The document provides an overview of immunology, covering topics such as:
- The anatomy of the primary and secondary defense organs including the bone marrow, thymus, lymph nodes, and spleen.
- The difference between the innate (naive) and adaptive (learned) immune systems.
- The myeloid and lymphoid lineages that originate from hematopoietic stem cells in the bone marrow and give rise to different immune cells.
- Key immune cells and components such as T-cells, B-cells, antibodies, cytokines, complement systems, and more.
Bound for the medical students who seek legal knowledge and for the law students who seek medical knowledge at the interface of two disciplines in teratology litigation.
1. Gametogenesis is the process by which primordial germ cells mature into functional gametes through meiosis and cellular differentiation. In females, primordial germ cells become oogonia then enter meiosis to become primary oocytes, while in males they become gonocytes then spermatogonia.
2. Primordial germ cells form early in development and migrate to the developing gonads, inducing their formation. In the gonads, germ cells proliferate then enter gender-specific meiotic and developmental pathways.
3. Differences between male and female gametogenesis include the timing and location of meiosis. In females, oocytes arrest in prophase I until ovulation, while in males
1. The lecture provides an overview of human embryonic development from fertilization through the first three weeks. It examines how a single fertilized egg develops into a complex adult through cell differentiation, formation of the three germ layers, and stem cell formation.
2. Key events covered include cleavage, blastocyst formation, implantation, formation of the bilaminar embryonic disc, and gastrulation. Gastrulation involves the morphogenetic movements that generate the three germ layers - ectoderm, mesoderm, and endoderm - and establish the body plan.
3. The lecture discusses embryonic stem cells, embryonic induction, organization of the germ layers and early tissues, and clinical correlations of defects
This document provides an overview of the history and techniques of embryology. It discusses how embryology has advanced from early observations to the use of microscopes and experimental techniques. Key developments included the cell theory, theories of preformation and epigenesis, and von Baer's laws of development. Modern techniques allow for prenatal screening and diagnosis using ultrasound, maternal serum screening, amniocentesis, and chorionic villus sampling. Fetal therapy is also possible through transfusions, medications, and even surgery. The field also studies concepts like stem cell potency, differentiation, and regeneration. A variety of methods are used like histology, tracing, transplantation, and culture techniques.
Gametogenesis is the development of gametes (sperm and eggs) through meiosis. Key genetic processes in gametogenesis include reducing chromosome number and independent chromosome segregation through meiotic cell division. While sperm and egg development differ morphologically, the underlying genetic processes are the same. Fertilization allows for the transfer of DNA from parents to offspring, promoting species continuity.
concept of competence and differentiation of embryonic cellspavithra M
The document discusses the concepts of competence and differentiation of embryonic cells. It defines competence as the ability of cells to respond to specific inductive signals, which allows organs to develop through cell-cell communication and interactions. It describes how the protein Pax6 confers competence on ectodermal tissue to respond to signals from the optic vesicle and form the eye. The document also outlines the process of embryonic differentiation, where embryonic cells specialize into different tissue types through cleavage, gastrulation and the formation of germ layers which give rise to organs and systems.
Gametogenesis is the process by which organisms produce gametes (reproductive cells). In humans, gametogenesis occurs through meiosis in the gonads to produce either sperm or eggs with half the number of chromosomes.
Spermatogenesis is the process where special somatic cells in the testes undergo meiosis and maturation to form sperm. During oogenesis in females, follicles in the ovaries develop through the ovarian cycle, with one follicle undergoing maturation and ovulation to release an egg. If fertilization occurs, the remaining follicle forms the corpus luteum to secrete progesterone.
The uterine cycle is regulated by hormones and involves the menstrual, proliferative, and secretory phases. It prepares the uterus for potential implantation
Bound for the medical students who seek legal knowledge and for the law students who seek medical knowledge at the interface of two disciplines in teratology litigation.
1. Gametogenesis is the process by which primordial germ cells mature into functional gametes through meiosis and cellular differentiation. In females, primordial germ cells become oogonia then enter meiosis to become primary oocytes, while in males they become gonocytes then spermatogonia.
2. Primordial germ cells form early in development and migrate to the developing gonads, inducing their formation. In the gonads, germ cells proliferate then enter gender-specific meiotic and developmental pathways.
3. Differences between male and female gametogenesis include the timing and location of meiosis. In females, oocytes arrest in prophase I until ovulation, while in males
1. The lecture provides an overview of human embryonic development from fertilization through the first three weeks. It examines how a single fertilized egg develops into a complex adult through cell differentiation, formation of the three germ layers, and stem cell formation.
2. Key events covered include cleavage, blastocyst formation, implantation, formation of the bilaminar embryonic disc, and gastrulation. Gastrulation involves the morphogenetic movements that generate the three germ layers - ectoderm, mesoderm, and endoderm - and establish the body plan.
3. The lecture discusses embryonic stem cells, embryonic induction, organization of the germ layers and early tissues, and clinical correlations of defects
This document provides an overview of the history and techniques of embryology. It discusses how embryology has advanced from early observations to the use of microscopes and experimental techniques. Key developments included the cell theory, theories of preformation and epigenesis, and von Baer's laws of development. Modern techniques allow for prenatal screening and diagnosis using ultrasound, maternal serum screening, amniocentesis, and chorionic villus sampling. Fetal therapy is also possible through transfusions, medications, and even surgery. The field also studies concepts like stem cell potency, differentiation, and regeneration. A variety of methods are used like histology, tracing, transplantation, and culture techniques.
Gametogenesis is the development of gametes (sperm and eggs) through meiosis. Key genetic processes in gametogenesis include reducing chromosome number and independent chromosome segregation through meiotic cell division. While sperm and egg development differ morphologically, the underlying genetic processes are the same. Fertilization allows for the transfer of DNA from parents to offspring, promoting species continuity.
concept of competence and differentiation of embryonic cellspavithra M
The document discusses the concepts of competence and differentiation of embryonic cells. It defines competence as the ability of cells to respond to specific inductive signals, which allows organs to develop through cell-cell communication and interactions. It describes how the protein Pax6 confers competence on ectodermal tissue to respond to signals from the optic vesicle and form the eye. The document also outlines the process of embryonic differentiation, where embryonic cells specialize into different tissue types through cleavage, gastrulation and the formation of germ layers which give rise to organs and systems.
Gametogenesis is the process by which organisms produce gametes (reproductive cells). In humans, gametogenesis occurs through meiosis in the gonads to produce either sperm or eggs with half the number of chromosomes.
Spermatogenesis is the process where special somatic cells in the testes undergo meiosis and maturation to form sperm. During oogenesis in females, follicles in the ovaries develop through the ovarian cycle, with one follicle undergoing maturation and ovulation to release an egg. If fertilization occurs, the remaining follicle forms the corpus luteum to secrete progesterone.
The uterine cycle is regulated by hormones and involves the menstrual, proliferative, and secretory phases. It prepares the uterus for potential implantation
Gametogenesis is the process by which haploid gametes are formed from diploid germ cells through meiosis. It occurs in the gonads (ovaries in females and testes in males) and results in the production of eggs in females through oogenesis and sperm in males through spermatogenesis. Both processes involve germ cells undergoing cell division and differentiation through meiosis to form mature haploid gametes - eggs in females and sperm in males - that can fuse during fertilization to form a new diploid organism.
The document summarizes the process of gastrulation in humans. It discusses how the embryo develops two germ layers, the epiblast and hypoblast, just before implantation. It describes the formation of the primitive streak around day 15, which defines the body axes. Cells migrate through the primitive streak during gastrulation to form the definitive endoderm, intraembryonic mesoderm, and ectoderm. Key cellular processes in gastrulation include epithelial-to-mesenchymal transition and convergent extension.
Spermatogenesis is the process by which spermatogonial stem cells in the seminiferous tubules of the testes proliferate and differentiate into mature sperm. Spermatogonial stem cells self-renew to maintain spermatogenesis throughout a male's life and can also differentiate into sperm. These stem cells can be identified by markers and cultured in vitro while maintaining their stem cell properties. Transplantation of spermatogonial stem cells into testes has resulted in donor-derived spermatogenesis, offering potential applications such as preservation of fertility.
Primordial germ cells originate in the yolk sac and migrate through the dorsal mesentery to reach the developing gonads. The indifferent gonad develops from the mesothelium, mesenchyme and primordial germ cells. In XY embryos, SRY expression causes testes development from the medulla while the cortex regresses. In XX embryos lacking SRY, the cortex develops into ovaries while the medulla regresses. Gametogenesis occurs through meiotic cell division in the gonads, producing haploid sperm in males through spermatogenesis and primordial follicles in females.
This document discusses engineering the microenvironment of ovarian follicles for in vitro culture through the application of tissue engineering principles. It begins with an overview of follicle development in vivo and the current state of in vitro follicle culture systems. Two-dimensional culture systems disrupt follicle architecture, while three-dimensional systems better maintain cell-cell interactions but have room for improvement. The field of tissue engineering can provide tools to better control the biochemical and mechanical signals within engineered follicle culture systems. The challenges of selecting appropriate biomaterials and manipulating their properties to regulate factor transport and mechanical cues throughout follicle development are discussed.
Gametogenesis is the process by which haploid gametes are formed from diploid germ cells in the gonads. There are two types: spermatogenesis and oogenesis. Spermatogenesis occurs in the testes and involves the formation of sperm from spermatogonia over 74 days, involving multiplication, growth, and maturation phases. Oogenesis occurs in the ovaries and also involves three phases to form ova from oogonia. The resulting gametes, sperm and ovum, differ in structure according to their roles in fertilization. Sperm are small, motile cells specialized for movement, while ovum are larger stationary cells specialized to receive sperm and support development.
Embryology is the science that treats of the origin and development of the individual organism.
It is a gradual bringing to completion both in structure and in function. Its chief characteristic is cumulative change in a progressive direction.
This document discusses oogenesis, the process by which eggs are produced in female organisms. It begins by outlining the objectives and introducing oogenesis and its three phases: proliferative, growth, and maturation. During these phases, significant biochemical changes occur in the nucleus, cytoplasm, RNA, yolk proteins, and hormones of the developing egg. As the egg grows and matures, it accumulates mitochondria, RNA polymerases, DNA polymerases, ribosomes, and other cellular components needed to support development upon fertilization. The process is regulated by hormones like FSH and LH and allows for the production of haploid eggs through meiosis.
This document provides an overview of human embryology and assisted reproductive technology (ART). It discusses the development of eggs and embryos, including follicular development, fertilization, early embryonic development, and implantation. It also mentions screening embryos for genetic diseases and some clinical correlations with contraception and ART.
Developmental biology is the study of how organisms grow and develop. It involves processes like gametogenesis, fertilization, growth, differentiation, pattern formation and morphogenesis. Gametogenesis refers to the formation of gametes or sex cells through meiosis. In spermatogenesis, spermatogonia undergo mitosis and meiosis to form spermatids that then differentiate into spermatozoa. In oogenesis, oogonia undergo mitosis and meiosis to form a secondary oocyte and first polar body, with the secondary oocyte then undergoing a second meiotic division. Fertilization occurs when a sperm fuses with an ovum, forming a zygote. Development then progresses through
1. In vertebrates, primordial germ cells (PGCs) arise early in development and migrate into developing gonads to form germ cells.
2. The mechanism of PGC migration varies between species, with frogs and zebrafish migrating chemotactically in response to signaling proteins, while birds and reptiles migrate through the bloodstream.
3. In mammals, PGCs form in the posterior epiblast and migrate directly into the endoderm and then genital ridges over successive days of development.
Sexual reproduction involves combining the chromosomes of two parents so that no two offspring are identical. Most organisms reproduce sexually. The evolution of sex is puzzling given its costs, but it provides genetic variation that helps populations adapt to changing environments, as proposed by the Red Queen Hypothesis. Meiosis during gamete formation and fertilization contributes to this genetic variation between offspring.
Gametogenesis is the process by which haploid gametes are formed through meiosis and differentiation of diploid or haploid cells. It occurs in the gonads through meiosis of diploid germ cells or mitosis of haploid germ cells. This results in various gametes. Spermatogenesis and oogenesis are the specific processes for male and female gamete formation, respectively, which both start from diploid germ cells and end with haploid gametes through meiosis.
The document summarizes the processes of spermatogenesis and oogenesis. It describes how sperm are produced in the testes through mitosis, meiosis and differentiation. Millions of sperm are produced daily starting at puberty. Oogenesis occurs in the ovaries, with one egg maturing each month through meiosis. Only one egg is produced per month from fetal development to menopause. The three hormones that regulate spermatogenesis - FSH, LH, and testosterone - are also outlined.
Spermatogenesis is the process by which germ cells differentiate into spermatozoa. It occurs within the seminiferous tubules of the testis and can be divided into three main phases: proliferation of spermatogonia, meiotic reduction division producing spermatocytes, and differentiation of spermatids into spermatozoa. Spermatogenesis progresses through cycles of the seminiferous epithelium, where each stage is defined by the association of germ cells at a specific developmental phase. Repeated cycles ensure continuous production of spermatozoa.
The document discusses the development of the male and female genital tracts. It begins with an overview that the gonads arise from mesoderm and the genital ducts arise from paired mesonephric and paramesonephric ducts. The mesonephric ducts develop into male genital ducts if the SRY gene is present, while the paramesonephric ducts develop into female genital ducts if SRY is absent. It then goes into detail about the development of the testes, ovaries, and genital ducts in both sexes.
The document discusses the process of fertilization in mammals. It describes how the sperm and egg communicate through signaling pathways to ensure fertilization occurs properly. First, the zona pellucida, which surrounds the egg, acts as a species-specific barrier and prepares the sperm. The zona pellucida is made up of three glycoproteins - ZP3 mediates sperm binding, ZP2 mediates subsequent binding, and ZP1 provides structural integrity. Upon contact with the egg, the sperm undergoes an acrosome reaction where its membrane fuses, releasing enzymes to penetrate the zona pellucida. This is triggered by a calcium signaling pathway initiated through binding of sperm galactos
Definition of spermatogenesis
structure of the sperm
The process of spermatogenesis
The spermatogenic cycle
meisosis
chromosome terminology
meitic cycle
spermiogenesis
1) Human development begins with the fertilization of an egg (oocyte) by sperm. The fertilized egg, called a zygote, undergoes cell division and differentiation over a period of 9 months to form a baby.
2) Both males and females undergo meiosis to produce gametes (sperm and eggs, respectively) with half the normal number of chromosomes. Fertilization restores the full chromosome number.
3) Key events in early development include formation of the embryo and fetal periods, during which most development occurs, though important changes also happen after birth through childhood and adulthood.
This document provides information on an international course on developmental biology to be held in Paris in October 2011. The course will be held at Pierre and Marie Curie University and the Curie Institute. It is intended for master's and PhD students and will include 3 weeks of practical laboratory sessions and 2 weeks of lectures. The practical sessions will cover topics like early mouse development, chick embryo culture, Drosophila imaginal discs, Xenopus embryos, C. elegans, and zebrafish. The lecture sessions will feature talks from researchers on various topics within developmental biology.
The document summarizes the key organs of the immune system. It describes the thymus and bone marrow as the primary lymphoid organs where lymphocyte maturation occurs. The lymph nodes, spleen, gut-associated lymphoid tissue, and skin-associated lymphoid tissues are described as the secondary lymphoid organs that trap antigens and allow immune cell interaction. The document also provides examples of how disruption or aging of the primary lymphoid organs like the thymus can impair immune function.
The lymphatic system consists of cells, tissues, and organs that monitor the body for harmful substances. The main components are lymphocytes, lymphatic tissues found in lymph nodes and other structures, and lymphatic organs like the spleen, thymus, bone marrow, and lymph nodes. Lymphatic tissues contain lymphocytes that fight infection and other threats. The lymphatic system's functions include monitoring the body, responding to harmful substances, and producing immune cells. Key lymphatic organs are the thymus, which produces T cells, and lymph nodes, spleen, and skin/mucosal tissues, which help the immune response.
Gametogenesis is the process by which haploid gametes are formed from diploid germ cells through meiosis. It occurs in the gonads (ovaries in females and testes in males) and results in the production of eggs in females through oogenesis and sperm in males through spermatogenesis. Both processes involve germ cells undergoing cell division and differentiation through meiosis to form mature haploid gametes - eggs in females and sperm in males - that can fuse during fertilization to form a new diploid organism.
The document summarizes the process of gastrulation in humans. It discusses how the embryo develops two germ layers, the epiblast and hypoblast, just before implantation. It describes the formation of the primitive streak around day 15, which defines the body axes. Cells migrate through the primitive streak during gastrulation to form the definitive endoderm, intraembryonic mesoderm, and ectoderm. Key cellular processes in gastrulation include epithelial-to-mesenchymal transition and convergent extension.
Spermatogenesis is the process by which spermatogonial stem cells in the seminiferous tubules of the testes proliferate and differentiate into mature sperm. Spermatogonial stem cells self-renew to maintain spermatogenesis throughout a male's life and can also differentiate into sperm. These stem cells can be identified by markers and cultured in vitro while maintaining their stem cell properties. Transplantation of spermatogonial stem cells into testes has resulted in donor-derived spermatogenesis, offering potential applications such as preservation of fertility.
Primordial germ cells originate in the yolk sac and migrate through the dorsal mesentery to reach the developing gonads. The indifferent gonad develops from the mesothelium, mesenchyme and primordial germ cells. In XY embryos, SRY expression causes testes development from the medulla while the cortex regresses. In XX embryos lacking SRY, the cortex develops into ovaries while the medulla regresses. Gametogenesis occurs through meiotic cell division in the gonads, producing haploid sperm in males through spermatogenesis and primordial follicles in females.
This document discusses engineering the microenvironment of ovarian follicles for in vitro culture through the application of tissue engineering principles. It begins with an overview of follicle development in vivo and the current state of in vitro follicle culture systems. Two-dimensional culture systems disrupt follicle architecture, while three-dimensional systems better maintain cell-cell interactions but have room for improvement. The field of tissue engineering can provide tools to better control the biochemical and mechanical signals within engineered follicle culture systems. The challenges of selecting appropriate biomaterials and manipulating their properties to regulate factor transport and mechanical cues throughout follicle development are discussed.
Gametogenesis is the process by which haploid gametes are formed from diploid germ cells in the gonads. There are two types: spermatogenesis and oogenesis. Spermatogenesis occurs in the testes and involves the formation of sperm from spermatogonia over 74 days, involving multiplication, growth, and maturation phases. Oogenesis occurs in the ovaries and also involves three phases to form ova from oogonia. The resulting gametes, sperm and ovum, differ in structure according to their roles in fertilization. Sperm are small, motile cells specialized for movement, while ovum are larger stationary cells specialized to receive sperm and support development.
Embryology is the science that treats of the origin and development of the individual organism.
It is a gradual bringing to completion both in structure and in function. Its chief characteristic is cumulative change in a progressive direction.
This document discusses oogenesis, the process by which eggs are produced in female organisms. It begins by outlining the objectives and introducing oogenesis and its three phases: proliferative, growth, and maturation. During these phases, significant biochemical changes occur in the nucleus, cytoplasm, RNA, yolk proteins, and hormones of the developing egg. As the egg grows and matures, it accumulates mitochondria, RNA polymerases, DNA polymerases, ribosomes, and other cellular components needed to support development upon fertilization. The process is regulated by hormones like FSH and LH and allows for the production of haploid eggs through meiosis.
This document provides an overview of human embryology and assisted reproductive technology (ART). It discusses the development of eggs and embryos, including follicular development, fertilization, early embryonic development, and implantation. It also mentions screening embryos for genetic diseases and some clinical correlations with contraception and ART.
Developmental biology is the study of how organisms grow and develop. It involves processes like gametogenesis, fertilization, growth, differentiation, pattern formation and morphogenesis. Gametogenesis refers to the formation of gametes or sex cells through meiosis. In spermatogenesis, spermatogonia undergo mitosis and meiosis to form spermatids that then differentiate into spermatozoa. In oogenesis, oogonia undergo mitosis and meiosis to form a secondary oocyte and first polar body, with the secondary oocyte then undergoing a second meiotic division. Fertilization occurs when a sperm fuses with an ovum, forming a zygote. Development then progresses through
1. In vertebrates, primordial germ cells (PGCs) arise early in development and migrate into developing gonads to form germ cells.
2. The mechanism of PGC migration varies between species, with frogs and zebrafish migrating chemotactically in response to signaling proteins, while birds and reptiles migrate through the bloodstream.
3. In mammals, PGCs form in the posterior epiblast and migrate directly into the endoderm and then genital ridges over successive days of development.
Sexual reproduction involves combining the chromosomes of two parents so that no two offspring are identical. Most organisms reproduce sexually. The evolution of sex is puzzling given its costs, but it provides genetic variation that helps populations adapt to changing environments, as proposed by the Red Queen Hypothesis. Meiosis during gamete formation and fertilization contributes to this genetic variation between offspring.
Gametogenesis is the process by which haploid gametes are formed through meiosis and differentiation of diploid or haploid cells. It occurs in the gonads through meiosis of diploid germ cells or mitosis of haploid germ cells. This results in various gametes. Spermatogenesis and oogenesis are the specific processes for male and female gamete formation, respectively, which both start from diploid germ cells and end with haploid gametes through meiosis.
The document summarizes the processes of spermatogenesis and oogenesis. It describes how sperm are produced in the testes through mitosis, meiosis and differentiation. Millions of sperm are produced daily starting at puberty. Oogenesis occurs in the ovaries, with one egg maturing each month through meiosis. Only one egg is produced per month from fetal development to menopause. The three hormones that regulate spermatogenesis - FSH, LH, and testosterone - are also outlined.
Spermatogenesis is the process by which germ cells differentiate into spermatozoa. It occurs within the seminiferous tubules of the testis and can be divided into three main phases: proliferation of spermatogonia, meiotic reduction division producing spermatocytes, and differentiation of spermatids into spermatozoa. Spermatogenesis progresses through cycles of the seminiferous epithelium, where each stage is defined by the association of germ cells at a specific developmental phase. Repeated cycles ensure continuous production of spermatozoa.
The document discusses the development of the male and female genital tracts. It begins with an overview that the gonads arise from mesoderm and the genital ducts arise from paired mesonephric and paramesonephric ducts. The mesonephric ducts develop into male genital ducts if the SRY gene is present, while the paramesonephric ducts develop into female genital ducts if SRY is absent. It then goes into detail about the development of the testes, ovaries, and genital ducts in both sexes.
The document discusses the process of fertilization in mammals. It describes how the sperm and egg communicate through signaling pathways to ensure fertilization occurs properly. First, the zona pellucida, which surrounds the egg, acts as a species-specific barrier and prepares the sperm. The zona pellucida is made up of three glycoproteins - ZP3 mediates sperm binding, ZP2 mediates subsequent binding, and ZP1 provides structural integrity. Upon contact with the egg, the sperm undergoes an acrosome reaction where its membrane fuses, releasing enzymes to penetrate the zona pellucida. This is triggered by a calcium signaling pathway initiated through binding of sperm galactos
Definition of spermatogenesis
structure of the sperm
The process of spermatogenesis
The spermatogenic cycle
meisosis
chromosome terminology
meitic cycle
spermiogenesis
1) Human development begins with the fertilization of an egg (oocyte) by sperm. The fertilized egg, called a zygote, undergoes cell division and differentiation over a period of 9 months to form a baby.
2) Both males and females undergo meiosis to produce gametes (sperm and eggs, respectively) with half the normal number of chromosomes. Fertilization restores the full chromosome number.
3) Key events in early development include formation of the embryo and fetal periods, during which most development occurs, though important changes also happen after birth through childhood and adulthood.
This document provides information on an international course on developmental biology to be held in Paris in October 2011. The course will be held at Pierre and Marie Curie University and the Curie Institute. It is intended for master's and PhD students and will include 3 weeks of practical laboratory sessions and 2 weeks of lectures. The practical sessions will cover topics like early mouse development, chick embryo culture, Drosophila imaginal discs, Xenopus embryos, C. elegans, and zebrafish. The lecture sessions will feature talks from researchers on various topics within developmental biology.
The document summarizes the key organs of the immune system. It describes the thymus and bone marrow as the primary lymphoid organs where lymphocyte maturation occurs. The lymph nodes, spleen, gut-associated lymphoid tissue, and skin-associated lymphoid tissues are described as the secondary lymphoid organs that trap antigens and allow immune cell interaction. The document also provides examples of how disruption or aging of the primary lymphoid organs like the thymus can impair immune function.
The lymphatic system consists of cells, tissues, and organs that monitor the body for harmful substances. The main components are lymphocytes, lymphatic tissues found in lymph nodes and other structures, and lymphatic organs like the spleen, thymus, bone marrow, and lymph nodes. Lymphatic tissues contain lymphocytes that fight infection and other threats. The lymphatic system's functions include monitoring the body, responding to harmful substances, and producing immune cells. Key lymphatic organs are the thymus, which produces T cells, and lymph nodes, spleen, and skin/mucosal tissues, which help the immune response.
The document discusses the lymphatic system and lymph nodes. It describes the components and function of the lymphatic system in transporting lymph and immune cells throughout the body. It details the different types of lymph nodes, their locations in the head and neck region, and which areas of the body drain into specific lymph nodes. The causes and clinical evaluation of swollen or enlarged lymph nodes (lymphadenopathy) are also covered.
The document provides an overview of the cells and organs of the immune system. It discusses:
- Primary lymphoid organs that develop lymphocytes
- Secondary lymphoid organs that trap antigens and allow lymphocyte interaction
- Leukocytes (white blood cells) that circulate in blood/lymph and participate in immune responses
- Hematopoiesis, the development of blood cells from stem cells in the bone marrow
Blood circulates through the body and consists of plasma and three main cell types: red blood cells, white blood cells, and platelets. It performs critical functions like transporting oxygen, nutrients, hormones, and waste. Bone marrow produces blood cells through a process involving sinusoids, adventitial cells, and migration of cells into blood vessels. The spleen, thymus, lymph nodes, and lymphatic system work with bone marrow to produce and transport immune cells throughout the body and remove aging or damaged blood cells from circulation.
The document summarizes the key organs and tissues of the immune system. It discusses the primary lymphoid organs of bone marrow and thymus, where lymphocytes mature. It also describes the secondary lymphoid organs of lymph nodes, spleen, and lymphoid tissues like Peyer's patches and tonsils, which are the sites where immune responses occur. Mucosal-associated lymphoid tissues contain aggregates of immune cells that defend against antigens entering mucosal surfaces.
The document outlines the key components and functions of the lymphatic and immune systems. It begins by defining the lymphatic system and explaining its role in absorbing excess fluid, transporting fats, producing lymphocytes, and defending the body. It then describes the structure of the lymphatic system including lymphatic vessels, lymph nodes, and other organs. Key differences between the lymphatic and immune systems are highlighted such as their circulatory nature and roles in long-term immunity. Finally, common diseases of the lymphatic system like lymphedema are discussed.
The lymphatic system removes excess fluid from tissues, absorbs fat and transports white blood cells and antigens. It comprises a network of lymphatic vessels that carry lymph fluid towards the heart. Lymph is filtered through lymph nodes which contain lymphocytes and phagocytes that help fight infection and disease. The major components are lymph, lymph vessels, lymphoid tissues and lymphocytes.
The thymus is a primary lymphoid organ where T cells mature. It contains cortical and medullary regions with different cell types that support T cell development. Immature T cell precursors from the bone marrow enter the thymus and undergo selection processes as they migrate between the regions. Positive selection in the cortex ensures T cells can recognize self-MHC, while negative selection in the medulla eliminates self-reactive T cells. Most immature T cells undergo apoptosis during this process before exiting the thymus as mature single positive T cells.
The immune system consists of lymphoid and reticuloendothelial components that are responsible for both specific and nonspecific immunity. The lymphoid tissues are organized into primary and secondary lymphoid organs. Primary organs like the thymus and bone marrow develop lymphocytes. Secondary organs like lymph nodes, spleen, tonsils and Peyer's patches interact with antigens and mature lymphocytes. These organs contain B and T cell areas and mediate both humoral and cell-mediated immune responses.
The lymphatic system consists of lymph, lymph vessels, lymph nodes, and lymphocyte-containing tissues. It collects fluid that leaks from blood vessels, known as lymph, and returns it to the circulatory system. The lymph flows through a network of thin-walled lymphatic vessels and passes through lymph nodes, which contain immune cells. Any foreign substances are filtered out before the lymph rejoins the bloodstream in larger veins in the neck.
The document summarizes the organs and tissues of the immune system. It describes the primary lymphoid organs of bone marrow and thymus, which develop immune cells. It then discusses the secondary lymphoid organs - lymph nodes, spleen, and mucosal tissues - which host immune cell interactions and responses to pathogens. It also mentions the tertiary lymphoid tissues that can develop during inflammation.
The document summarizes the organs of the immune system. It describes the primary lymphoid organs as the thymus and bone marrow, where lymphocyte maturation occurs. The secondary lymphoid organs, such as lymph nodes, spleen, and mucosal tissues trap antigens and allow interaction between lymphocytes and antigens. T cells mature in the thymus, while B cells mature in the bone marrow. The immune system organs work together to provide a systemic immune response to infections.
This document discusses the lymphatic system and its primary and secondary lymphoid organs. It describes that the lymphatic system consists of lymphatic organs and lymph fluid, and lymphoid organs are classified as primary or secondary. Primary lymphoid organs, such as the bone marrow and thymus, are the sites of lymphocyte development. Secondary lymphoid organs, including the spleen, lymph nodes, and MALT tissues, are where adaptive immune responses are initiated through interactions between immune cells and antigens. The document then provides more detailed descriptions of the structure and functions of the thymus, bone marrow, lymph nodes, and spleen as examples of primary and secondary lymphoid organs
The document summarizes the histology of lymphoid organs. It describes the primary lymphoid organs of thymus and bone marrow which are responsible for lymphocyte development and maturation. The secondary lymphoid organs discussed include lymph nodes, spleen, tonsils, and mucosa-associated lymphoid tissue. For each organ, it outlines their location, vascular supply, cellular composition of cortex and medulla, and role in the immune system. The maturation processes of B and T lymphocytes in the bone marrow and thymus respectively are also summarized.
Lymphadenopathy refers to abnormal lymph nodes in size, number, or consistency. It can be generalized, involving two or more non-contiguous lymph node groups, or localized to a single group. Common causes include infections, cancers, autoimmune diseases, and medications. A thorough history and physical exam are important to evaluate potential causes and symptoms. Red flags suggesting possible malignancy include supraclavicular adenopathy, hard/tender nodes, matted nodes, and nodes that do not regress after 3 weeks or fever resolution. Careful assessment of lymphadenopathy guides further diagnostic workup and management.
The document summarizes the major lymphoid organs of the immune system. It describes the primary lymphoid organs, the thymus and bone marrow, where lymphocyte maturation occurs. The secondary lymphoid organs, lymph nodes, spleen, MALT and GALT, trap antigens and allow interactions between lymphocytes and antigens. The thymus specifically mediates T cell maturation and selection, while lymph nodes contain B cell follicles and T cell zones to initiate adaptive immune responses to lymph-borne pathogens and antigens.
Cells and organs of the immune system.pptxGirjaPrasad
This document provides an overview of the immune system and its cells. It discusses the origin of immune cells from hematopoietic stem cells in the bone marrow. The two main types of immune cells are lymphocytes and granulocytes. Lymphocytes include B cells, T cells, and natural killer cells which develop acquired immunity. Granulocytes such as neutrophils, eosinophils, and basophils contribute to innate immunity. The immune system protects the body through non-specific and specific responses mediated by these cells and their interaction with antigens and cytokines.
The document summarizes the major immune organs in the body. It describes the primary lymphoid organs of bone marrow and thymus, which support the development of immune cells. It also outlines the secondary lymphoid organs of lymph nodes, spleen, and mucosal-associated lymphoid tissue that trap antigens and allow immune cell interaction. Additionally, it discusses the lymphatic system and how blood and lymph vessels connect the immune organs into a coordinated network.
This document discusses isoimmunization in pregnancy. It covers topics like the immunology of gestation, innate and adaptive immune responses, the development of the fetal immune system, and the management of Rh-sensitized pregnancies. Specifically, it details the nine mandatory conditions for Rh-immunization, describes the fetal inflammatory response syndrome, and provides an algorithm for managing Rh-sensitized pregnancies. It also includes case analyses of relevant malpractice law cases.
An unconventional analysis focusing on the detail missed by the Crown (in 1884) and by the related publications. Forgot/omitted a slide where I also argued about the inaccurate testimony of the slaughter. Punching "Jugular Vein" typically leads to death by embolism, not by hemorrhage. It is most likely that the defendants had cut Parker's Carotid Artery (not the Jugular Vein) because they had drunk blood after the slaughter. Although this correction would not update the prosecution process, my point is that the prosecution and the judges did not pay attention to this technical reality and kept repeating and rewriting the case from the verbiage of initial testimony. The same content is presented by Naira as a lecture on youtube.com
This was my reputation at Boston University (BU), before the Armenian diabolic rats and BU-outsiders (Paul Noroian/MA, Karine Martirosyan/MA, Marina Noble/MA, Ara Khachatryan/NY) would contact BU with lunatic tirades to demonize and ruin me. Learning about Dori Hutchinson's positive reference years after their malicious attacks, they contacted Dori again, this time challenging her letter. Having Dori's confused response, they then promulgated that latter across the entire global web. Also, Zlatka Russinova and E. Sally Rogers (from BU) were part of this hoax. The Armenian morbid/catatonic jealousy syndrome must be coded as a separate disease in the ICD system. Ask NOT why did the "Armenian genocide happen in 1915." Not only the historical "evidence" (half of what are grossly staged photos) is inaccurate, but also the Armenian leadership (if so existed) was guiltier than the Ottoman Turks. The Armenians lie that they were "massacred over their Christian religion." The neighboring Georgians are Christians too, with way better lands plus access to the sea. Please, do not hire me if you have an Armenian in your team, and do not invite me for a party if you have an Armenian guest, sweeper, butler, or janitor.
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A comprehensive guide to the laws governing surrogacy arrangements in North Transatlantic (the UK, the USA, and Canada). DOI: 10.13140/RG.2.1.4485.2888
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1. I M M U N O L O G YI M M U N O L O G Y
A brief survey
Naira Renault (former Naira Roland Matevosyan) MD, PhD, MSJ
Seton Hall Law School. Emory University. CDC
10.01.2017
2. CONTENTSCONTENTS
Anatomy of Defense
- Primary and Secondary Defense Organs
Naȉve and Learned Immunity
Workhorses of Defense
- Myeloid and Lymphoid Lineages
Major Histocompatibility Complexes: MHC- I and MHC-II
Human Leukocyte Antigens (HLA) and Associated Diseases
Immunoglobulins (Ig) and Ig Deficiency Syndromes
T-cells: Regulated and Educated Assassins
T-cell Deficiency Syndromes
Interleukins: High-yield Cytokines
Compliment Systems: The Confusing Cascade
Complement Deficiencies and Associated Disorders
Hypersensitivity Responses: Types 1 - 4
Graft Immunity: High-yield Immunosuppressants
Review Q & A and Court Holdings
4 - 14
15
16
17
18
19 - 21
22
23
24
25
26
27 - 28
29
30 - 31
3. Foreword
I find nothing more gratifying than talking about the human immunology with my
students, although obstetrics-gynecology is my specialty.
An up-to-the-minute institution, immune defense could serve as a model for man-made
military establishments, be that Department of Defense, Artillery, Navy, Air Force,
Coast Guard Reserve, or Cyber-security.
There is much to observe and imprint from: for instance, how the thymic cortex
“educates” (positive selection) T-cells toward distinct certification (killers, helpers,
regulators) and how those who “fail the tests” for being either “paranoid or
hypersensitive ” are blocked from the peripheral mechanisms (negative selection) to
prevent autoimmune conflict.
At the risk of witticism, some resemblance between the military maneuvers and
immune defense tactics are presented below. As you see, when it comes to immune
defense, there is no place for petty guerrilla warfare:
MILITARY MANEUVERS IMMUNE DEFENSE MILITARY MANEUVERS IMMUNE DEFENSE
Reconnaissance patrol
MHC I and MHC II,
thymic cortex, spleen's
white pulp, AIRE, mT
Leapfrogging
Th2, Ig switching,
IL-4, CD4+ T-cells
Hull-down
IL-1, IL-2, IL-3, TNF-α,
CD40 ligand
Center Peel
Complement 5 ,
IL-8, opsonization
Linear Ambush APCs, IL-10, IL-12 Coup de grace
CD8+, C5b-9,
cytokines
4. Anatomy of Defense
PRIMARY LYMPHOID ORGANS (bone marrow and thymus) function as
“boarding schools” for immature progenitor cells to generate, mature, and
educate young lymphocytes in an antigen-independent manner.
– Bone Marrow: A critical primary defense organ, it consists of red
marrow (the bone parenchyma, containing hematopoietic stem-cells
which generate all blood cell lines, including B and T cells), and yellow
marrow (the stroma, a supportive adipose tissue).
– Thymus: The high cellular-density cortex is for positive selection of
immature T-cells, the cortico-medullar junction for negative selection of
T-cells through apoptoric signal, and the low-cellular density medulla for
housing both positively and negatively selected mature thymocites.
SECONDARY LYMPOID ORGANS (peripheral lymph nodes, jugular and
subclavian trunks, parotid nodes or tonsils, occipital, mastoid and
mediastinal nodes, adenoid, appendix, spleen*, mucosa-associated
lymphoid tissue or MALT, etc) are where lymphocytes differentiate and
undergo clonal expansion (quantitative growth) in an antigen-dependent
fashion (i.e. to act only when there is a foreign invader). *See slide 11.
4
5. Thymus
THYMUS is a central, yet temporary organ of immune defense. It bridges
between the innate (naive) and adaptive (learned) immune systems. As a
primary lymphoid organ (along with the bone marrow), it is responsible
for de novo generation of immunocompetent T-cells with a diverse
repertoire of antigen-recognition.
Thymus originates from the ventral wings of the 3rd branchial
(pharyngeal) pouch at 5-6 weeks of gestation, extending laterally and
backward into the surrounding mesoderm and neural crest-derived
mesenchyme (later to be the capsule) in front of the ventral aorta. (The
dorsal wing of the same 3rd branchial pouch gives rise to the inferior pair
of parathyroids and the 9th cranial nerve – glossopharyngeus).
5
Complex thimyc embryology (endoderm, mesoderm)
explains why the phagocytes of thymic medulla
negatively select auto-reactive CD4+ and CD8+
thymocytes and eliminate T-cells bearing
autoreactive T-cell antigen receptors (TCRs), and
why thymic cortex positively selects cadet T-cells.
6. Thymus (continued)
Branches of the
internal thoracic artery
and superior thyroid
artery supply the gland.
Veins fall in the left
brachiocephalic vein
(innominate vein) and
in thyroid veins.
Nerves are exceedingly
minute and derived
from the vagus and
sympathetic n. system.
Branches from the descended hypoglossi and phrenic nerves reach
the investing capsule, but do not penetrate into the substance of the
organ. 6
7. Thymus (concluding)
The two main components of thymus,
lymphoid thymocytes and thymic
epithelial cells, have distinct
embryonic origins. Such a network
forms an adventitia to the blood
vessels.
The medullar reticulum is coarser than
the cortex; lymphoid cells are relatively
fewer and peculiar bodies with the
unknown function (corpuscles of
Hassall) are found, composed of
granular cells encapsulated by
eosinophilic type VI epithelial cells.
Autoimmune regulator gene (AIRE) is
expressed by thymic medulla, to drive
the transcription of organ-specific
genes (insulin receptor genes) to allow
maturing thymocytes be exposed to
more complex set of self-antigens than
that in the cortex. 7
8. Thymic cortex is where positive selection takes
place, ensuring that T-cells have the bare minimum
functionality of binding cell-surface proteins major
histocompatibility complex class I (MHC-I) and II
(MHC-II). Most immature T-cells do not pass this
stage and therefore undergo apoptosis. The ones
that get “certified” for binding with MHC-I are CD8+
T-cells (assassins), those who are assigned to bind
with MHC-II are CD4+ T-cells (helpers).
Corticomedullary junction is where T-cells undergo
negative selection. Positive-selection finalists are
presented with self-antigens. If their specificity is
too high (“paranoid” T-cells), they see body's own
normal antigens as alien invaders) for what they
are destroyed by apoptotic signal. Some highly
autoreactive cells, however, are able to pass the
negative selection, but are eliminated by
peripheral mechanisms (anergy, regulatory T-
cells). If such last-resort mechanisms fail, then
body becomes predisposed to autoimmune
diseases.
9. Lymph Nodes
Secondary lymphoid organs (spleen,
lymphoid nodes, tonsils, adenoids, MALT)
are sites where lymphocytes undergo
differentiation with an antigen-dependent
intelligence.
Lymph nodes are encapsulated and
trabeculated with multiple afferent
vessels and with only one efferent vessel
(many ways in and only one way out!).
Flow through the node: Afferent vessel
→ subcapsular sinus → trabecular sinus
(phagal filtration) → efferent vessels.
9
Each anatomical division of the node has its specific function. Medulla consists of
cords, densely packed lymphocytes, and sinuses (reticular cells, macrophages).
Paracortex contains endothelial venues for the entering B and T-cells and enlarges
during the cellular adaptive response. Cortex has follicles to host the migrating B-
cells. Primary follicles are densely packed and dormant; secondary follicles (after
antigen response activation) are large and contain pane germinal cells.
10. Spleen
Known as a defense
and purifying organ
but not a vital one,
spleen is typical to
nearly all vertebrates,
with an exception of
lampreys and
hagfishes. In a healthy
adult human, spleen is
a shoe-shape,
singleton, obliquely
oriented parenchymal
organ positioned
beneath the T-9th
and
10
T-11th
ribs in the left hypochondriac region, between the gastric fundus and diaphragm,
and separated by costodiaphragmatic recess. The convex (pariental, phrenic) surface looks
at the diaphragm and the concave visceral surface (hilus) faces the porta, pancreatic islet,
left kidney, stomach, and the spleno-omental fold of Morgenstern known as the "criminal
fold." Vessels entering or exiting the hilus form letter "S," if one connects the upper polar,
hilar, and lower polar vessels. Spleen undergoes involution after 60 years.
11. Spleen (continued)
Spleen functions as a secondary
“lymphoid organ.”Yet, thinking of
spleen as the “largest lymphatic
organ” is a confusion* (see slide
4). Spleen can't be a “giant lymph
node” since there is no
connection of splenic lymphatic
net with other lymph vessels.
Rather, spleen is the bulky
component of the
reticuloendothelial complex.
The splenic primordium becomes
detectable during the 5th
gestation weeks as an outgrowth
11
of dorsal mesogastrium. Splenic lobules form around the central arteries in the
13th
-14th
weeks of pregnancy.
Spleen has 3 to 5 vascular segments named S1-S5 (slide 12). Subsequent to its
origin from the celiac trunk, the splenic artery courses leftward and
retroperitoneally under the posterior wall of the omental bursa, along the
posterior-superior edge of the pancreatic islet, with multiple branches into
pancreatic parenchyma.
12. Spleen (circulation)
Splenic aretery is a branch of the celiac trunk, arising
together with common hepatic and left gastric arteries.
Its length (8 - 32 cm) and characteristic tortuous
appearance is easy to identify with angiographic
studies. The artery's termination in the splenic porta is
unpredictable, due to the number of branches to
spleen and neighboring organs (left kidney, stomach,
omentum). Branches of splenic artery include:
12
short gastric arteries,
posterior gastric artery,
left gastroepiploic artery,
dorsal pancreatic artery,
transverse pancreatic
artery, great pancreatic
artery, caudal pancreatic
artery, as well as multiple
collateral and atypical
branches.
13. The only splenic vein joins the superior mesenteric vein to
form the portal vein. Splenic vein originates from several
veins leaving the splenic hilum and joining at variable
distances. These venules closely follow the arterial
distribution.
Spleen weighs 1/4 of lymphoid mass of the body (while
lymph in bone marrow corresponds to the 1% of body's
weight). Spleen is approximately ½ of the weight of liver.
The lymphatic vessels of spleen form the splenic capsule
and some of the larger trabeculae. One of the paradoxal
features is the scarce lymphatic net of the splenic pulp.
Sympathetic -noradrenergic
innervation of spleen (supplied by the
medial and anterior parts of the
celiac plexus) is regional and unique.
Postganglionic nerve fibers enter
spleen with splenic artery, run along
the trabecular plexi, extend into the
white pulp along the central artery
and end in periarterial lymphatic
sheath. Regions of T-cells and plasma
cells (not B-cells) are targeted.
14. Spleen (concluding)
Most of the blood flow passes through the splenic marginal zone and directly via the
white pulp, ensuring an efficient monitor. While the white pulp is mainly for the
adaptive immunity, the marginal zone is involved in both innate and adaptive
responses through specific metallomorphic macrophages and B-cells.
In addition to pattern-recognition receptors (Toll-like receptors) expressed by most
tissue macrophages, marginal-zone metallomorphic macrophages express a C-type
lectin SIGNR1 and type-I scavenger receptor MARCO. SIGNR-1 efficiently binds
polysaccharide antigens (Micobacterium Tuberculosae, Streptococcus Pneumoniae, E-
coli, Staphylococcus aureus).
Marginal-zone macrophages lack the expression of MHC class II molecules and
subsequent activation of marginal-zone-B cells occurs through shedding of pathogen-
degradation products that are opsonized by complement.
When signaling through LT-β receptors (LT-βR) or TNF receptor 1 (TNFR1) is lacking,
levels of homeostatic chemokines CXCL13, CCL19 and CCL21 are reduced in spleen,
resultant in disorganization of the white-pulp. Chemokines CCL19, CCL21 (produced by
the stromal cells of T-cell zone) play a crucial role in regulating T-cell zone integrity.
Splenectomy leads to mild thrombocytosis (spleen can store 1/3 of total body
platelets, so removal allows more circulate in plasma), Howell-Jolly bodies (RBC
remnants), poorer response to vaccines, and higher risk of certain infections:
Haemophilus influenzae, Neisseria meningitidis, Salmonella typhi - “SHiNS”. 14
15. Naive and Learned Immunity
Innate (naive) immune system
is characterized by fast and
non-specific to infection and
lack of immune memory. It
recognizes foreign antigens
that are highly conserved over
time and across pathogenic
species. For example,
lipopolysaccharide (LPS) is a
component of the cell-wall
conserved between gram
15
-negative bacteria. Toll-like receptors are able to recognize LPS and, once bound, activate
the release of inflammatory cytokines. Constituents of innate immunity include:
phagocytes (neutrophils, macrophages, dendritic cells), natural killers (NK), mast cells,
complement system, and epithelial (mucose, epidermal, entothelial) barriers.
Adaptive (learned) immune system is featured with slow initial response to the 1st-
time antigen exposure and more rapid/robust/diverse antigen-specific responses
during subsequent exposures secondary to “immune recollections.” It is divided into
humoral (circulating antibodies) and cell -mediated immunity (antigen-specific CD+ T-
cells, antigen presenting cells (APCs) like B-cells, dendritic calles, macrophages).
16. Workhorses of Defense
All cells of immune system originate from hematopoietic stem-cells of the bone marrow. These
are multipotent cells (are able to form all blood cell lines) and have the capacity of self-renewal.
They further differentiate to form myeloid and lymphoid cell-lines:
MYELOID LINEAGE
➔ Basophil: Mature cell with bilobed nucleus and large blue granules.
➔ Dendritic cell: Have long cytoplasmic arms capable of efficient antigen presentation to
lymphocytes (professional antigen-presenting cells [APCs]).
➔ Eosinophil: Mature cell with bilobed nucleus and large pink granules containing major
basic protein that attacks parasitic and helminthic agents.
➔ Macrophage: Tissue histocyte (differentiated monocyte) capable for phagocytosis, as well
as synthesis and secretion of various cytokines (IL-1, IL-6, IL8, IL-12, TNF-α).
➔ Mast cell: Has small nucleus and large cytoplasmatic granules containing histamine and
other allergic mediators in response to allergies, hives, anaphylaxis.
➔ Monocyte: Circulating phagocytic cell to be further stimulated and differentiated to the
tissue macrophage.
LYMPHOID LINEAGE
➔ B-lymphocytes: Cells that undergo differentiation into either memory B-cells or plasma cells
(that produce antibodies).
➔ T-lymphocytes: Cells that further differentiate to either CD4+ helpers, CD8+ cytotoxic cells,
regulatory T-cells, and memory T-cells.
➔ Natural Killers (NK): CD56+ lymphocytes containing cytoplasmic toxic granules (granzymes)
and are able to kill malignant, virus-infected, and antibody-coated (opsonized) cells. 16
17. Major Histocompatibility Complexes: MHC- 1, MHC-2
MHC system helps us discern ourselves from everything else, as well as detect
when body's own cells are either infected or undergo malignant changes. Two
structurally and functionally distinct classes of MHC are involved:
MHC Class I is present in all nucleated cells of our body and is encoded by
human leukocyte antigen genes HLA-A, HLA-B, HLA-C. MHC is a cell-surface
protein that displays peptide fragments from inside the cell to out. Normally,
the antigen loaded onto MHC-I is an autoreactive antigen and cytotoxic CD8+
T-cells will not react to it. However, if a virus infects a cell, it produces viral
proteins using the host's cellular machinery. These viral proteins too, are
loaded onto MHC-I. This makes cytotixic CD8+ confer immunity to viral
infection, and by recognizing the viral antigen they target to destroy it – if a
costimulatory signal (for anergy) isn't present (discussed in slide 23).
MHC Class II is only present on antigen-coated cells (macrophages, dendritic
cells), is encoded by the HLA genes HLA-DP, HLA-DQ, HLA-DR, and composed
of two α- and β- subunits. After phagocytosing the microbe, the APCs process
and load antigens onto MHC-II. Then, MHC-II is inserted into the cell
membrane to make it recognizable by CD4+ T-cells (helpers) which after
activate B-cells and trigger local inflammation. 17
19. Immunoglobulins
Antibody formation is accomplished by mature plasma B-cells which
synthesize and release immunoglobulins (Ig) after being activated by the
appropriate mechanisms of antigen stimulation. The number of
antigens is unlimited; so too the number of activation mechanisms. This
is called antibody diversity and is built on four main processes:
1) Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
2) Random combination of various heavy chains with light chains
3) Somatic hypermutation in germinal centers (after antigen stimulation)
4) Terminal deoxynucleotidyl transferase (TdT) addition of DNA to the heavy
and light chains.
The common antibody isotypes are IgM and IgG. Isotope switching
occurs after antigen stimulation and activation of B-cells, resulting in
alternative splicing of messenger - mRNA. The resultant post-
translational modification of mRNA dictates the isotype of plasma B-
cells (IgA, IgG, IgE, IgM, etc).
19
20. Ig and Ig Deficiency Syndromes
IgA: Occurs as a monomer in bloodstram and as a diamer when secreted
(epithelial cell component). IgA is secreted onto mucosal surfaces (GI, GUI,
respiratory) to block attachment of pathogens to mucose membranes.
IgD: Found on the surface of mature B-cells. Function is unclear.
IgE: Implicated in allergic response (type-1 hypersensitivity) because it
binds with both mast cells and basophils and undergoes cross-linking after
exposure to appropriate antigen.
IgG: The main antibody in the secondary (slow) antigenic response. Occurs
as a monomer in complement fixing job, cross the placenta to provide
passive immunity to developing fetus, opsonize bacteria, neutralize various
toxins and viruses. IgD does not make multimers and therefore, it does
cross the placenta.
IgM: Found on the surface of mature B-cells. Produced in the primary, fast
antigen response. Occurs as a monomer and commonly as a pentamer for
more efficient trapping and complement fixing. As a pentamer is does not
cross the placenta. 20
21. B-cell Deficiency and Ig Deficiency Syndromes
● COMMON VARIABLE IMMUNODEFICIENCY: Most common form of
primary B-cell deficiency with distinct low levels of IgG and IgA (rarely IgM)
resultant in high rates of lymphomas and gastric cancer.
● HYPER IgM SYNDROME: Normal level of B-cells, with diminished levels
of IgG and IgA and higher levels of IgM. Associated with increased risk for
Pneumocystis infections (fungi). Conditioned with inability of isotype
switching and sequential secondary deficiency in CD40 ligand on Th2 cells.
● SELECTIVE IgA DEFICIENCY: Most common type of Ig deficiency,
associated with increased respiratory, GI, GUI infections, and high risk of
anaphylaxis from blood-product transfusions.
● X-LINKED AGAMMAGOBULINEMIA (Bruton agammaglobulinemia):
Results from a mutation in the receptor tyrosine kinase (BTK). Present
exclusively in males. Children with XLA are usually healthy for the first
months of infancy, as they are protected by the maternal antibodies. After,
they begin to develop recurrent infections, resistant to anti-microbal
treatment. 21
22. T-cells: Regulated and Educated Assassins
As noted before, T-cells originate from the lymphoid lineage of
hematopoietic differentiation. They are “born” in the bone-marrow and
“trained” in the thymus. It is in thumys where they get “certifications” of
helpers (CD4) or assassins (CD8).
CD4+ T Cells: These “helpers” (Th) will undergo further differentiation
after appropriate stimulation by interleukins to become either Th1 or
Th2 with specific functions to help regulate both humoral and cell-
mediated immunity.
- Th1 are involved in regulation of cell-mediated response, and are
activated by APCs and secret interferon-gamma (IFN-γ) which in turn
activates APCs for efficient killing. They also secrete IL-2 which activates
CD8+ to kill virally infected cells.
- Th2 are involved in activating B-cells and enhancing isotype
switching by secreting IL-4, IL-5, and IL-6.
CD8+ T Cells: These cytotoxic cells are responsible for seeking out and
eliminating virus/parasite-infected cells, cancer cells, and other foreign
cells.
22
23. T-cell Deficiency Syndromes
Viral infection has unique activation arrays. When an APC (dendritic cell, macrophage) is
exposed to viral antigen, it will load the latter onto MHC-II for presentation to the CD4+
T-cell. It will also express co-stimulatory signal. The T-cell receptor (TCR) then interacts
with antigen-positive MHC-II on the APC. Yet, a single signal is not enough. Immune
system's checks and balances require a second signal for an appropriate activation. This
B7 costimulatory signal on the APC must interact with CD28 on CD4+ T-cell while the
TCR-MHC II interaction is occurring. If these conditions are met, then CD4+ T-cell will
also release IL-2 to activate CD8+ killers and differentiate CD4+T-cell in autocrine
manner. If TCR, weirdly sees and binds to host antigens (autoreactivity), immune system
tackles with this issue by anergy command, i.e. deactivating self-reactive T-cells. If this
process fails as well, then autoimmune disorders occur.
T-CELL DEFICIENCT SYNROMES:
- Acquired Immunodeficiency Syndrome (AIDS): The final stage of the decremental
quantity and quality of T-cells (CD4+) caused by HIV.
- Ataxia Telangiectasia: A T-cell deficiency along with cerebellar ataxia and increased
risk for various types of cancer (impaired double-strand DNA repair).
- DiGeorge Syndrome: 22q11.2 deletion syndrome resultant in CATCH-22 (Cardiac
defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalciemia).
- Severe Combined Immunodeficiency (SCID): The common form of X-linked disorder
with suspectibility to numerous pathogenic infections with diarrhea, pneumonia, otitis,
sinusitis.
23
24. Interleukins: High-yield Cytokines
IL-1: An acute phase reactant produced by macrophages, inflicting fever,
leukocyte recruitment, adhesion molecule activation, and stimulation of
further chemokines.
IL-2: Secreted by Th cells to enable growth, maturation, and proliferation of
CD4+ and CD8+ T-cells.
IL-3: Stimulates the bone marrow.
IL-4: Secreted by the Th2 it furthers the B-cell development and enhances Ig
isotype switching to IgG.
IL-5: Secreted by the Th2 cells it enhances Ig class switching to IgE and
increases production of eosinophils (allergic response).
IL-6: Like IL-1, this is an acute-phase reactant produced by Th and
macrophages to further an acute inflammatory response and to stimulate
antitel production.
IL-8: The neutrophil chemotactic factor.
IL-10: Secreted by the regulatory T-cells, it suppresses cell-mediated
immunity and stimulates humoral immunity.
IL-12: Secreted by the macrophages, it enhances NK-cells and T-cells. 24
25. Compliment Systems: The Confusing Cascade
Complement is a system of liver-derived serum proteins that - once activated
trigger a cascade of proteolytic cleavage reactions to further the cascade and
convert pro-proteins into functional and active immune constituents.
There are three main initial pathways that activate C5 and initiate the final
response - formation of the membrane attack complex (MAC):
● Classical pathway → antigen → antibody complexes
● Mannan-binding lectin pathway → microbial lectin particles
● Alternative pathway → microbial surfaces like LPS/endotoxin.
Main functions of the complement system include:
1. Opsonization → C3b
2. Neutrophil chemotaxis → C5a
3. Viral neutralization → C1, C2, C3, C4
4. Lysis (membrane attack complex) → C5b-9
5. Anaphylactic reaction → C3a, C5a. 25
26. Complement Deficiency and Associated Conditions
26
C1 esterase inhibitor deficiency: Hereditary angioedema
Decay-accelerating factor (CD55)
deficiency:
Paroxysmal nocturnal
hemoglobinuria
Protectin (CD59) deficiency: Paroxysmal nocturnal
hemoglobinuria
C3 deficiency: Propensity to develop severe
recurrent pyogenic infections of the
sinus and respiratory tract
MAC deficiency: Propensity to develop Neisseria
bacteremia (gonorrhea or meningitis)
27. Hypersensitivity Responses: Types 1, 2
TYPE 1 (Allergy): Occurs when presensitized mast cells or basophils with
antigen-specific IgE are exposed to a particular antigen. The antigen binds
the Fab portion of IgE, cross-linking and immediately releasing performed
vasoactive substances (histamine, for instance). Examples: allergic
rhinitis, atopic dermatitis (eczema), hives (urticaria), asthma, and
anaphylaxis. Anaphylactic reactions occur in same Type-1 fashion but in
fast and widespread vasodilation and subsequent shock (normovolemic
or hypovolemic hypotension).
TYPE 2 (Antibody-dependent Cytotoxicity): Occurs when either IgM
or IgG bind to the cell surface antigen leading to cytotoxic destruction by
various mechanisms, including opsonization (for neutrophils),
complement activation, and interference with cellular functioning.
Examples: autoimmune hemolyitc anemia, idiopathic thrombocytopenic
purpura (ITP), acute transfusion reactions with hemolysis, rheumatic
fever, Goodpasture syndrome, bullous pemphigoid, vulgar pemphigus,
Graves disease, myasthenia gravis. 27
28. Hypersensitivity Responses: Types 3, 4
TYPE 3 (Immune Complex Disease): Occurs when antigen-antibody
(mainly IgG) complexes are formed and deposited in tissues, resulting in
activation of complement systems and recruitment of neutrophils leading
to the tissue injury. Examples: systemic lupus erythematosus (SLE),
rheumatoid arthritis, Arthus reaction, serum sickness, post-streptococcal
glomerulonephritis.
TYPE 4 (Delayed, Antibody-dependent Cytotoxicity): Being not
antibody related, these are the only reactions that are not transferred by
serum. These are slow, cell-mediated reactions occurring when the
learned T-cell interacts with the same antigen, resulting in lymphokine
production and activation of other players (macrophages). Examples:
contact dermatitis, nickel allergy, PPD test,, GVHD test, multiple
sclerosis, Gullian-Barré syndrome.
28
29. Graft Immunity: High-yield Immunosuppressants
TYPES OF TISSUE TRANSPLANTANTS
● Autograft: Transplanting tissue back to the same host but in a different location.
● Allograft: Transplanting tissue/organ/fluid/cell from one human to another.
● Xenograft: Transplanting tissue from animals to a human being.
TYPES OF REJECTION
Hyperacute rejection: Rapid failure resultant from complement activation and
neutrophil migration into the donor organ.
Acute rejection: T-cell-mediation rejection occurring within weeks to months,
reversible with immunusuppressants.
Chronic rejection: Long-lasting failure with progressive loss of function of the
transplant – secondary to vascular fibrosis.
HIGH-YIELD IMMUNOSUPPRESSANTS
Azathioprine: A prodrug converted in vivo to 6-mercaptopurine (6-MP) to inhibit
purine metabolism and proliferation of T and B cells. Used in acute rejection and
autoimmune disorders.
Cyclosporine: Binds to cyclophilin, which inhibits calcineurin and therefore prevents
transcription of IL-2 in T-cells. Used in tissue transplantation only.
Tacrolimus: Binds to FK-binding protein, inhibits calcineurin (and IL-2). Used as
ciclosporine replacement.
Microphenolate mofetil: Inhibits inosine monophosphate dehydrogenase, the rate-
limiting enzyme in guanosine monophosphate (GMP) synthesis. Used in organ
transplantation only.
29
30. Review Q & A
Q1. Which type of immunization a patient with a compliment disorder
involving deficiency of the membrane attack complex (MAC) should
specifically receive?
A1. That patient is at risk for Neisseria infections, therefore is at high
risk for meningococcal infections. S/he should receive meningococcal (MCV-
4) vaccine.
Q2. A teenage African male with sickle-cell anemia presents for a regular
exam. The peripheral smear shows sickle cells together with RBCs and large
numbers of platelets. Your guess.
A2. The peripheral smear with thrombocytosis and Howell-Jolly bodies
suggests that the patient is after splenectomy or autosplenectomy (from the
chronic splenic infections).
Q3: Which cell type in the human body does not express MHC class I?
A3: MHC-I is expressed by all nucleated cells. Therefore, mature RBC
(erythrocytes) no longer express MHC class I on their membranes. 30
31. Kennedy v. Collagen Corp. (1998)1
● PROCEDURAL HISTORY: Plaintiff alleges injuries sustained by defendant
(Collagen Corporation) and its employees for negligently injecting her Zyderm,
a substance made from the skin, tendons, and connective tissue of bovine
animals, for purposes of cosmetically curing her facial wrinkles. The claimed
side-effect is systemic lupus erythematosus (SLE), for what strict liability, breach
of express and implied warranty, battery, and conspiracy are incorporated in
this malpractice claim. Former two summary judgments, entered for defendant,
were based on insufficient expert testimony (a poor cause-effect relationship
affidavit) on part of plaintiff.
● HOLDING: The district court abused its discretion by improperly applying the
Daubert test, as it failed to consider relevant scientific evidence presented by
plaintiff's expert witness.
● JURISPRUDENCE: Daubert v. Merrell Dow Pharmaceuticals (1993) 2
● DISPOSITION: Judgment of the former court is reversed and remanded.
● REASONING: Daubert's court has established that the trial judge, in making
initial assessment as to the admission of evidence, must determine whether
the expert's testimony reflects (1) "scientific knowledge," and (2) will assist the
trier of fact to understand or determine a material fact at issue. This requires a
preliminary assessment of a number of factors.
1) 161 F. 3d 1226 - Court of Appeals, 9th Circuit 1998; 2) 509 US 579 - Supreme Court 1993
32. DISCLAIMERDISCLAIMER
This presentation does not constitute a medical or
legal advice. The burden for determining its
completeness, suitability or appropriateness for
intended use or purpose rests solely on the reader
accessing this information.
The author declares no commercial, strategic, or
financial interest or trusteeship with the names of
entities either used or omitted.
32