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Introduction to Immunology
    Science of Immunity
        Dr.T.V.Rao MD




           Dr.T.V.Rao MD     1
Immunology
• Immunology:
 – Study of the molecules, cells, organs, and
   systems responsible for the recognition and
   disposal of foreign (nonself) material
 – Study of the MECHANISMS that protect an
   individual from injury from:
   • Exogenous microorganisms – bacteria, fungi,
     viruses
   • Exogenous chemicals – pollen, poison ivy, etc.
   • Endogenous cells – malignant or senescent cells
 – IMMUNE RESPONSE: Broad range of defense
   mechanisms including inflammation,
   phagocytosis, antibody synthesis, etc.
Edward Jenner, “ the founder of modern immunology”
  1796- Introduction of protective vaccine against small pox:
             based on cow pox (in Latin - vaccinia )
What is the immune system?
• The body’s defense against disease
  causing organisms, malfunctioning cells,
  and foreign particles
A Short History of Immunology
• ~ 430 B.C: Peloponesian War, Thucydides
  describes plague – the ones who had
  recovered from the disease could nurse
  the sick without getting the disease a
  second time
• 15th centurry: Chinese and Turks use
  dried crusts of smallpox as ”vaccine”
• 1798: Edward Jenner – smallpox vaccine
Dr.T.V.Rao MD   6
Immunology
• Contains Basic science
• Clinical Application
  Host defense reactions to foreign
  Antigen
  Substance is not self
  Antigen recognizing Cell Mediated
  Host defense functions
                Dr.T.V.Rao MD         7
Jenner - Smallpox vaccine
   • Noticed that milkmades that had contracted cowpox
     did NOT get smallpox
   • Test on an 8 year old boy, injected cowpox into him
     (NOT very nice……)
   • Follwed by exposure to smallpox
   • Vaccine was invented (latin vacca means ”cow”)




Pierre Dönnes             Andreas Hildebrandt     Annette Höglund
pierre@bioinf.uni-sb.de   anhi@bioinf.uni-sb.de   annette@bioinf.uni-sb.de
Subjects In Immunology

• Cell mediated host defense functions
• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including
  Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation
                   Dr.T.V.Rao MD           9
What is Response to Infection

• Immunity can be
  Innate
  Nonadapative
• Adaptive -
  Acquired.

               Dr.T.V.Rao MD   10
What is immunity?
- Resistance to a
  disease causing
  organism or
  harmful
  substance
- Two types
    - Active Immunity
    - Passive
      Immunity
Immunology is a Complex
       Subject




         Dr.T.V.Rao MD    12
Dr.T.V.Rao MD   13
The Invaders . . .
• Bacteria           http://www.hhs.gov/asphep/presentation/images/bacteria.jpg




• Viruses
• parasites
  such as
  fungi,        http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html




  & worms
                        worm trichura.jpg
Different types of Immunity
A   - Non specific
                1
Species
                2
Racial
                3
Individual

B Specific
1.Species
2 Racial
 3 Individual       Dr.T.V.Rao MD   15
THE EVOLUTION OF
             IMMUNITY
                    Immunity

Non-specific Immediate onset              Specific Delay onset
 Innate immunity                   Acquired immunity


    Humoral                               Cellular
 Immune Response                      Immune Response
  Antibodies production                   T-cell activation
                          Dr.T.V.Rao MD                          16
Innate Immunity
Innate Immunity is resistance that is
preexisting and is not acquired through
contact with a nonself ( Foreign
known as antigen
Individual has innate Immunity by genetic
or constitutional Make Up
Non related to prior contact with
Microorganisms or Immunization
                 Dr.T.V.Rao MD              17
Organs Of Immune System
• Primary Lymphoid Organs
 – Bone Marrow and Thymus
 – Maturation Site
• Secondary Lymphoid Organs
 – Spleen, lymph nodes,
 – MALT (mucosal associated lymph
   tissue)
 – GALT (gut associated lymph tissue)
 – Trap antigen, APC, MD
                  Dr.T.V.Rao
                             Lymphocyte   18
   Proliferation
DEFENSE MECHANISMS OF THE
       HUMAN HOST
• Innate Mechanisms (Innate immunity)
  – First line of defense
  – Non-specific
• Adaptive Mechanisms (Adaptive
  immunity)
  – Second line of defense
  – Highly specific with memory
• Cooperation between mechanisms
                    Dr.T.V.Rao MD   19
It is Dependent on

•   Species
• Race ( Racial )
• Individual

               Dr.T.V.Rao MD   20
Species and Immunity
• Immunity refers to total resistance to
  a Pathogen by all members of the
  species
• Eg Human do not get plant diseases
•     Humans do not get some animal
  diseases
• Dependent on Human configuration
  physiology ? Biochemical difference
                 Dr.T.V.Rao MD         21
Immune system is distributed all over
            the Body




                                   22
                Dr.T.V.Rao MD
Dr.T.V.Rao MD   23
Race - Immunity

• Genetic resistance
  Plasmodium
  falciparum malaria
  resistance in Africa
• In sickle cell
  anemia immune to
  malaria

                    Dr.T.V.Rao MD   24
Individual - Immunity
• Twins
  homozygous twins
  exhibit similar
  resistance
• Susceptibility
  similar in Leprosy
• Tuberculosis
  similar resistance
                  Dr.T.V.Rao MD   25
Factors Influencing Innate Immunity
• Placenta prevent
  infection
• But still can infected
  with Toxoplasmosis,
  Rubella, CMV and
  Herpes infection.
• Can produce
  congenital
  malformations


                       Dr.T.V.Rao MD   26
Immunity In Adults
• Polio infection ,
  and Chickenpox
  highly severe in
  adults.
• Enlargement of
  prostate lead to
  UTI

                      Dr.T.V.Rao MD   27
Hormonal Influces on
      Immunity
• Diabetes mellitus
• Hypothyroidism in adults
• Adrenal dysfunction
• Stress increases steroids
  predisposes to Infection
            Dr.T.V.Rao MD     28
Nutrition
• Immunodefic
  iency
• Some
  protection in
  some
  diseases
             Dr.T.V.Rao MD   29
Our   1st   Line of Defense...
• The Integumentary System…
  –Skin
  –Mucous membranes
  –Mucous
• provides a physical barrier
  preventing microbial access
Mechanisms of Immunity
• Epithelial surfaces
  Skin and Epithelial surfaces cover the
 body and protects the individuals
Healthy skin poses bactericidal influence,
 salt, drying sweat , Long fatty acids
Wet hand predisposes to Mycotic and
 pyogenic infections

                   Dr.T.V.Rao MD             31
Mucous Membranes
• Respiratory
  tract
  Shape of
  Nose,
  Nasal
  orifice  Dr.T.V.Rao MD   32
• Cilia in
  Respiratory tract
• Propel the
  foreign particles
• Respiratory
  secretion contain


                 Dr.T.V.Rao MD   33
Oral Cavity
• Saliva
• Stomach Hcl
• Large
  intestine large
  number of
  bacteria
               Dr.T.V.Rao MD   34
Conjunctiva
• Contain lachrymal
  secretions
• Tears contains
  antibacterial
  substances
• Lysozyme present
  except in CSF,
  Sweat, Urine


                      Dr.T.V.Rao MD   35
The First Line of Defense
      What’s the first thing you do
       when you~Saliva~ finger?
                  cut your



- Saliva contains many
  chemicals that break down
  bacteria
- Thousands of different
  types of bacteria can
  survive these chemicals,
  however
Other Mechanisms

• Flushing action
  of urination
  drives out
  Microbes in the
  Urethra
• Spermine in
  Semen
                Dr.T.V.Rao MD   37
Antibacterial Substances
• May be present Blood as
  Complement
• Antibacterial substances in Blood
  Betalysin,
  Leukin
  Lacto peroxidase in Milk
               Dr.T.V.Rao MD          38
Interferons in Immunity
• Interferons (IFNs) are natural
  proteins produced by the cells of the
  immune system of most vertebrates in
  response to challenges by foreign agents
  such as viruses, parasites and tumour
  cells. Interferons belong to the large class
  of glycoproteins known as cytokines
• Interferons are more useful than
  Antibodies
                    Dr.T.V.Rao MD                39
Microbial Antagonists
          Normal flora Help us

• Normal Microbial flora




                     Dr.T.V.Rao MD   40
Normal Flora Help Us
• We harbour near 1014 bacteria. This group
  of organisms, traditionally referred to as
  "normal flora" (although they are not
  plants) is composed of a fairly stable set of
  genera, mostly anaerobes. While each
  person has a relatively unique set of
  normal flora, members of the
  Streptococcus and Bacteroides make up a
  large percentage of the inhabitants. These
  organisms contribute to our existence in
  several ways’      Dr.T.V.Rao MD            41
Normal Flora Help Us
• Help us by competing with pathogens
  such as Salmonella
• Help us by providing vitamins or
  eliminating toxins (e.g. Bacteroides)
• Harm us by promoting disease (e.g. dental
  caries)
• Cause neither help nor harm (e.g.
  "commensals").
                  Dr.T.V.Rao MD           42
Normal Bacterial Flora of
     Conjunctiva




         Dr.T.V.Rao MD      43
Cellular Factors in Innate
           Immunity
• Metichinkoff 1883
• Cells called as Phagocytic cells
        Microphages,
        Macrtophages
Microphages Polymorphonuclear neutrophils
Macrophages Histiocytes wandering Amoeboid
  cells
Monocytes in Blood
Cells in Reticuloendothelial System
These cells remove foreign particles

                   Dr.T.V.Rao MD             44
Role of phagocytes
• Phagocytes are several types of white
  blood cells (including macrophages and
  neutrophils) that seek and destroy
  invaders. Some also destroy damaged
  body cells.
• Phagocytes are attracted by an
  inflammatory response of damaged cells.
How Phagocytes act
• Phagocytic cells
  reach the site o
  Inflammation
• Attracted by
  Chemo tactic
  substances
• Ingest particle
  material
                     Dr.T.V.Rao MD   46
Dr.T.V.Rao MD   47
Capsule In Innate immunity
• Some bacteria have
  capsules
• Streptococcus
  pneumonia
• Klebsiella pneumonia
• Bacteria with capsules
  are not ingested by
  Phagocytes unless in the
  presence of opsonins
• Bacteria are fixed against
  fixed surface such as
  alveoli

                         Dr.T.V.Rao MD   48
Innate Host Defenses Against Infection

• Anatomical barriers
   – Mechanical factors
   – Chemical factors
   – Biological factors
• Humoral components
   – Complement
   – Coagulation system
   – Cytokines
• Cellular components
   –   Neutrophils
   –   Monocytes and macrophages
   –   NK cells
   –   Eosinophils
Anatomical Barriers - Mechanical
               Factors
 System or Organ            Cell type              Mechanism

Skin               Squamous epithelium         Physical barrier
                                               Desquamation
Mucous Membranes Non-ciliated epithelium       Peristalsis
                 (e.g. GI tract)
                   Ciliated epithelium (e.g.   Mucociliary elevator
                   respiratory tract)
                   Epithelium (e.g.            Flushing action of
                   nasopharynx)                tears, saliva,
                                               mucus, urine
Anatomical Barriers - Chemical
                  Factors
 System or Organ            Component               Mechanism

Skin                Sweat                       Anti-microbial fatty
                                                acids
Mucous Membranes HCl (parietal cells)           Low pH
                 Tears and saliva               Lysozyme and
                                                phospholipase A
                    Defensins (respiratory & GI Antimicrobial
                    tract)
                    Sufactants (lung)           Opsonin
Anatomical Barriers - Biological Factors

 System or Organ          Component       Mechanism

Skin and mucous    Normal flora       Antimicrobial
membranes                             substances
                                      Competition for
                                      nutrients and
                                      colonization
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
                     Β-lysin from platelets – a cationic detergent
Lactoferrin and      Compete with bacteria for iron
transferrin
Lysozyme             Breaks down bacterial cell walls

Cytokines            Various effects
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
                   Antigen presentation for specific immune
                   response
NK and LAK cells   Killing of virus-infected and altered self targets

Eosinophils        Killing of certain parasites
Leucocytes
Innate immunity is mediated largely by GRANULOCYTES

Adaptive immunity mediated by LYMPHOCYTES

The growth, development and activities of granulocytes and
lymphocytes are interconnected and often co-operative.
Neutrophils
• 60% of WBCs
• ‘Patrol tissues’ as they squeeze out of the
  capillaries.
• Large numbers are released during
  infections
• Short lived – die after digesting bacteria
• Dead neutrophils make up a large
  proportion of puss.
                   Dr.T.V.Rao MD                57
Macrophages
• Larger than neutrophils.
• Found in the organs, not the blood.
• Made in bone marrow as monocytes,
  called macrophages once they reach
  organs.
• Long lived
• Initiate immune responses as they display
  antigens from the pathogens to the
  lymphocytes.     Dr.T.V.Rao MD           58
Mechanism of Phagocytosis

• Bacteria are
  phagocycosed into
  vacuole (Phagosome)
• Forms
  phagolysosome
• Lytic enzymes
  destroy the Bacteria
• Brucella and Leprosy

                   Dr.T.V.Rao MD   59
Lymphocyte subsets

*DC, *NK
                                   CLP
           T CELLS                                      B CELLS
                                    Common
                                    lymphoid
                     T              precursor         B


      Th                   CTL                   PC
 Activate B cells        Kill virus-            Produce antibodies
 and macrophages         infected cells         PLASMA CELLS
 T HELPER CELLS          CYTOTOXIC T
                         LYMPHOCYTES
Natural Killer cells
    NK cells




       Dr.T.V.Rao MD   61
Dr.T.V.Rao MD   62
Role of Natural killer Cells
• Natural killer cells (or NK cells) are
 a type of cytotoxic lymphocyte that
 constitute a major component of the Innate
 immune system. NK cells play a major role
 in the rejection of tumours and cells
 infected by viruses. The cells kill by
 releasing small cytoplasmic granules of
 proteins called perforin and granzyme that
 cause the target cell to die by apoptosis
                 Dr.T.V.Rao MD             63
Role of inflammation
• Inflammation is signaled by mast cells,
  which release histamine.
• Histamine causes fluids to collect around
  an injury to dilute toxins. This causes
  swelling.
• The temperature of the tissues may rise,
  which can kill temperature-sensitive
  microbes.
Inflammation
• Tissue Injury
• Irritation
• Arterioles constrict initially and then
  dilate
• Slow the Blood flow and Margi nation
  of Leucocytes
• Escape into tissues by diapedesis
  and accumulate in large numbers
                 Dr.T.V.Rao MD          66
Dr.T.V.Rao MD   67
Inflammation
• Outpour plasma,
  and dilute the
  toxic material
• Produce fibrin
  barrier and
  localized the
  infection
               Dr.T.V.Rao MD   68
Fever
• Natural defense
  Mechanisms
• Destroy infectious
  agents
• Therapeutic –
  Trepanoma pallidum
• Production of
  Interferons

                   Dr.T.V.Rao MD   69
Acute Phase proteins
• Infection and Injury produces Acute
  phase proteins
• C- Reactive proteins CRP
• Mann in binding proteins
• CRP activates alternative pathway
• Increases host defenses
• Prevents issue injury
• Repair inflamed lesions.
                Dr.T.V.Rao MD           70
Do not Forget to Immunise
        Your Child




          Dr.T.V.Rao MD     71
• Programme Created by Dr.T.V.Rao
   MD for Medical and Paramedical
  Students in the Developing World
               • Email
      • doctortvrao@gmail.com


              Dr.T.V.Rao MD      72

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Introduction to immunity

  • 1. Introduction to Immunology Science of Immunity Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  • 2. Immunology • Immunology: – Study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign (nonself) material – Study of the MECHANISMS that protect an individual from injury from: • Exogenous microorganisms – bacteria, fungi, viruses • Exogenous chemicals – pollen, poison ivy, etc. • Endogenous cells – malignant or senescent cells – IMMUNE RESPONSE: Broad range of defense mechanisms including inflammation, phagocytosis, antibody synthesis, etc.
  • 3. Edward Jenner, “ the founder of modern immunology” 1796- Introduction of protective vaccine against small pox: based on cow pox (in Latin - vaccinia )
  • 4. What is the immune system? • The body’s defense against disease causing organisms, malfunctioning cells, and foreign particles
  • 5. A Short History of Immunology • ~ 430 B.C: Peloponesian War, Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time • 15th centurry: Chinese and Turks use dried crusts of smallpox as ”vaccine” • 1798: Edward Jenner – smallpox vaccine
  • 7. Immunology • Contains Basic science • Clinical Application Host defense reactions to foreign Antigen Substance is not self Antigen recognizing Cell Mediated Host defense functions Dr.T.V.Rao MD 7
  • 8. Jenner - Smallpox vaccine • Noticed that milkmades that had contracted cowpox did NOT get smallpox • Test on an 8 year old boy, injected cowpox into him (NOT very nice……) • Follwed by exposure to smallpox • Vaccine was invented (latin vacca means ”cow”) Pierre Dönnes Andreas Hildebrandt Annette Höglund pierre@bioinf.uni-sb.de anhi@bioinf.uni-sb.de annette@bioinf.uni-sb.de
  • 9. Subjects In Immunology • Cell mediated host defense functions • Antibody related defense mechanisms • Hypersensitivity reactions ( Including Allergy ) • Auto Immunity • Immunodeficiency • Transplantation Dr.T.V.Rao MD 9
  • 10. What is Response to Infection • Immunity can be Innate Nonadapative • Adaptive - Acquired. Dr.T.V.Rao MD 10
  • 11. What is immunity? - Resistance to a disease causing organism or harmful substance - Two types - Active Immunity - Passive Immunity
  • 12. Immunology is a Complex Subject Dr.T.V.Rao MD 12
  • 14. The Invaders . . . • Bacteria http://www.hhs.gov/asphep/presentation/images/bacteria.jpg • Viruses • parasites such as fungi, http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html & worms worm trichura.jpg
  • 15. Different types of Immunity A - Non specific 1 Species 2 Racial 3 Individual B Specific 1.Species 2 Racial 3 Individual Dr.T.V.Rao MD 15
  • 16. THE EVOLUTION OF IMMUNITY Immunity Non-specific Immediate onset Specific Delay onset Innate immunity Acquired immunity Humoral Cellular Immune Response Immune Response Antibodies production T-cell activation Dr.T.V.Rao MD 16
  • 17. Innate Immunity Innate Immunity is resistance that is preexisting and is not acquired through contact with a nonself ( Foreign known as antigen Individual has innate Immunity by genetic or constitutional Make Up Non related to prior contact with Microorganisms or Immunization Dr.T.V.Rao MD 17
  • 18. Organs Of Immune System • Primary Lymphoid Organs – Bone Marrow and Thymus – Maturation Site • Secondary Lymphoid Organs – Spleen, lymph nodes, – MALT (mucosal associated lymph tissue) – GALT (gut associated lymph tissue) – Trap antigen, APC, MD Dr.T.V.Rao Lymphocyte 18 Proliferation
  • 19. DEFENSE MECHANISMS OF THE HUMAN HOST • Innate Mechanisms (Innate immunity) – First line of defense – Non-specific • Adaptive Mechanisms (Adaptive immunity) – Second line of defense – Highly specific with memory • Cooperation between mechanisms Dr.T.V.Rao MD 19
  • 20. It is Dependent on • Species • Race ( Racial ) • Individual Dr.T.V.Rao MD 20
  • 21. Species and Immunity • Immunity refers to total resistance to a Pathogen by all members of the species • Eg Human do not get plant diseases • Humans do not get some animal diseases • Dependent on Human configuration physiology ? Biochemical difference Dr.T.V.Rao MD 21
  • 22. Immune system is distributed all over the Body 22 Dr.T.V.Rao MD
  • 24. Race - Immunity • Genetic resistance Plasmodium falciparum malaria resistance in Africa • In sickle cell anemia immune to malaria Dr.T.V.Rao MD 24
  • 25. Individual - Immunity • Twins homozygous twins exhibit similar resistance • Susceptibility similar in Leprosy • Tuberculosis similar resistance Dr.T.V.Rao MD 25
  • 26. Factors Influencing Innate Immunity • Placenta prevent infection • But still can infected with Toxoplasmosis, Rubella, CMV and Herpes infection. • Can produce congenital malformations Dr.T.V.Rao MD 26
  • 27. Immunity In Adults • Polio infection , and Chickenpox highly severe in adults. • Enlargement of prostate lead to UTI Dr.T.V.Rao MD 27
  • 28. Hormonal Influces on Immunity • Diabetes mellitus • Hypothyroidism in adults • Adrenal dysfunction • Stress increases steroids predisposes to Infection Dr.T.V.Rao MD 28
  • 29. Nutrition • Immunodefic iency • Some protection in some diseases Dr.T.V.Rao MD 29
  • 30. Our 1st Line of Defense... • The Integumentary System… –Skin –Mucous membranes –Mucous • provides a physical barrier preventing microbial access
  • 31. Mechanisms of Immunity • Epithelial surfaces Skin and Epithelial surfaces cover the body and protects the individuals Healthy skin poses bactericidal influence, salt, drying sweat , Long fatty acids Wet hand predisposes to Mycotic and pyogenic infections Dr.T.V.Rao MD 31
  • 32. Mucous Membranes • Respiratory tract Shape of Nose, Nasal orifice Dr.T.V.Rao MD 32
  • 33. • Cilia in Respiratory tract • Propel the foreign particles • Respiratory secretion contain Dr.T.V.Rao MD 33
  • 34. Oral Cavity • Saliva • Stomach Hcl • Large intestine large number of bacteria Dr.T.V.Rao MD 34
  • 35. Conjunctiva • Contain lachrymal secretions • Tears contains antibacterial substances • Lysozyme present except in CSF, Sweat, Urine Dr.T.V.Rao MD 35
  • 36. The First Line of Defense What’s the first thing you do when you~Saliva~ finger? cut your - Saliva contains many chemicals that break down bacteria - Thousands of different types of bacteria can survive these chemicals, however
  • 37. Other Mechanisms • Flushing action of urination drives out Microbes in the Urethra • Spermine in Semen Dr.T.V.Rao MD 37
  • 38. Antibacterial Substances • May be present Blood as Complement • Antibacterial substances in Blood Betalysin, Leukin Lacto peroxidase in Milk Dr.T.V.Rao MD 38
  • 39. Interferons in Immunity • Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, parasites and tumour cells. Interferons belong to the large class of glycoproteins known as cytokines • Interferons are more useful than Antibodies Dr.T.V.Rao MD 39
  • 40. Microbial Antagonists Normal flora Help us • Normal Microbial flora Dr.T.V.Rao MD 40
  • 41. Normal Flora Help Us • We harbour near 1014 bacteria. This group of organisms, traditionally referred to as "normal flora" (although they are not plants) is composed of a fairly stable set of genera, mostly anaerobes. While each person has a relatively unique set of normal flora, members of the Streptococcus and Bacteroides make up a large percentage of the inhabitants. These organisms contribute to our existence in several ways’ Dr.T.V.Rao MD 41
  • 42. Normal Flora Help Us • Help us by competing with pathogens such as Salmonella • Help us by providing vitamins or eliminating toxins (e.g. Bacteroides) • Harm us by promoting disease (e.g. dental caries) • Cause neither help nor harm (e.g. "commensals"). Dr.T.V.Rao MD 42
  • 43. Normal Bacterial Flora of Conjunctiva Dr.T.V.Rao MD 43
  • 44. Cellular Factors in Innate Immunity • Metichinkoff 1883 • Cells called as Phagocytic cells Microphages, Macrtophages Microphages Polymorphonuclear neutrophils Macrophages Histiocytes wandering Amoeboid cells Monocytes in Blood Cells in Reticuloendothelial System These cells remove foreign particles Dr.T.V.Rao MD 44
  • 45. Role of phagocytes • Phagocytes are several types of white blood cells (including macrophages and neutrophils) that seek and destroy invaders. Some also destroy damaged body cells. • Phagocytes are attracted by an inflammatory response of damaged cells.
  • 46. How Phagocytes act • Phagocytic cells reach the site o Inflammation • Attracted by Chemo tactic substances • Ingest particle material Dr.T.V.Rao MD 46
  • 48. Capsule In Innate immunity • Some bacteria have capsules • Streptococcus pneumonia • Klebsiella pneumonia • Bacteria with capsules are not ingested by Phagocytes unless in the presence of opsonins • Bacteria are fixed against fixed surface such as alveoli Dr.T.V.Rao MD 48
  • 49. Innate Host Defenses Against Infection • Anatomical barriers – Mechanical factors – Chemical factors – Biological factors • Humoral components – Complement – Coagulation system – Cytokines • Cellular components – Neutrophils – Monocytes and macrophages – NK cells – Eosinophils
  • 50.
  • 51. Anatomical Barriers - Mechanical Factors System or Organ Cell type Mechanism Skin Squamous epithelium Physical barrier Desquamation Mucous Membranes Non-ciliated epithelium Peristalsis (e.g. GI tract) Ciliated epithelium (e.g. Mucociliary elevator respiratory tract) Epithelium (e.g. Flushing action of nasopharynx) tears, saliva, mucus, urine
  • 52. Anatomical Barriers - Chemical Factors System or Organ Component Mechanism Skin Sweat Anti-microbial fatty acids Mucous Membranes HCl (parietal cells) Low pH Tears and saliva Lysozyme and phospholipase A Defensins (respiratory & GI Antimicrobial tract) Sufactants (lung) Opsonin
  • 53. Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous Normal flora Antimicrobial membranes substances Competition for nutrients and colonization
  • 54. 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 Β-lysin from platelets – a cationic detergent Lactoferrin and Compete with bacteria for iron transferrin Lysozyme Breaks down bacterial cell walls Cytokines Various effects
  • 55. 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 Antigen presentation for specific immune response NK and LAK cells Killing of virus-infected and altered self targets Eosinophils Killing of certain parasites
  • 56. Leucocytes Innate immunity is mediated largely by GRANULOCYTES Adaptive immunity mediated by LYMPHOCYTES The growth, development and activities of granulocytes and lymphocytes are interconnected and often co-operative.
  • 57. Neutrophils • 60% of WBCs • ‘Patrol tissues’ as they squeeze out of the capillaries. • Large numbers are released during infections • Short lived – die after digesting bacteria • Dead neutrophils make up a large proportion of puss. Dr.T.V.Rao MD 57
  • 58. Macrophages • Larger than neutrophils. • Found in the organs, not the blood. • Made in bone marrow as monocytes, called macrophages once they reach organs. • Long lived • Initiate immune responses as they display antigens from the pathogens to the lymphocytes. Dr.T.V.Rao MD 58
  • 59. Mechanism of Phagocytosis • Bacteria are phagocycosed into vacuole (Phagosome) • Forms phagolysosome • Lytic enzymes destroy the Bacteria • Brucella and Leprosy Dr.T.V.Rao MD 59
  • 60. Lymphocyte subsets *DC, *NK CLP T CELLS B CELLS Common lymphoid T precursor B Th CTL PC Activate B cells Kill virus- Produce antibodies and macrophages infected cells PLASMA CELLS T HELPER CELLS CYTOTOXIC T LYMPHOCYTES
  • 61. Natural Killer cells NK cells Dr.T.V.Rao MD 61
  • 63. Role of Natural killer Cells • Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the Innate immune system. NK cells play a major role in the rejection of tumours and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis Dr.T.V.Rao MD 63
  • 64. Role of inflammation • Inflammation is signaled by mast cells, which release histamine. • Histamine causes fluids to collect around an injury to dilute toxins. This causes swelling. • The temperature of the tissues may rise, which can kill temperature-sensitive microbes.
  • 65.
  • 66. Inflammation • Tissue Injury • Irritation • Arterioles constrict initially and then dilate • Slow the Blood flow and Margi nation of Leucocytes • Escape into tissues by diapedesis and accumulate in large numbers Dr.T.V.Rao MD 66
  • 68. Inflammation • Outpour plasma, and dilute the toxic material • Produce fibrin barrier and localized the infection Dr.T.V.Rao MD 68
  • 69. Fever • Natural defense Mechanisms • Destroy infectious agents • Therapeutic – Trepanoma pallidum • Production of Interferons Dr.T.V.Rao MD 69
  • 70. Acute Phase proteins • Infection and Injury produces Acute phase proteins • C- Reactive proteins CRP • Mann in binding proteins • CRP activates alternative pathway • Increases host defenses • Prevents issue injury • Repair inflamed lesions. Dr.T.V.Rao MD 70
  • 71. Do not Forget to Immunise Your Child Dr.T.V.Rao MD 71
  • 72. • Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 72