Introduction to Immunity & Innate immunity MBBS class

1. Introduction to Immunology &
Innate Immunity
Sayantan Banerjee
AIIMS Kalyani

2. Immune System: Overview
• To be effective the immune system must:
1. Recognize and destroy a diversity of pathogens.
(bacteria, fungi, viruses, protozoans, helminths)
2. Recognize and destroy altered, effete, or damaged self.
(apoptotic, necrotic and cancerous cells)
3. Exhibit “tolerance” to self
(avoid chronic inflammation, autoimmunity)

3. Immune System
There are two major line of defences:
• Innate Immunity
• Adaptive Immunity

5. INNATE IMMUNITY ADAPTIVE IMMUNITY

8. Immune System
•Innate Immunity
•Adaptive Immunity
Humoral
Humoral
Cellular
Cellular

9. INNATE ADAPTIVE
Characteristic
Specificity for molecules shared by groups of
related microbes and molecules
produced by damaged host cells
For specific antigens (Microbial or
non-microbial)
Diversity
Limited; germline encoded
very large; receptors are produced
by somatic recombination of gene
segments
Memory None Yes
Nonreactivity to Self Yes Yes
Components
Cellular and Chemical
Barriers
skin, mucosal epithelia; antimicrobial
molecules
Lymphocytes in epithelia;
antibodies secreted at epithelial
surfaces
Blood Proteins Complement, others Antibodies
Cells Phagocytes (macrophages, neutrophils),
natural killer cells
Lymphocytes

10. Components of the innate immune System
•Comprise four defensive barriers
:
1. Anatomic : Physical barriers
2. Physiologic
• Mechanical: Reflexes, flushing
motions etc.
• Humoral
• Nonspecific
• Pattern Specific
3. Cellular
• Phagocytes
• Natural Killer Cells
4. Inflammation : a consorted
effort

11. Components of the innate immune System
• The Physical barriers:
• Skin, Mucous Membrane
• The Mechanical responses of the physical
barriers:
• Cough reflex
• Sneeze reflex
• Peristalsis
• Urinary flushing
• Ciliary action of the Respiratory epithelia

12. Physical & Anatomical Barriers
• Epithelial Surfaces serve as the 1st primary
barrier:

13. •Skin
•pH 3-5
•Commensal
Flora:
• Proprionibacterium
• Staphylococcus
epidermidis
• Diptheroids

14. • Mucus Membranes:
• Epithelial cells layers
• Mucociliary escalator

15. Physiological & chemical mediators
Body temperature

16. Pathogen breaches anatomical barriers
• Soluble Proteins in
lymph & blood:
• C Reactive Protein
• Complement
• Phagocytes:
• Macrophage-
• 1st cellular defense against
an infection!
Phagocytosis Cytokine
production
Induces Inflammation & calls
in neutrophils
Pathogen
persists
Antigen Presentation & Adaptive Immune
Response initiated

17. Components of the innate immune System
•Comprise four defensive barriers :
1. Anatomic : Physical barriers
2. Physiologic
• Mechanical: Reflexes, flushing motions etc.
• Humoral
• Nonspecific
• Pattern Specific
3. Cellular
• Phagocytes
• Natural Killer Cells
4. Inflammation : a consorted effort

18. Components of the innate immune System
• The nonspecific chemicals (Humoral components):
• Hydrochloric acid, Lysozymes, Intestinal Enzymes
• Coagulation system: form a clot can act to immobilize microorganisms
and prevent them from entering the blood and lymph
• Fibrinolytic system: decompose the clot when it is no longer needed,
thus promoting wound healing
• Kinin system: they widen the lumens of blood vessels and increase
capillary permeability. This increases the supply of soluble and
cellular materials to the infected site
• Complement system: Participate in the direct destruction of the
invading pathogen and the migration and activation of cellular
components of the innate immune system
• Acute Phase Reactants

19. MAC membrane attack complex
Complement

22. Antimicrobial peptides:
Where are they?
• In everything from Amoebas to Humans
• Abundant in vertebrates in:
• External Mucosa
• eyes, mouth, genitourinary, skin, lung, trachea
• Immune cells
• neutrophils
• Intestinal tract (duodenum)
• in humans: Paneth cells are the source

23. Antimicrobial peptides:
What are they?
• Cationic, Amphipathic
• Linear -helical (20-35 AA)
• Magainin, cecropins, histatin
• Pro-Arg rich (more polar)
• bac 5 and 7 (30-50 AA; 70% pro/arg)
• Disulfide Rich -structure
• amoebapores, NK-lysin
• Disulfide Rich -structure
• Defensins: three or more disulfide (30-70 AA)
• “Loops” (11-22 AA)
• tachpyylesins, protegrins ,ranalexin, polymyxin

24. Antimicrobial peptides

25. Components of the innate immune System
• Comprise four defensive barriers :
1. Anatomic : Physical barriers
2. Physiologic
• Mechanical: Reflexes, flushing motions etc.
• Humoral
• Nonspecific
• Pattern Specific
3. Cellular
• Phagocytes
• Natural Killer Cells
4. Inflammation : a consorted effort

26. How does the
Innate Immune
response
distinguish self
from nonself?
Pattern Recognition Proteins:
Proteins that recognize
molecular patterns unique
to pathogens
(LPS, peptidoglycan,
teichoic acids, etc.)

27. Pattern : Recognition
• Microbial substances that stimulate innate immunity are
called –
Pathogen associated molecular Patterns (PAMP)
• Receptors that bind these conserved structures are called –
Pattern recognition receptors (PRR)

28. Pathogen associated molecular Patterns (PAMP)
Different classes of microbes express different PAMPs
• Nucleic acids : ds RNA in replicating viruses
CpG DNA in bacteria
• Proteins : N-formylmethionine typical of bacteria
• Carbohydrates :LPS in GNB
Teichoic acid in GPB
Mannose-rich oligosaccharides in microbial cell walls
• Glucans present in fungal cell walls
 Not found in healthy mammalian tissue

29. 3 Types of Pattern recognition Proteins (PRP)
• Secreted soluble proteins that circulate in the blood & lymph.
• Cell surface receptors that induce phagocytosis.
• Cell surface receptors that when bound will induce the cell to make
cytokines.

30. Pattern recognition receptors (PRR)
PRRs of innate immunity are Germline encoded
Two classes :
• Cell associated PRRs
Toll-like receptors
C-type lectins
Scavenger receptors
Nod-like receptors ( or Nod-like proteins )
• Soluble recognition molecules
Pentraxins
Collectins
Ficolins

31. Pattern recognition receptors (PRR)

32. Cellular location of Pattern recognition receptors

33. Soluble Pattern recognition receptors
(C-reactive Protein)

35. •Lectins- proteins
that bind to sugars

37. PRProteins & receptors are on the
Mf?
• Mf Mannose Receptor:
• C-type Lectin (PRP)
• Binds mannose, N acetylglucosamine, &
fucose residues on pathogen surface
molecules

38. • Scavenger Receptors:
• Group of at least 6 molecular forms.
• Recognize lipoproteins on Gm + & Gm –
bacteria.
• Involved in elimination of old & apoptotic
cells.
• Glucan receptor-
• Dectin-1: C-type lectin (PRP)
• Binds b-glucans (LPS)

39. • LPS Receptor
• Works with the Toll Like Receptors to
stimulate cytokine production in the
macrophage.
Toll Like Receptors-
- Recognize different component of pathogens.
- Associates with other receptor & involved
with signal transduction.
CR3- Opsonization.

41. Damage associated molecular patterns (DAMP)
• The innate immune system also recognizes endogenous
molecules that are produced by or released from damaged
and dying cells.
• These substances are called damage associated molecular
patterns (DAMPs).

42. Damage associated molecular patterns (DAMP)
• Stress-induced proteins : Heat Shock Proteins (HsP)
• Crystals: Monosodium urate
• Nuclear proteins: HMgb1

43. TOLL – LIKE Receptors
• TLRs are evolutionarily conserved family of pattern recognition
receptors expressed on many cell types, recognize products of a wide
variety of microbes.
• Originally ‘Toll’ identified as a gene from the fruit fly, Drosophila spp.
• TLRs comprise a subfamily within the larger superfamily of Interleukin
(IL) receptors, based on similarity within their cytoplasmic regions

44. TOLL – LIKE Receptors
• There are 9 different functional TLRs in humans, named TLR1 to TLR9

45. TOLL – LIKE Receptors
Cell membrane
Associated TLRs

46. TOLL – LIKE Receptors
Cell endosome
Associated TLRs

47. TOLL – LIKE Receptors
Recognition domain

48. TOLL – LIKE Receptors

49. NOD – LIKE
Receptors

50. The interaction of Mf with pathogens

51. How do phagocytes kill the pathogens?
1. Acidification of the phagosome- ATP Synthase

52. How do phagocytes kill the pathogens?

53. 2. Oxygen dependent killing mechanisms:
• A) Enzymes to make Reactive oxygen radicals (ROIs):
• NADPH oxidase- phagosomal membrane
• Multicomplex protein.
• Reduction of O2  superoxide anion (O2-):
• SOD: converts superoxide to H2O2
• Myeloperoxidase- lysosomal protein
• Produces Hypochlorous acid (OCl-) & Hydroxyl
Radicals.

55. B) Reactive Nitrogen Intermediates (RNIs).
• nitric oxide synthetase (NOS):
• NO can be easily converted to peroxynitrite anion & nitrogen
dioxide.
NADPH NADP

57. 3. Oxygen-Independent Killing mechanisms:
• Hydrolytic enzymes:
• Lysozyme
• Proteases
• RNases & DNases.
• Defensins:
• cationic peptides (cysteine); 29-35 AA.
• Competitors-
• Lactoferrin- compete cells for iron

58. Components of the innate immune System
•Comprise four defensive barriers :
1. Anatomic : Physical barriers
2. Physiologic
• Mechanical: Reflexes, flushing motions etc.
• Humoral
• Nonspecific
• Pattern Specific
3. Cellular
• Phagocytes
• Natural Killer Cells
4. Inflammation : a consorted effort

59. NK Cells

60. NK Cells

62. Components of the innate immune System
•Comprise four defensive barriers :
1. Anatomic : Physical barriers
2. Physiologic
• Mechanical: Reflexes, flushing motions
etc.
• Humoral
• Nonspecific
• Pattern Specific
3. Cellular
• Phagocytes
• Natural Killer Cells
4. Inflammation : a consorted
effort

63. inflammation.
• 1- Increase in vascular diameter.
• 2- Increase in vascular permeability
• 3- Endothelial cells activated to express adhesion molecules.

66. THANK
YOU