This document provides information on complement, including:
- It defines complement and describes the classical, alternative, and lectin pathways.
- Complement proteins are synthesized in the liver as inactive zymogens and are activated by proteolysis, cleaving them into larger and smaller fragments.
- The pathways differ in their initiation but then follow identical later stages, forming C3 convertase, C5 convertase, and the membrane attack complex (MAC).
- Complement has roles in targeting cell lysis, inflammation, opsonization, immune complex removal, and viral neutralization. Microorganisms have evolved mechanisms to evade complement. Regulatory proteins tightly control complement activation. Deficiencies can increase disease susceptibility
Complement system and its synthesis + activationVaisHali822687
Proteins normally found in serum in inactive form, but when activated they augment the immune responses.
Complements constitute about 5% of normal serum proteins.
Their level does not increase following either infection or vaccination.
There are four main stages in the activation of any of the complement pathways.
Initiation of the pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of membrane attack complex (MAC)
There are three pathways of complement activation: the classical pathway, which is triggered directly by pathogen or indirectly by antibody binding to the pathogen surface; the MB-lectin pathway; and the alternative pathway, which also provides an amplification loop for the other two pathways
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
Complement system and its synthesis + activationVaisHali822687
Proteins normally found in serum in inactive form, but when activated they augment the immune responses.
Complements constitute about 5% of normal serum proteins.
Their level does not increase following either infection or vaccination.
There are four main stages in the activation of any of the complement pathways.
Initiation of the pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of membrane attack complex (MAC)
There are three pathways of complement activation: the classical pathway, which is triggered directly by pathogen or indirectly by antibody binding to the pathogen surface; the MB-lectin pathway; and the alternative pathway, which also provides an amplification loop for the other two pathways
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 presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
Vital component of defense system having integral role not only in the innate immunity but also adaptive immunity.
Provides good defense against harmful infectious agents by process like direct cell lysis or augmenting inflammation and phagocytosis.
Complement system is composed of more than 30 serum proteins present normally as inactive zymogen form (nine central component C1-C9).
Zymogen proteins are activated in a cascade manner.
Complement proteins interact with each other and perform range of functions from direct cell lysis, enhancement of phagocytosis, inflammation and activation of B & T lymphocytes.
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.
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.
Vital component of defense system having integral role not only in the innate immunity but also adaptive immunity.
Provides good defense against harmful infectious agents by process like direct cell lysis or augmenting inflammation and phagocytosis.
Complement system is composed of more than 30 serum proteins present normally as inactive zymogen form (nine central component C1-C9).
Zymogen proteins are activated in a cascade manner.
Complement proteins interact with each other and perform range of functions from direct cell lysis, enhancement of phagocytosis, inflammation and activation of B & T lymphocytes.
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.
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.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
2. Learning objectives
At the end of this session students should be able to
• Define complement
• Understand classical, alternate and lectin pathway
• Role of complement
Essentials of Medical Microbiology
3. Complement
• Represents a group of proteins normally found in serum in
inactive form, but when activated they augment the immune
responses.
• Complements constitute about 5% of normal serum proteins.
• Their level does not increase following either infection or
vaccination.
Essentials of Medical Microbiology
4. GENERAL PROPERTIES
• Bind to Fc region of antibody
• Role of antigen
• Species nonspecific
• Heat labile
Essentials of Medical Microbiology
5. Complement Components
• Complement system comprises of about 30 serum proteins
grouped into complement components, the properdin system
and the regulatory proteins.
• Complement components are named by numerals. There are
nine components; C1 to C9. C1 has three subunits- C1q, C1r and
C1s.
• Properdin system and the regulatory proteins are named by letter
symbols, e.g., factor-B
Essentials of Medical Microbiology
6. Synthesis
• Liver is the major site of synthesis of complement proteins.
• Minor sites include blood monocytes, tissue macrophages,
and epithelial cells of GIT and genitourinary tract.
Essentials of Medical Microbiology
7. Complement activation
• All the complement proteins are synthesized in inactive form (e.g.
zymogens) and are activated by proteolysis.
• Complements have two unequal fragments (large and small
fragment).
• The larger fragments are usually designated as ‘b’ (e.g. C3b) and
the smaller fragments are designated as ‘a’ (e.g. C3a). An
exception is C2a which is larger fragment.
• During proteolysis, the smaller fragment is removed exposing the
active site of the larger fragment.
Essentials of Medical Microbiology
8. Complement activation
• The larger fragment participates in the cascade reaction of
complement pathway and the smaller fragment diffuses away to
mediate other functions.
• Cascade reaction- Fragments of complements interact in a definite
sequential manner with a cascade like effect, which leads to
formation of complex. Such complex having enzymatic activity is
designated by putting a bar over the number or symbol
(e.g. C 3bBb).
Essentials of Medical Microbiology
9. COMPLEMENT PATHWAYS
• Classical pathway- Antibody dependent pathway. Pathway is
triggered by the antigen antibody complex formation.
• Alternative pathway- Antibody independent pathway, triggered
by the antigen directly.
• Lectin pathway is a recently described pathway. It resembles
classical pathway but it is antibody independent.
Essentials of Medical Microbiology
10. Stages of complement activation
• There are four main stages in the activation of any of the
complement pathways.
o Initiation of the pathway
o Formation of C3 convertase
o Formation of C5 convertase
o Formation of membrane attack complex (MAC)
• All the three pathways differ from each other in their initiation till
formation of C3 convertase. Then, the remaining stages are
identical in all the pathways.
Essentials of Medical Microbiology
11. CLASSICAL PATHWAY
• Antibody dependent
• Not all antibodies can bind to complements of classical pathway.
• Decreasing order of ability of antibodies to fix complement is- IgM
(most potent) > IgG3> IgG 1> IgG2.
• The other classes of antibodies do not fix complements. CH2
domain on IgG, CH4 on IgM participate in complement binding.
• The classical pathway begins with activation of C1 and binding to
antigen-antibody complex.
Essentials of Medical Microbiology
12. • The first step is the binding of C1 to the antigen- antibody complex.
• The first binding portion of C1 is C1q, which reacts with the Fc
portion of IgM or IgG bound to antigen.
• C1q is a hexamer having six globular heads each acting as a
combining site.
• Effective activation of classical pathway begins only when C1q is
attached to the Fc portion of antibody by at least two of its globular
binding sites.
Essentials of Medical Microbiology
CLASSICAL PATHWAY -
Initiation
13. • IgM being pentameric, has five Fc regions, hence one molecule of
IgM can initiate the pathway.
• Whereas IgG is monomeric, therefore two IgG molecules are
needed to initiate the process. Hence IgM is much efficient
stimulator of classical pathway.
• C1q binding in the presence of calcium ions, in turn activates
sequentially C1r followed by C1s.
Essentials of Medical Microbiology
CLASSICAL PATHWAY -
Initiation
14. • Activated C1s acts as an esterase (C1s esterase), which can cleave C4
to produce C4a (an anaphylatoxin), and C4b which binds to C1 and
participates further in complement cascade.
o C14b in the presence of magnesium ions cleaves C2 into C2a,
which remains linked to complement complex, and C2b (has kinin
like activity), which is released outside.
o C14b2a is referred to as C3 convertase of the classical pathway.
Essentials of Medical Microbiology
CLASSICAL PATHWAY -
Formation of C3 convertase
15. • C3 convertase hydrolyses many C3 molecules into two fragments:
o C3a (an anaphylatoxin)
o C3b which remains attached to C14b2a to form C14b2a3b
complex which acts as C5 convertase of classical pathway.
Essentials of Medical Microbiology
CLASSICAL PATHWAY -
Formation of C5 convertase
16. • Begins with C5 convertase cleaving C5 into C5a (an anaphylatoxin, released
into the medium) and C5b, which continues with the cascade.
o C5b is extremely labile, gets stabilized by binding soon with C6 and C7
to form C5b67 followed by addition of C8.
o Hydrophobic regions on C7 and C8 help in penetration into the target
cell membrane.
o This inserted membrane complex (C5b678) has a catalytic property to
bind to C9 molecule and then it polymerizes the C9 into a tubular
channel of 10 nm diameter
Essentials of Medical Microbiology
CLASSICAL PATHWAY –
Formation of Membrane attack complex
17. • Penetration of C9 - channels or pores on the target cell membrane
• Each tubular channel - hydrophobic outside, hydrophilic inside -
free passage of ions and water into the cell - cellular swelling - lysis.
• C5b6789 destroys the target cell by attacking the cell membrane –
MAC,
• Process of cytolysis is referred to as complement-mediated
cytotoxicity.
Essentials of Medical Microbiology
CLASSICAL PATHWAY –
Formation of Membrane attack complex
19. ALTERNATIVE PATHWAY
• Independent of antibody; hence is considered as a part of innate
immunity.
• Four stages.
• Differs from the classical pathway in first two stages.
• Three complement components C1, C4 and C2 are not involved.
Requires three other complement proteins present in serum named
factor B, factor D and properdin.
Essentials of Medical Microbiology
20. Antigens from pathogen Non microbial initiators
Endotoxin or LPS
(lipopolysaccharide) from Gram
negative bacteria
Human antibodies in complexes-
IgA, IgD
Teichoic acid from Gram positive
bacteria
Tumor cells
Fungal cells Cobra venom factor
Yeast cells Heterologous RBCs from mouse,
rabbit and chicken
Parasites like Trypanosomes Anion polymer like dextran
sulphate
Virus infected cells Pure carbohydrates like agar, inulin
Essentials of Medical Microbiology
ALTERNATIVE PATHWAY-
Initiation
21. • First complement component to be involved in alternative
pathway is free C3 in the serum.
• C3 hydrolyzes spontaneously, to generate C3a which diffuses
out and C3b fragment which attaches to foreign cell surface
antigen.
Essentials of Medical Microbiology
ALTERNATIVE PATHWAY
22. • Factor B binds to C3b coated foreign cells.
• Factor D - acts on factor B, and cleaves it into
Ba (diffuses out) and Bb (remains attached).
• C3bBb - C3 convertase.
• C3bBb has a very short half-life of 5 minutes.
• Stabilized by properdin (half-life is increased
to 30 minutes).
Essentials of Medical Microbiology
ALTERNATIVE PATHWAY-
Formation of C3 convertase
23. • Formation of C5 convertase.
• Formation of MAC
Essentials of Medical Microbiology
ALTERNATIVE PATHWAY
Identical to that of
classical pathway.
25. LECTIN PATHWAY
• Complement pathway of innate immunity -works independent of
antibody.
• Mediated through lectin proteins of the host that interact with
mannose residues present on microbial surface.
• Lectin pathway involves all complement components used for
classical pathways except C1.
• Instead of C1, host lectin protein called mannose binding lectins
mediate the first ‘initiation’ stage.
Essentials of Medical Microbiology
26. • Activation - Mannose carbohydrate residues of glycoproteins
present on microbial surfaces.
• Mannsoe binding lectins (MBL) bind to mannose residues on
microbial surface.
• MBL is an acute phase reactant protein, similar to C1q in structure.
Essentials of Medical Microbiology
LECTIN PATHWAY-
Initiation
27. • After binding of MBL to microbial surface,
another host protein called MASP (MBL
associated serine protease) gets complexed
with MBL.
• MASP is similar or C1r and C1s and mimics
their functions.
• MBL-MASP complex cleaves C4 which in turn
splits C2 and the MBL/MASP-C4b2a acts as
C3 convertase.
Essentials of Medical Microbiology
LECTIN PATHWAY-
Initiation
28. • Formation of C5 convertase.
• Formation of MAC
Essentials of Medical Microbiology
ALTERNATIVE PATHWAY
Identical to that of
classical pathway.
30. Differences between the three complement pathways
Classical
pathway
Alternative pathway Lectin pathway
Activator (initiator) Antigen antibody
complex
Endotoxin
IgA, IgD, Cobra venom,
Nephritic factor
Carbohydrate residue of bacterial cell
wall (mannose binding protein) that
binds to host lectin antigen.
1st complement
activated
C1 C3b C4
C3 convertase C14b2a C3bBb MBL/MASP-C4b2a
C5 convertase
(C3 convertase + 3b)
C14b2a3b C3bBb3b MBL/MASP-C4b2a3b
Complement level in
the serum
All C1-C9: Low C1,C4,C2- Normal
Others- Low
C1- Normal
Others- Low
Immunity Acquired Innate Innate
Essentials of Medical Microbiology
31. EFFECTOR FUNCTIONS OF COMPLEMENT
• MAC and other complement by-products produced during the
activation augment the immune response in many ways.
o Target cell lysis by MAC
o Inflammatory response
o Opsonization
o Removing the immune complexes from blood-
o Viral neutralization
Essentials of Medical Microbiology
32. Target cell lysis by MAC-
complement mediated cell lysis
• MAC makes pores or channels in the target cell membrane.
• Allows the free passage of various ions and water into the cell
leading to cell swelling, lysis and death.
• E.g. Bacteria, enveloped viruses, damaged cells, tumor cells, etc
Essentials of Medical Microbiology
33. Inflammatory response
• C3a, C4a and C5a - Anaphylatoxins.
• Bind to surface receptors of mast cells and induce their
degranulation leading to release of histamine and other
inflammatory mediators.
• Cause vasoconstriction, and increased vascular permeability.
Essentials of Medical Microbiology
34. Opsonization
• C3b and C4b - major opsonins - coat the
immune complexes and particulate antigens.
• Phagocytic cells express complement receptors
(CR1, CR3 and CR4) for complement
components (C3b, C4b).
• Bind to complement coated antigens and
enhance phagocytosis.
• C5a - enhances the CR1 expression on
phagocytes by 10 folds.
Essentials of Medical Microbiology
35. Removing the immune complexes from blood
• C3b - important role.
• C3b bound immune complexes -
Recognized by complement receptor CR1
present on RBCs.
• Immune complexes bound to RBCs are
taken to liver and spleen where they are
phagocytosed after being separated from
the RBCs.
Essentials of Medical Microbiology
36. Viral neutralization
• Complements coated on virus surfaces neutralize the viral
infectivity by blocking their attachment sites.
• C3b mediated opsonization of viral particles
• Lysis of the enveloped viruses by:
Activation of classical pathway (most viruses)
Alternative or lectin pathways (viruses like Epstein Barr virus,
rubella etc)
Essentials of Medical Microbiology
37. COMPLEMENT RECEPTORS
CR Ligands Distribution Function
CR1
(CD35)
C3b,
C4b
RBCs, phagocytes
All blood cells
1. Regulates complement pathway by
inhibiting C3 convertase
2.Helps in removal of immune complexes
CR2 (CD21) C3d, C3dg B cells, T cells,
Follicular dendritic
cells
1. Forms a part of B cell co-receptor-
involved in humoral responses
2. Acts as EBV receptor
CR3, CR4 iC3b Phagocytes 1. Opsonization
2. Binding and extravasation of
neutrophils
CR3a, CR4a,
CR5a
C3a, C4a, C5a Mast cells, Basophils Degranulation of mast cells and basophils
Essentials of Medical Microbiology
38. EVASION OF COMPLEMENT SYSTEM BY MICROORGANISMS
Mechanisms Examples
Shown by Gram negative bacteria
Long polysaccharide side chain of bacteria can prevent MAC
insertion
Escherichia coli
Salmonella
Non covalent interactions between bacterial cell wall
components can prevent MAC insertion
Neisseria gonorrhoeae
Elastases destroy C3a & C5a Pseudomonas
Essentials of Medical Microbiology
39. EVASION OF COMPLEMENT SYSTEM BY MICROORGANISMS
Mechanisms Examples
Shown by Gram positive bacteria
Thick peptidoglycan cell wall prevents MAC insertion Staphylococcus
Streptococcus
Bacterial capsule forms a physical barrier between C3b and
CR1 interaction
Streptococcus pneumoniae
Shown by other microbes
Proteins mimicking complement regulatory proteins Vaccinia virus,
Herpes simplex virus,
Epstein-Barr virus, Trypanosoma cruzi,
Candida albicans
Essentials of Medical Microbiology
40. REGULATION OF COMPLEMENT PATHWAYS
Regulatory proteins Pathway affected Type of
protein
Regulatory function
C1 regulator
C1 inhibitor
(C1 Inh, or C1 esterase inhibitor)
Classical only Soluble It is a glycoprotein, inhibits the action of C1q
by splitting C1qrs into C1rs and C1q. Thus the
whole classical pathway is inhibited
C3 convertase regulators
C4b-binding protein (C4bBP) Classical and lectin Soluble It blocks formation of C3 convertase by
binding C4b;
It acts as cofactor for cleavage of C4b by factor
I
CR-1(Complement-receptor-1) All three pathways Membrane
bound
Blocks formation of C3 convertase by
binding C3b or C4b
MCP(Membrane-cofactor protein)
Factor H Alternative only
Essentials of Medical Microbiology
41. REGULATION OF COMPLEMENT PATHWAYS
Regulatory proteins Pathway affected Type of
protein
Regulatory function
C3 convertase regulators..
DAF (Decay accelerating factor)
or CD55
All three pathways Membrane
bound
Accelerates dissociation of C3 convertase
Factor-I All three pathways Soluble Cleaves C4b or C3b by using C4b-binding
protein
MAC formation regulators
S protein
All three pathways
Soluble Binds soluble C5b67 and prevents its
insertion into cell membrane
Membrane inhibitor of reactive
lysis (MIRL or CD59)
Membrane
bound
Inhibit MAC formation by blocking C9 binding
Homologous restriction
factor
Membrane
bound
Inhibit MAC formation by blocking C9 binding
Essentials of Medical Microbiology
42. COMPLEMENT DEFICIENCIES
Complement protein
deficiencies
Pathway(s) involved Disease/pathology
C1, C2, C3, C4 C1, C2,C4-Classical
pathway
C3- Common deficiency
SLE, glomerulonephritis &
pyogenic infections
Properdin, Factor D Alternative pathway Neisseria and pyogenic
infection
Membrane attack complex (C5-C9) Common deficiency Disseminated Neisseria infection
Essentials of Medical Microbiology
43. COMPLEMENT DEFICIENCIES
Complement regulatory protein deficiencies Diseases
C1 esterase inhibitor Overactive classical pathway Hereditary angioneurotic edema
DAF (Decay accelerating factor)
& CD59
Deregulated C3 convertase
Increased RBC lysis
PNH (Paroxysmal nocturnal
hemoglobinurea)
Factor I Deregulated classical pathway
with over consumption of C3
Immune complex disease;
recurrent pyogenic infections
Factor H Deregulated alternative
pathway with increased C3
convertase activity
Immune complex disease;
pyogenic infection
Essentials of Medical Microbiology