The document discusses innate immunity and inflammation. It describes the innate immune system, including macrophages and their polarization. Macrophages are primary phagocytic cells that can be polarized into M1 and M2 phenotypes. The document also discusses phagocytosis, inflammation, acute and chronic inflammation, and the inflammatory response mechanism involving pathways such as TLR and NF-κB. Pattern recognition receptors activate these pathways to trigger innate and inflammatory responses.

1. INNATE IMMUNITY AND
INFLAMMATION
Presented by: AJAYKUMAR K

2. INNATE IMMUNITY & INFLAMMATION
 Introduction
 Innate Immune System
 Macrophage and its polarization
 Phagocytosis
 Inflammation
 Acute and Chronic Inflammation
 Inflammatory Response Mechanism
 Pathways
 Summary
 References

3. Introduction
 Immunology is the Study of Host defense mechanism.
 Immunity is the ability of host to protect itself against the
foreign organisms.
 Immune system comprises the cells, tissues and
molecules, which mount the immune response.

4. INNATE IMMUNITY
 First Line of defense system
 Comprises of :
 Mechanical barriers: Skin, Mucus membrane
 Chemical barriers: Acid in Stomach, Lysosome in tear, saliva
 Various process involved are:
 PRR Signaling: PAMP, DAMP and TLR
 Phagocytosis: Neutrophils and Macrophages
 Important Immune Cells:
 Neutrophils
 Macrophages
 Mast cells
 Basophils
 Eosinophils

5. Macrophages
 Primary phagocytic cells in Immune System
 Myeloid Lineage

6. Differentiation and distribution of
Macrophages

7. Polarization of Macrophages
M1 Phenotype M2 Phenotype
 Induced with cytokines INF-
ϒ,TNF- α, GM-CSF
 Can produce IL-1,IL-6,IL-12,IL-
23and TNF- α.
 Exhibit cytotoxicity towards
organism and Cancer cell and
participate in Th1- polarized
response.
 M1 cells express high levels of
CCR7
 Induced with cytokines IL-4, IL-
10, IL-13 and Seroids
 Can produce IL-10 and TGF-β
 Promotes tumor Growth and
participate in Th2- polarized
response.
 M2 cells express CD14, CD 163 &
CD206 as well as CXCR2

8. Complement System

9. Process of Phagocytosis

10. Macrophages in Innate Immunity

11. Inflammation
 A Biological Response

12. Acute & Chronic Inflammation

13. Inflammatory Response Mechanism
 Pattern Recognition Receptor Activation
 Activation of inflammatory pathways:
 TLR pathway
 NF- κB pathway
 MAPK
 JAK-STAT
 Targets for Transcription Factors:
 AP-1
 NF-κB
 Signal Transducer and Activator of Transcription Factors (STAT1)
 Interferon Regulatory Factors (IRFs)

14. Cellular locations of TLRs

15. TLR pathway

16. Overview

17. Summary
 Immunity is the state of protection against foreign pathogens or substances
(antigens).
 Innate responses are the first line of defense, utilizing germ-line-encoded
recognition molecules and phagocytic cells.
 Some white blood cell types (macrophages and neutrophils) are activated to
rapidly engulf and destroy extracellular microbes through the process of
phagocytosis.
 Families of PRRs (TLRs, CLRs, RLRs, and NLRs) recognize a wide variety of PAMP
(and DAMP) ligands and trigger signaling pathways that activate genes
encoding proteins that contribute to innate and inflammatory responses.
 Local innate and inflammatory responses usually are beneficial for eliminating
pathogens and damaged or dead cells and promoting healing.
 Defects in PRRs and signaling pathways activating innate responses lead to
increased susceptibility to certain infections, while other defects that
constitutively activate inflammasomes contribute to a variety of inflammatory
disorders.

19. References
 Tsung-Han Wu et al, Culture supernatants of different colon cancer cell lines induce
specific phenotype switching and functional alteration of THP-1 cells, Cellular
Immunology 290 (2014) 107–115
 Baig M.S. et al, NOS1-derived nitric oxide promotes NF-κB transcriptional activity
through inhibition of suppressor of cytokine signaling-1 JEM 2015 Vol.202
 Anjali Roy et al, Potential therapeutic targets for inflammation in toll-like receptor 4
(TLR4)-mediated signaling pathways, Int. Immunopharmacology40 (2016) 79-89
 Yanxian Feng et al, A toll-like receptor agonist mimicking microbial signal to generate
tumor-suppressive macrophages, Nature Communications (2019) 10:2272
 Paqui G. Trav´es et al Macrophages, Inflammation, and Tumor Suppressors: ARF, a
New Player in the Game
 Howard L Kaufman1, Carl E Ruby, Tasha Hughes and Craig L Slingluff Jr , Current
status of granulocyte–macrophage colony-stimulating factor in the immunotherapy of
melanoma. Journal for ImmunoTherapy of Cancer 2014, 2:11
 Kuby Immunology
 https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-
types/complement-deficiencies