microbes
are engulfed
into cell.
2 Microbes
are engulfed
into cell.
2
Vacuole
containing
microbes
forms.
3 Vacuole
containing
microbes
forms.
3 Vacuole
containing
microbes
forms.
3
Vacuole
and lysosome
fuse.
4 Vacuole
and lysosome
fuse.
4 Vacuole
and lysosome
fuse.
4
Toxic
compounds
and lysosomal
enzymes
destroy microbes.
5 Toxic
compounds
and lysosomal
enzymes
destroy microbes.
5 Toxic
compounds
and lysosomal
enzymes
destroy microbes.
5
Microbial
debris is
released by
exocytosis.
6 Microbial
debris is
released by
exocytosis.
6 Microbial
debris is
released by
exocytosis.
6
Microbes
MACROPHAGE
Vacuole Lysosome
containing
enzymes
Microbes
MACROPHAGE
Vacuole Lysosome
containing
enzymes
Fagocyten uitleg uit 5H: bruggetje 2 naar specifieke afweer
Beroemd filmpje fagocyt
Fagocytose: hoe is dat voor een bacterie?
9. Adenoid
Tonsil
Lymph
nodes
Spleen
Peyer’s patches
(small intestine)
Appendix
Lymphatic
vessels
Masses of
lymphocytes and
macrophages
Tissue
cells
Lymphatic
vessel
Blood
capillary
Lymphatic
capillaryInterstitial
fluid
Lymph
node
AdenoidAdenoid
TonsilTonsil
Lymph
nodes
Lymph
nodes
SpleenSpleen
Peyer’s patches
(small intestine)
Peyer’s patches
(small intestine)
AppendixAppendix
Lymphatic
vessels
Masses of
lymphocytes and
macrophages
Masses of
lymphocytes and
macrophages
Tissue
cells
Lymphatic
vessel
Lymphatic
vessel
Blood
capillary
Blood
capillary
Lymphatic
capillary
Lymphatic
capillaryInterstitial
fluid
Interstitial
fluid
Lymph
node
Lymph
node
Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
1
Figure 43.5
Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
2
Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
3
Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
4
Figure 43.5
Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
2
Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
3
Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
4
Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
2 Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
2 Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
2
Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
3 Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
3
Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
4 Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
4 Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
4
Macrofagen is een type fagocyt die zich verplaatst door het hele
lichaam en voornamelijk in het lymfestelsel
14. Er zijn verschillende soorten witte bloedcellen in dit
plaatje die (op subtiele wijze) verschillen van elkaar
• Neutrofielen
• Basofiel
• Eosinofielen
• Monocyten & Macrofagen
Mini-speeddate
• Jullie krijgen er 1 soort toegewezen
• Zoek op: wat doet jouw cel precies?
• Waar ontstaat hij/woont hij?
• Waarin verschilt hij van zijn ‘broertjes’?
Zorg dat je deze uitleg in 2 minuten kunt geven;
maak het niet te moeilijk/lang, bij twijfel laten checken!
Granulocyten & monocyten
Opdracht 3: witte bloedcellen
16. Dendritische cellen
1: In huid & slijmvliezen: controleren het lichaam op
pathogenen.
Kunnen cytokines maken die dit pathogeen onschadelijk
proberen te maken.
2: kunnen aan fagocytose doen en antigenen aanbieden
aan specifiek afweer systeem
Bruggetje naar specifieke afweer
Immuuntherapie in t nieuws
17. aangeboren immuniteit:
stap 1 - Herkennen van bepaalde moleculaire patronen op
de membraan van pathogeen/ microbe
TLR (toll-like receptor) & manose receptor
binden aan ‘vreemde stoffen (zoals manose, en dubbel
RNA)
Gevolg:
Transcriptie en translatie DNA;
aanmaken chemische stoffen
-> Antimicrobiële stoffen (vallen direct aan)
& cytokinen
18. Antimicrobiële eiwitten
Vallen microben direct aan of onderbreken hun vermenigvuldiging
Net als bij vertebraten
Antimicrobiële eiwitten & Cytokinen
Cytokines
• Verzamelnaam chemische stoffen die voor van alles zorgen in het
afweersysteem (vergelijkbaar met hormonen)
• We gaan ze nog vaak tegenkomen in verschillende soorten en maten, ook
in specifieke afweer
19. Cytokines zoals:
• interferonen: vallen pathogenen aan (vooral virus) zorgen dat buurcellen niet
geïnfecteerd kunnen worden
• Ontstekings-cytokinen: zoals interleukine I - zorgen voor ontstekingsreactie
• Histamine: veroorzaakt ontstekingsreactie
• Chemokines: trekken fagocyten aan (chemotaxis)
• Activeringsstofjes: zoals Interleukine II - activeren lymfocyten
(Bruggetje naar specifieke afweer 1)
20. Complement systeem
Eiwitten in bloedplasma; werken samen in een cascade effect
(vergelijkbaar met bloedstolling)
• lysis(=kapotprikken) lichaamsvreemde pathogenen;
membraan attack complex:
https://www.youtube.com/watch?v=E_fdPaBBPic)
• aantrekken fagocyterende cellen (dmv lokstoffen; chemotaxis)
Later: verband tussen het complement systeem en de rest van de witte
bloed lichamen van het verworven immuniteit
Bruggetje naar specifieke afweer 4
21.
22. • Signaal moleculen, zoals histamine en andere chemicaliën komen vrij uit de
beschadigde cellen (vanuit specifieke afweer: mestcellen)
• Stimuleren verwijding en doorlaatbaarheid (Permeabiliteit) van bloedvaten:
meer vloeistof en antimicrobiele eiwitten het weefsel ingaat (hogere permeabiliteit
bloedvaten)
• Chemokines trekken fagocyten aan (chemotaxis)
• Ontstekingsreactie
• lokaal of
• door het hele lichaam voorkomen (systemisch)
Koorts is een systemische ontsteking
(geactiveerd door pyrogenen uit macrofagen en door toxische stoffen uit pathogenen)
•
‘Sepsis of septische shock’ is een levensgevaarlijke conditie door een extreme
ontsteking reactie (50% overleven)
• Bij alle ontstekingsreacties ontstaat PUS
Ontstekingsreactie
23. Ontstekingsreactie
Figure 43.8
Pathogen Pin
Macrophage
Chemical signals
Capillary
Phagocytic cells
Red blood cell
Blood
clotting
elements
Blood clot
Phagocytosis
Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
2Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
1 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
3 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals.
4
24. Soorten immuniteit
• Een dierlijke cel moet zich verdedigen tegen pathogenen (zoals virussen en bacteriën).
• Je kan onderscheid maken in twee afweer systemen:
• aangeboren immuniteit (ook wel niet-specifieke afweer)
• verworven immuniteit (ook wel specifieke afweer)
ontwikkeld na blootstelling
aan antigen:
• micro-organismen
• toxische stoffen
• andere lichaams- vreemde stoffen
• Dit heeft te maken met een andere type witte bloedcellen:
lymfocyten.
25. • Er zijn twee soorten lymfocyten in vertebraten:
• B lymfocyten (B-cellen) -> de B staat voor beenmerg: maken antistoffen
• T lymfocyten (T-cellen) -> de T staat voor thymus
Verworven immuniteit
Bone marrow
Lymphoid
stem cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T cell
Thymus
26. Lymfocyten
• Alle Lymfocyten kunnen specifieke pathogenen herkennen: specifieke
antigenen
• Dit herkennen gebeurt met verschillende soorten receptoren
• Receptoren van lymfocyten binden aan
een epitoop gedeelte van
een antigen.
27. B en T lymfocyten hebben receptoren
• Elke B-cel en T-cel hebben op hun plasmamembraan 100.000
antigen receptoren voor hetzelfde epitoop: 1 receptor=1 epitoop
Antigen-
binding
sitesAntibody A
Antigen
Antibody B
Antibody C
Epitopes
(antigenic
determinants)
NB: Antistoffen zijn eigenlijk ook een speciaal soort van receptoren,
en passen op epitopen van antigenen!
28. • B-cel receptoren binden aan epitoop van een specifiek intact antigen.
• B-cel receptor=membraangebonden-antilichamen of membraan-
immunoglobulinen
B lymfocyten = humorale afweer
Figure 43.8a
Antigen-
binding
site
Antigen-
binding site
Disulfide
bridge
Light
chain
Heavy chains
Cytoplasm of B cell
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
(a)
Variable
regions
Constant
regions
Transmembrane
region
Plasma
membrane
B cell
C C
30. Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Bacterium
Virus Bacteria
Soluble
antigens Foreign cell
Complement
proteins
MAC
Pore
Enhances (dmv opsonisation)
Phagocytosis
Leads to
Cell lysis
MacrophageFigure 43.19
34. 43.3 Humoraal en cel-verkregen immuniteit
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgM
(pentamer)
IgG
(monomer)
IgA
(dimer)
J chain
Secretory
component
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgM
(pentamer)
IgG
(monomer)
IgA
(dimer)
J chain
Secretory
component
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgM
(pentamer)
IgG
(monomer)
IgA
(dimer)
J chain
Secretory
component
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgM
(pentamer)
IgG
(monomer)
IgA
(dimer)
J chain
Secretory
component
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
•Passieve immuniteit =
externe antilichamen, dus geen geheugen (bijv. bij foetus of injectie)
35. Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
IgA
(dimer)
IgE
(monomer)
Secretory
component
J chain
Transmembrane
region
IgD
(monomer)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
IgA
(dimer)
IgE
(monomer)
Secretory
component
J chain
Transmembrane
region
IgD
(monomer)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
IgA
(dimer)
IgE
(monomer)
Secretory
component
J chain
Transmembrane
region
IgD
(monomer)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
IgA
(dimer)
IgE
(monomer)
Secretory
component
J chain
Transmembrane
region
IgD
(monomer)
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
36. • T-cel receptoren twee verschillende polypeptiden: α keten en β keten
T lymfocyten
Antigen-
Binding site
chain
Disulfide bridge
chain
T cell
A T cell receptor consists of one
chain and one chain linked by
a disulfide bridge.
(b)
Variable
regions
Constant
regions
Transmembrane
region
Plasma
membrane
Cytoplasm of T cell
Antigen-
Binding site
chain
Disulfide bridge
chain
T cell
A T cell receptor consists of one
chain and one chain linked by
a disulfide bridge.
(b) A T cell receptor consists of one
chain and one chain linked by
a disulfide bridge.
(b)
Variable
regions
Variable
regions
Constant
regions
Constant
regions
Transmembrane
region
Transmembrane
region
Plasma
membrane
Plasma
membrane
Cytoplasm of T cell
V V
C C
37. DNA of
undifferentiated
B cell
DNA of differentiated
B cell
pre-mRNA
mRNA Cap
B cell
B cell receptorLight-chain polypeptide
Intron
Intron
Intron
Variable
region
Constant
region
V1 V2 V3
V4–V39
V40 J1 J2 J3 J4 J5
V1 V2
V
3
J5
V3 J5
V3 J5
V C
C
C
C
C
Poly (A)
Figure 43.13
Deletion of DNA between a V segment
and J segment and joining of the segments
1
Transcription of resulting permanently rearranged,
functional gene
2
RNA processing (removal of intron; addition of cap
and poly (A) tail)
3
4 Translation
Hoe kan het dat elke receptor zo anders is??
V= Variabel
J= Junction
C-constant
recombinase
38. B lymfocyten, humorale afweer
• Elke jonge B-cel ondergaat dit proces
Gevolg: heel veel verschillende varianten jonge b cellen (met verschillende
receptoren, die verschillende antistoffen kunnen maken)
Waarom vallen cellen lichaamseigen antigenen niet aan?
->heel jonge B en T cellen worden hierop geselecteerd: als ze door
recombinatie van DNA toevallig lichaamseigen antigenen ‘herkennen’ treedt
proces van apoptose in gang..
Als dit toch misgaat: auto-immuunziekte
39. 1a. Er zijn een stukje B-lymfocyt en een stukje T-lymfocyt in detail getekend. Om welke
reden zijn deze details getekend?
b. Zijn deze details ook onder een lichtmicroscoop zichtbaar?
c. Noem twee verschillen tussen een antistof en een T-cel receptor.
d. Wat is de overeenkomst tussen een monocyt (= macrofaag) en een granulocyt?
e. Wat is het verschil tussen een monocyt (= macrofaag) en een granulocyt?
Totaaloverzicht van de belangrijkste leu
42. • 2a. Leg uit waarom een antistof op een B-lymfocyt een antigeenreceptor is.
b. In de figuur zijn antigenen en drie B-lymfocyten getekend. De tekenaar heeft drie
B-lymfocyten in plaats van slechts één B-lymfocyt getekend. Leg dat uit.
c. In de plasmacellen zijn organellen getekend die niet in de geheugen-B-cellen
getekend zijn. Welke organellen zijn dat?
d. Waarom zullen deze organellen talrijker zijn in plasmacellen dan in geheugen-B-
cellen?
e. De tekening geeft klonale selectie weer. Waar vindt selectie plaats in de
tekening? Waar vindt kloneren plaats in de tekening?
f. Noem twee verschillen tussen plasmacellen en geheugen B-cellen.
43. • Er zijn twee soorten lymfocyten in vertebraten:
• B lymfocyten (B-cellen) -> de B staat voor beenmerg: maken antistoffen
• T lymfocyten (T-cellen) -> de T staat voor thymus
43.2 Verworven immuniteit
Bone marrow
Lymphoid
stem cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T cell
Thymus
45. • T-cel binden aan kleine fragmenten van een antigen die gebonden zijn aan
normale celoppervlakte eiwitten (MHC-moleculen).
• MHC-moleculen zijn afkomstig van een groep genen (genaamd Major
Histocompatibility Complex)
• Geinfecteerde cellen produceren MHC moleculen welke binden aan het
antigen fragment en ‘presenteren’ die aan het celoppervlakte.
• Een T-cel die in de buurt is kan het antigen fragment herkennen die aan het
celoppervlakte is.
T lymfocyten: cellulaire afweer
47. • Klasse I MHC moleculen (bijna in alle cellen van het lichaam gevonden met een
celkern) presenteren peptide antigenen aan cytotoxische T-cellen.
MHC I in actie
Figure 43.12a
Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
(a) Cytotoxic T cell
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
48. • Cytotoxische T cellen produceren CD8 (oppervlakte eiwit) dat de
binding tussen klasse I MHC-antigen en de T cel receptor
versterkt
• Cytotoxische T cellen binden aan geïnfecteerde cellen,
kankercellen, transplantaten
• Binding aan een klasse I MHC complex van een geïnfecteerde cel
activeert een cytotoxische T cel tot een actieve ‘killer’
Cytotoxic T cell
Perforin
Granzymes
CD8TCR
Class I MHC
molecule
Target
cell Peptide
antigen
Pore
Released
cytotoxic
T cell
Apoptotic
target cell1
2
3
Waar ken je dit ‘presenteren’ nog meer van?
49. Klasse II MHC moleculen (voornamelijk aanwezig in dendritische
cellen, macrofagen en B-cellen) presenteren peptide antigenen
aan T lymfocyten.
MHC II in actie
Microbe Antigen-
presenting
cell
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
(b)
50. Verkregen immuniteit heeft twee takken:
-Humorale immuunrespons activeert en
selecteert B cellen, welke resulteert in de
productie van uitgescheiden antistoffen
- celverkregen/cellulaire/celgemedieerde
immuunrespons activeert en selecteert
cytotoxische T cellen
T helpercellen
de managers van je immuunsyteem
Figure 43
Humoral immune response Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate Activate Activate
Gives rise to Gives rise to Gives rise to
B cell
Helper
T cell
Cytotoxic
T cell
Plasma
cells
Memory
B cells
Active and
memory
helper
T cells
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Defend against infected cells, cancer
cells, and transplanted tissues
Secreted
cytokines
activate
51. • Helper T cellen produceren CD4 (oppervlakte eiwit) dat
de binding tussen klasse II MHC-antigen en de T cel
receptor versterkt
• Helper T cellen worden dan geactiveerd
• Geactiveerde helper T cellen scheiden verschillende
cytokinen uit die andere lymfocyten stimuleren
Cell-mediated
immunity
(attack on
infected cells)
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Dendritic
cell
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
Cytokines
Cytotoxic T cell
B cell
1
2 3
52. • Activatie van B cellen wordt veroorzaakt door cytokinen en
antigenbinding aan helper T cellen
• B cellen kunnen antigenen aan geactiveerde helper t cellen
aanbieden (met MHC II)
• De B cellen worden dan plasmacellen (de effector cellen van de
humorale immuniteit)
2
1
3
B cell
Bacterium
Peptide
antigen
Class II
MHC
molecule
TCR
Helper T cell
CD4
Activated
helper T cell Clone of memory
B cells (geheugencellen)
Cytokines
Clone of plasma cells
Secreted antibody
molecules
Endoplasmic
reticulum of
plasma cell
Macrophage
53. NB MHC moleculen moeten zo veel mogelijk ‘matchen’ bij orgaantransplantaties;
Menselijke MHC moleculen worden ook wel HLA genoemd: HLA matching systeem
Coreceptor CD4=t helpercel + monocytes + macrofaag + dendritische cel,
Coreceptor CD8=cytoxische t cel, NKC, dendritische cel
55. Blauwe pijl=chemisch signaal door cytokinen (interleukine)
http://www.bioplek.org/animaties/afweer/inhoudafweer.html
56. Herhaling:
https://www.youtube.com/watch?v=Nw27_jMWw10
Humoral immune response Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate Activate Activate
Gives rise to Gives rise to Gives rise to
B cell Helper
T cell
Cytotoxic
T cell
Plasma
cells
Memory
B cells
Active and
memory
helper
T cells
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Defend against infected cells, cancer
cells, and transplanted tissues
Secreted
cytokines
activate
https://www.youtube.com/watch?v=U1FyrtDZ3aE
https://www.youtube.com/watch?v=zQGOcOUBi6s
57. Maak een mindmap met verbindingen
gebruik (teken!) de volgende begrippen en hun onderlinge relatie:
• Macrofaag
• Dendritiche cel
• Complementsysteem
• Antistof
• Naieve B cel
• Effector B cel/plasmacel
• B geheugencel
• Cytotoxische T cel
• Helper T cel
• Cytokinen
• MHC I
• MHCII
• T geheugencel
• CD4
• CD8
• Natural Killercel
• Apecifieke afweer
• Specifieke afweer
58. Aanval op het immuunsysteem: HIV
• Human immunodeficiency virus (HIV) infecteerd helper T cellen
• HIV bindt aan CD4 receptoren (en infecteerd daardoor ook in
mindere mate macrofagen en hersencellen)
• HIV blijft bestaan in de gastheer—ondanks de immuun respons—
omdat het heel veel en snel muteert, en daardoor veel antigen
variatie vertoont (-> net als het griepvirus bijvoorbeeld)
• Uiteindelijk zal HIV het afweersysteem compeet lam leggen: AIDS
59. Latency (latente fase) AIDS
Relative anti-HIV antibody
concentration
Relative HIV
concentration
Helper T cell
concentration
Years after untreated infection
HelperTcellconcentration
inblood(cells/mm3)
800
600
400
200
0
0 1 2 3 4 5 6 7 8 9 10
Primaire infectie
61. • Het immuunsysteem heeft een gevoelige balans, als dit
verstoort wordt dan kan het effect op een individu ernstig
zijn (allergie, auto-immuun ziektes, immuundeficiëntie).
Allergie
• Allergie is een overgevoelige reactie op sommige
antigenen (allergenen)
• In bekende allergieën, zoals hooikoorts, zullen IgE
antilichamen direct geproduceerd worden door
plasmacellen na de eerste blootstelling aan het allergeen
Immunologische ziektes
62. • De volgende blootstelling zullen mastcellen die gesensibiliseerd zijn
met IgE de stof histamine (en andere ‘communicatie’-stoffen)
vrijgeven die de onstekings symptomen geeft (kan zelfs tot een
anafylactische shock leiden door verwijding bloedvaten).
• Histamine:
• Verhoogd diameter van bloedvaten, permeabiliteit van bloedvaten voor
plasma, maagzuurproductie en adrenaline productie.
• Neurotransmitter die leidt tot alertheid en zorgt ervoor dat mensen
wakker zijn.
63.
64. • Allergische reactie:
Figure 43.20
IgE antibodies produced in
response to initial exposure
to an allergen bind to
receptors or mast cells.
1 On subsequent exposure to the
same allergen, IgE molecules
attached to a mast cell recog-
nize and bind the allergen.
2 Degranulation of the cell,
triggered by cross-linking of
adjacent IgE molecules,
releases histamine and other
chemicals, leading to allergy
symptoms.
3
1
2
3
Allergen
IgE
Histamine
Granule
Mast cell
Immunologische ziektes
65. • Het immuunsysteem vernietigd alle
lichaamsvreemde stoffen, dus ook bij de
meeste lichaamsvreemde transplantaten
(bloedtransfusie=bloedtransplantaat!).
• Bij bloed is het afhankelijk van de
aanwezige antigenen (bepaald type A, B,
AB, of O en rhesus factor)
• Antilichamen voor lichaamsvreemde
bloedtypes A en B zijn al vanaf een jaar na
de geboorte in het lichaam
aanwezig, dus zal
bloedcellen ‘altijd’ afbreken
na transfusie.
Resus antistoffen daarentegen
worden pas gemaakt na een 1e
blootstelling (bijvoorbeeld tijdens
zwangerschap)
HLA systeem=menselijk MHC systeem:
moet matchen bij donatie
66. Typen antistoffen
• Anti-A en Anti b versus resus..
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
IgM
(pentamer)
IgG
(monomer)
IgA
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
IgM
(pentamer)
IgG
(monomer)
IgA
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
IgM
(pentamer)
IgG
(monomer)
IgA
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
IgM
(pentamer)
IgG
(monomer)
IgA
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
68. Immunologische ziektes
• Auto-immuunziekte:
‘Lichaams-eigen’ antigen = allergen; Een individu met een auto-
immuun ziekte zal de tolerantie naar sommige eigen moleculen van
het lichaam verliezen.
• T-helper & B-cellen afhankelijke ziekten ->
immuundeficientie
• primaire immuundeficiëntie; aangeboren afwijking dat zorgt
voor incorrect functioneren van humorale, en/of cel-verkregen
verdediging
• secundaire immuundeficiëntie; door blootstelling aan
chemische of biologische factor gaan cellen/ moleculen van
het immuunsysteem incorrect functioneren
69. Aanpak van de tumorcel
• Plan A: tumorcellen
produceren celvreemde
eiwitten die als antigen
gepresenteerd kunnen
worden door MHC klasse I aan
CD8 cytotoxische T-
lymfocyten
• Plan B: de NK-cellen die lysis
gebruiken bij bestrijding van
tumorcellen (aspecifiek),
wanneer er geen goede MHC
klasse I eiwitten (meer) zijn
Tumor Cellen
