Innate Immunity. Natural or native immunity

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Transcription:

Innate Immunity 1

Innate Immunity Natural or native immunity 2

When microbes enter in the body 3

Secondly, it also stimulates the adaptive immune system 4

Immunologic memory 5

Components of Innate Immunity 1. Anatomical barriers 2. Mechanical components 3. Normal flora 4. Antigen-nonspecific antimicrobial molecules 5. Innate immun system cells 6. Some molecules 6

1 Anatomical barriers are physical barriers Skin Dry Acidic Lower temperature Hair follicles and Sweat gland Lyozyme Toxic lipids Epithelial cells Defensin Cathelicidin 7

The respiratory tract, the gastrointestinal tract, and the genitourinary tract 8

Mucous membrane secretes mucus Lysozyme Lactoferrin Lactoperoxidase 9

A cilium is an organelle 10

These processes remove pathogens cough sneezing diarrhea 11

Fluids such as urine sweat tear saliva 12

2 Normal flora Approximately 100 trillion bacteria and other microorganisms Produce metabolic products Cover the surface Use nutrients Stimulate immune system 13

3 Antigen-nonspecific antimicrobial molecules There are many antigen-nonspecific antimicrobial chemicals Hydrochloric acid and enzymes 14

15

Defensins form pores 16

Cathelicidins are proteins produced by 17

Lactic and fatty acids, found in 18

Lactoferrin and transferrin trap iron 19

5 Innate immun system cells 5a.-Phagocytes 5b.-Cells that release inflamatory mediators 5c.-Lymphoctes 20

5a There are two types of phagocytes mononuclear phagocytes 21

The other family of phagocytes polymorphonuclear granulocytes 22

Monocyte normally make up 2-8% of white blood cells (WBC) 23

Resident macrophages are found 24

Monocyte has a horseshoe-shaped nucleus and granules the primary (azurophilic) granules lysosomes Peroxidase Acide hydrolase Phagocyte Present antigens Secrete cytokines Long-lived Multiply 25

Macrophages have special receptors Special receptors Microbes Cytokines IFN-γ Opsonin molecules 26

27

There are tree types of polymorphonuclear granulocytes irregular and lobed nucleus Neutrophil granules Eosinophil Basophil 28

Neutrophils are the first type of leukocytes to respond to microbial infections 54-75 % of WBCs 29

Neutrophils are important phagocytes. phagocytes the primary (azurophilic) granules lysosomes Acid hydrolases, Myeloperoxidase, Muramidase (Lysozyme) Defensins Cathepsin G Cationic protein Bacterial permeabily increasing protein the secondary granules Lactoferrin Lysozyme Collagenase Elastase 30

The granules are also often released extracellularly 31

They release the enzyme kallikrein and other enzymes 32

Neutrophils express adhesion molecules and reseptors 33

Neutrophils The life span is few hours They do not multiply 34

5b Eosinophils normally make up 1-4% of the WBCs Bilobed nucleus Many cytoplasmic granules Acid phosphates Peroxidases Major basic protein Potent toxin Induces histamin release Activates neutrophils and platelets Eosinophil cationic protein (ECP) Eosinophil derived neurotoxin 35

They are capable of phagocytosis Fungi, protozoa and helmints Leukotrienes, prostoglandins 8-12 days 36

5b Basophils are found in very small numbers in the circulation 0,2 % Mast cells Their functions are the same Many granules Histamine Leukotrienes Prostoglandins Heparin PAF Secrete IL-4 IL-13 Basophils have much less life span 37

The stimulus for the degranulation of mast cell or basophil is often an allergen. 38

5c Lymphocytes Natural Killer Cell (NK) Natural Killer T Cell (NKT) Intraepithelial lymphocytes B1 lymphocytes 39

NK cells are able to recognize and kill infected cells, cancer cells, and stressed cells Absent T cell reseptors B cell receptors Function Killing Virus-infected cells Tumor cells Stressed cells Secretion IFN-γ 40

NK cells use a dual receptor system 41

Stress-induced glycoproteins are secreted by 42

Viruses, stress, and malignant transformation 43

The NK cell then releases pore-forming proteins perforin granzyme 44

Cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12) 45

NK cells also play a role in adaptive immune responses antibody-dependent cellular cytotoxicity (ADCC) 46

NKT cells are a subset of lymphocytes IL-4, IL-10 47

γδ T cells may protect the mucosal surface of the body Epidermis Mucosal epithelia Intraepithelial lymphocytes PAMP-TCR 48

B-1 cells are found mostly in the peritoneal and pleural cavities T-independent antigens Natural antibodies 49

6 The molecules involved in natural immun system Complement system Acute phase proteins Cytokines 50

The complement system is a series of proteins C3 convertase 51

52

Many plasma proteins increase rapidly after infection 53

54

Recognation of Microbes by Innate Immune System 55

Innate immunity recognize molecules are not found in mammalian cells. Pathogen-associated molecular patterns (PAMPs) LPS Porin protein Lipoprotein Lipid 56

Pathogen-associated molecular patterns (PAMPS) Peptidoglycan Teichoic acid Lipoteichoic acid 57

Lipoarabinomannan 58

Mannose-rich glycans 59

60

61

Damage associated Molecular Pattern Pathogen-associated molecular patterns (PAMPs) Stressed Injured Infected Transformed 62

Damage-associated molecular patterns (DAMPs) Heat-shock protein, altered membrane phospholipids 63

In order to recognize PAMPs Pattern-Recognation Receptors 64

Many pattern-recognition receptors are located 65

Endocytic Pattern-Recognition Receptors Signaling Pattern-Recognition Receptors 66

Endocytic pattern-recognition receptors LPS Peptİdoglycan teichoic acid CRP C3b, C4b Surfactant protein A and D 67

Signaling Pattern-Recognition Receptors Binding of microbial PAMPs to signalling type of PRRs toll-like receptors (TLRs) 68

Different TLRs directly or indirectly bind different microbial molecules 69

Another cell surface PRR is CD14 70

71

T-independent antigens-1 are pathogen-associated molecular patterns (PAMPs) 72

TLRs also play role in adaptive immunity 73

Signaling PRRs found in the membranes of the endosomes 74

75

NOD proteins, RIG-1 and MDA-5 are cytoplasmic sensors 76

In response to certain pathogen associated molecular patterns neutrophil extracellular traps (NETs) 77

The Response of Innate Immune System 78

When effectors cells of innate immun system recognize microbial antigens 79

Diapedesis In order to perform effector functions 80

The resident macrophages recognize the microbe and produce cytokines 3 4 6 7 1 2 5 8 81

Diapedesis selectin-mediated rolling integrin-mediated firm adhesion chemokine-mediated motility 82

The recognition of microbes by neutrophils or macrophages 83

Several enzymes in the phagolysosomes are activated. 84

The escaping from phagocytosis 85

86

Leave cell before the fusing of lysosome to phagosome 87

The inhibition of the fusing of lysosome to phagosome. 88

The removing of MAC complex 89

The escaping from phagocytosis The leaving phagocytic cell before the fusing of lysosome to phagosome The inhibition of the fusing of lysosome to phagosome The resistance to and destroying of microbicidal enzyme in phagolysosome. The inhibition of comlement activation. The production of enzyme for killing of the phagocytes. The stimulation of apoptosis of macrophages. 90

Full activation of antigen specific lymphocytes requires two signals 91

Microbes, or IFN-γ produced by NK cells in response to microbes 92

Blood-borne microbes activate the complement system by the alternative pathway 93

The second signals also guide the nature of the adaptive immune response. 94

95

96