Cells of the Immune System and Antigen Recognition.
-
Upload
thomasina-gibbs -
Category
Documents
-
view
226 -
download
0
Transcript of Cells of the Immune System and Antigen Recognition.
![Page 1: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/1.jpg)
Cells of the Immune System and Antigen
Recognition
![Page 2: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/2.jpg)
Overview of the immune system
• Purpose:• Protection from pathogens
• Intracellular (viruses, some bacteria and parasites)• Extracellular (most bacteria, fungi, and parasites)
• Eliminate modified or altered “self”• Cancer or transformed cells
• Sites of action:• Extracellular• Intracellular
![Page 3: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/3.jpg)
Overview- extracellular pathogens
• Ab are primary defense• Neutralization• Opsonization• Complement activation
![Page 4: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/4.jpg)
Overview- intracellular pathogens
• Cell-mediated responses are primary defense• Ab are ineffective• Two scenarios:
• Pathogen in cytosol • Cytotoxic T cell (CD8)
• Pathogen in vesicles• Th1 (CD4) releases cytokines• Activates macrophages
![Page 5: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/5.jpg)
Cells of the immune system
![Page 6: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/6.jpg)
Development of the immune system
NK cell
Stem cell
Macrophage
Lymphoidprogenitor
Myeloidprogenitor
T cell
B cell
Plasma Cell
Granulocyte
Monocyte
Mast cell
Dendritic cell
![Page 7: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/7.jpg)
Phagocytosis and Intracellular killing
Neutrophils and Macrophages
![Page 8: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/8.jpg)
Phagocytes – neutrophils (PMNs)
• Characteristic nucleus, cytoplasm• Granules• CD66 membrane marker
protein
Geimsa stainSource: www.dpd.cdc.gov
Neutrophil
![Page 9: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/9.jpg)
Characteristics of neutrophil granules
Primary granules Secondary granules
Azurophilic; young neutrophils Specific for mature neutrophils
Contain:cationic proteins, lysozyme, defensins, elastase and
Contain:Lysozyme, NADPH oxidase components and
myeloperoxidase Lactoferrin and B12-binding protein
![Page 10: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/10.jpg)
Phagocytes – macrophages
• Characteristic nucleus• lysosomes• CD14 membrane marker
proteinMacrophage
Source: Dr. Peter Darben, QueenslandUniversity of Technology, used with permission
![Page 11: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/11.jpg)
Non-specific killer cellsNK cells
Eosinophils
![Page 12: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/12.jpg)
Natural killer (NK) cells
• Also known as large granular lymphocytes (LGL)• Kill virus-infected or
transformed cells• Identified by the
CD56+/CD16+/CD3-• Activated by IL-2 and IFN-γ to
become LAK cells
![Page 13: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/13.jpg)
Eosinophils
• Characteristic bi-lobed nucleus• Cytoplasmic granules, stain with
acidic dyes (eosin)• Major basic protein (MBP)• Potent toxin for helminths
• Kill parasitic worms
Source: Bristol Biomedical Image Archive,used with permission
![Page 14: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/14.jpg)
Mast cells
• Characteristic cytoplasmic granules• Responsible for burst release of
preformed cytokines, chemokines, histamine• Role in immunity against
parasites
Source:
![Page 15: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/15.jpg)
Cells of the immune system: innate
• Phagocytes• Monocytes/macrophages• PMNs/neutrophils
• NK cells• Basophils and mast cells• Eosinophils• Platelets
![Page 16: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/16.jpg)
Cells of the immune system: APC
• Cells that link the innate and adaptive arms• Antigen presenting cells (APCs)
• Heterogenous population with role in innate immunity and activation of Th cells• Rich in MHC class II molecules (lec 11-12)
• Examples• Dendritic cells• Macrophages• B cells• Others (Mast cells)
![Page 17: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/17.jpg)
Cells of adaptive immune response
T cells and B cells
![Page 18: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/18.jpg)
Cells of the immune system: adaptive
• Lymphocytes• B cells
• Plasma cells (Ab producing)• T cells
• Cytotoxic (CTL)• Helper (Th)
• Th1• Th2• Th17• T-reg
![Page 19: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/19.jpg)
Major distinguishing markers
Marker B cell CTL T-helper
Antigen R BCR (surface Ig) TCR TCR
CD3 -- + +
CD4 -- -- +
CD8 -- + --
CD19/ CD20 + -- --
CD40 + -- --
![Page 20: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/20.jpg)
Specificity of adaptive immune response
• Resides with Ag R on T and B cells• TCR and BCR – both specific for
only ONE antigenic determinant• TCR is monovalent• BCR is divalent
T cellTCR Ag
B cellBCR
Ag
Ag
![Page 21: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/21.jpg)
Specificity of adaptive immune response
• Each B and T cell has receptor that is unique for a particular antigenic determinant on Ag• Vast array of different AgR in both T and B cell populations• How are the receptors generated?
• Instructionist hypothesis• Does not account for self vs non-self
• Clonal selection hypothesis• AgR pre-formed on B and T cells and Ag selects the clones with the correct receptor
![Page 22: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/22.jpg)
Four principles of clonal selection Hθ
1. Each lymphocyte has a SINGLE type of AgR2. Interaction between foreign molecule and AgR with high affinity
leads to activation3. Differentiated effector cell derived from activated lymphocyte
with have the same AgR as parental lymphocyte (clones)4. Lymphocytes bearing AgR for self molecules are deleted early in
lymphoid development and are absent from repertoire
![Page 23: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/23.jpg)
Specificity of adaptive immune response
• Clonal selection Hθ can explain many features of immune response• Specificity• Signal required for activation• Lag in adaptive immune response• Discrimination between self and non-self
![Page 24: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/24.jpg)
Development of the immune system
NK cell
Stem cell
Macrophage
Lymphoidprogenitor
Myeloidprogenitor
T cell
B cell
Plasma Cell
Granulocyte
Monocyte
Mast cell
Dendritic cell
Bone Marrow ThymusTissues
2° Lymphoid
![Page 25: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/25.jpg)
Lymphocyte recirculation
• Relatively few lymphocytes with a specific AgR• 1/10,000 to 1/100,000
• Chances for successful encounter enhanced by circulating lymphocytes• 1-2% recirculate every hour
![Page 26: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/26.jpg)
Lymphocyte recirculation
• Lymphocytes enter 2° lymphoid organs via high endothelial venules (HEVs)• Ag is transported to
lymph nodes via APC• Upon activation,
lymphocytes travel to tissues
T cell B cellMonocyteDC
APC
T cell
T cell B cell
B cell
B cellT cell
Bone marrow
Thymus
Tissues
Virginlymphocytes
Spleen and lymph nodes
Primed lymphocytes
![Page 27: Cells of the Immune System and Antigen Recognition.](https://reader035.fdocuments.in/reader035/viewer/2022081504/5697bf9a1a28abf838c92670/html5/thumbnails/27.jpg)
Lymphocyte recirculation
• After activation, new receptors (homing R) are expressed to direct to tissues• R on lymphocytes
recognize CAMs on endothelial cells• Chemokines at
infection help attract activated lymphocytes
T cell B cellMonocyteDC
APC
T cell
T cell B cell
B cell
B cellT cell
Bone marrow
Thymus
Tissues
Virginlymphocytes
Spleen and lymph nodes
Primed lymphocytes