The document discusses innate immunity, which is the first line of defense against infection. It has no memory and acts quickly through physical, chemical, and biological barriers as well as cellular and soluble components. Pattern recognition receptors recognize pathogen associated molecular patterns to initiate innate immune responses without prior exposure. Phagocytic cells play a key role through mechanisms like phagocytosis, respiratory burst, and degranulation to destroy pathogens intracellularly or extracellularly. Inflammation is induced as a secondary response to aid in pathogen elimination and tissue repair.
Overview of the Immune System: Innate vs. Adaptive Defenses
Innate-Nonspecific Defenses
First Line of defense: Physical barriers
Second Line of defense:
- Major cellular components
Phagocytes
Basophils
Eosinophils
NK cells
- Chemical signals
Interferons
Complement Proteins
Inflammation
Fever (pyrogens)
Overview of the Immune System: Innate vs. Adaptive Defenses
Innate-Nonspecific Defenses
First Line of defense: Physical barriers
Second Line of defense:
- Major cellular components
Phagocytes
Basophils
Eosinophils
NK cells
- Chemical signals
Interferons
Complement Proteins
Inflammation
Fever (pyrogens)
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
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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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
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.
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 Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
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!
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
2. • Most primitive type of immune system found in
virtually all multicellular animals
• high discrimination of host and pathogen
• First line of defense against infection
• no need for prolonged induction
• act quickly
immediate direct response 0-4 hrs
rapid induced 4-96 hrs
• antigen-independent
Innate Immunity - characteristics
3. Innate Immunity – characteristics (contd.)
• dependence on germ line encoded receptors
• always present and active, constitutively expressed
(some components can be up-regulated)
• Nonspecific; not specifically directed against any
particular infectious agent or tumor
• no clonal expansion of Ag specificity
• Same every time; no ‘memory’ as found in the
adaptive immune system
• failure ==> adaptive immune response
4. Components of Innate Immunity
First line Second line
1 Physical barriers A- cells
2 Chemical & biochemical barriers 1- Natural killer
3 Biological barriers (Normal flora) 2- Phagocytes
3- inflammatory cells
B- Soluble factors
C- Inflammatory barriers
5. Anatomical /Physical/Mechanical
Barriers
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrier
(intact skin)
Desquamation
Mucous Membranes Non-ciliated epithelium (e.g.
GI tract)
Peristalsis
Ciliated epithelium, hairs
(e.g. respiratory tract)
Mucociliary elevator,
Coughing, sneezing
Epithelium (e.g.
nasopharynx)
Flushing action of
tears, saliva, mucus,
urine; blinking of eye
lids
6. Biological Factors
System or Organ Component Mechanism
Skin and mucous
membranes
Normal microflora Antimicrobial
substances
Competition for
nutrients and
colonization
7. Chemical Factors
(at surfaces and in body cavities)
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty
acids, high salt conc.
Mucous Membranes HCl (parietal cells)
Tears and saliva
Low pH
Lysozyme and
phospholipase A
Defensins (respiratory & GI
tract)
Antimicrobial
Sufactants (lung) Opsonin
8. Chemical Factors
(Humoral Components)
Component Mechanism
Complement Lysis of bacteria and some viruses, Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability, Recruitment of phagocytic
cells, -lysin from platelets – a cationic detergent,
antibacterial
Acute phase protein Antibacterial
Lysozyme Breaks down bacterial cell walls
Lactoferrin and transferrin Compete with bacteria for iron
Cytokines Various effects
Interferon Anti-viral protein
9. Pathways of complement activation
CLASSICAL
PATHWAY
ALTERNATIVE
PATHWAY
activation
of C5
LYTIC ATTACK
PATHWAY
antibody
dependent
LECTIN
PATHWAY
antibody
independent
Activation of C3 and
generation of C5 convertase
10. THE ACUTE PHASE PROTEINS
‘Acute phase proteins’ are a large group of plasma proteins whose
concentration increases (or decreases) (by 25% or more) during
inflammation (acute or chronic), such as injury and in disease states.
Proinflammatory cytokines stimulate hepatocytes in the liver to synthesize
and secrete acute phase proteins.
Examples of acute phase proteins are CRP, MBP, haptoglobin, SAA,
fibrinogen, α1-antitrypsin, and complement components C3 and C4.
C-reactive protein (CRP) binds to membrane phospholipids in microbial
membranes.
Mannose binding protein (MBP) binds to mannose sugars found in many
bacteria and fungi.
These functions as opsonins, soluble pattern-recognition receptors, activate
the complement pathway or be involved in sequestration of essential
nutrients.
11. • Antimicrobial peptides forms pores in the cytoplasmic
membrane of a variety of bacteria causing leakage of cellular
needs, e.g. lysozymes, lactoferrins, defensins, protegrins,
granulozymes, etc
• Lysozyme, in serum, mucus, plasma, tissue fluids and tears,
breaks down the bacterial cell wall (peptidoglycan)
• Beta-defensins are short peptides found in blood plasma and
mucous.
• Transferrin & lactoferrin competitively binds iron in blood,
tissues and milk thereby preventing its availability to
microorganisms
Antimicrobial Peptides (AMPs)
12. Interferons (IFN)
• Interferons (IFNs) comprise a family of secreted α-helical cytokines induced in
response to specific extracellular biomolecules of viruses or other pathogens
through stimulation of Toll-like receptors (TLRs).
• Act in paracrine or autocrine modes for regulating innate and acquired
immunity, resistance to viral infections, and normal and tumor cell survival and
death.
• There are five types of human interferon: alpha, beta, gamma, delta and
omega (α -IFN, β -IFN, γ-IFN, ξ-IFN, and ω-IFN, respectively) .
• Virus infected cells produce IFN-α and IFN-β.
• Interferons are host-cell-specific, but not virus-specific
• Gamma-IFN, also called as immune interferon, activates neutrophils, NK cells
and macrophages.
• Interferons also result in
resistance to viral replication; induce enzymes to degrade viral mRNA
increased MHC I expression
activate NK cells, T-cells and macrophages
13. Interferons
Virus-infected cells (double-stranded RNA)
Interferon
Uninfected cells
Induces enzymes (inactive) capable of degrading mRNA
Uninfected cells become infected with a virus
Activation of enzymes
Degradation of viral and cellular mRNA
Blocks viral and cellular protein synthesis
Death of the infected cell
14. Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered self targets
Tissue repair
NK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
16. Inflammation
• Inflammation is an attempt by the body to
eliminate the noxious agent and restore and
maintain homeostasis after injury to a tissue.
• The injury is often caused by invading
organisms.
• It is the second line of defense.
19. The Good Side of Inflammation
The inflammatory response to tissue damage is
of great value by:
• isolating the damaged area
• mobilizing effector cells and molecules to the
site, and
• in the late stages — promoting healing
Inflammation protects the body
(innate immunity)
20. The Bad Side of Inflammation
Often the inflammatory response is out of
proportion to the threat it is dealing with. The result
can be more damaging to the body than the agent
itself would have produced.
Allergies and Autoimmune Diseases are
examples of inflammation in response to what
should have been a harmless, or at least
noninfectious, agent
22. Phagocytosis
Phagocytosis is the ingestion of microorganisms or
particulate matter by a cell.
Phagocytosis is performed by phagocytes—
certain types of white blood cells or derivatives of
them.
All phagocytes
eat, digest
and extrude
23.
24. Phagocytic Cells
Myeloid Macrophage-
Monocyte
Basophils
Neutrophils Eosinophils
• Rapid phagocytosis, but cannot
phagocytose repeatedly
• Has granules which contain
bactericidal enzymes
• Short lived
• NO ABILITY TO PRESENT ANTIGEN
•Slow but can phagocytose
repeatedly.
•Contain bactericidal
enzyme.
•Long lived
•Selected cells HAVE
ability to present Ag.
26. Chemotaxis & attachment
• Attraction by chemotactic substances (microbes, damaged tissues,
complement components, vasoactive amines, etc )
• Attachment by receptors on surfaces of phagocytes.
Ingestion and phagosome formation
• Phagocytes’ produce pseudopodia surrounding organism forming
phagosome
• Opsonins and co-factors enhance phagocytosis
Phagolysosome formation
• Fusion of phagosome with lysosomal granules of phagocyte take
place by help of cytoskeleton followed by the release digestive and
degradative enzymes
27. The Process of Phagocytosis - ingestion
Following attachment, polymerization and depolymerization of actin
molecules send pseudopods out to engulf the bacterium
28. The Process of Phagocytosis - phagosome formation
Following engulfment, the bacterium is placed in a vesicle called a phagosome.
29. Lysosomes move along the cytoskeleton and fuse with phagosomes to form
phagolysosomes.
30. The Process of Phagocytosis - Destruction
The lysosome, its digestive enzymes and microbicidal chemicals fuses with
the phagosome containing the ingested bacteria to form a phagolysosome
and the bacterium is killed.
31. Intra-cellular killing (two microbicidal routes)
• Oxygen-dependent system (powerful microbicidal agents)
Oxygen converted to superoxide anion, hydrogen peroxide,
activated oxygen and hydroxyl radicals.
• Oxygen-independent system (anaerobic conditions)
Digestion and killing by lysozyme, lactoferrin, low pH, cationic
proteins and hydrolytic and proteolytic enzymes
36. Effector Molecule Function
Mediators of Oxygen-independent Killing in
the Phagolysosome
Cationic proteins (cathepsin) Damage to microbial
membranes
Lysozyme Hydrolyses mucopeptides in
the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms
37. Some cytokines
can also induce
phagocytic cells,
particularly
macrophages, to
produce nitric oxide
(NO), which is toxic
to microorganisms
and malignant cells
Nitric Oxide
Nitric Oxide Dependent Killing
38.
39. Nitric Oxide Dependent Killing
Nitric oxide also possess antiviral properties:
• inhibition of viral RNA synthesis
• inhibition of viral protein accumulation
• inhibition of virus release from infected cell
40. Extracellular Destruction of Bacteria by a Phagocyte
• If the phagocyte is
overwhelmed with
microorganisms, the
phagocyte will empty the
contents of its lysosomes by
a process called
degranulation in order to kill
the microorganisms or cell
extracellularly. These
released lysosomal contents,
however, also kill
surrounding host cells and
tissue. Most tissue
destruction associated with
infections is a result of this
process
41. FACTORS AFFECTING PHAGOCYTOSIS
OPSONINS “natural ketchup”
Proteins which coat the antigen to facilitate phagocytosis
e.g. Antibodies
Complement Components
Certain Liver proteins
Generally both bacteria and cells that are suspended in body fluids
have negative charges (Zeta Potential). Therefore they tend to
repel each other. Opsonins, provide positive charges and
coating with opsonins promotes phagocytosis.
42. ANTIGEN OPSONIN EFFICIENCY OF
PHAGOCYTOSIS
None +
+++
+++
Antibody
Complement
Antibody Plus Complement
++++
44. Fever
Activated macrophages and other leukocytes release
proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1
These cytokines stimulate the anterior hypothalamus of the
brain to produce prostaglandins that lead to an increase in
body temperature – fever.
Fever increases the physiological temperature above the
optimum growth temperature for many microorganisms.
Fever leads to the production of heat shock proteins
resulting in the production of inflammation-promoting
cytokines.
Fever elevates the temperature of the body increasing the
rate of enzyme reactions, and speeding up metabolism
within the body
47. Pattern-Recognition Receptors
Innate immunity recognize a few highly conserved structures
present in many different microorganisms - the pathogen-
associated molecular patterns (PAMPs) as well as danger
signals released from damaged or dying (necrotic) cells
(DAMPs)
These PAMPs/DAMPs are recognized by pattern recognition
receptors (PRRs), expressed on/in the innate immunity cells.
PRRs can also recognize host molecules containing damage-
associated molecular patterns (DAMPs), molecules that are
often released from necrotic cells damaged by invading
pathogens
These PRRs include Toll-like receptors (TLRs), nucleotide-
binding domain (NOD) and leucine-rich repeat containing
receptors (NLRs), and retinoic acid-inducible gene-I (RIG-)-like
receptors (RLRs). lectins, and scavenger receptors.
50. PAMPs binding to PRRs on defense cells
The PRRs recognize approximately 103 molecular patterns
51. Innate immune responses encountered by microbes.
Microbes are detected by pattern recognition receptors (PRRs) expressed in innate immune
cells, such as macrophages. The detection of microbes by the PRRs rapidly activates
signalling cascades and generates inflammatory responses. Microbial encounter also leads to
maturation of macrophages and dendritic cells into antigen presenting cells. PAMP, pathogen-
associated molecular pattern; TCR, T-cell receptor.
52. PAMP PRR
Biological
Consequence of
Interaction
Microbial cell wall
components
Complement Opsonization;
Complement activation
Mannose-containing
carbohydrates
Mannose-binding protein Opsonization;
Complement activation
Lipoproteins of Gram
positive bacteria, yeast
cell wall components
TLR-2 (Toll-like receptor 2) Macrophage activation;
Secretion of
inflammatory cytokines
Double stranded RNA TLR-3 Production of
interferon (antiviral)
LPS (lipopolysaccharide
of Gram –ve bacteria
TLR-4 Macrophage activation;
Secretion of
inflammatory cytokines
Flagellin (bacterial
flagella)
TLR-5 Macrophage activation;
Secretion of
inflammatory cytokines
53. DAMPs
• Damage-associated molecular patterns (DAMPs) are endogenous
danger molecules that are released released upon cellular stress or
tissue injury from damaged or dying cells and activate the innate
immune system by interacting with pattern recognition receptors
(PRRs).
• DAMPs activate the innate immune system by inducing potent
inflammatory responses during non-infectious inflammation
• These DAMPs are recognized by macrophages, and inflammatory
responses are triggered by different pathways, including TLRs and
inflammasomes
• DAMPs can originate from different sources and include:
– extracellular proteins, e.g. biglycan and tenascin C,
– intracellular proteins, e.g. high-mobility group box 1 (HMGB1),
histones, S100 proteins, heat-shock proteins (HSPs), and
– plasma proteins, e.g. fibrinogen, Gc-globulin, and serum amyloid
A (SAA)
55. Toll-like receptors (TLRs) - 1
Play a major role in innate immunity and the
induction of adaptive immunity.
Different combinations of TLRs appear in different cell
types and seem to appear in pairs; 13 recognized so far
Different TLRs directly or indirectly bind different
microbial molecules.
TLRs are found both on the surface and within the
phagolysosomes of phagocytes.
Surface TLRs recognize molecules on the surface of
microbes such as cell wall components
Internal TLRs recognize microbial molecules released
upon phagocytosis of the microbe.