The document provides an overview of the complement system. It discusses the history and components of the three complement pathways: the classical pathway, lectin pathway, and alternative pathway. It also describes the roles of complement components in opsonization, chemotaxis, and formation of the membrane attack complex to lyse cells. The complement system is regulated to prevent damage to host cells. Deficiencies in complement proteins can increase susceptibility to certain infections.
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
Humoral immunity is defined as the immunity mediated by antibodies, which are secreted by B lymphocytes.
B lymphocytes secrete the antibodies into the blood and lymph
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
Humoral immunity is defined as the immunity mediated by antibodies, which are secreted by B lymphocytes.
B lymphocytes secrete the antibodies into the blood and lymph
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
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
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
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
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.
Introduction Autoimmune Disease by Dr. Kelly CobbNouriche Medspa
The immune system represents an interface between a constant ever-changing external environment and an internal system that is striving to maintain homeostasis and defend its boundaries from harmful foreign invaders.
immunoglobulin are produce by the body against specific stimuli i.e antigen. antibody are of different types and these are classify according to there nature, temperature of reaction, structure and crossing of placenta. antibody are of Y shaped structure which is composed of different region. classification is based on the type of heavy chain, there are 5 major classes of antibodies, IgA, Igd, Igm, ige, most important of these are igm and igg, although each and every have there own significance.
This presentation gives detailed explanation about the anatomical structure and function of bacteria, classification and morphology are also discussed.
The presentation was part of introduction to microbiology course at university of somalia (uniso) based in Mogadishu , the capital city of Somalia.
I am very proud to share the world with this presentation, thanks for everyone who come across to it.
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.
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. This pathway involves complement components C1, C2, and C4. The pathway is triggered by antibody-antigen complexes binding to C1, which itself has three subcomponents C1q, C1r, and C1s. Typically, the complement system acts as a part of the innate immune system, but it can work with the adaptive immune system if necessary. The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous complement component 3 (C3) hydrolysis, foreign material, pathogens, or damaged cells. Anaphylatoxins generated through complement activation interact with their receptors expressed on various cells, thereby modulating their inflammatory properties. Mast cells are widely distributed in the connective tissue around blood vessels and are among the first responders during inflammation.
This presentation describes the Fish Complement system and different types of pathways involved and the mechanism behind the regulation of complement proteins. It gives a basic and a detailed explanation regarding the topic.
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
Through this presentation you will be able to learn about the detailed knowledge of complement system and its functions along with the complement activation pathways [classical, alternative, lectin pathway ]
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
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
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Complement system
1. Santosh Yadav
M.Sc. Clinical Microbiology
Dept. of Microbiology
Institute of Medicine
Tribhuvan Univarsity Teaching Hospital, Nepal
COMPLEMENT SYSTEM
2. Santosh
HISTORY
Research on complement began in the 1890s, when
Jules Bordet at the Institut Pasteur in Paris
showed that sheep antiserum to the bacterium Vibrio
cholerae caused lysis of the bacteria and that heating
the antiserum destroyed its bacteriolytic activity.
He named those substances as
Alexins.
Paul Ehrlich coined the term
complement.
3. Santosh
It is named “complement system” because it was first identified as
a heat-labile component of serum that “complemented or augment”
antibodies in the killing of bacteria.
Consists of serum and cell surface proteins involved in defense
against pathogens and tissue damage mediated by antibodies
The Complement system is the major effector of cellular and
humoral branch of immune system.
Plays major role in both innate and adaptive immunity.
INTRODUCTION
4. Santosh
Complement system represents a group of about 30
proteins which augment or complement the immune
response.
Most of these proteins are found in serum or on cell surfaces.
Synthesized in liver as inative precursors and are activated by
proteolysis durig their interaction in a sequential manner.
Also produced by blood monocytes, tissue macrophages and
epithelial cells of he gastrointestinal and genitourinary
tract.
5. Santosh
General properties
Present in serum of all animals but its concentration is
maximum in serum of guinea pig.
Complement of one species are able to react with
antibodies of other species but not to the same extent.
C- proteins constitute about 5% of normal serum protein
.
Are glycoproteins.
Are synthesized rapidly in inflammatory responses –
hence are called acute phase proteins.
Heat labile and lost activity at 56⁰ C for 30 mins and
inactivated. Immunoglobulins are not inactivated at this
temperature.
Binds with Fc potion of immunoglobulns .
6. Santosh
Three main effects of complement are:
1. Lysis of cells (bacteria, allografts, tumor cells)
2. Generation of mediators of inflammation
3. Opsonization – enhancement of phagocytosis
7. Santosh
Over 30 serum and cell surface proteins:
Complement components-
- Components are designated by numbers (E.g. ; C1 – C9) or latters
(E.g. : Factor D)
- (in serum inactive, activated sequentially as a cascade)
Complement receptors
(cell surface, recognize activated components)
Regulatory proteins of complement
(both in serum and cell surface, inhibit activated components)
system
8. Santosh
Complement proteins: are proenzymes - activation by cleavage.
Example: C4
Exception: C2: C2a = large fragment
C2b = small fragment
a = smaller fragment.
-Diffusion
b= larger fragment.
-remains bound to microbe
C4a C4b
9. Santosh
Complement Pathway
Three pathway of complement activation
1.Classical pathway:-
Is antibody dependent pathway and triggered by
formation of soluble antigen-antibody complex or by
binding of the antibody to the antigen present on the
target cell surface.
2.Alternative pathway:-
Is antibody independent pathway stimulated by
antigen directly eg. Bacterial cell surface components.
3.Lectin Pathway:-
Also antibody independent but resembles classical
pathway.
10. Santosh
Stages of complement Activation
Three main stages in the activation of complement by
any pathway are
Formation of C3 convertage
Formation C5 convertage
Formation of membrane attack complec(MAC)
• The initiation and formation of C3 convertage are
different in classical and alternative pathway . These
then follow the parralel route to merge at C5 convertage
stage and finally generate the MAC by a common route.
11. Santosh
Sequential activation of complement components occurs
via one of three pathways:
the classic pathway,
the lectin pathway, and
the alternative pathway .
Of these pathways, the lectin and the alternative
pathways are more important the first time we are
infected by a microorganism because the antibody
required to trigger the classic pathway is not present.
The lectin pathway and the alternative pathway are,
therefore, participants in the innate arm of the immune
system.
12. Santosh
All three pathways lead to the production of
C3b, the central molecule of the complement
cascade.
The presence of C3b on the surface of a
microbe marks it as foreign and targets it for
destruction. C3b has two important functions:
(1) It combines with other complement
components to generate C5 convertase, the
enzyme that leads to the production of the
membrane attack complex and
(2) it opsonizes bacteria because phagocytes
have receptors for C3b on their surface.
13. Santosh
• C-activation: alteration of C proteins such that they
interact with the next component
• C-fixation: utilization of C by Ag-Ab complexes
• C-inactivation: denaturation (usually by heat) of an
early C-component resulting in loss of hemolytic
activity
• Convertase/esterase: altered C-protein which acts
as a proteolytic enzyme for another C-component
Some Definitions
14. Santosh
Classical pathway
Part of acquired immunity.
In the classic pathway, antigen–antibody complexes
activate C1 to form a protease, which cleaves C2 and
C4 to form a C4bC2a complex, C2a and C4b split off.
The C4bC2a is C3 convertase, which cleaves C3
molecules into two fragments, C3a and C3b.
C3b forms a complex with C4b,2b, producing a new
enzyme, C5 convertase (C4b2a3b), which cleaves C5
to form C5a and C5b
C5b binds to C6 and C7 to form a complex that
interacts with C8 and C9 to produce the membrane
attack complex (C5b,6,7,8,9), which causes cytolysis.
Note that the "b" fragment continues in the main
pathway, whereas the "a" fragment is split off and has
other activities except C2a which binds and C2b which
15. Santosh
Only IgM and IgG fix complement.
One molecule of IgM can activate complement;
however, activation by IgG requires two cross-linked
IgG molecules.
Of the IgGs, only IgG1, IgG2, and IgG3 subclasses fix
complement; IgG4 does not.
C1 is bound to a site located in the Fc region of the
heavy chain.
C1 is composed of three proteins, C1q, C1r, and C1s.
C1q is an aggregate of 18 polypeptides that binds to
the Fc portion of IgG and IgM.
It is multivalent and can cross-link several
immunoglobulin molecules.
C1s is a proenzyme that is cleaved to form an active
24. Santosh
Classic Pathway
Components of the Classical Pathway
Native component Active component(s) Function(s)
C1(q,r,s)
C1q
Binds to antibody that has bound
antigen, activates C1r.
C1r
Cleaves C1s to activate protease
function.
C1s Cleaves C2 and C4.
C2
C2a Unknown.
C2b
Active enzyme of classical pathway;
cleaves C3 and C5.
C3
C3a Mediates inflammation; anaphylatoxin.
C3b
Binds C5 for cleavage by C2b.
Binds cell surfaces for opsonization
and activation of alternate pathway.
C4
C4a Mediates inflammation.
C4b
Binds C2 for cleavage by C1s. Binds
cell surfaces for opsonization.
25. Santosh
Classic Pathway
Components of the Membrane-Attack Complex
Native component Active component(s) Function(s)
C5
C5a
Mediates inflammation;
anaphylatoxin, chemotaxin.
C5b
Initiates assembly of the
membrane-attack complex
(MAC).
C6 C6
Binds C5b, forms acceptor for
C7.
C7 C7
Binds C5b6, inserts into
membrane, forms acceptor for
C8.
C8 C8
Binds C5b67, initiates C9
polymerization.
C9 C9n
Polymerizes around C5b678 to
form channel that causes cell
lysis.
26. Santosh
Alternative pathway
Ab independnt pathway.
In the alternative pathway, many unrelated cell surface
substances, e.g., bacterial lipopolysaccharides
(endotoxin), fungal cell walls, and viral envelopes, can
initiate the process by binding C3 and factor B.
This complex is cleaved by a protease, factor D, to
produce C3bBb.
This acts as a C3 convertase to generate more C3b.
Alternative pathways are more important the first
time we are infected by a microorganism because the
27. Santosh
• Usually activated by products of micro-organisms like
endotoxin
• Other activators include:
1. Complexes containing IgA
2. Some virus-infected cells (e.g. EBV)
3. Many gram negative and gram positive organisms
4. Parasites – Trypanosomes, Leishmania
5. Erythrocytes
6. Carbohydrates (agarose)
29. Santosh
Alternative Pathway
Components of the Alternate Pathway
Native component
Active
component(s)
Function(s)
C3
C3a
Mediates inflammation;
anaphylatoxin.
C3b
Binds cell surfaces for
opsonization and activation
of alternate pathway.
Factor B
B
Binds membrane bound
C3b. Cleaved by Factor D.
Ba Unknown.
Bb
Cleaved form stabilized by
P produces C3 convertase.
Factor D D
Cleaves Factor B when
bound to C3b.
Properdin P
Binds and stabilizes
membrane bound C3bBb.
30. Santosh
Lectin Pathway
Also known as the MBL Pathway
In the lectin pathway, mannan-binding lectin (MBL)
(also known as mannose-binding protein) binds to the
surface of microbes bearing mannan (a polymer of the
sugar, mannose).
Binding causes activation of MASP (MBP- associated
serine proteases) cleave C2 and C4 and activate the
classic pathway.
Note that this process bypasses the antibody-requiring
step and so is protective early in infection before
antibody is formed.
34. Santosh
Membrane attack complex
Cleavage of C5 into C5a and C5b.
C5 (structurally homologous to C3 and C4, lacks
internal thioester bond )
C5b initiates formation of MAC (complex of C5b,
C6, C7, C8 and multiple C9 molecules ) binds to
C6, and C7 , recruits C8 and complex penetrates
more deeply into the membrane.
C9, a pore-forming molecule with homology to
perforin. The complex of C5b678 forms a nidus for
C9 binding and polymerization
Penetrates membrane bilayers to form pores
Disrupt the osmotic barrier, leading to swelling and
lysis of susceptible cells Abbas et.al.Cellular&Molecular immunology 6th edition
36. Santosh
Biologic Effects of complement:
1. Opsonization
• C3b & C1q; enhance phagocytosis
2. Chemotaxis
• C5a and C5,6,7 complex attract neutrophils
• C5a – enhance adhesiveness of neutrophils to the
endothelium
3. Anaphylatoxin (C3a, C4a, C5a)
• Cause degranulation of mast cells
• Bind directly to smooth muscles of bronchioles
bronchospasm
37. Santosh
C3b is an opsonin
Opsonins are molecules that
bind both to bacteria and
phagocytes
Opsonization increases
phagocytosis by 1,000 fold.
38. Santosh
4. Cytolysis (MAC)
• Disrupt the membrane & the entry of water and
electrolytes into the cell
5. Enhancement of antibody production
• Binding of C3b to its receptors on the surface of
activated B cells enhanced antibody production
39. Santosh
Regulation of Complement System
1. C1 inhibitor
• Important regulator of classic pathway
• A serine protease inhibitor (serpin)
• Irreversibly binds to and inactivates C1r and
C1s, as well as MASP in lectin pathway
2. Factor H
• Regulate alternative pathway
• Reduce amount of C5 convertase available
• With both cofactor activity for the factor I-
mediated C3b cleavage, and decay accelerating
activity against C3bBb (C3 convertase)
40. Santosh
3. Properdin
• Protects C3b and stabilizes C3 convertase
4. Factor I
• Cleaves cell-bound or fluid phase C3b and C4b
inactivates C3b and C4b
5. Decay accelerating factor (DAF)
• Glycoprotein on surface of human cells
• Prevents assembly of C3bBb or accelerates
disassembly of preformed convertase no
formation of MAC
• Acts on both classical and alternative
41. Santosh
6. C4b-binding protein (C4BP)
• Inhibits the action of C4b in classical pathway
• Splits C4 convertase and is a cofactor for factor I
7. Complement Receptor 1 (CR-1)
• Co-factor for factor I, together with CD46
8. Protectin (CD59) and Vitronectin (S protein)
• Inhibits formation of MAC by binding C5b678
• Present on “self” cells to prevent complement
from damaging them
42. Santosh
Clinical Aspects of
complement
1. Deficiency of C5-C8 & Mannan-binding lectin
• Predispose to severe Neisseria bacteremia
2. Deficiency of C3
• Severe, recurrent pyogenic sinus & resp. tract
infections
3. Deficiency of C1 esterase inhibitor
• Angioedema inc. capillary permeability and
edema
4. Deficiency of DAF
• Increased complement-mediated hemolysis
paroxysmal nocturnal hemoglobinuria
43. Santosh
5. Transfusion mismatches
• Activation of complement generate
large amounts of anaphylatoxins & MAC
red cell hemolysis
6. Autoimmune diseases
• Immune complexes bind complement
low complement levels + activate
inflammation tissue damage
7. Severe liver disease
• Deficient complement proteins
predispose to infection with pyogenic
bacteria
44. Santosh
8. Factor I deficiency
• Low levels of C3 in plasma due to
unregulated activation of alternative
pathway recurrent bacterial infections
in children
• Mutations in factor I gene implicated in
development of Hemolytic Uremic
Syndrome