M&I Week 1 Flashcards
Emerging Infectious Disease
An infectious disease that has newly appeared in a population or that has been known for some time but is rapidly increasing in incidence or geographic range
Endemic
A disease that is consistently found in a population at low prevalence
Epidemic
A disease that affects many people at the same time period and in the same region
Pandemic
A global epidemic
Pustule
A small pus-filled bump on the skin
Scab
A dry, rough protective crust that forms over a cut, wound, or pustule during healing
Vaccination
The induction of immunity to a pathogen by injection of a vaccine
Variolation
The deliberate introduction of a weakened form of smallpox (variola) virus into a healthy person in the hope to elicit protective immunity
Adhesin
Structure on the surface of bacteria that is utilized to bind a cellular receptor of the host
Capsule
Polysaccharide layer that surrounds the cell wall of many bacteria
Cell Wall
Rigid external covering of the cytoplasmic membrane
Colonoization
The act of establishing a colony or colonies
Endospore
A thick-walled spore formed in the bacterial cell (mother cell)
Envelope
The structures that form the surface of bacteria
Flagellum (flagella pl.)
Thin, filamentous appendage on cells composed of the protein flagellin, responsible for motility
Infection
Invasion by and multiplication of pathogenic microorganisms in a bodily part or tissue, which may produce subsequent tissue injury and progress to overt disease through a variety of cellular toxic mechanisms
Lipopolysaccharide (LPS)
Complex structures composed of sugars and fatty acids in the outer membrane of Gram-Negative bacteria
Outer Membrane Protein (OMP)
proteins in the outer membrane of Gram-Negative bacteria
Pathogen
A microorganism capable of causing disease
Pathogenicity
Ability of an organism to cause disease
Petidoglycan (or Murein)
Large polymer that provides the rigid structure of the bacterial cell wall, consisting of acetylglucosamine, acetylmuramic acid, and a tetrapeptide
Perplasmic Space
Space between the cytoplasmic and outer membrane Gram-Negative bacteria
Permease
Enzyme-like proteins in the cytoplasmic membrane that mediate nutrient transport
Pilus/Fimbria (Pili/Fimbriae pl.)
Surface appendages of certain bacteria composed of the protein pilin
Pleomorphic
Having different morphological forms within one species
Porin
Channel containing proteins in the outer membrane of Gram-Negative bacteria
Septum
A crosswall
Sporulation
The process of forming spores
Teichoic Acid
A polymer of ribitol phosphate and glycerol phosphate found in the cell walls of certain Gram-Positive bacteria
Virulence
Degree of pathology caused by an organism
Zoonosis
Disease of animals that can be transmitted to humans
Adaptive (Acquired or Specific) Immunity
The response of antigen-specific lymphocytes to antigen; it is generated by clonal selection and characterized by immunological memory
Antibody (or Immunoglobulin)
Protein produced by B cells that specifically binds with a particular substance or antigen
Antigen
A substance that can be recognized by the specific immune system, usually by antibodies
Cell-Mediated Immunity
Specific immunity mediated by T cells
CD (Cluster of Differentiation) Molecules
Cell surface molecules that are recognized by specific diagnostic antibodies. Often used as markers for specific subsets of cells. No known function for some. Often function as cell-cell interaction molecules, adhesion molecules, mediate signal transduction, etc.
CD3
A marker expressed by a T-cells and plays a critical role in T cell receptor signaling
CD4
Expressed by a subset of T lymphocytes called helper T cells that recognize peptide antigens presented by MHC class II molecules and influence the functions of other immune cells by producing cytokines
CD8
Expressed by a subset of T lymphocytes called cytotoxic T cells that recognize peptide antigens presented by MHC Class I molecules and directly kill virally infected or tumor cells
Chemotaxis
Movement of an organism in response to a chemical stimulus
Cytokines
Proteins produced by cells that affect the behavior of other cells
Interleukins
Cytokines produced by WBCs
Lymphokines
Cytokines produced by lymphocytes
Monokines
Cytokines produced by monocytes/macrophages
Interferons
Cytokines that can induce cells to resist viral replication
Chemokines
Small cytokines involved in the activation and migration of cells
Colony Stimulating Factors
Cytokines that regulate the production of leukocytes in bone marrow
Effector Lymphocyte
A lymphocyte that has been induced to differentiate into a form that is capable of mounting a specific immune response
Fc (Fragment Crystalline or Crystallizable)
Composed of the homodimer of the carboxy terminal portion of the heavy chains; fragment tends to aggregate and crystalize in solution. Fc portion of antibody differs and plays key role in eliciting the effector functions of antibodies, as it can interact with other components of the immune system
Humoral Immunity
Specific immunity mediated by antibodies
Immunoglobulin Fold or Motif
A protein motif that consists of two Beta-Pleated sheets held together with a disulfide bond, characteristic of antibodies and other proteins of the immunoglobulin superfamily
Discovery of Bacteria
Netherlands, 17th century, under a microscope witnessed “moving animals”
Development of Vaccinations
In the context of smallpox, 18th century, first disease to be eradicated altogether
Development of Antibiotics
Revolutionized treatment of infectious diseases, staphylococcal bacteria plated on petri dishes and on same plate grew mold (penicillin), which killed bacteria around it
What Impact Did Smallpox Have?
Epidemic in Europe led to selective immunity to smallpox. When Europeans emigrated, natives were introduced to smallpox and other diseases. Discovery of vaccination started with smallpox
Describe How Vaccination First Started With Smallpox?
Early forms were called variolation (blowing up the nose, poking in arm, etc.). Milking cows formed lesions/blisters on hand (cowpox), and resistance to smallpox was conferred. Edward Jenner took material out of lesion and scratched/injected it into arm. The would then variolate smallpox to see if subject was immune. First disease to become completely eradicated
Describe the HIV/AIDS Epidemic and How Vaccinations and Treatment Have Affected Different Rates?
Primarily 75%, and in eastern and southern Africa. Locations with extreme poverty more likely to have higher prevalence. Number of new infections started declining since 1995. Number of deaths have been decreasing, but number of individuals infected are increasing. Number of infected individuals on therapy also increasing. How? Therapeutics are allowing infected individuals to live longer.
Three types of infectious disease emergence and definitions?
Newly emerging (outbreaks, Zika); Reemerging (due to antibiotic resistance); Deliberately emerging (purposes of bioterrorism, particularly after 9/11, Anthrax, Category A, but also Category B and C exist
Factors and Explanations Involved in the Emergence of Diseases?
Production of Food (feed for poultry may contain antibiotics, which increase likelihood of these foods carrying salmonella); Transmission of Diseases (from other animals, Swine Flu, H1N1); Encroachment in Nature (animals can carry infectious diseases; Medical Interventions (can result in bacterial infection from improper or non-sterile tube placement, immune deficiencies due to chemotherapeutic agents, etc.)
Koch’s Postulates for Establishing a Causal Relationship Between Microoganism and Disease
1) Agent must be the direct cause of the disease as it appears naturally
2) Causal agent must be isolated in pure culture and specific characteristics determined
3) When host is injected with pure culture, characteristic symptoms of the disease myst be present
4) Causal agent must then be re-isolated and determined to be the same organism, usually by the same technique as before
Features of Prions
Disease causing protein is pathologic version of protein with function relatively unknown. Normal protein has alpha helices, where disease causing protein contains beta-pleated sheets and becomes resistant to proteolysis. Change can happen spontaneously (CJD), through genetic causes (fatal familial insomnia), or transmitted (mad cow disease, CES)
Viruses
Contain DNA or RNA and are recognized by the immune system. Encapsulated in protein capsule, sometimes has lipid bilayer. Enveloped have lipid bilayer and are sensitive to destruction in the environment
Bacteria
Prokaryotes
Differences Between Bacteria (Prokaryotes) and Eukaryotes?
Single (haploid) circular DNA, contains episomes/plasmids which can self-replicate (important for genetic engineering), do not have a nucleus or other cellular components, has one or two phospholipid bilayers and a cell wall. Protein synthesis is more efficient, transcription and translation occur at the same time, no introns. First amino acid is N-formyl-Met. Sigma factors bind DNA promoter and induce different genes. Polycistronic meaning multiple genes for multiple proteins with one single promoter
Different Shapes of Bacteria?
Spiral shaped are called spirilla, round are cocci, rod shaped are baccili. Can be a hybrid (bacilococci) or no shape (pleiomorphic). Other distinct shapes include diplococci (two balls); neisseriae (coffee-beaned shaped); tetrads (cocci in four); sarcinae (cocci in packets of 8, 16, or 32); steptococci (cocci in chains); micrococci and staphylococci (irregular clumps of balls); corynebacteria (palisades arrangement); streptomycetes (moldlike filamentous bacteria); vibrious (curved rods)
Flagella Function
Some bacteria have flagella, and strains with flagella are more likely to be pathogenic. Flagella is mad of flaggelin. For bacteria with multiple flagella, tend to bundle in counterclockwise and spread out of clockwise. In single flaggela, counterclockwise turn of left-handed helix = move forward, clockwise rotation = tumble
Pilla Structure and Function
Hollow structures made of pillin and can be used to transfer genetic information/plasmids via a sex pillus (conjugation) or adhere to cells
Gram-Positive
Thick layer of peptidoglycans above single phospholipid bilaer, bound by adherence proteins, have teichoic acids recognized by immune system, and if attached to lipids, lipteichoic acids
Gram-Negative
Has thin layer of peptidoglycans in between its inner and outer phospholipid bilayers. Also contains lipopolysaccharides, utilized for resistance, which are only seen in Gram Negative, and recognized by the immune system, associated with runaway infections (septic shock)
Peptidoglycans
N-Acetylglucosamine and N-Acetylmuramic Acid linked by short peptide chains
Sugar Capsule in Bacteria
Can protect bacteria (1) against drying, (2) prevent uptake by phagocytes, and (3) attack by the alternative complement pathway
Fungi Structure and Function
Rounded yeast cells or slender filamental hyphaae. Yeast typically divide by budding. Molds produce specialized reproductive structures called fruiting bodies, produce spores. Contain cell walls also, and can be recognized by the immune system. Lipid bilayers require sterols (ergosterol) and help direct treatment. Has layers of branched sugars (glucans) and mannoproteins, which can act as signals. B-1,3) glucan synthease can be targeted by anti-fungal theray. Chitin is the cells armor.
Thermal Dimorphism (Fungi)
Fungi can grow as rounded yeast cells at body temperature, but slender filamental hyphae (molds) at room temperature.
Protozoa
Single celled eukaryotes that lack a cell wall. Many have complex life cycles alternating between proliferative stages and dormant stages
Helminths
Parasitic worms, multicellular organisms with complex life cycles often alternating between sexual reproduction in the definite host and asexual multiplication in an intermediate host or vector. Roundworms (nematodes), Flukes (trematodes), and Tapeworms (cestodes)
Ectoparasites
Include various arthrpods such as insects (e.g lice, bedbugs, and fleas) and arachnids (e.g. ticks, mites, and spiders) which live on or in the skin. Arthropods can also serve as vectors for other pathogens. Disease vectors
Stages of Clinical Infection
Incubation: organism is replicating
Prodromal: fair amount of replication (start to not feel well, can be infectious before symptoms)
Period of Invasion: immune response
Convalescent Period: feeling better but can still remain infectious
Key Elements of An Infection Cycle
Infectious Agent, Reservoir, Portal of Exit, Transmission, Portal of Entry, Susceptible Host
Infectious Agent (Key Elements
Bacteria, Viruses, Fungi, Protozoa, Parasites, Prions
Reservoir (Key Elements)
Location where the agent normally lives and multiplies (including humans, animals, environment)
Portal of Exit (Key Elements)
The route by which the infectious agent leave the human host
Transmission (Key Elements)
from the natural reservoir to the host may occur either directly, via contact or via droplets, or indirectly (i.e airborne, vehicle borne, or vector borne)
Portal of Entry (Key Elements)
Manner by which the pathogen enters a susceptible host
Susceptible Host (Key Elements)
Susceptibility of the host depends on genetic or constitutional factors, specific immunity, and non-specific factors that influence infection
Principles of Innate Immunity
Low specificity, small diversity, no memory, does not rely on gene rearrangement, and present in invertabrates. Can recognize many different things such as LPS, DNA, proteoglycans, etc. Responds to pathogens in very similar ways. Has physical barriers such as skin and mucous membranes, but also complementary proteins which can attach to bacteria and kill them directly, or recruit other cells to come. Cytokines are produced to have regulatory effects. Phagocytes and NK cells are also a part of the innate immune system
Principles of the Adaptive/Acquired Immune System
Adapt to cells, highly specific, receptors on cells, recognize one particular component of a pathogen, large diversity, exhibits immunologic memory (where second response is larger and quicker), B cells and T cells generate millions of different receptors (gene rearrangement), only found in vertebrates. B cells are a source of antibodies and T cells. Receptors on these cells are similar but unique
Explain how the two immune systems (innate and adaptive) rely on each other?
Two systems are not exclusive and rely on each other. Adaptive immunity can only eliminate pathogens with the help of components from innate immunity system (activation of receptor on phagocyte)
Surface Epithelia (Innate)
Skin and mucosal tissue is the first line of defense; mechanical (tight junctions), chemical (short anti-microbial peptides called defensins); and microbiological (good bacteria) are barriers to infection
Complement System (Innate)
Plasma proteins that can attack and kill microbes in three different pathways, classical, alternative, and lectin binding. Recruitment of inflammatory cells, opsonization of pathogens, or killing of pathogens
Classical Pathway of Complement System
Antigen:Antibody complexes
Alternative Pathway of Complement System
Pathogen surfaces
Lectin Binding Pathway of Complement System
Lectin binding to pathogen surfaces
Phagocytes
Includes neutrophils, macrophages, and dendritic cells. Interact via pathogen associated molecular patterns (PAMPS) on the pathogen, and pattern recognition receptors (PRRs)
Neutrophils (Phagocytes)
Most abundant and kill pathogens
Macrophages (Phagocytes)
Killing machines that produce a lot of cytokines and clear up dead cells and debris
Dendritic Cells (Phagocytes)
Sentinels critically important for initiating adapative immune responses
Natural Killer Cells
Recognize and kill some virally-infected or tumor cells via conserved, non-specific receptors. Usually associated with a decreased MHC Class I expression. Recognize stressed host cells via innate receptors that bind with ligands whose expression is altered as compared with normal cells
Cytokines
Important innate cytokines include pro-inflammatory, anti-inflammatory, antiviral, and chemotactic cytokines
Other Innate Immunity Cells
Eosinophils, Basophils, and Mast Cells play critical roles in innate immune response against helminths and allergic responses to environmental antigens
Humoral Immunity
Mediated by antibodies or immunoglobulins (produced in B cells) that can be secreted and present in the fluid part of blood to bind antigens. Most effective dealing with extracellular versions of microorganisms. Can be transferred passively. Can be used for therapeutic purposes during infections or following exposure to venom
Cell Mediated Immunity
Mediated by T cells. Express T cell receptors that do not bind with intact antigen and are never secreted. Interact with processed form of protein antigens (short peptides) associated with host proteins, called major histocompatibility complex molecules, expressed at the surface of other cells. MHCI present antigen-derived peptides to CD8-expressive T-Cells (kill directly), where MHCII molecules present antigen-derived peptides to CD4-expressive T cells (secrete cytokines to recruit other cells (B-cells/Macrophages). Can be transferred passively through cells of the blood. Many issues with graft rejection
Cardinal Features of Humoral and Cell-Mediated Immune Response
Specificity, where receptors expressed by B and T lymphocytes are highly specific;
Diversity, where there is a large amount of structural variability in the receptors expressed by B and T cells, allowing them to recognize a virtually unlimited number of different antigens, generated by DNA rearrangement;
Memory, where exposure to the immune system to antigen enhances its ability to respond again to this antigen
Self-Limitation, where after elimination of the antigen, the immune response wanes down, caused by regulatory mechanisms of the immune system; and
Self/Non-self Discrimination, where the immune system is tolerant against self-antigens. Self tolerance is maintained by elimination or functional inactivation of lymphocytes. Abnormalities in this process can lead to autoimmune disease
Five Phases of an Acquired Immune Response
Recognition, where naive lymphocytes recognize the antigen for the first time, mediated by B and T cell receptors
Activation, where lymphocytes start to proliferate, and differentiate into functional effector cells
Effector, where elimination of antigen with the weapons produced by the lymphocytes occurs. Also involves components of the innate and immune system
Decline, where at the end of the immune response most of the progeny of the antigen-specific lymphocytes escapes death and differentiates into memory B and T cells. Memory lymphocytes respond more quickly and effectively to antigen than naive lymphocytes
Clonal Selection Hypothesis
A single progenitor cell gives rise to a large number of lymphocytes, each with a different specificity. Potentially self-reactive immature lymphocytes are removed by clonal deletion, leaving a pool of mature naive lymphocytes. Proliferation and differentiation of activated specific lymphocytes form a clone of effector cells
Clusters of Differentiation (CD) antigens
Cell surface molecules recognized by specific diagnostic antibodies. Used as markers for specific subsets of cells. No known functions for some
Cytokines, Interleukins (ILs), and More
Cytokines are the protein hormones of the immune system. Might be autocrine, paracrine, or endocrine. Works by interacting with specific receptors, for example IL1 recognized by IL1 receptor
Important Questions for Immunology
How does a particular immune factor or cell interact with other immune factors or cells, especially interactions between the innate and adaptive arms of the immune system? What would be the phenotype of a human or mouse lacking a particular immune factor or cell type? How could a particular immune factor or cell be targeted for immunotherapy of disease?
Lymphangitis
Inflammation of afferent lymphatic vessel
Lymphadenitis
Inflammation of a lymph node
Lymphadenopathy
Swollen lymph nodes (glands). Enlargement of a lymph node may be a sign of a distant infection or a more ominous sign of a lymphoma or the metastatic spread of a primary tumor to a metastatic location
Lymphadema
Noticeable accumulation of a lymph in a region (usually an extremity) when the outflow lymphatic pathways are congenitally absent or blocked or damaged during surgery
Lymphoma
A neoplastic growth and expansion of lymphocytes that cause enlargement of lymph nodes along regional lymphatic chains
Functions of the Lymphatic System (3)
Formation of lymph and its exit from tissue; immune defense; fat absorption
Formation of Lymph and Its Exit From Tissue (Function of Lymphatic System)
Endothelial cells in lymphatic vessels lack tight junctions. Overlapping endothelial junctions are anchored to filaments and when fluid increases in the tissue, the anchors pull open the gaps in the cells. Fluids, proteins, and particles gain access to the lumen of the lymphatic capillaries. Outflow can be obstructed
Immune Defense (Function of Lymphatic System)
If pathogens enter the body, they will be transported with the interstitial fluid and enter lymphatic capillaries. They will then enter the lymph nodes, preventing their systemic spread
Fat Absorption and Lacteals (Function of Lymphatic System)
Lacteals are highly absorptive lymphatic capillaries in the villi of the intestine. Takes up lipids and fat soluble vitamins. Lymphatic vessels converge into trunks, and these trunks become congested after eating a fatty meal. Lipophilic particles suspended in lymph are called chylomicrons. These trunks then drain the lymph into the chyle cistern.
Chylomicrons
Lipophilic particles suspended in lymph
Define the drainage regions that govern whether lymph returns to the bloodstream at either the right or left jugulovenous angle
Right arm, right chest, and right back drain into the right lymphatic duct and right venous angle, where everthing else goes through the thoracic duct and to the left venous angle
How do you plan to assess the specific anatomical sites where a primary tumor may have started
Sentinel node mapping. Can work backwards.
Superficial Lower Extremities Pathway
Lymph flows distal to proximal and must move upward against gravity, flows into inguinal lymph nodes which are divided into two groups
Vertical Inguinal Lymph Nodes
Receives lymph from lymphatic vessels and nodes positioned along the great saphenous vein which includes everything in the lower extremity except the lateral thigh
Horizontal Inguinal Lymph Nodes
Receives lymph draining downward from anterior abdominal wall below the umbilicus as well as from the hip, buttocks, perineum, and upper lateral thigh
Superficial Upper Extremities Pathway
Lymph also flows distal to proximal and medially, flows into the axilla
Superficial Anterior and Posterior Trunk Pathway
In anterior body wall, skin above umbilicus drains upward to the axilla. Cutaneous lymphatic capillaries drain to nodes on the same side (i.e right thorax drains to right axillary nodes)
Superficial and Deeper Lymphatic Drainage Patterns within Head and Neck
Head is encircled with a pericervical collar of lymph nodes that can be palpated if swollen, capillaries drain downward following venous return patterns and move into deep lymphatics to form a juggular lymphatic chain alongside the internal jugular vein. Dumps lymph into the right or left jugulovenous angle
Deep Lymphatic Drainage System
Located within the pelvic, abdominal and thoracic cavities, majority of lymph is shunted towards the chyle cistern (a collecting reservoir that is located deep within the abdominal region). Receives lymph from the inguinal nodes (external iliac chain which parallel the veins of the same name). Flow upward to the common iliac nodes and these form right and left lumbar trunks. Lymph continues upwards where it collects in the chyle cistern. Intestinal trunks also drain into chyle cistern
Thoracic Duct
Begins at the upper end of the chyle cistern at the L2 level. Passes posterior to the diaphragm, enters the thorax, passes upward, receives lymph vessels draining the left intercostal spaces, bends leftward at the T5 level and dumps chyle-containing lymph into the junction of the left subclavian and left internal juggular veins. Final common pathway for 3/4 of the lymphatic system
Predict the regional pattern of lymphatic flow through the groupings of axillary lymph nodes
Anterior (Pectoral), Posterior (Subscapular), and Lateral (Humeral) nodes drain into a central and then apical node. They then move to the subclavian node and then drain into the right (or left) venous angle
Devise a simple anatomical explanation of sentinel node mapping that is suitable for use with a patient
Lymphatic drainage has a high degree of non-predictability. Sentinel node mapping has become an increasingly used technique in the staging of (breast) cancer. If cancer cells have not metasticized to anterior nodes, the prognosis is much better than if there is a central group or apical group involvement. Often spares a women the risk of having lymph node dissection
Primitive Hematopoiesis
During fetal life, erythrocytes and leukocytes are formed in several organs before the differentiation of the bone marrow. “Yolk Sac Phase” of hematopoiesis begins int he third week of gestation. Formation of “blood islands” in the wall of the yolk sac. RBCs are nucleated and express embryonic globin chains
Definitive Hematopoiesis
Begins when hematopoietic centers appear in the liver and lymphoid tissues early in fetal development (~35-42 days). Hepatic phase, RBCs are non-nucleated and express fetal or adult globins. Liver is major blood forming organ in the fetus during the second trimester. Primarily making RBCs but some WBCS are made too. Bone marrow begins developing in bones by the second trimester. After birth, blood cells are derived from precursor cells and located in red bone marrow and lymphatic tissue
Red Bone Marrow
Active bone marrow, color is due to the presence of blood and blood forming cells. It is the type of marrow found in all newborns. Main function is to produce blood cells, but also to destroy worn out RBCs and storage of iron inside macrophages. As individuals age, red bone marrow decreases and is found primarily in the epiphyses or ends of long bongs and in flat bones
Yellow Bone Marrow
Non-active bone marrow, color is due to the presence of many adipocytes. Found primarily in medullary cavities of long bones in adults. It retains hematopoietic potential (and when necessary severe hypoxia or bleeding) it can revert to red bone marrow to resume hematopoiesis
Describe How Blood Cells Are Derived From Precursors int he Bone Marrow
Pluripotent stem cells are capable of producing all blood cell types, also capable of self-renewal. They form daughter cells with reduced potentiality (unipotential or bipotential progenitor cells. Two cell lineages, lymphoid and myeloid
Lymphoid Cells
Includes lymphocytes, including B Cells and T Cells and NK Cells; and dendritic cells
Myeloid Cells
Includes platelets and RBCs, mononuclear cells (monocytes/macrophages), and polymorphonuclear (granulocytes: neutrophils, eosinophils, and basophils; phagocytes, and mast cells); dendritic cells
Describe the Factors That Regulate Hematopoiesis
Primarily controlled by cytokines (colony stimulating factors, often induced during infection to promote the generation of WBCs)
Give an Example of Regulation of Hematopoiesis
Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF) promotes differentiation of granulocytes and monocytes. Cytokines such as GM-CSF can be administered to patients with failing immune systems (i.e due to chemotherapy following cancer or prior to bone marrow or stem cell transplantation)
Lymphocytes
Definitive cell type (effector) of the system, and key elements in immune response (B-Cells, T-Cells, and NK Cells). Majority (70%) are part of circulating pool and migrate back and forth between the circulation and the lymphoid tissue (immunocompetent cells). 30% are short lived, immature cells or are activated and destined for a particular tissue such as the CT underlying the epithelium of the GI and respiratory tracts
B Cells
Produced in the bone marrow, bear highly diverse receptors on their surface and secrete antibodies referred to as plasma cells
T Cells
Mature in Thymus gland, bear highly diverse receptors on their surface
NK Cells
Part of innate immune response and contributes to immunity against tumors and viruses
Myeloid Cells
WBCs consisting of granulocytes, mast cells, and monocytes/macrophages
Granulocytes
Relatively short lived, have oddly shaped nuclei often called polymorphonuclear leukocytes
Neutrophils
Most abdunant and have phagocytic properties with granules pink or neutral in color
Eosinophils
Have a role in defense against parasitic infections and contributes to allergic reactions, granules stain bright red or pink
Basophils
Have similar functions as mast cells, found primarily in circulating blood and their granules stain an intense blue/purple
Mast Cells
Reside in tissue, and are a main culprit in allergic reactions, contributes to immune response against parasites
Monocytes
Circulate in blood and when activated, differentiate into macrophages and migrate into tissues, where they are often called histiocytes
Macrophages
In the liver often called Kuppffer cells, those in the brain are referred to as microglia, and those in bone as osteoclasts
Dendritic Cells
Accessory cells critically important for the initiation of adaptive immune responses, most effective in activating naive T Cells, capable of phagocytosis and macropinocytosis. Bone marrow-derived, with subsets that originate from both the lymphoid and myeloid progenitors. Found in lymphoid and non-lymphoid tissues. Dendritic cells in skin are referred to as Langerhans Cells
Follicular Dendritic Cells
Not derived from the bone marrow, not related to conventional dendritic cells. Found within specialized lymphoid tissues, termed germinal centers of lymphoid nodules, are adept at capturing and displaying antigens at the cell surface, and are important for interacting with B cells to promote antibody responses
Central Lymphoid Organs
Include bone marrow and the thymus. B Cells originate in bone marrow, T Cells mature in thymus. After maturation, they enter the bloodstream and migrate to peripheral lymphoid organs
Peripheral Lymphoid Organs
Sites here antigens come into contact with B and T Cells of the Immune System
What 3 Characteristics Do All Lymphoid Organs Share?
(1) All have a means of collecting antigen and carrying it to the lymphoid microenvironment; (2) All have specialized vascular adapatations to recruit lymphocytes, especially lymphocytes from the blood; (3) All have distinct B and T cell zones
Describe the shape and character of the Thymus Gland?
Bi-lobed developed from the endoderm. Multipotent stem cells destined to become T cells migrate to the thymus. Lymphoid cells begin occupying spaces between the epithelial cells resulting in an “lymphoepithelial” organ of dual embryonic origin
How is the cortex and medulla of the thymus separated?
The thymus is surrounded by a dense CT capsule from which trabeculae extend penetrating through the gland, organizing it into a dense cortex and lighter medulla
Describe the Cortex of the Thymus
Contains small T lymphocytes which occupy spaces surrounded by epithelioreticular cells. Macrophages also present and are responsible for phagocytosis of T cells that do not become thymic educated
Describe the Medulla of the Thymus
Light inner portion of the thymus gland, also contains epithelioreticular cells and larger lymphocytes with paler-staining nuclei and more abundant cytoplasm
Hassall’s Corpuscles
Near terminal differentiation, the epithelioreticular cells form these, which are the characteristic histological feature of the thymus gland. Isolated masses of cells that exhibit flat nuclei, keratohyalin granules and intermediate filaments. The core often appears keratinized. Function is unknown , but increases with age
Describe the Vessels that Enter and Exit the Thymus
Both the capsule and trabeculae contain blood vessels and efferent lymphatic vessels and nerves. No afferent lymphatic vessels in the thymus gland. The Blood-Thymic barrier protects developing T Cells from exposure to antigens. As blood vessels pass from trabeculae into the substance of the thymus gland, it is ensheathed by epithelioreticular cells
Describe the Components of the Blood-Thymic Barrier
(1) Capillary endothelium; (2) Underlying thick basal lamina associated with the endothelium. Thickness makes these vessels impermeable to proteins preventing most circulating antigens from reaching the small T cells in the cortex; (3) Macrophages that will phagocytose any antigenic molecules that escape from the capillary lumen; (4) Basal lamina of the epithelioreticular cells; (5) Epithelioreticular cells that surround the capillary wall and provide further protection to developing T Cells
Lymph Nodules
Localize concentrations of lymphocytes, referred to as follicles; not encapsulated but easily defined
Describe the difference between primary and secondary nodules
Primary nodule contains small lymphocytes. A secondary nodule contains lymphocytes that have recognized an antigen and returned to the nodule to proliferate. Secondary nodules are identified by a stained or pale germinal center. Lighter staining is due to the presence of larger lymphocytes or lymphoblasts that have dispersed euchromatin. Macrophages also usually in abundance in the germinal centers. Surrounding the center is a corona or “mantle zone” of small lymphocytes. Secondary nodule indicates cascade of events has occurred
What is the Cascade of Events that a Secondary Nodule Indicates Has Happened
(1) Proliferation of lymphocytes; (2) Differentation into plasma cells; (3) antibody production
Mucosal-Associated Lymphoid Tissue (MALT), Gut-Associated Lymphoid Tissue (GALT)
When follicles are in association with mucosal epithelia or Peyer’s patches in the gut
Histological Features of Tonsils
Tonsils are incompletely encapsulated and consist of aggregates of lymphatic nodules that form a ring around the oropharynx. Three main types:
Palatine consists of diffuse lymphocytes and lymphoid nodules disposed under a stratified squamous epithelium because it projects to the lumen, Pharyngeal, and Lingual
Depict the Role of M Cells in Peyer’s Patches
M Cells are important for the intiation of an immune response, lined at the gut of the lumen with specialized epithelial cells called microfold or M cells. M Cells take up molecules and particles from the gut lumen by endocytosis or phagocytosis and then release the material at the basement cell membrane (transcytosis). Antigens may then be taken up by antigen-presenting cells, in particular dendritic cells in the Peyer’s patches
Distinguishing Structural Feature of Lymph Nodes
Small, bean-shpaed, encapsulated organs lying along the course of lymphatic vessels. Serve as lymph filters that collect and process antigens. Convex surface is where site of entrance for lymphatic vessels lie. Concave depression (hilum) is where arteries and nerves enter and veins and lymphatic vessels leave. Surrounded by a dense CT capsule. Directly underneath capsule are subcapsular and trabecular lymphatic sinuses. Remainder of organ is composed of reticular tissue filled with reticular cells, reticular fibers, lymphocytes (B and T Cells), macrophages, antigen-presenting cells, and plasma cells. Follicular cells are located in the germinal centers interdigitated between B cells
Describe the Structural Features of the Cortex of Lymph Nodes
Two regions: (a) a periphery where nodules, with or without germinal centers are located. Formed mainly of B cells embedded in a population of stromal cells. Germinal centers are of intense B cell proliferation organized around follicular dendritic cells. and (b) deeper paracortical region, without boundaries, heavily populated with T cells. Thymus dependent. High endothelial venules. Naive lymphocytes can leave blood stream and enter cortex by interacting with counter receptors expressed by high endothelial venules
Describe Structural Features of the Medulla of Lymph Nodes
Inner portion of lymph node, cords of cells separated by lymphatic or medullary sinuses. Connect to the trabecular lymphatic sinuses so that lymph moves from the periphery and percolates down towards the center of the node. Sinuses are lined by endothelium that is discontinuous where it faces the lymphatic parenchyma. Sinuses join at the hilum. Majority of lymphocytes in this region are B lymphocytes. Efferent vessels remove/take the lymph away, leaving the node through the hilar region on the concave surface of the node
Structure and Function of the Spleen
Largest accumulation of lymphoid tissue in the body and the only one where lymph is interposed with blood circulation. Plays a role in defense against foreign invaders that penetrate circulation, acts as a blood filter that removes damaged RBCs. Site of production of mature or activated lymphocytes, also site of RBC maturation. RBCs are groomed here and vacuoles or abnormal inclusions are removed from damaged RBCs to return them to normal
Supporting Tissue of the Spleen
Consists of a dense CT capsule that extends trabeculae into the tissue by dividing the pulp or parenchyma of the spleen into incomplete compartments. Trabeculae carry nerves and arteries into the splenic pulp (contains no lymphatic vessels). Few smooth muscle cells and myofibroblasts within the capsule and trabeculae. Contain contractile elements that help to discharge RBCs into the circulation. Reticular tissue containing reticular cells and fibers plus lymphoid cells and macrophages make up the remainder of the supporting tissue or stroma of the spleen
