how recovery take place after bacterial infection....

1. RECOVERY FROM INFECTIONRECOVERY FROM INFECTION
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SHIV VARAN SINGHSHIV VARAN SINGH
VBMVBM
M-5547M-5547

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3. REASON OF INFECTION
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6. WHO STIMULATE HOST?
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7. PURPOSE OF RECOVERY
• Prevent progression in recently
exposed individuals
• Prevent reactivation in persistently
infected individuals
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9. DIFFERENT TYPE OF STRETEGIESDIFFERENT TYPE OF STRETEGIES
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14. 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
persistsAntigen Presentation & Adaptive Immune
Response initiated

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17. SECOND LINE OF DEFENSE MEDIATED BY
RECOGNITION OF BACTERIAL COMPONENTS
• PAMPS- recognized by pattern recognition
receptors
• Essential for bacterial growth
• PAMPS activate cells via TLRs- expressed on
phagocytes, dendritic cells, epithelial cells.
• Recognition of bacteria also occurs in absence of
cells via-
– Complement
– C- reactive protein
– Mannose binding lection
– Surfactant protein in lungs
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18. PhagocytosisPhagocytosis
• Ingestion of microorganisms or particulateIngestion of microorganisms or particulate
matter by a cellmatter by a cell
1. Attraction (Chemotaxis)
2. Attachment (Opsonization / Coating with Protein)
3. Ingestion
4. Digestion (Lysosomal Enzymes and Oxidizing
Agents)
5. Expulsion
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19. Mechanism of PhagocytosisMechanism of Phagocytosis
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The interaction of Mφ with pathogens

21. What PRProteins & receptors are on the
Mφ?
• Mφ Mannose Receptor:
–C-type Lectin (PRP)
–Binds mannose, N
acetylglucosamine, &
fucose residues on
pathogen surface
molecules.
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22. • Scavenger Receptors:
– Group of @ 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 β-glucans (LPS)
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23. Killing mechanism of phagocyteKilling mechanism of phagocyte
• Oxygen dependent
• Oxygen independent
• TNF-α & IFN-γ causes
production of NO
synthase
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24. • 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.

26. Oxygen-Independent Killing mechanisms:
• . Oxygen-Independent Killing mechanisms:
– Hydrolytic enzymes:
• Lysozyme
• Proteases
• RNases & DNases.
– Defensins:
• cationic peptides (cysteine); 29-35 AA.
– Competitors-
• Lactoferrin- compete cells for iron
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27. B) Reactive Nitrogen Intermediates (RNIs).
– nitric oxide synthetase (NOS):
• NO can be easily converted to peroxynitrite anion &
nitrogen dioxide.
NADPH NADP

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29. LYMPHOCYTE- INDEPENDENT
BACTERIAL RECOGNITION PATHWAY
• Alternate complement pathway
– Bacteria with outer lipid bi-layer- susceptible to lytic complex (C5b-9)
– C5a- anaphlatoxins-
– neutrophil recruitment
– mast cell degranulation- histamine, Opsonins- C3 derivatives-
phagocytosis
• Pro-inflammatory cytokines increase adhesive properties of
vascular endothelium
– Macrophages- TNF & IL-1
• Macophages- IL-12, IL-18 - NK cells- IFN-γ- activates macrophages
(first day of infection)
• SCID mice (defect in lymphocyte maturation) can resist Listeria
monocytogenes infection
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30. Natural killer (NK) cellsNatural killer (NK) cells
• Natural killer (NK)
cells use the same
effectors to kill virus-
infected cells and
tumors.
• Do not require
stimulation, nor do
they exhibit memory.
• NK cells respond in
the absence of MHC
proteins.
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31. NK T cells
• Thymus derived cells
• In between innate and adaptive immunity
• Phenotypically and functionally similar to NK
cells
• It express TCR
• Marker NK1.1, which recognize an MHC-
associated CD1 receptor expressed on APC
• Cytokine production, IL-4 and INF- ϒ
(Immunoregulatory role) & kill target cells
• Rapidly produce large amounts of different
cytokines upon activation. 31

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33. Specific Immune Strategies
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Endogenous Pathway Exogenous Pathway

36. Antibody mediated strategy
• Antibody plays a crucial role in dealing with bacterial toxins
– Ab neutralizes diphtheria toxin- blocks attachment of the toxin to the
target cells
– Ab blocks locally acting toxins or extracellular matrix degrading
enzymes which act as spreading factors
• Interfere with motility of flagella
• IgA- immune evasion & immune exclusion mechanism- mucosal
immunity
• Ab to bacterial cell surface block functional requirements of the
organism- intake of nutrients or iron-chelating compounds
• Immunity to non-toxigenic bacteria- more efficient targeting of
complement
• Bacteria that resist alternative complement pathway are damaged
by compliment or coated with C3 products- enhance phagocytosis
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37. Antigen contact antigen-
specific B cell that processes the
antigen and presents it to an
antigen-specific TH
2 cell. The
activated TH
2 cell then signals
the antigen-specific B cell to
produce antibody.
Activated B cells live for
years as memory cells and can
rapidly produce large quantities
(high titers) of antibodies upon
re-exposure to antigen.
Cont…Cont…
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38. T- lymphocytesT- lymphocytes
 The antibody or TCR does not interact with the antigenic
macromolecule as a whole but only against a distinct portion of
the molecule called an antigenic determinant or epitope.
 T cells recognize antigens presented by antigen-presenting cells
(APCs) or by pathogen-infected cells.
 At the molecular level, TCRs bind peptide antigens presented by
major histocompatibility complex (MHC) proteins. Class I MHC
proteins are found on the surfaces of all nucleated cells.
 Class II MHC proteins are found only on the surface of B
lymphocytes, macrophages, and dendritic cells, all of which are
APCs.
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39. molecular interactions stimulate T cells to kill antigen-bearing cells or tomolecular interactions stimulate T cells to kill antigen-bearing cells or to
produce cell-stimulating proteins known as cytokines.produce cell-stimulating proteins known as cytokines.
MHC- I MHC-II
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40. T-Helper CellsT-Helper Cells
• TH
1 and TH
2 cells
play pivotal roles in
CMI & and
antibody-mediated
immune responses.
• TH1 inflammatory
and TH2 helper
cells each stimulate
effector cells
through the action
of cytokines.
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42. T-Cytotoxic CellsT-Cytotoxic Cells
 T-cytotoxic (TC
) cells
recognize antigens
on virus-infected
host cells,
intracellular
bacteria and tumor
cells through
antigen-specific
TCRs. Antigen-
specific recognition
triggers killing via
perforin and
granzymes.
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43. CONT…CONT…
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44. CONCLUSIONSCONCLUSIONS
• Non specific barrier viz; skin, mucus membrane
etc.
• Secretion of body viz; lysozyme, Hcl,
antimicrobial substance etc.
• Normal flora of body.
• Fever, inflammation etc.
• CMI and HMI
• Complement system
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