The innate immune system provides the body's first line of defense against pathogens through physical, chemical, and cellular barriers. It responds quickly but non-specifically. Components of innate immunity include physical barriers like skin, mucous membranes, and microbiota; physiological barriers like low pH and natural killer cells; cellular barriers comprising phagocytes and cytokines; and inflammatory responses. Pattern recognition receptors expressed by innate immune cells recognize pathogen-associated molecular patterns and damage-associated molecular patterns to detect and respond to infections.
B Cell Receptor & Antibody Production-Dr C R MeeraMeera C R
Antibody production is the function of B lymphocytes. These slides describe the structure of B cell receptor and steps involved in antibody production by B lymphocytes
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricus.
B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
B Cell Receptor & Antibody Production-Dr C R MeeraMeera C R
Antibody production is the function of B lymphocytes. These slides describe the structure of B cell receptor and steps involved in antibody production by B lymphocytes
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricus.
B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
Antigen processing and presentation by Dr K.Geetha, Associate Professor, Department of Biotechnology, Kamaraj College of Engineering & Technology, Near Virudhunagar, Madurai Dist.
Antigen processing and presentation by Dr K.Geetha, Associate Professor, Department of Biotechnology, Kamaraj College of Engineering & Technology, Near Virudhunagar, Madurai Dist.
The human body has a special design, it protects itself against any invaders. In this presentation you will learn about the self defense mechanisms of the body.
Immune system and immunity ppt by DR.C.P.PRINCEDR.PRINCE C P
Immunity is the power to resist and overcome infection caused by particular organism.
RESISTANCE EXHIBITED BY THE HOST AGAINST MICROBES AND THEIR PRODUCTS
Innate immunity:“Innate” because shared by all animals (Pre-existing/ By birth) and Non-specific
Adaptive immunity (Acquired Immunity):Responsive and Specific
The immune system recognizes, attacks, destroys, and remembers each pathogen that enters the body.
The Immune System includes all parts of the body that help in the recognition and destruction of foreign materials.
White blood cells, phagocytes and lymphocytes, bone marrow, lymph nodes, tonsils, thymus, and your spleen are all part of the immune system.
prepared by:
DR.PRINCE C P
HOD & Associate Professor
Department of Microbiology
Mother Theresa Post Graduate & Research Institute of Health Sciences (Government of Puducherry Institution)
Pondicherry
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
We all have good and bad thoughts from time to time and situation to situation. We are bombarded daily with spiraling thoughts(both negative and positive) creating all-consuming feel , making us difficult to manage with associated suffering. Good thoughts are like our Mob Signal (Positive thought) amidst noise(negative thought) in the atmosphere. Negative thoughts like noise outweigh positive thoughts. These thoughts often create unwanted confusion, trouble, stress and frustration in our mind as well as chaos in our physical world. Negative thoughts are also known as “distorted thinking”.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
3. Objectives
• At the end of this presentation we should be able to
describe;
Innate immunity and its components
Acquired immunity and its components
4. Learning Outcomes
• Explain the components & characteristics of innate and
adaptive immune responses.
• Describe effector mechanisms used by the innate
immune system, the cells and molecules involved in
each mechanism,
• Discus mechanisms used by the adaptive immune
system, and the cells involved.
• Explain the deference between the innate immune
response and adaptive immune response
• Describe how innate responses help to ensure that an
effective adaptive immune response is generated for a
specific pathogen.
5. INTRODUCTION
• Defense against microbes is mediated by sequential and
coordinated responses, that are called innate and
adaptive immunity.
• Innate immunity (natural/native immunity) is essential for
defending against microbes in the first few hours or days
of infection, before adaptive immune responses have
developed.
• Innate immunity is mediated by mechanisms that are in
place even before an infection occurs (hence innate) and
that facilitate rapid responses to invading microbes.
6. Introduction..
• In contrast, there are other immune responses that are
stimulated by exposure to infectious agents and increase
in magnitude and defensive capabilities with each
successive exposure.
• Because this form of immunity develops as a response
to infection and adapts to the infection, it is called
adaptive immunity (specific/acquired immunity).
• The adaptive immune system recognizes and reacts to a
large number of microbial and nonmicrobial substances,
9. INNATE IMMUNE
• Innate immunity is mediated by mechanisms that are in
place even before an infection occurs (hence innate) and
that facilitate rapid responses to invading microbes.
• Charactorised by
Immediate response to the pathogen
Doesn't confer long-lasting protective immunity
Nonspecific defense system
Broad reactivity uniform in all members of a species
Pathogens can be detected and destroyed within minutes or
hours
Do not rely on expansion of antigen-specific lymphocytes.
The innate immune system uses a limited number of secreted
proteins and cell-associated receptors to detect infection.
• These are called innate receptors because they are inborn
10. Properties & functions of innate immune
response
• The innate immune system maintains physical and
chemical defenses at epithelial barriers such as
the skin and lining of the gastrointestinal and
respiratory tracts, which block microbial entry.
• Innate immune responses are the initial reactions
to microbes that serve to prevent, control, or
eliminate infection of the host by many pathogens.
• Innate immunity eliminates damaged cells and
initiates the process of tissue repair.
11. Properties & functions of innate immune
response….
• Innate immune responses stimulate adaptive immune
responses and can influence the nature of the adaptive
responses to make them optimally effective against
different types of microbes.
• The two major types of protective reactions of the innate
immune system are
i. Inflammation
By recruiting phagocytes and other leukocytes that destroy the
microbes
ii. Antiviral defence.
By blocking viral replication or killing virus-infected cells without
a need for an inflammatory reaction
12. Components of Innate Immunity
• Comprise four types of defensive barriers:
1. Physical/Anatomic barriers
2. Physiologic barriers
1. Phagocytic barriers
2. Inflammatory barriers
13. Components…
• Anatomical and physical barriers
Mechanical factors
Chemical factors
Biological factors
• Humoral components
Complement
Coagulation system
Cytokines
• Cellular components
Neutrophils
Monocytes and macrophages
NK cells
Eosinophils
14. 1. Physical and anatomic Barriers
1. Skin
Two layers: epidermis and dermis.
• The epidermis contains several layers of tightly packed
epithelial cells and dead cells filled with a waterproofing
protein called keratin.
• Dermis composed of connective tissue, contains blood
vessels, hair follicles, sebaceous glands, and sweat
glands..
15. 1. Physical and anatomic Barriers
2. Mucosal Surfaces/membrane
• lining of Conjunctivae, alimentary, respiratory, and
urogenital tracts.
• Prevent entry by inhibiting binding of pathogens to the
epithelial cells via actions of:
Saliva, tears and mucosal secretion
Secreted juice
Viscus fluid (mucus) secreted by epithelial cells.
16. 1. Physical and anatomic Barriers…
3. Normal flora
• Nonpathogenic organisms colonizing epithelial cells of
mucosal surfaces.
• Outcompete pathogens for attachment sites on the
epithelial cell surface and for necessary nutrients.
• Bactericide production
17.
18. Components of Innate Immunity
• Comprise four types of defensive barriers:
1. Physical/Anatomic barriers
2. Physiologic barriers
3. Phagocytic barriers
4. Inflammatory barriers
19. 2. Physiologic barriers
1 Temperature
• Normal body temperature inhibits growth of some
pathogens
• Fever also inhibit growth of some microbes
2. Low pH
• Gastric acidity allow very few microorganisms to survive
20. 2. Physiologic barriers…
(Molecules/humoral components)
3. Lysozyme
• Cleaves the peptidoglycan layer of the bacterial cell wall
4. Surfactant proteins (collectins)
• Kill certain bacteria directly either by disrupting their lipid
membranes or aggregating the bacteria to enhance their
susceptibility to phagocytosis
21. 2. Physiologic barriers
5. Interferon
• Group of proteins produced by virus infected cells to bind
to nearby cells and induce a generalized antiviral state.
6. Complement
• A group of serum proteins that circulate in an inactive state
• Activated complement has ability of either destroying the
pathogens or facilitate their clearance.
24. Components of Innate Immunity
• Comprise four types of defensive barriers:
1. Physical/Anatomic barriers
2. Physiologic barriers
3. Inflammatory barriers
4. Phagocytic barriers
25. 2. Inflammatory Response
Characterized by release of cytokines from macrophages
and other inflammatory mediators.
• Response occurs rapidly and limit spread of pathogen
until adaptive response is initiated.
• Triggered by injury – trauma, heat, chemical irritation,
infection, etc.
26. Inflammatory mediators
1. Macrophages release cytokines like IL-1, TNF-α, and
derivatives of arachidonic acid
2. Acute-phase proteins-chemical mediators released
increases in response to tissue damage;
C-reactive protein is a major acute-phase protein
produced by the liver in response to tissue damage
Binds to the C-polysaccharide cell-wall component
found on a variety of bacteria and fungi activates
the complement system
27. Inflammatory mediators..
3. Histamine
• Released by a variety of cells in response to tissue injury
• Binds to receptors on nearby capillaries and venules,
causing vasodilation and increased permeability
The cardinal signs of inflammation are Redness Heat,
Swelling and Pain
28. Events of an inflammatory response
1. Vasodilation;
• The vessels that carry blood away from the affected area
constrict, resulting in engorgement of the capillary
network
• Resulting in tissue redness (erythema) and an increase
in tissue temperature
29. Events of an inflammatory response…
2. An increase in capillary permeability
• Facilitates an influx of fluid and cells from the engorged
capillaries into the tissue.
• Accumulation of exudates contributes to tissue swelling
(edema)
3. Influx of phagocytes into the tissues
• Release lytic enzymes, which can damage nearby
healthy cells
• Accumulation of dead cells, digested material, and fluid
forms pus.
30.
31. Components of Innate Immunity
• Comprise four types of defensive barriers:
1. Physical/Anatomic barriers
2. Physiologic barriers
3. Inflammatory barriers
4. Phagocytic barriers
32. C. Cellular innate immunity
• The common myeloid progenitor (CMP) is the precursor
of the macrophages, granulocytes (i.e. neutrophils,
eosinophils, and basophils), mast cells, and dendritic
cells of the innate immune system.
• Macrophages, granulocytes, and dendritic cells make up
the three types of phagocytes in the immune system.
33. Innate Immune Cells
Phagocytes
• Specialized phagocytic cells, primarily macrophages
and neutrophils, are the first line of defense against
microbes that breach epithelial barriers.
• Some macrophages are always present in most
tissues and function as sentinels of infection, while
other phagocytes, including monocytes and
neutrophils, are recruited into infected tissues in
response to microbes or signals generated by the
sentinel cells.
34. Innate Immune Cells
Dendritic Cells
• DCs detect invading microbes because of their
location in tissues and their expression of numerous
pattern recognition receptors for PAMPs and DAMPs.
• They secrete inflammatory cytokines that promote
recruitment of additional leukocytes from the blood.
35. Dendritic Cells….
• The plasmacytoid subset of DCs is a major source of the
antiviral cytokines, type I interferons, produced in
response to viral infections.
• The reactions of DCs to microbes in the early innate
response enhance the ability of the DCs to activate T
cells in the subsequent adaptive immune response
36. Innate Immune Cells
Cytokine-Producing Innate Lymphoid Cells (ILCs)
ILCs are bone marrow–derived cells with lymphocyte
morphology that were discovered as cells that
produced cytokines similar to those made by T cells
but lacked TCRs.
There are different subsets of ILCs that arise from the
same common lymphoid precursor that gives rise to B
and T cells, but the precise steps in ILC development
are not fully understood, especially in humans.
37. Cytokine-Producing Innate Lymphoid Cells…
• Three subsets of innate lymphoid cells, called ILC1,
ILC2, and ILC3, produce different cytokines and express
different transcription factors.
• The cytokines each subset produces determine the roles
of these cells in defense.
38.
39. Cytokine-Producing Innate Lymphoid Cells…
– NK cells, often considered the first known ILC, are
cytotoxic cells that play important roles in innate
immune responses, mainly against viruses and
intracellular bacteria.
– NK cells also secrete IFN-γ and are sometimes
referred to as a type of ILC1.
– NK cells have granules that contain proteins that
mediate killing of target cells. When NK cells are
activated, granule exocytosis releases these proteins
adjacent to the target cells. E.g perforin, granzymes
40.
41. Innate Immune Cells
Mast Cells
– Contain abundant cytoplasmic granules filled with
various inflammatory mediators that are released
when the cells are activated.
– The granule contents include vasoactive amines (e.g
histamine) that cause vasodilation and increased
capillary permeability, and proteolytic enzymes
– Mast cells also synthesize and secrete lipid mediators
(e.g prostaglandins) and cytokines (e.g TNF).
42. Recognition Of Microbes And Damaged Self By
The Innate Immune System
The innate immune system recognizes molecular
structures that are produced by microbial pathogens.
• The microbial substances that stimulate innate
immunity are often shared by classes of microbes and
are called pathogen-associated molecular patterns
(PAMPs).
• The innate immune system recognizes microbial
products that are often essential for survival of the
microbes.
43. Pathogen associated molecular patterns
(PAMPs)
• Unique microbial molecules recognized by the immune
system.
• Highly conserved, general, only to microorganism. e.g,
virus; Capsid, spike, viral envelope,
genome
Bacteria; cell wall (LPS), flagella, cilia bacteria
genome
• Different types of microbes (e.g., viruses, gram-negative
bacteria, gram-positive bacteria, fungi) express different
PAMPs as shown below
45. Damage associated and molecular patterns
(DAMPs)
The IIM also recognizes endogenous molecules that
are produced by or released from damaged and dying
cells.
– DAMPs, as a result of cell damage caused by
infections, but they may also indicate sterile injury due
to chemical toxins, burns, trauma, or loss of blood
supply.
– In some cases, endogenous molecules that are
produced by healthy cells are released when the cells
are damaged, and they then stimulate innate
responses.
47. Recognition Of Microbes And Damaged Self By
The Innate Immune System
• The innate immune system uses several types of cellular
receptors, present in different locations in cells, and
soluble molecules in the blood and mucosal secretions,
to recognize PAMPs and DAMPs.
• Cell-associated recognition molecules of are expressed
by phagocytes, dendritic cells, epithelial cells that form
the barrier interface between the body and the external
environment, mast cells, and many other types of cells
that reside in tissues.
48. Pattern recognition receptors (PRRs)
• The cellular receptors for pathogen- and damage associated
molecular patterns are called pattern recognition receptors..
• Receptor expressed on the plasma membrane of cell of
innate immunity
• Macrophages, neutrophils, dendritic cells
• Also present in cellular compartments
• Endosomes, lysosomes, cytosol
• Thus unable to detect both intercellular and extracellular
stress
49.
50. Pattern recognition receptors (PRRs)
• 3 Types of PRR
• Membrane bound (TLRs, CLRs)
• Cytoplasmic sensor (NLRs, RLRs)
• Inflammasomes
• Each PRR can detect multiple pathogenic species which
share same PAMPs.
• PRRS
• TLRs – toll like receptors
• CLRs – c-type lectin receptors
• RLRs – RIG-like receptors
• NLRs – NOD-like receptors
53. Oxygen-dependent Killing Mechanisms
• Activated phagocytes produce a number of reactive oxygen
intermediates (ROIs) and reactive nitrogen intermediates
that have potent antimicrobial activity.
• During phagocytosis, a metabolic process known as the
respiratory burst occurs in activated macrophages.
• This process results in the activation of a membrane-bound
oxidase that catalyzes the reduction of oxygen to superoxide
anion, a reactive oxygen intermediate that is extremely toxic
to ingested microorganisms.
53
54. Oxygen-dependent Killing Mechanisms
• The superoxide anion also generates other powerful
oxidizing agents, including hydroxyl radicals and
hydrogen peroxide.
• As the lysosome fuses with the phagosome, the activity
of myeloperoxidase produces hypochlorite from
hydrogen peroxide and chloride ions.
• Hypochlorite (bleach) is toxic to ingested microbes.
54
55.
56. Nitric Oxide Dependent Killing
Mechanisims
• When macrophages are activated with bacterial cell-wall
components such as lipopolysaccharide (LPS) or, muramyl
dipeptide (mycobacteria), and a T-cell–derived cytokine
(IFN-ϒ),
• Express high levels of nitric oxide synthetase (NOS), an
enzyme that oxidizes L-arginine to yield L-citrulline and
nitric oxide (NO) gas:
• L-arginine + O2+ NADPH →NO + L-citrulline + NADP
57. Nitric Oxide Dependent Killing
mechanisims
• Nitric oxide has potent antimicrobial activity; it also can
combine with the superoxide anion to yield even more
potent antimicrobial substances.
• Much of the antimicrobial activity of macrophages
against bacteria, fungi, parasitic worms, and protozoa is
due to nitric oxide and substances derived from it.
57
58. Oxygen-independent Killing Mechanisms
Activated macrophages also secrete;
• Lysozyme
Which contains various hydrolytic enzymes which degrades
antigen without oxygen requirement.
• Defensins
– group of antimicrobial and cytotoxic peptides, form ion-
permeable channels in bacterial cell membranes to kill a
variety of bacteria, including Staphylococcus aureus,
Streptococcus pneumoniae, Escherichia coli,
Pseudomonas aeruginosa, and Haemophilus influenzae.
• Tumor necrosis factor (TNF-α), a cytokine that
has a variety of effects and is cytotoxic for some
tumor cells.
6/21/2023 58
61. Adaptive Immunity
• Unlike innate immunity, it is stimulated by exposure to
infectious agents and increase defensive capabilities
with each successive exposure to a particular microbe.
• Develops as a response to infection and adapts to the
infection, so it is called adaptive immunity
(specific/acquired immunity).
• The adaptive immune system recognizes and reacts to a
large number of microbial and nonmicrobial substances,
called antigens.
62. Adaptive immunity..
• It is capable of recognizing and selectively eliminating
specific foreign microorganisms and molecules (i.e,
foreign antigens).
• Can be antibody mediated (humoral), cell mediated
(cellular), or both.
• The Adaptive Immune System Requires Cooperation
Between Lymphocytes and Antigen-Presenting Cells
(APC)
63. Cells of adaptive immunity
1. Lymphocytes
• WBCs which leave the bone marrow, circulate in the
blood and lymphatic systems, reside in various lymphoid
organs.
• Express antigen binding cell-surface receptors and hence
their specificity, diversity, memory, and self/nonself
recognition.
• The two major types:
B cells and T cells
64. Cells of adaptive immunity….
2. Antigen-presenting Cells
• Immune cells that mediate the cellular immune response
by processing and presenting antigens for recognition by
certain lymphocytes such as T cells
• Classical APCs include dendritic cells, macrophages,
Langerhans cells.
• They all express class II MHC molecules on their
membranes
65. Features of Adaptive immunity
• Display four main charactoristics
i. Antigenic specificity
ii. Diversity
iii. Immunologic memory
iv. Self/nonself recognition
66. Features of Adaptive immunity
Antigenic diversity.
• It is estimated that the immune system of an individual can
discriminate 107 to 109 distinct antigenic determinants.
• This ability of the lymphocyte repertoire to recognize a very
large number of antigens, called diversity, is the result of
variability in the structures of the antigen binding sites of
lymphocyte receptors for antigens.
67. Features of Adaptive immunity
Antigenic specificity
• As an antigen binds to a particular T or B cell and
stimulates it to divide repeatedly into a clone of cells
with the same antigenic specificity as the original
parent cell (clonal selection)
• Only lymphocytes whose receptors are specific for a
given epitope on an antigen will be clonally expanded
and thus mobilized for an immune response
68. Features of Adaptive immunity
Immunologic memory :
A consequence of clonal selection. During clonal selection,
the number of lymphocytes specific for a given antigen is
greatly amplified.
Amplified population of memory cells accounts for the rapidity and
intensity secondary immune response
Moreover memory cells have a longer life span than the naïve from
which they are derived
• Two reasons for stronger secondary immune response
1. Memory cells accumulate and become more numerous than the
naïve lymphocytes.
2. Memory cells react more rapidly and vigorously to antigen
challenge than do naive lymphocytes
69. Adaptive immune response
Self/nonself discrimination;
• One of the most remarkable properties of every
normal individual’s immune system is its ability to
recognize, respond to, and eliminate many foreign
(nonself) antigens while not reacting harmfully to that
individual’s own (self) antigens.
• Immunologic unresponsiveness is also called
tolerance. Tolerance to self antigens, or self-
tolerance, is maintained by several mechanisms.
70. Humoral immune response
It is an antibody mediated immunity
• Involve interaction of B cells with antigen and their
subsequent proliferation and differentiation into antibody-
secreting plasma cells.
• Antibodies are glycoproteins consist of two identical
heavy polypeptide chains and two identical light
polypeptide chains
71. B lymphocytes
• B lymphocytes arise and mature
within the bone marrow
• Expresses a unique antigen-binding
receptor on its membrane, a
membrane-bound antibody
molecule.
• B cells have about 105 molecules of
membrane-bound antibody per cell.
All the antibody molecules have
the same antigenic specificity can
interact directly with antigen.
71
72. B cell …
• When a naive B cell first encounters the antigen, the
antigen bind to the antibody
• Causes rapidly cell differentiation to memory B cells and
effector B cells called plasma cells.
• Memory B cells have a longer life span than naive cells,
and they express the same membrane-bound antibody
as their parent B cell.
73. B cell …
• Secreted antibodies are the major effector molecules of
humoral immunity.
• They bind to antigen and neutralizing it or facilitating its
elimination by:
Phagocytosis
Activation of the Complement system which lyse
foreign organism.
Neutralization of toxins or viral particles by coating
with antibody which prevents binding to host cells.
74. Cell mediated immunity
• Effector T cells generated in response to antigen are
responsible for cell-mediated immunity
• Both activated TH cells and cytotoxic T lymphocytes
(CTLs) serve as effector cells in cell-mediated immune
reactions.
• Cytokines secreted by TH cells can activate various
phagocytic cells, enabling them to phagocytose and kill
microorganisms more effectively.
75. Cell mediated immunity
• Cell-mediated immune response is especially important
in ridding bacteria and protozoa contained by infected
host cells.
• CTLs participate in cell-mediated immune reactions by
killing altered self-cells
• play an important role in the killing of virus infected
cells and tumor cells.
76. Types of T lymphocytes
• There are two types of T cells:
– T helper (TH) and T cytotoxic (TC) cells distinguished
from one another by the presence of either CD4 (TH
cells ) or CD8 ( TC cells) membrane glycoproteins on
their surfaces
• Postulated third type a T suppressor (TS) cell,
– recent evidence suggests that it may not be distinct
from TH and TC subpopulations.
77. T cells…..
• CD4+ T cells recognize only antigen bound to class II
MHC molecules.
• CD8+ T cells recognize only antigen associated with
class I MHC molecules.
In general, CD4+ cells act as helper cells and CD8+
cells act as cytotoxic cells.
• Both types of T cells express about 105 identical
molecules of the antigen binding T-cell receptor (TCR)
per cell
all with the same antigenic specificity.
78. T cell role
• When a naive T cell encounters antigen combined with a
MHC molecule on a cell, the T cell proliferates and
differentiates into memory T cells and various effector T
cells.
• TH cell recognizes and interacts with an antigen to form
an antigen -MHC class II molecule complex and activate
it to an effector T cell
– Effector cell secretes various growth factors known
collectively as cytokines.
79. T cell role ….
• The secreted cytokines activate B cells, TC cells,
macrophages, and various other cells that participate in
different types of immune response.
• Under the influence of TH-derived cytokines, a TC cell
that recognizes an antigen–MHC class I molecule
complex proliferates and differentiates into an effector
cell called a cytotoxic T lymphocyte (CTL).
80. T cell role ….
• The CTL generally do not secrete many cytokines and
instead exhibits cell-killing or cytotoxic activity.
• The CTL monitors the cells of the body and eliminates
any that display antigen, such as virus-infected cells,
tumor cells, and cells of a foreign tissue graft.
• Cells that display foreign antigen complexed with a class
I MHC molecule are called altered self-cells; these are
targets of CTLs.
81.
82. MHC
Major Histocompatibility Complex molecules;
Antigen-recognition molecules that do not possess the
fine specificity for antigen characteristic of antibodies and
T-cell receptors.
• Each bind to a spectrum of antigenic peptides
Two major classes of membrane-bound glycoproteins:
Class I MHC molecules are expressed on nearly all
nucleated cells.
Class II MHC molecules are expressed only on antigen
presenting cells e.g. Monocytes, Macrophages, dendritic
cells, B cells
82
83. Antigen recognition by Lymphocytes
• Antigens which are generally very large and complex, are
not recognized in their entirety by lymphocytes.
• Both B and T lymphocytes recognize immunologically active
regions on a complex antigen called antigenic determinants,
or epitopes.
• Where as B cells can recognize an epitope alone; T cells
can recognize an epitope only when it is associated with an
MHC molecule
83
84. Recognition molecules in immune
response
• Distinct cell-membrane molecules are responsible
for antigen recognition by the immune system:
Membrane-bound antibodies on B cells
T-cell receptors
Class I MHC molecules
Class II MHC molecules
• Each of these molecules plays a unique role in antigen
recognition, ensuring that the immune system can
recognize and respond to the different types of antigen
that it encounters.
84
85. Anti-Viral Immunity
Anti-viral activity of interferons (IFNs)
• Virus infected cells produce INF-α;
• INF-α inhibit intracellular replication of viruses
• IFN-α activate NK-cells to kill virus infected cells
• IFNs have no direct effect on extracellular virus
• IFNs act early in viral diseases before antibody
• INFs activity is not specific
87. Anti-Viral Immunity
Humoral immunity:
• Virus neutralization
– In viremic infections, Antibodies neutralize virus,
preventing its attachment to receptor sites on
susceptible cells
e.g. Poliovirus, mumps, measles, rubella
– In superficial non-viremic infections (influenza)
Secretory IgA neutralizes virus infectivity at the
mucous surfaces
88. Anti-Viral Immunity
• Antibodies destroy free virus particles directly by:
Aggregation of virus and opsonization
Complement mediated lysis
• Both mechanisms also act on virus infected cells
89. Anti-Viral Immunity
Cell mediated immunity:
• Cell mediated cytotoxicity, mediated by ;
– Cytotoxic T-cells (CTLs)
– NK cells
– Activated macrophages
• CMI acts on virus infected cells through:
– CTLs kill virus infected cells directly after recognition
of viral antigens on cell surface in association with
MHC I
90. Anti-Viral Immunity
– TH-cells stimulated by viral antigens release
cytokines which attract and activate macrophages to
kill virus infected cells
– Nk-cells destroy virus infected cells early in infection
before appearance of antibodies
– Antibody-dependent cell mediated cytotoxicity
(ADCC): Antibody binds to virus infected cells such
cells are lysed by NK cells, macrophages and
polymorphs
91. Anti-Fungal Immunity
Immune response to fungi consist mainly of :
1) Innate immunity is mediated by:
- Neutrophils and macrophages
- Fungi are readily eliminated by phagocytes
2) Acquired immunity (cell mediated immunity)
- CMI acts in a manner similar to its action against
intracellular bacteria
* Disseminated infection are seen in: immunodeficiency
92. Comparison of immunity
• Innate immune response is rapid which utilizes a pre-
existing but limited repertoire of responding components.
• Adaptive immunity has slower onset, and have ability to
recognize a much wider repertoire of foreign substances,
and ability to improve during a response, whereas innate
immunity remains constant.
92
93. Comparison of immunity
• Secondary adaptive
responses are
considerably faster than
primary responses.
• With overlapping roles,
the two systems together
form a highly effective
barrier to infection.
93
94. Relationship between innate and adaptive
immunity
• Two systems work together to eliminate a foreign invader
through the carefully regulated interplay
The phagocytic cells crucial to nonspecific immune
• Responses are intimately involved in activating the specific
immune response.
• Conversely, various soluble factors produced by a specific
immune response augment the activity of these phagocytic
cells.
95. Relationship…
• Interactions between receptors on macrophages and
microbial components generate soluble proteins that
stimulate and direct adaptive immune responses.
Also secretes cytokines that can direct adaptive
immune responses
• Adaptive immune system produces signals and
components that stimulate and increase the
effectiveness of innate responses
• Some T cells, when they encounter appropriately
presented antigen, synthesize and secrete cytokines that
increase the ability of macrophages to kill the microbes
they have ingested.
96. Relationship….
• Antibodies produced against an invader bind to the
pathogen, marking it as a target for attack by
complement and serving as a potent activator of the
attack.
• inflammatory response produce soluble mediators that
attract cells of the immune system
97. Refferences
1. Kuby Immunology, 6th edition, 2007.
2. Jawetz, Melnick, & Adelberg’s Medical Microbiology 26th Edition
3. Really Essential Medical Immunology 2nd edition
4. Textbook of microbiology by Surinder Kumar
Editor's Notes
Immune system is a biological structures and processes that protects organisms against pathogens and tumor cells causing diseases.
The mechanisms of innate immunity provide the initial defense against infections. Adaptive immune responses develop later and require the activation of lymphocytes. Only selected cell types are shown. ILC, Innate lymphoid cell; NK, natural killer.
The importance of innate immunity is illustrated by several immunodeficiencies that result when it is impaired, which increase susceptibility to infection even in the presence of an intact adaptive immune system.
The importance of innate immunity is illustrated by several immunodeficiencies that result when it is impaired, which increase susceptibility to infection even in the presence of an intact adaptive immune system.
comprise four types of defensive barriers:
Anatomic eg skin, mucous membrane, normal flora Physiologic eg temp, low pH, chemical mediators Phagocytic cells eg MQ, monocytes
Inflammatory response
Sebum consists of lactic acid and fatty acids, which maintain the pH of the skin between 3 and 5 that inhibits the growth of most microorganisms.
The Mucosal Surfaces/membrane
Saliva, tears, and mucous secretions wash away pathogens.
Secreted fluids also contain antibacterial or antiviral substances like acid in gastric juice, spermine &zinc in semen, lactoperoxidase in milk and lysozymes in tears and nasal secretions.
The viscous fluid called mucus secreted by epithelial cells of mucous membranes, entraps foreign microorganisms and remove by mechanical stratagems like ciliary movement, coughing and sneezing.
Example invasion of vaginal pathogens limited by lactic acid produced by commensals which metabolize glycogens secreted by vagina epithelium.
A totally different mechanism is that of microbial antagonism where the normal bacterial flora of the body suppresses the growth of many potentially pathogenic bacteria and fungi. This is due to competition for essential nutrients or by the production of microbicidal substances.
If microorganisms do penetrate the body, two further innate defensive operations come into play, the destructive effect of soluble chemical factors such as bactericidal enzymes and the mechanism of phagocytosis
Newborns are susceptible to some diseases because their low stomach acidic contents
Lamella bodies are lysosomal like organell highly enriched with phospholipid. Difensin are cysteine rich cationic protein. Cathelicidin are third general class of epithelial antimicrobial that are expressed in the intestinal epithelium and kill microganism by membrane disruption. Surfactants are che chemicals that prevent surface tention in alviola.
Beneficial effects
Prevents spread of injury
Disposes of cellular debris & pathogens
Promotes repair
Derivatives of arachidonic acid like prostaglandins and leukotrienes. Events in the inflammatory response are initiated by a complex series of events involving a variety of chemical mediators Sources of Inflammatory mediators: Invading microorganisms, Damaged cells in response to tissue injury, Plasma enzyme systems, White blood cells participating in the inflammatory response.
Signs reflect the three major events of an inflammatory response
Engorgement = swelling
Exudate is fluid leak out from the blood vessl to nearby tissue.
comprise four types of defensive barriers:
Anatomic eg skin, mucous membrane, normal flora Physiologic eg temp, low pH, chemical mediators Phagocytic cells eg MQ, monocytes
Inflammatory response
DCs express more different types of TLRs and cytoplasmic pattern recognition receptors than any other cell type, making them the most versatile sensors of PAMPs and DAMPs among all cell types in the body.
This feature of plasmacytoid DCs is due in part to the fact that these cells express abundant amounts of the endosomal nucleic-acid specific TLRs (TLRs 3, 7, 8, 9), as well as cytosolic RNA and DNA sensors, all of which recognize viral nucleic acids inside cells
In addition, depending on the nature of the microbe that induces the innate response, a DC will direct naive T cell differentiation into distinct types of effector cells, such as IFN-γ–producing Th1 cells or IL-17–producing Th17 cells.
We call them “lymphoid cells,” not “lymphocytes,” because they do not express clonally distributed diverse antigen receptors like the T lymphocytes they otherwise resemble.
ILC1s produce IFN-γ and express the transcription factor T-bet, like Th1 cells.
ILC2s produce IL-5, IL-9, and IL-13, and express the transcription factor GATA-3, like Th2 cells.
ILC3s produce IL-22 and/or IL-17 and express the transcription factor RORγt, like Th17 cells.
Because ILCs do not express T cell receptors, they must be activated by different mechanisms than helper T cells to produce these cytokines.
The best defined stimuli for ILC cytokine production are other cytokines, released in the context of innate responses to infections and tissue damage; each ILC subset is activated by different cytokines
Cytokine producing innate lymphoid cell subsets. The three major subsets of cytokine producing innate lymphoid cells (ILCs) develop from the common lymphoid progenitor that also gives rise to B and T lymphocytes, and NK cells.
A common ILC precursor identified by the Id2 transcription factor differentiates into three major subsets of cytokine-producing ILCs. Each differentiated subset is distinguished by expression of distinct transcription factors and by cytokines produced when activated, as indicated.
The cytokines that drive differentiation into ILC1, 2, or 3 subsets, as well as the cytokines that activate ILCs to produce their own subset-specific cytokines, are shown. The major known functions of the ILCs are also indicated.
The “natural killer” designation derives from the fact that their major function is killing infected cells, similar to the adaptive immune system’s killer cells, the cytotoxic T lymphocytes (CTLs), and they are ready to do so once they develop, without further differentiation hence natural.
One NK cell granule protein, called perforin, facilitates the entry of other granule proteins, called granzymes, into the cytosol of target cells. The granzymes are proteolytic enzymes that initiate a sequence of signaling events that cause death of the target cells by apoptosis.
Functions of NK cells.
NK cells recognize ligands on infected cells or cells undergoing other types of stress and kill the host cells. In this way, NK cells eliminate reservoirs of infection as well as dysfunctional cells.
NK cells respond to IL-12 produced by macrophages and secrete IFN-γ, which activates the macrophages to kill phagocytosed microbes.
Mast cells are sentinel cells present in the skin, mucosal epithelium, and connective tissues that rapidly secrete proinflammatory cytokines and lipid mediators in response to infections and other stimuli.
Mast cell products also provide defense against helminths and are responsible for symptoms of allergic diseases.
Because mast cells are usually located adjacent to blood vessels, their released granule contents rapidly induce changes in the blood vessels that promote acute inflammation.
Mast cells express TLRs, and TLR ligands can induce mast cell degranulation.
This evolutionary adaptation of innate immune recognition is important because it ensures that microbes cannot evade innate immunity by mutational loss of the molecules recognized by the host.
An example of a target of innate immunity that is indispensable for microbes is double-stranded viral RNA, which is an essential intermediate in the life cycle of many viruses.
Similarly, LPS and lipoteichoic acid are structural components of bacterial cell walls that are recognized by innate immune receptors; both are required for bacterial survival
Body recognizes as non self (repeating molecular pattern) on microbes
PAPMS are absent in human cell
Many innate immune cells, such as macrophages, DCs, and mast cells, are always present in most tissues, where they function as sentinels to keep watch for invading microbes.
by recruiting phagocytes and other leukocytes that destroy the microbes, in the process called inflammation, 5-C-Phosphate – G guanine (in +ssRNA)
These molecules are a subset of DAMPs and are often called alarmins because their presence outside cells alarms the immune system that something is causing cell death.
DAMPs are generally not released from cells dying by apoptosis.
Many innate immune cells, such as macrophages, DCs, and mast cells, are always present in most tissues, where they function as sentinels to keep watch for invading microbes. SHP= Stress shock proteins
by recruiting phagocytes and other leukocytes that destroy the microbes, in the process called inflammation,
When these cell-associated pattern recognition receptors bind to PAMPs and DAMPs, they activate signal transduction pathways that promote the antimicrobial and proinflammatory functions of the cells in which they are expressed.
They are expressed on the surface, in phagocytic vesicles, and in the cytosol of various cell types, all of which are locations where microbes may be present
In addition, there are many proteins present in the blood and extracellular fluids that recognize PAMPs. These soluble molecules are responsible for facilitating the clearance of microbes from the blood and extracellular fluids by enhancing uptake into phagocytes or by activating extracellular killing mechanisms.
Nucleoside oligomerisatio receptors (NOD). NLR = NOD like receptors
Eg. All GNB bacteria all have LPS TLR. First to be discovered, defens against viral, bacteria and fungal, membrane spaning proteins, ligand binding pocket is horseshoe shaped.
10 are known eg.
CLRS… Recognize the carbohydrates of all microorganins, abt 15 of them, RLRs = (retinoic acid inducible gene 1 like) soluble recepteo, sence viral infection, present in cytosol
NLRs - present in cyotosol, sense intracellural bacteria invasion (nod.. Nucleotide oligomerization domain).. Reffers to the ability of this receptor to bind a region of finite numbers(oligomer) of DNA nucleotides (NOD1 , NO2- recognize peptidoglycan of bacteria cell wall
There are also numerous connections between innate and adaptive immune responses. The innate immune response to microbes provides early danger signals that stimulate adaptive immune responses.
Conversely, adaptive immune responses often work by enhancing the protective mechanisms of innate immunity, making them more capable of effectively combating microbes. pathogens have evolved to resist the innate immune
Unlike innate immune responses, adaptive immune responses are not the same in all members of a species but are reactions to specific antigenic challenges.
Unlike innate immunity, adaptive immunity is highly specific, has immunologic memory, and can respond rapidly and vigorously to asecond antigen exposure.
Which are derived from lymphoid progenitors
ANTIGEN-PRESENTING CELLS
heterogeneous group of immune cells,…
Major APC’s Features
They all express class II MHC molecules on their membranes
They are able to deliver a co-stimulatory signal that is necessary for TH-cell activation.
Antigenic specificity-capable of distinguishing subtle differences among antigens Antibodies can distinguish between two protein molecules that differ in only a single amino acid
Diversity-The immune system is capable of generating tremendous diversity in its recognition molecules allowing it to recognize billions of unique structures on foreign antigens
Immunologic memory a second encounter with the same antigen induces a heightened state of immune reactivity Attribute to life-long immunity to many infectious agents after an initial encounter.
Self/nonself recognition-the immune system normally responds only to foreign antigens Avoids damaging self-tissues (self-tolerance).
Although plasma cells live for only a few days, they secrete enormous amounts of antibody (2000 molecules of antibody per second) during this time.
e.g. CD4*CD25 regulatory cells modulate the immune responses to self antigens an infectious agents n human