innate and adaptive immunity
DESCRIPTION
Innate and Adaptive Immunity. Types of Adaptive Immunity. Lecture 2. Cells and Tissues of the Immune System. OVERVIEW OF THE IMMUNE SYSTEM Cells: lymphocytes, macrophages & monocytes , dendritic cells, granulocytes. All arise from pluripotent hematopoietic stem cells in bone marrow. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/1.jpg)
Innate and Adaptive Immunity
![Page 2: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/2.jpg)
Types ofAdaptiveImmunity
![Page 3: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/3.jpg)
Cells and Tissues of the Immune
System
Lecture 2
![Page 4: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/4.jpg)
OVERVIEW OF THE IMMUNE SYSTEM
Cells: lymphocytes, macrophages & monocytes, dendritic cells, granulocytes. All arise from pluripotent hematopoietic stem cells in bone marrow.
Organs: lymph nodes (found in various locations), thymus, spleen - these constitute the lymphoid organs
Thymus and bursa (bone marrow) are called central lymphoid organs
Peripheral Lymphoid Organs: Except lymph nodes, spleen, and tonsils, liver, intestine and skin are also
are also important parts of the immune system.
![Page 5: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/5.jpg)
Hematopoiesis
Pluripotent
![Page 6: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/6.jpg)
Lymphocytes
![Page 7: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/7.jpg)
![Page 8: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/8.jpg)
• B Cells• T Cells• NK Cells
Lymphocytes
![Page 9: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/9.jpg)
Jacques Miller found that removal of thymus (thymectomy) from neonatal mice resulted in fewer lymphocytes and no antibody to sheep red blood cells (1962). Later on, in thymectomized animals, the ability to reject allografts and to mount delayed hypersensitivity responses was drastically reduced.
By the mid-1960s, immunologists were convinced that there were indeed two separate arms of the immune system: one dealing exclusively with the production of circulating antibodies (humoral immunity), and another that is involved in the delayed hypersensitivity-type reactions and graft rejections (cell-mediated immunity). To have a good immune response, both have to exist.
Origin of T Cells
![Page 10: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/10.jpg)
![Page 11: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/11.jpg)
Classes of Lymphocytes
![Page 12: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/12.jpg)
• Do Not Express Classical Lymphocyte Markers
• Predominantly NK Cells (CD56)• Eliminate Tumor Cells and Virally
Infected Cells• Express Low Affinity FcRIII (CD16)• Using CD16 They Can Carry Out
ADCC• Reduction of MHC I Can Activate
Them
Null Cells (NK Cells)
![Page 13: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/13.jpg)
A T Cell ?
![Page 14: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/14.jpg)
A B Cell?
![Page 15: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/15.jpg)
Immune Cells Can Be Analyzed by Flow Cytometry
![Page 16: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/16.jpg)
B CellCD19+
T HelperCD4+
T CytotoxicCD8+
Phenotypic Markers to DistinguishLymphocyte Subsets
![Page 17: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/17.jpg)
Naive Activated EffectorPhases of
LymphocyteActivation
![Page 18: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/18.jpg)
![Page 19: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/19.jpg)
T vs B Cells
T cells B cells
Ag receptor TCR related to Ig BCR is membrane-bound Igbut not Ig (plus accessory molecules)
Ag recognition in context of MHC can recognize Ag aloneon APC or accessory cells
Functional Th (helper) and subsets of B cells only subsets Tc (cytolytic) subtly different in function
Secrete Cytokines Ig (as Ab) and cytokines
When Become (proliferating) Become lymphoblasts, then activated lymphoblasts become plasma cells
![Page 20: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/20.jpg)
• Mononuclear Phagocytes– Monocytes and Macrophages
• Dendritic Cells
Accessory Cells
![Page 21: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/21.jpg)
• Functions– Phagocytosis– Antigen processing
and presentation (APCs)
– Activation of T cells
Monocytes and Macrophages
![Page 22: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/22.jpg)
Origin and Development of Macrophages
![Page 23: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/23.jpg)
MONOCYTES AND MACROPHAGES
Monocytes are immature macrophages; monos circulate in blood & accum-ulate at sites of inflammation. Macrophages may differentiate in tissue inabsence of antigen (Kupffer cells in liver, e.g.) or differentiate in response toinflammation. They are Ag-presenting cells (APC). Also phagocytose microbes; contain bacteriocidal mechanisms.
macrophage in tissue, H&E stain
• mono in blood smear• Wright-Giemsa
![Page 24: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/24.jpg)
Activated MacMonocyte
![Page 25: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/25.jpg)
*Express CD14, a receptor for a wide variety of bacterial envelope molecules: LPS, components of bacterial cell walls. Ligation of CD14 leads to macrophage activation.
*Are activated by T cell derived cytokines such as interferons: leading to increased phagocytosis and microbicidal activity (increased activity of degradative enzymes, nitrogen and oxygen free radical production and prostaglandins etc.).
*Express receptors for Ab (FcR) and complement.
*Act as scavengers for apoptotic cells, cell debris and senescent cells (e.g., Kupffer cells in the liver bind "old" erythrocytes).
MONOS AND MACS CONTINUED
![Page 26: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/26.jpg)
Dendritic Cells
• Transport Antigens to L. nodes• Initiation of T Cell Responses
![Page 27: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/27.jpg)
Dendritic Cell Subsets
![Page 28: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/28.jpg)
• Do Not Express MHC II Molecules
• Found in Lymph Follicles (Rich in B Cell)
• Express FcR For Antibodies and Complement
• Ag-Ab Complex Shown To Last Very Long (weeks to months)
Follicular DCs
![Page 29: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/29.jpg)
(Myeloid DC)
![Page 30: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/30.jpg)
Neutrophil
Eosinophil
Basophil
Granulocytes
![Page 31: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/31.jpg)
![Page 32: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/32.jpg)
Lymphoid Organs
• Primary (Generative) Lymphoid Organs– maturation site of
lymphoid cells– bone marrow, bursa
of Fabricius, thymus,
• Secondary Lymphoid Organs– efficient at trapping
and concentrating foreign substances
– site of Ag-driven proliferation and differentiation; e.g. Ab production
– spleen, lymph nodes, diffuse tissues, payers patch, tonsils
![Page 33: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/33.jpg)
Organs Of Immune System
• Primary Lymphoid Organs– Bone Marrow and Thymus– Maturation Site
• Secondary Lymphoid Organs– Spleen, lymph nodes,– MALT (mucosal associated lymph
tissue)– GALT (gut associated lymph tissue)– Trap antigen, APC, Lymphocyte
Proliferation
![Page 34: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/34.jpg)
![Page 35: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/35.jpg)
ORGANS OF THE IMMUNE SYSTEM PRIMARY LYMPHOID ORGANS
Primary lymphoid organs are where lymphocytes arise and mature in the absence of antigenic stimuli. They are the bone marrow and thymus.
Bone marrow: Source of all hematopoietic progenitor (stem) cells, site of B cell maturation post-birth in mammals.
About 1 in every 10,000 to 15,000 bone marrow cells is thought to be a stem cell. In the blood stream 1 in 100,000 blood cells. Chicken Bursa
![Page 36: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/36.jpg)
PRIMARY LYMPHOID ORGANS: THYMUS
Thymic epithelial cells are derived from the third pharyngeal pouch.
The thymus is the site where T cells develop.
It gradually enlarges during childhood but after puberty it undergoes a process of involution.
The thymus is arranged into an outer cortex and an inner medulla. Immature lymphoid cells in the cortex. Mature T cells are in the medulla from where mature T lymphocytes enter the circulation.
![Page 37: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/37.jpg)
LYMPH NODES: filter lymphatic fluid; sites of Ag presentation & cell traffic
SECONDARY LYMPHOID ORGANS
Peripheral lymphoid organs: lymph nodes, spleen, tonsils, adenoids, and lymphoid tissue associated with other organ systems (gut, skin, mucosa).
![Page 38: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/38.jpg)
Lymph nodes have a fibrous capsule from which trabeculae extend towards the center, forming a framework for the lymphatic parenchyma (cortex, paracortex, and medulla).
1 - cortex (B Cells) 2 - paracortical zone (T Cells) 3 – medulla(T, B, Mac) 4 - medullary cords 5 - lymphoid follicle of the cortex 6 - capsule 7 - subcapsular sinus 8 - cortical sinus 9 - medullary sinus
LYMPH NODES
![Page 39: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/39.jpg)
LYMPH NODES, CONTINUEDFunctions of structural elements of lymph nodes
Subcapsular Sinus
Lymph afferent lymphatics, sinuses lined with macrophages efferent lymphatic (ultimately all drain into the portal vein).
Lymphocytes enter the node primarily from the blood via HEV efferent lymphatics.
DCs migrating from tissue enter the node into the T cell areas.
B cells entering nodes from blood must cross the T rich area in transit to the B cell rich areas thus optimizing T-B cooperation.
![Page 40: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/40.jpg)
The spleen serves two major functions: *It is responsible for the destruction of old red blood cells (RBCs) - this occurs in the red pulp;*It is a major site for mounting the immune response - the white pulp. The spleen behaves like a lymph node, but instead of filtering lymph, it filters blood.Has the hematopoiesis function in mice.
SPLEEN Stained with haematoxylin and eosin 1 - lymphoid follicle (white pulp) 2 - red pulp 3 - capsule 4 - trabeculae (connective tissue)
LYMPH NODES, CONTINUED
![Page 41: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/41.jpg)
INSIDE THE SPLEEN
Red pulp
White pulp
Mouse splenic CD3 expression inperiarteriolar lymphocyte sheath of white pulp and in scattered cells in red pulp.
![Page 42: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/42.jpg)
Lymphoid tissue found at the gastrointestinal tract, respiratory tract and urogenital tract.
MALT consists of aggregates of lymphocytes, macrophages, DCs, and other accessory cells.
MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT)
![Page 43: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/43.jpg)
This is comprised of: * tonsils, adenoids (Waldeyer's ring) * Peyer's patches * lymphoid aggregates in the appendix and large intestine * lymphoid tissue accumulating with age in the stomach * diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut
GUT-ASSOCIATED LYMPHOID TISSUE (GALT)
![Page 44: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/44.jpg)
SKIN-ASSOCIATED LYMPHOID TISSUE (SALT)
Skin is an active participant in host defense. It has the capability to generate and support local immune and inflammatory responses to foreign Ags that enter the body via the skin.
Cells of SALT include keratinocytes, Langerhans cells (immature DCs found in skin), intraepiethelial T cells, and melanocytes.
Langerhans cells form a continuous epidermal meshwork: they capture Ag, then migrate to draining lymph nodes, where they act as Ag-presenting cells.
![Page 45: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/45.jpg)
(T Cell Progenitors)
Effect of Thymectomy?
![Page 46: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/46.jpg)
Site of T Cell Maturation
![Page 47: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/47.jpg)
Effect of Thymectomy in Adult
![Page 48: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/48.jpg)
![Page 49: Innate and Adaptive Immunity](https://reader033.vdocuments.site/reader033/viewer/2022061604/5681644c550346895dd616f3/html5/thumbnails/49.jpg)
Circulation of Naïve and Activated/Memory T Lymphocytes
Activated/Memory Lymphocyte Circulation in pig?