Innate immunity is the body's first line of defense against pathogens. It includes mechanical, chemical, and biological barriers that block pathogen entry. If a pathogen breaches these barriers, the innate immune system responds through cells and proteins. Key components of the innate response are phagocytic cells, complement proteins, acute phase proteins, cytokines, and inflammation. The complement system helps eliminate pathogens through opsonization, cell lysis, and inflammation. Innate immunity provides non-specific protection and helps activate the adaptive immune response.
Antibody(Ab) or immunoglobulin(Ig) is the large Y shaped glycoprotein produced by the body’s immune system when it detects harmful substances are called antigens.
They are synthesized by B lymphocytes and secreted by plasma cells.
Depending on the electrophoretic migration, 3 types of globulins are present in the blood, namely α, β and γ
So antibodies are gamma (γ) globulin.
I took major content from this website i came across. https://www.thevirtualnotebook.com
it's legit since it's sources are books. My other references are mentioned in the last second clip.
An antibody (Ab), also known as an immunoglobulin (Ig), is a Y-shaped protein produced mainly by B- plasma cells that is used to neutralize pathogens such as bacteria, viruses etc.These slides will reflect the introduction, structure and types of antibodies.
Antibody(Ab) or immunoglobulin(Ig) is the large Y shaped glycoprotein produced by the body’s immune system when it detects harmful substances are called antigens.
They are synthesized by B lymphocytes and secreted by plasma cells.
Depending on the electrophoretic migration, 3 types of globulins are present in the blood, namely α, β and γ
So antibodies are gamma (γ) globulin.
I took major content from this website i came across. https://www.thevirtualnotebook.com
it's legit since it's sources are books. My other references are mentioned in the last second clip.
An antibody (Ab), also known as an immunoglobulin (Ig), is a Y-shaped protein produced mainly by B- plasma cells that is used to neutralize pathogens such as bacteria, viruses etc.These slides will reflect the introduction, structure and types of antibodies.
This topic covers the brief introduction of Ag and Ab in detail. Types and functions of Ig is explained in detail. Paraproteinemias is explained with simple pictures.
by Dr. N.Sivaranjani, MD
what is innate immunity, its mechanism, principal, diagrams, features of innate immunity, factors affecting innate immunity, mechanism described by the help of diagrams and also the different barriers of innate immunity.
The Complement System lecture 8 chapter 8.pptxOsmanHassan35
Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through
This topic covers the brief introduction of Ag and Ab in detail. Types and functions of Ig is explained in detail. Paraproteinemias is explained with simple pictures.
by Dr. N.Sivaranjani, MD
what is innate immunity, its mechanism, principal, diagrams, features of innate immunity, factors affecting innate immunity, mechanism described by the help of diagrams and also the different barriers of innate immunity.
The Complement System lecture 8 chapter 8.pptxOsmanHassan35
Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through
Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
Complement System comprises of Complement proteins that function to augment the antibodies in killing bacteria by the formation of Membrane Attack Complex.
This ppt describes the different pathways of activation complement proteins and MAC formation.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
1. Lec.1 : Innate immunity
By
Dr/ Eman Ahmed AbdAlrahman
Lecturer of Medical Microbiology and
Immunology
2. 1) Components of Innate Immunity
a) First Line of Natural defense: Mechanical Barriers,
Chemical barrier and Biological barrier
b) Second Line of Natural defense
• Cells of innate immunity
• Complement System
• Other Plasma Proteins of Innate Immunity.
• Cytokines of Innate Immunity.
2) Innate Immune Reactions
a) Inflammation
b) Phagocytosis and Destruction of Microbes.
c) Tissue Repair
d) Antiviral Defense
e) Regulation of Innate Immune Responses
f) Microbial Evasion of Innate Immunity
g) Role of Innate Immunity in Stimulating Adaptive
Lec.1 : Innate immunity
Agenda
3. Innate (Natural/Native) immunity
• Innate immunity is the natural inborn barrier
against invasion by microorganisms.
• It is non-specific, acting against any foreign
invader e.g. microorganisms.
• It is not acquired through previous exposure
to the infectious agents.
4. a- First Line of Natural defense: which prevent the
entry of the microorganisms:
Mechanical Barriers
• The intact skin and mucous membranes are
effective barriers against most microorganisms.
• The hair at the nares, coughing and sneezing help
to expel foreign particles.
• Mucous secretions trap many organisms.
• The blinking reflex and tears expel foreign
particles or bacteria entering the conjunctiva.
1) Components of Innate Immunity
5. a- First Line of Natural defense.
Chemical Barriers :
• Sweat and sebaceous secretions have antimicrobial
actions by acidic pH and high fatty acids content.
• Hydrolytic enzymes in the saliva, HCl of the stomach,
proteolytic enzymes in the small intestine are
bactericidal.
• Lysozyme, an enzyme that dissolves bacterial cell walls
(by breaking down peptidoglycan). It is present on the
skin, in tears and cervical secretions.
• Acidic pH in the adult vagina is protective.
6. Biological barrier
e.g microbiota that suppresses the growth of
many pathogenic bacteria and fungi by
competition for essential nutrients or by
production of inhibitory substances such as
colicins or acids.
a- First Line of Natural defense.
7. If the invading organism gets through the first line of
defense and enters the tissues, other non-specific host
defenses operate. These include:
1) Cells of innate immunity
2) Circulating effector proteins in serum and body
fluids suppress the growth and promote killing of
microbes:
• Complement
• Acute phase proteins
b- Second Line of Natural defense.
8. 1)Cells of innate immunity
• Phagocytes: Neutrophils and Monocytes/
Macrophages
• Dendritic Cells
• Mast Cells
• Innate Lymphoid Cells
• Natural Killer Cells
• Lymphocytes with Limited Diversity
9. A) Phagocytes:
If a microorganism crosses an epithelial barrier and begins
to replicate in the tissues of the host, in most cases, it is
immediately recognized by resident phagocytic cells.
The main classes of phagocytic cells in the innate
immune system are : macrophages
• monocytes
• Granulocytes
• dendritic cells.
Macrophages are the major phagocyte population
resident in most normal tissues at homeostasis.
10. Origin of macrophage:
a) Progenitor cells that enter the tissues during
embryonic development(arise from either
the fetal liver, the yolk sac), and then self-
renew at steady state during life
b) Circulating monocytes.
11. Innate (Natural/Native) immunity
Acute phase proteins
Synthesized in the liver in response to certain
cytokines namely, IL-1, IL-6 and TNF- α which
are produced by macrophages when
stimulated by microbial products.
Present at low levels in the blood of healthy
individuals, but it is produced in increased
amounts during the acute-phase response
12. Acute phase proteins
Examples
1) Pentraxins :
These proteins are formed from five identical subunits.
Prominent members of this family include :C-reactive
protein (CRP) and serum amyloid P (SAP).
The C-reactive protein:it binds to the phosphocholine portion
of certain bacterial and fungal cell-wall lipopolysaccharides.
C-reactive protein binds to and opsonize the bacterium
It can also activate the complement cascade by binding to
C1q, the first component of the classical pathway of
complement activation.
13. 2)Collectins
• Three members of this family serve as soluble effector
molecules in the innate immune system; these are:
• Mannose-binding lectin (MBL) and surfactant proteins
SP-A and SP-D.
a) Mannose-binding lectin (MBL), which is a soluble
pattern recognition receptor that binds carbohydrates
with terminal mannose
• It can activate the lectin pathway of complement by
recognizing mannose residues on microbial surfaces
• MBL can also function as an opsonin by binding to and
enhancing phagocytosis of microbes.
Acute phase proteins
14. 2)Collectins
b) Surfactant protein A (SP-A) and surfactant
protein D (SP-D) are collectins with lipophilic
properties shared by other surfactants.
• They are found in the alveoli of the lungs, and
their major functions are to maintain the ability
of lungs to expand and as mediators of innate
immune responses in the lung.
• They bind to various microorganisms and act as
opsonins, facilitating ingestion by alveolar
macrophages.
Acute phase proteins
15. 3)Ficolins
• Ficolins are plasma proteins that are structurally
similar to collectins. but instead of a C-type lectin
domain, they have a fibrinogenntype
carbohydrate recognition domain (see Fig. 4-11).
• Ficolins bind to several species of bacteria,
opsonizing them and activating complement in a
manner similar to that of MBL.
• The molecular ligands of the ficolins include :
1) N-acetylglucosamine
2) The lipoteichoic acid
Both of them are components of the cell walls of
gram-positive bacteria
Acute phase proteins
16.
17. The Complement System
The complement system is one of the major effector
mechanism of innate and humoral immunity .
The name complement is derived from experiments
performed by Jules Bordet shortly after the discovery of
antibodies.
He demonstrated that if fresh serum containing an
antibacterial antibody is added to the bacteria at
physiologic temperature (37°C), the bacteria are lysed. If,
however, the serum is heated to 56°C or more, it loses its
lytic capacity. This loss of lytic capacity is not due to decay
of antibody activity because antibodies are relatively heat
stable, and even heated Serum is capable of agglutinating
the bacteria.
18. The Complement System
Bordet concluded that the serum must
contain another heat-labile component that
assists, or complements, the lytic function of
antibodies, and this component was later
given the name “COMPLEMENT”
19. The Complement System
They are set of group of plasma proteins
Made constrictively by liver
Present in blood, lymph and extracellular fluid
They are proteolytic enzymes
Circulate in inactive form
20. Pathways of Complement Activation
There are three major pathways of complement
activation:
The classical pathway
The alternative pathway
The lectin pathway
Although the pathways of complement activation differ
in how they are initiated, all of them result in the
generation of enzyme complexes that are able to cleave
the most abundant complement protein, C3.
21. The alternative and lectin pathways are effector
mechanisms of innate immunity, whereas the
classical pathway is a major mechanism of adaptive
humoral immunity.
Complement activation depends on the generation
of two proteolytic complexes:
a) C3 convertase, which cleaves C3 into two proteolytic
fragments called C3a and C3b;
b)C5 convertase, which cleaves C5 into C5a and C5b.
Pathways of Complement Activation
22. 1) The Classical Pathway
• The classical pathway is initiated by
binding of the complement protein C1
to the fc portion of IgG or IgM
molecules that have bound antigen
• C1 is a large, multimeric protein
complex composed of C1q, C1r, and
C1s subunits;
• C1r and C1s form a tetramer
composed of two C1r and two C1s
molecules.
• C1q binds to the antibody, and C1r
and C1s are proteases.
23. Among IgG antibodies, IgG3 and IgG1 (in humans) are
more efficient activators of complement than are
other subclasses.
Only antibodies bound to antigens, and not free
circulating antibodies, can initiate classical pathway
activation
24. • The reason for this is that each C1q
molecule must bind to at least two
Ig Fc region to be activated .
• Because each IgG molecule has only
one Fc region, multiple IgG
molecules must be brought close
together before C1q can bind, and
multiple IgG antibodies are brought
together only when they bind to a
multivalent antigen( an antigen molecule
that carries a number of different epitopes
some times may reach hundreds epitope).
25.
26. • Even though free (circulating) IgM is
pentameric, it does not bind C1q because the Fc
regions of free IgM are in a configuration that is
inaccessible to C1q.
• Binding of the IgM to an antigen induces a
conformational change that exposes the C1q
binding sites in the Fc regions and allows C1q to
bind.
• Because of its pentameric structure, a single
molecule of IgM can bind two C1q molecules,
and this is one reason that IgM is a more
efficient complement-binding (also called
complement fixing) antibody than IgG is.
27. • Binding of C1q to the Fc regions of IgG or IgM leads
to enzymatic activation of the associated C1r, which
cleaves and activates C1sActivated
• C1s cleaves C4, to generate C4b and C4a (C4a small
fragment which is released and has some biologic
activities).While C4b bind to the cell surface.
• The next complement protein, C2, then complexes
with the cell surface–bound C4b and is cleaved by a
nearby C1s molecule
• to generate a soluble C2b fragment of unknown
28. The Lectin Pathway
• The lectin pathway of complement activation is
triggered by the binding of microbial polysaccharides
to circulating lectins, such as plasma mannose binding
lectin (MBL), or to ficolins
• MBL and ficolins associate with MBL-associated serine
proteases (MASPs) including MASP1, MASP2, and
MASP3.
• The MASP proteins are structurally homologous to the
C1r and C1s proteases.
• MASP2 is the protease that cleaves C4 and C2.
Subsequent events in this pathway are identical to
those that occur in the classical pathway
29.
30. The Alternative Pathway
The alternative pathway of complement activation is
triggered by spontaneous hydrolysis of C3 in plasma at a low
level.
The breakdown products of C3 are unstable, and, in the
absence of infection, are rapidly degraded and lost.
However, when a breakdown product of C3 hydrolysis, called
C3b, is deposited on the surface of a microbe, it forms stable
covalent bonds with microbial proteins or polysaccharides.
The microbe-bound C3b binds another protein called Factor B,
which is then cleaved by a plasma protease called Factor D to
generate the Bb fragment. This fragment remains attached to
C3b, and the C3bBb complex functions as a proteolytic
enzyme, called the alternative pathway C3 convertase.
31. The alternative pathway C3 convertase, that breaks
down more C3. The C3 convertase is stabilized by
properdin, a positive regulator of the complement
system.
As a result of this enzymatic activity, many more
C3b and C3bBb molecules are produced and
become attached to the microbe. Some of the
C3bBb molecules bind an additional C3b molecule,
and the resulting C3bBb3b complexes function as
C5 convertases, to cleave the complement protein
C5 and initiate the late steps of complement
activation.
32.
33.
34. The terminal phase of complement
activation
• The products of either pathways (C4b2a3b
and C3bBbC3b act as C5 convertase leading to
of cleavage C5. C5b activates and complexes
with factors C6, C7, C8 and C9 to form
membrane attack unit C5b6789. A potent cell
membrane disrupter is the factor C9.
35.
36. The late steps of complement activation are initiated by the
binding of C5 to the C5 convertase and subsequent proteolysis of
C5, generating C5b.
The remaining components, C6, C7, C8, and C9, bind sequentially
to a complex nucleated by C5b. The final protein in the pathway,
C9, polymerizes to form a pore
in the cell membrane through which water and ions can enter,
causing death of the microbe. The C5-9 complex is called the
membrane attack complex (MAC).
37. Difference between innate and acquired
immune response
Classic Alternate Lectin
Type of immunity Acquired Innate Innate
Initiated by Antigen-antibody
complex
Microbial cell
surface products.
Mannose-binding
lectin (MBL) binds to
mannose residues
on surface of
microbe
Activation of All components
starting with C1, C4,
C2.
Starts with
activation of C3 by-
pass C1, C4, C2
All components
starting C1*, C4, C2,
C3
Properdin system*
involved
No Yes No
Complement
mediated defense
mechanisms
Specific after
antibody appears
Non-specific before
antibody appears
Non-specific before
antibody appears
38. Functions of the Complement System
1) Opsonization.
Microbes coated with C3b are phagocytosed by
phagocytes (which express complement receptor type
1 (CR1, or CD35). Thus, C3b functions as an opsonin.
39. 2) Cell lysis. The MAC can induce osmotic lysis of
cells, including microbes. MAC-induced lysis is
effective only against microbes that have thin
cell walls and little or no glycocalyx, such as the
Neisseria species of bacteria.
40. 3) Inflammation :
The small peptide fragments C3a and C5a, which are
produced by proteolysis of C3 and C5, are chemotactic
for neutrophils, stimulate the release of inflammatory
mediators from various leukocytes, and stimulate
movement of leukocytes and plasma proteins across the
endothelium into tissues to eliminate microbes.
41. 4)Antibody production.
• C3d (a break down product of
C3b), is recognized by
complement receptor type 2
(CR2) on B lymphocytes.
• Signals delivered by this
receptor enhance B cell
responses against the
microbe.
42. 5-Immune complex clearance: Immune
complexes with C3b on their surfaces become
bound to C3b receptors (CR1) on erythrocytes
and are carried through the circulation to the
liver and spleen to be taken into phagocytes and
destroyed. C3 deficiency is associated with
immune-complex disease and susceptibility to
recurrent bacterial infections
43. Regulation of complement
activation.
A) C1 inhibitor (C1 INH) prevents the
assembly of the C1 complex, which
consists of C1q, C1r, and C1s proteins,
thereby blocking complement activation
by the classical pathway.
B) The lipid-linked cell surface protein
decay-accelerating factor (DAF) and the
type 1 complement
receptor (CR1) interfere with the
formation of the C3 convertase by
blocking the binding of Bb (in the
alternative pathway) or C2a (in the
classical pathway). Membrane cofactor
protein (or CD46) and CR1 serve
as cofactors for cleavage of C3b by a
plasma enzyme called factor I, thus
destroying any C3b that may be
formed (not shown).
44.
45.
46. Inherited deficiencies of complement
proteins
• Inherited deficiencies of complement proteins result in
immune deficiencies and, in some cases, increased
incidence of autoimmune disease. Deficiency of C3
results in increased susceptibility to bacterial infections
that may be fatal early in life.
• Deficiencies of the early proteins of the classical
pathway, C2 and C4, may have no clinical consequence,
may result in increased susceptibility to infections, or
are associated with an increased incidence of systemic
lupus erythematosus, an immune complex-mediated
autoimmune disease.
47. • The increased incidence of lupus may be because the classical
pathway functions to eliminate immune complexes from the
circulation, and these complexes accumulate in individuals lacking
C2 and C4.
• In addition, complement deficiencies may lead to defective
signaling in B cells and a failure of B cell tolerance (see Chapter 9).
Deficiencies of C9 and MAC formation result in increased
susceptibility to Neisseria infections. Some individuals inherit
polymorphisms in the gene encoding MBL, leading to production of
a protein that is functionally defective; such defects are associated
with increased susceptibility to infections. Inherited deficiency of
the alternative pathway protein properdin also causes increased
susceptibility to bacterial infection. Regulation of Complement
Activation Mammalian cells