1) The complement system consists of plasma proteins that work together through three activation pathways - classical, lectin, and alternative - to enhance immunity. Deficiencies in complement proteins result in increased risk of infection or autoimmune disease.
2) Evaluation of patients with suspected complement deficiency includes testing for complement protein levels (CH50, AH50), and functional activity. Deficiencies are associated with increased risk of recurrent infections, especially from encapsulated bacteria.
3) Hereditary angioedema is caused by C1-INH deficiency and results in recurrent swelling attacks. It is diagnosed through blood tests showing low C4 and C1-INH levels, and treated by targeting mediators of swelling. Pro
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
Describes the complement system components and their activation pathways, the regulation of the complement
system, the effector functions of various complement components,
and the consequences of deficiencies in them.
Describes the complement system components and their activation pathways, the regulation of the complement
system, the effector functions of various complement components,
and the consequences of deficiencies in them.
"Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,
All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.
The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
Blood transfusion is one of the commonest accompaniments of surgical practice. With a growing incidence of major polytrauma by vehicular accidents, bomb blasts and fires, awareness of the basic concepts underlying massive blood transfusion practice with special reference to the complications is essential. The paper outlines the pathophysiologic mechanisms underlying the various complications of massive blood transfusion.
Fresh Water resources
Global Overview
Volume of water stored in the water cycle's reservoirs
Scarcity of fresh water
Water consumption for food production (I)
Competing water uses
Fresh Water supply
Problems related to Water crisis
Threats to fresh water resources
Distribution of population and water resources
Pressure of freshwater ecosystem
Fresh Water Outlook
Water in China
Desalination of sea water as fresh water supply
This is a journal club presentation where we present good quality papers from leading journals of the world. This particular paper deals with new biomarkers for Rheumatoid Arthritis.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
3. The complement system
• Heat labile plasma proteins
• consists of several plasma proteins that work together
» normally inactive
» activated only under particular conditions
• Important effector mechanism of innate immunity
• One of the major effector mechanisms of humoral immunity
Abbas.Cellular and molecular immunology 7th edition
4. The most important biological functions
of the complement system
1. innate host defense:
– Opsonization
– initiation of an inflammatory response
– clearance of apoptotic debris
– direct lysis of gram negative bacteria
2. adaptive responses
– B cell activation
– T cell priming
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
7. Pathways of Complement Activation
• 3 major pathways
Pathways Activator
1. Classical -Ab bound to Ag (IC)
-Pentraxins (CRP,SAP, PTX3)
-SIGN R-1
-Apoptotic cell
2. Alternative Microbial cell surfaces (absence of Ab) ex. LPS
3. Lectin mannose residues on microbe
Abbas.Cellular and molecular immunology 7th edition
8. Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
- Alternative and lectin : effector
mechanisms of innate immunity
- Classical : major mechanism of
adaptive humoral immunity
Abbas.Cellular and molecular immunology 7th edition
16. Lectin pathways
• MBL and ficolins associate with MBL-associated
serine proteases (MASPs)
• MASP proteins
– structurally homologous to the C1r and C1s
proteases
– serve a similar function : cleavage of C4 and C2
Abbas.Cellular and molecular immunology 7th edition
Subsequent events in this pathway are
identical to those that occur in the
classical pathway
22. Complement receptors
Complement receptor of the immunoglobulin
family (CRIg)
• express on surface of macrophages in the liver (Kupffer cells)
• binds C3b and iC3b
• involved in the clearance of opsonized bacteria and other
blood-borne pathogens
Abbas.Cellular and molecular immunology 7th edition
29. Functions (cont.)
• Promote solubilization of immune complexes and their
clearance by phagocytes
• C3d protein binds to CR2 on B cells facilitates B cell
activation and initiation of humoral immune responses
Abbas.Cellular and molecular immunology 7th edition
31. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
32. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
33. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
34. COMPLEMENT DEFICIENCIES
• Deficiencies in classical pathway components
• Deficiencies in alternative pathway components
• Deficiencies in lectin pathway components
• Deficiencies in the terminal complement components
• Deficiencies in complement regulatory proteins
• Deficiencies in complement receptors
35. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in classical pathway components
36. C1q DEFICIENCY
• strongest known genetic risk factor for lupus
• early- onset SLE
• lupus seen in C1qD individuals is less steroid responsive
• increased rate of infection
– compromised opsonization
– mild decrease in B cell co-stimulation
• initial symptoms in the C1qD patients are more often
cutaneous symptoms of autoimmune disease than
infections
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
37. C1r,C1s DEFICIENCY
• Deficiencies of C1r and/or C1s are extremely rare
• frequently combined
• few cases of selective deficiencies
• Glomerulonephritis and lupus have been found in C1r/C1s
deficient patients
• 60% develop SLE or similar disease
• infections mainly due to encapsulated bacteria are frequent
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
38. C4 DEFICIENCY
• C4A deficiency
– 1–2% of general population
– up to 15% of patients with SLE
– risk factor for SLE
– severity of the disease is often less in patients with C4A
deficiency compared to complement sufficient hosts
• C4B deficiency
– 1–2% of population
– up to 15% of patients with invasive bacterial disease :
– impaired opsonization and a modestly compromised B cell
response to antigen
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
39. C2 DEFICIENCY
– most common of inherited classical complement
component deficiencies in Caucasians
– most common cause of death : sepsis
– most common organisms : S. pneumoniae and H.
influenzae
– Asymptomatic
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
40. C3 DEFICIENCY
• rarest of the 4 early component deficiencies
• most severe phenotype
– neutrophil dysfunction (abscesses)
– humoral deficiencies (sinopulmonary disease)
– complement deficiencies (sepsis, meningitis)
• 1/3 : Membranoproliferative glomerulonephritis
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
41. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in Alternative pathway components
42. FACTOR B DEFICIENCY
• A single case has been reported : meningococcemia
FACTOR D DEFICIENCY
• Neisserial infections : most common manifestation
• Systemic streptococcal infections have also been seen
• Other complement levels are typically normal
Deficiencies in Alternative pathway
components
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
43. PROPERDIN DEFICIENCY
• only X-linked complement deficiency
• occurs largely in Caucasians
• one or more episodes of meningococcal disease
• Other bacterial infections are also seen (less common)
• high fatality rate in meningococcal disease in contrast to
patients with terminal complement component deficiencies
Deficiencies in Alternative pathway
components
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
44. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in Lectin pathway components
45. MBL deficiency
• minimally to susceptibility to infections
• combination with other primary or secondary
immunodeficiency MBL deficiency has been
shown to be a risk factor in particular for respiratory
tract infections
– ex. C2 deficiency , CVID
• Also increased risk of cardiovascular disease
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in Lectin pathway components
46. MASP2 DEFICIENCY (mannose-binding protein-associated serine protease 2)
• combination of autoimmune symptoms and recurrent
respiratory infections
• more severe course of disease in MASP-2-deficient patient as
compared to MBL-deficient individuals
Ficolin-3 deficiency
• first case of ficolin-3 deficiency was described
– recurrent respiratory infections since early childhood and later in life
cerebral abscesses and several episodes of pneumonia
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in Lectin pathway components
47. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in terminal complement
components
- only with meningococcal infection with high recurrence rate
-rarely fatal (ǂ Properdin)
-C9 deficience : CH50 is diminished but not absent
48. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in complement regulatory
proteins& complement receptor
49. WAO Journal 2012; 5:182–199)
3 forms of HAE
(1) HAE-1
- C1-INH deficiency : low antigenic and functional C1- INH levels
(2) HAE-2
- C1-INH dysfunction : normal (or elevated) antigenic but low functional C1-INH
levels
(3) HAE-3
- normal C1-INH antigenic and functional levels
51. Type 3 HAE
• HAE with normal C1-INH
• very rare disease
• The symptoms are very similar to HAE-1/2
• A subset of HAE-3 patients exhibits mutations in factor XII
• The genetic abnormality of most HAE-3 patients has not
yet been defined
• Diagnosis requires a family history of angioedema
WAO Journal 2012; 5:182–199)
52. HAE : diagnosis
should be suspected :
• history of recurrent angioedema, esp. if hives are absent
• with
(1) positive family history
(2) onset of symptoms in childhood/adolescence
(3) recurrent abdominal pain attacks
(4) occurrence of upper airway edema
(5) failure to respond to antihistamines, glucocorticoid, or
epinephrine; and
(6) presence of prodromal signs or symptoms before swellings
• Suspicion of HAE-1/2 should prompt laboratory workup
WAO Journal 2012; 5:182–199)
53. HAE
- Extremities, face, or genitalia are most often involved
- Angioedema typically progresses for 1–2 days and
resolves in another 2–3 days
- Common precipitants are illness, hormonal
fluctuations, trauma, and stress
- Infections have rarely been reported in HAE in spite of the
associated hypocomplementemia
- very low levels of C4 ,C2 : enough for CP-dependent protection against
infection
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
54. HAE : work up
• blood levels of C4, C1-INH protein, and C1- INH function
• if abnormally low repeat to confirm the diagnosis
(Evidence grade: D, strength of recommendation: strong)
• normal results may need to be checked during an attack of
angioedema
WAO Journal 2012; 5:182–199)
C4
-C4 level is useful for screening
-cannot be relied upon to confirm or exclude Dx
- repeat C4 during an attack ↑probability
- False negative measurement of C4d
55. HAE-1/2 : work up
• The C1-INH antigenic level
– low in HAE-1 and acquired C1-INH deficiency patients
– normal in HAE-2 patients
• The C1-INH functional activity
– low in HAE-1 and HAE-2 and acquired C1-INH
deficiency patients
• In rare patients Gene analysis
– SERPING1 gene : HAE-1/2
– factor XII genes : HAE-3
WAO Journal 2012; 5:182–199)
• C3 levels : normal
• CH50 is not useful
57. Treatment
• All attacks that result in debilitation/dysfunction and/ or
involve the face, the neck, or the abdomen should be
considered for on-demand treatment
• Treatment of attacks affecting the upper airways is
mandatory
• treated attack as early
• Every patient with HAE-1/2 should be considered for
home therapy and self-administration training, once the
diagnosis of C1-INH deficiency is confirmed
WAO Journal 2012; 5:182–199)
59. WAO Journal 2012; 5:182–199)
Plasma-derived C1-INH (pdC1-INH)
recombinant C1 INH
B 2 receptor antagonist
kallikrein inhibitor
60. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in complement regulatory proteins
61. CD59 DEFICIENCY AND PNH
• CD59 is expressed on most hematopoietic cells and endothelial cells
where it confers protection from intravascular complement mediated lysis
• phenotypic resemblance to PNH
– recurrent episodes of hemoglobinuria due to
intravascular hemolysis
• The diagnosis of PNH is made by flow cytometry for CD59
or CD55 (DAF)
• DAF deficiency does not have a hemolytic phenotype
– CD59 is the more important than CD55
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
62. L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
Deficiencies in complement receptor
64. Evaluation
assess
patients with recurrent sepsis/systemic infection or sepsis
on the background of autoimmune disease
(or a family history of autoimmune disease)
CH50
AH50
MBL levels
Patients with a single meningococcal infection, either
meningitis or meningococcemia, probably deserve an
evaluation in non-endemic areas
CH50
AH50
patients with meningococcal disease with an unusual
serotype (serotypes X, Y, Z, W135 or 29E), on background of
a positive family Hx, or recurrent meningococcal disease
CH50
AH50
Patients with lupus CH50
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
65. Evaluation
assess
patients with Membranoproliferative glomerulonephritis
and HUS
-CH50
-AH50,
-C3 level
(factor H, I, MCP
mutation
analyses )
recurrent angioedema in the absence of allergic reactions,
patients with a family history of angioedema
patients with angioedema preceded by a reticular rash,
patients with angioedema after trauma
-C4 levels
-C1 inhibitor
antigen and
functional levels
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
66. Evaluation
• Deficiencies of all the cascade components lead to a
CH50 of 0 or near 0
– With the exception of C9 deficiency
• Low levels of CH50 or AH50 results should be repeated
due to
– mishandling of the serum is an extremely common
– C’ consumption due to active immune complex disease
– diminished hepatic production : liver disease, immaturity
of hepatic production seen in young infants
– Less common : regulatory protein defects leading to
consumption of C3 such as factor D, factor H, and factor I
deficiency
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
67. Evaluation
• abnormal CH50 or AH50 has been confirmed
serum levels of certain components (C3 and C4
primarily)
Kathleen E. Sullivan. Middleton's Allergy: Principles & Practice, 7th ed
68. Management
• completely dependent on the type of defect
– susceptibility to infectious agents
– course of the disease
• Treat infection, Autoimmune, associated
diseases
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
69. Management
• Prevention
– Replacement of the missing component
• C1-INH concentrate is the only product that is licensed
and is used in a regularly fashion
• FFP
– Antibiotic prophylaxis
– Vaccination
• Encapsulated bacteria : S. pneumoniae and H.
influenzae
• meningococcal vaccine (tetravalent serogroup A, C, Y and W-135)
– Hygienic measures
L. Skattum et al. Molecular Immunology 48 (2011) 1643–1655
70. Take home message
• The complement system : essential component of innate
immunity
– opsonize microbes
– promote the recruitment of phagocytes to site of infection
– in some cases to directly kill the microbes
• One of the major effector mechanisms of humoral immunity
• Also crucial role in the preservation of the immunological
homeostasis
• 3 pathways : Classical , Alternative, Lectin
– Activator, Regulatory protein
71. Take home message
• Complement deficiencies are uncommon
• infection susceptibility and disease susceptibility depend
on which factor is missing
• consequence can vary from almost none (C9 deficiency)
to very serious infections (C3 deficiency)
– C3 deficiency : severe, recurrent, often lethal bacterial
infections
• SLE , meningococcal disease : two most common
phenotypes associated with complement deficiencies
72. Take home message
• CP deficiencies : encapsulated bacteria
• AP and terminal pathway deficiencies : Neisseria species
• Complement deficiency does in general not confer
increased susceptibility to fungal, parasitic or viral
infections
• The diagnosis of most complement deficiencies begins
with the demonstration of a markedly low CH50 or AH50
• The identification of complement deficiency states is
important to ensure optimal prevention and treatment