Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of...
-
Upload
jayson-mosley -
Category
Documents
-
view
217 -
download
0
description
Transcript of Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of...
![Page 1: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/1.jpg)
Mechanisms of protection against infection and disease.
Primarily they can be divided into two major categories:
1. non-specific (innate)
2. specific (adaptive)
What is the immunity?
![Page 2: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/2.jpg)
Overview of the Immune System
Immune System
Innate(Nonspecific)
1st line of defense
Adaptive(Specific)
2nd line of defenseProtects/re-exposure
Cellular Components Humoral Components Cellular Components Humoral Components
Interactions between the two systems
![Page 3: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/3.jpg)
Non-specific Immunity (innate) Specific Immunity (adaptive)
Its response is antigen-independent.
Its response is antigen-dependent.
There is immediate response. There is a lag time between exposure and maximal response.
It is not antigen-specific. It is antigen-specific.
Exposure does not result in induction of memory cells.
Exposure results in induction of memory cells.
Some of its cellular components or their products may aid specific
immunity
Some of its products may help non-specific immunity.
Comparison of Innate and Adaptive Immunity
![Page 4: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/4.jpg)
Cells of the Immune System
Immune System
Myeloid Cells Lymphoid Cells
Granulocytic Monocytic T cells B cells
NeutrophilsBasophils
Eosinophils
MacrophagesKupffer cells
Dendritic cells
Helper cellsSuppressor cellsCytotoxic cells
Plasma cells
NK cells
![Page 5: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/5.jpg)
Development of the Immune System
ery pl
mye
neu mφ
lym
nk
thy
CD8+
CD4+
TH2
TH1
![Page 6: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/6.jpg)
Infection and Immunity Balance
infection immunity
Bolus of infection x virulenceimmunity
Disease =
![Page 7: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/7.jpg)
• Beneficial:
• Protection from Invaders• Elimination of Altered Self.
• Detrimental:
• Discomfort and collateral damage (inflammation)• Damage to self (hypersensitivity or autoimmunity)
Effects of the Immune System
![Page 8: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/8.jpg)
Innate (Nonspecific) Immunity
![Page 9: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/9.jpg)
Overview of the Immune System
Immune System
Innate(Nonspecific)
Adaptive(Specific)
Cellular Components Humoral Components Cellular Components Humoral Components
![Page 10: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/10.jpg)
Innate Host Defenses Against Infection
• Anatomical barriers– Mechanical factors– Chemical factors– Biological factors
• Humoral components– Complement– Coagulation system– Cytokines
• Cellular components– Neutrophils– Monocytes and macrophages– NK cells– Eosinophils
![Page 11: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/11.jpg)
Anatomical Barriers - Mechanical Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrierDesquamation
Mucous Membranes Non-ciliated epithelium (e.g. GI tract)
Peristalsis
Ciliated epithelium (e.g. respiratory tract)
Mucociliary elevator
Epithelium (e.g. nasopharynx)
Flushing action of tears, saliva, mucus, urine
![Page 12: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/12.jpg)
Anatomical Barriers - Chemical Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty acids
Mucous Membranes HCl (parietal cells)Tears and saliva
Low pHLysozyme and phospholipase A
Defensins (respiratory & GI tract)
Antimicrobial
Sufactants (lung) Opsonin
![Page 13: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/13.jpg)
Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous membranes
Normal flora Antimicrobial substancesCompetition for nutrients and colonization
![Page 14: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/14.jpg)
Humoral ComponentsComponent Mechanism
Complement Lysis of bacteria and some virusesOpsoninIncrease in vascular permeabilityRecruitment and activation of phagocytic cells
Coagulation system Increase vascular permeabilityRecruitment of phagocytic cellsΒ-lysin from platelets – a cationic detergent
Lactoferrin and transferrin
Compete with bacteria for iron
Lysozyme Breaks down bacterial cell walls
Cytokines Various effects
![Page 15: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/15.jpg)
Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killingInflammation and tissue damage
Macrophages Phagocytosis and intracellular killingExtracellular killing of infected or altered self targetsTissue repairAntigen presentation for specific immune response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
![Page 16: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/16.jpg)
Phagocytosisand
Intracellular Killing
![Page 17: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/17.jpg)
• Characteristic nucleus, cytoplasm
• Granules
• CD 66 membrane marker
Phagocytes - Neutrophils (PNMs)
![Page 18: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/18.jpg)
primary granules
contain cationic proteins, lysozyme, defensins, elastase and myeloperoxidase
secondary granules
contain lysozyme, NADPH oxidase components, lactoferrin and B12-binding protein
azurophilic; characteristic of young neutrophils;
specific for mature neutrophils
Characteristics of Neutrophil Granules
![Page 19: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/19.jpg)
• Characteristic nucleus
• Lysosomes
• CD14 membrane marker
Phagocytes - Macrophages
![Page 20: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/20.jpg)
Phagocyte Response to Infection
•Chemotaxis–N-formyl methionine-containing
peptides–Clotting system peptides–Complement products–Cytokines released by tissue
macrophages
•Phagocyte response–Vascular adherence–Diapedesis–Chemotaxis–Activation–Phagocytosis and killing
![Page 21: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/21.jpg)
Attachment via Receptors:
IgG FcR
Scavenger R
Complement R
Toll-like R
Initiation of Phagocytosis
![Page 22: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/22.jpg)
Phagocytosis
• Attachment
•Pseudopod extension
•Phagosome formation
•Granule fusion
•Phagolysosome formation
![Page 23: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/23.jpg)
*Toxic compounds – Superoxide anion (O2 -), Hydrogen peroxide (H2O2), Singlet oxygen (1O2) and Hydroxyl radical (OH*)
Respiratory BurstOxygen-Dependent Myeloperoxidase-Independent
Reactions
Pentose-P + NADPHG-6-P-dehydrogenase
Glucose +NADP+
NADPH oxidaseCytochrome b558
NADP++ O2-NADPH + O2
Superoxide dismutase H2O2 + 1O22O2- + 2H+
2O2- + H2O2
OH* + OH- + 1O2
![Page 24: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/24.jpg)
Respiratory Burst
Oxygen-Dependent Myeloperoxidase-Dependent Reactions
myeloperoxidaseOCl- + H2OH2O2 + Cl-
2OCl- + H2O1O2 + Cl-+ H2O
Toxic compounds – Hypochlorous acid (OCl-), and Singlet oxygen (1O2)
![Page 25: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/25.jpg)
Respiratory Burst
Detoxification Reactions
H2O2 + O2
Superoxide dismutase
H2O + O2
Catalase2O2
- + 2H+
2 H2O2
![Page 26: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/26.jpg)
Effector Molecule Function
Oxygen-Independent Killing in the Phagolysosome
Cationic proteins (cathepsin) Damage to microbial membranes
Lysozyme Hydrolyses mucopeptides in the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms
![Page 27: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/27.jpg)
Summary of Intracellular Killing Pathways
Intracellular Killing
OxygenDependent
OxygenIndependent
MyleoperoxidaseDependent
MyleoperoxidaseIndependent
![Page 28: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/28.jpg)
Nitric Oxide Dependent KillingIFNγ
TNF
TNF
Nitric OxideNitric Oxide
![Page 29: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/29.jpg)
Non-specific Killer Cells
NK and LAK cells
Killer cell
Activated macrophages
Eosinophils
They all kill foreign and altered self
targets
![Page 30: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/30.jpg)
Natural Killer (NK) cells
also known as large granular lymphocytes (LGL)
kill virus-infected or malignant cells
identified by the presence of CD56 & CD16 and absence of CD3
activated by IL2 and IFN-γ to become LAK cells
![Page 31: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/31.jpg)
Lymphokine Activated Killer (LAK) cell
IL2
IFNIFN
IL2
kills malignant
cells
kills transformed
and malignant cells
![Page 32: Introduction To Clinical Immunity PHCL 505 Dr: Wael H Mansy; MD Assistant Professor College of Pharmacy](https://reader035.fdocuments.net/reader035/viewer/2022062601/5a4d1c097f8b9ab0599f2968/html5/thumbnails/32.jpg)
K Cells
morphologically undefined
have Fc receptor
recognize antibody coated targets
could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)