immune system - introduction
DESCRIPTION
Immune system - introduction. Radek Spisek Institute of Immunology, 2nd Medical School, Charles University. Edward JENNER 1749-1823. Eradication of variola (smallpox). ‘Know Th e Enemy’. The immune system exists to prevent and combat infection - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/1.jpg)
Immune system - introduction
Radek SpisekInstitute of Immunology, 2nd Medical School, Charles University
![Page 2: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/2.jpg)
EdwardJENNER
1749-1823
![Page 3: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/3.jpg)
Eradication of variola (smallpox)
![Page 4: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/4.jpg)
‘Know The Enemy’
• The immune system exists to prevent and combat infection
• Everything else is secondary to this primary objective– Autoimmunity– Allergy– Tumour immunology– Transplantation
![Page 5: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/5.jpg)
The Enemy
Fungi
Viruses
HIVInfluenza
Parasites
Schistosomiasis
BacteriaE coli
Fungi
Mycobacteria
M TBCandida
![Page 6: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/6.jpg)
Antigens
• exo - antigens: microbes, foreign substances (alo, xeno-grafts, vaccines, sera, drugs – haptens
• auto-antigens: self tissue• Chemical structure: proteins, glykoproteins,
mucoproteins, polysacharides, lipids, glykolipids, fosfolipids
• Membrane receptors, enzymes, nuclear structures, secerned products (bacterial toxines)
![Page 7: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/7.jpg)
Components of the immune system
![Page 8: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/8.jpg)
Hematopoetic system
![Page 9: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/9.jpg)
Hematopoetic stem cell- CD34SCT- stem cell transplantation
![Page 10: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/10.jpg)
The Defence
• Non Specific barriers– Anatomical/Physiological
• Acute phase reactants and Inflammation– Complement/Interferons/CRP
• Innate cells– PMN/Macrophages/NK cells
• Adaptive immunity– B cells – Antibody– T cells – Orchestration, Cytokines, Lytic granules
Innate Defence
Adaptive Defence
![Page 11: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/11.jpg)
Why Differentiate between the Innate and Acquired Immunity ?
Innate Immunity• Characteristics:
– Universal– Rapid– Lacks memory– Non specific but ...
Acquired Immunity• Characteristics:
– Not universal– ‘Slow’ to develop– Possesses memory– Specific but….– ‘Plays to the tune of the
Innate immune system’
![Page 12: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/12.jpg)
Innate Immunity
• Mechanical barriers– Inhibit attachment and penetration of microorganisms
• Intact skin• Mucus• Cilia• Saliva,tears, urine for expelling microbes• Coughing, sneezing and shedding!
• Chemical barriers– HCL– Lysozyme– pH
![Page 13: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/13.jpg)
Innate Immunity
• Inflammation• Proteolytic cascades• Phagocytosis• Cytokines• Natural Killer cells
![Page 14: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/14.jpg)
Cell type Relative representation (%)
Neutrophil granulocytes 60 - 70
Eosinophil granulocytes 1 - 3
Basophil granulocytes < 2
Monocytes 5 - 10
Lymphocytes 20 - 40
![Page 15: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/15.jpg)
![Page 16: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/16.jpg)
![Page 17: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/17.jpg)
2. ANTIGEN NONSPECIFIC MECHANISMS;
PHAGOCYTES, GRANULOCYTES
![Page 18: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/18.jpg)
PHAGOCYTOSIS
NEUTROPHIL GRANULOCYTES REMOVAL OF BACTERIA; PUS
MACROPHAGES – MAINLY REMOVAL OF DAMAGED AND DYING CELLS
MECHANISMS:
RECEPTORS OF “FOREIGN“ STRUCTURES (TLR, LECTINS) OPSONIZATION (Ig, COMPLEMENT) – BINDING TO
Fc-RECEPTORS, COMPLEMENT RECEPTORS ENGULFMENT “KILLING”
- FUSION WITH LYSOSOMES (LOW pH, ENZYMES,
DEFENSINS)
- OXIDATIVE BURST
![Page 19: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/19.jpg)
OXIDATIVE (RESPIRATORY) BURST
Prodution of reactive oxygen compounds by the enzyme NADPH-oxidase
Localized in the phagosome membrane and catalyses the reactions:
(surface) O2 → O2- (superoxide anion-radical)
_________________________________________
(cytoplasm) NADPH → NADP+ + H+
Superoxide reacts further to produce toxic compounds (“singlet oxygen“, H2O2, ClO-)
![Page 20: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/20.jpg)
PHAGOCYTOSIS
![Page 21: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/21.jpg)
![Page 22: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/22.jpg)
ESSENTIAL LINK BETWEEN THE
INNATE AND ADAPTIVE SYSTEMS:
DENDRITIC CELLS
![Page 23: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/23.jpg)
![Page 24: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/24.jpg)
DENDRITIC CELLS MUST BE PRE-STIMULATED BY DANGER SIGNALS
TO BE ABLE TO ACTIVATE T LYMPHOCYTES
![Page 25: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/25.jpg)
DANGER SIGNALS:
- EXOGENOUS (PAMPs)
- ENDOGENOUS (e.g. STRESS PROTEINS RELEASED FROM NECROTIC CELLS)
![Page 26: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/26.jpg)
TOLL-LIKE RECEPTORS
![Page 27: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/27.jpg)
![Page 28: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/28.jpg)
![Page 29: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/29.jpg)
Adaptive Immunity
Effector cells APCs
![Page 30: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/30.jpg)
Lymphoid Tissues
Primary (Central)Lymphoid organs
Secondary (Peripheral)Lymphoid organs
ThymusBone Marrow
SpleenLymph nodesMALTGALT
![Page 31: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/31.jpg)
![Page 32: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/32.jpg)
THYMUS
• T cell selection takes place in the thymus
• Requirement for antigen presentation to T cells
• Positive/negative selection • Emergence of self tolerant
CD4 T cells and CD8 T cells
![Page 33: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/33.jpg)
Lymph Node
• The lymph node is the meeting point of recirculating T cells B cells and APC with foreign antigen
• B cell development continues in the LN through the process of CLONAL SELECTION
• SHM and CSR are important changes that occur here
• Plasma cells (Ig producing factories) return to the BM
![Page 34: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/34.jpg)
The soldiers and artillery of the Adaptive defense
CD4 T cells
![Page 35: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/35.jpg)
The soldiers and artillery of the Adaptive defense
CD8
• CD8 T cells are the CTLs
• Exocytosis of granules or a FAS/FASL sytem operates to mediate apoptotic cell death in the target cell
• Targeted to MHC class I presented viral peptides
![Page 36: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/36.jpg)
The soldiers and artillery of the Adaptive defense
B cells
• Antibodies specific for a pathogen can engage multiple effector responses
• The Fc region determines the effector response that is used
• The Fab region provides the specificity
![Page 37: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/37.jpg)
Immunoglobulin structure
![Page 38: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/38.jpg)
Cytotoxic T cells Helper Th1 Helper Th2
![Page 39: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/39.jpg)
SELF-TOLERANCE
![Page 40: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/40.jpg)
BIG PROBLEM:
HOW TO MAINTAIN SELF-TOLERANCE AND PREVENT
AUTOIMMUNITY?
![Page 41: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/41.jpg)
![Page 42: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/42.jpg)
IMMUNOLOGICAL HIT (WITH EMBARRASSING HISTORY…)
REGULATORY (= SUPPRESSOR) T LYMPHOCYTES
(Treg, Ts, Th3, Tr1…)
![Page 43: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/43.jpg)
![Page 44: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/44.jpg)
REGULATORY T LYMPHOCYTES ARISE IN:
- THYMUS (SUPPRESS AUTOIMMUNITY) - PERIPHERY (THESE DOWN-REGULATE EXCESSIVE IMMUNE RESPONSES
![Page 45: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/45.jpg)
Imunitní reakce.exe
Immune reaction
![Page 46: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/46.jpg)
Disorders of immunity
• immune deficiencies
• allergy
• autoimmunity
• tumors
![Page 47: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/47.jpg)
Imunodeficiencies
• Decreased resistance to infections• Primary (inherited)- genetic disorders• aquired – malnutrition• - infection (HIV, mumps..) - metabolic diseases - drugs, iatrogenic - stress
![Page 48: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/48.jpg)
Allergy
Inhalation allergy – hay fever, asthmaatopic ekzema
food allergy
drug allergy
![Page 49: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/49.jpg)
Imunopatologická reakce I.typu - časná přecitlivělost
alergen
IgEFc- receptor
degranulace histamin
fosfolipáza A2
cyklooxygenáza
lipoxygenáza
leukotrienyprostaglandinytromboxany
kyselina arachidonová
žírná buňka
![Page 50: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/50.jpg)
Autoimmune diseases
systemic- lupus erytematodes revmatoid artritis Sjogren syndrom vasculitis
Organ specific - endocrinopathies (thyreoiditis,
type I. diabetes, multiple sclerosis)
![Page 51: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/51.jpg)
Antitumor immunity
1. Tumor recognition by DC
2. Effector mechanisms (TH1 a TC cells, macrofages, NK cells)
![Page 52: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/52.jpg)
![Page 53: Immune system - introduction](https://reader033.vdocuments.site/reader033/viewer/2022061507/56815de7550346895dcc0d52/html5/thumbnails/53.jpg)
Transplantation immunity
alo-transplantacexeno-transplantace
donor recipient
rejection Graft versus host