Lecture 1: Organization and Development of the Immune System Flashcards
Roles of the Immune System
Innate Immunity
- Patrol Barriers
- Respond to Injury and Trauma
- Inflamation
Adaptive Immunity
- Specific Response to Pathogen
- Immune Surveilance
- Autoimmunity
Patrol Barriers
- Skin
- Respiratory Track
- GI Track
- Urogenital Track
- Epithelium
Skin
- Langerhans cell
- Intraepithelial T cells
Langerhans Cell
Epidermal dendritic cells that can pick up antigen and present the antigen, migrating to lymph nodes wgere tge present the antigen to T cells
Respiratory Track
- Alveolar macrophages
- Organized lympoid nodules - these nodules are not permanent and can reform (small)
- Tonsils
GI Track
- Pyers patches
- Lymphoid nodules
- Lymphocytes
- Granulocytes
- Maccrophages
- Dendritic Cells in the lamina propria
- Intra-epithelial T-cells
Urogenital Track
- Macrophages
- Mast Cells
- Dendritic CElls
- Lymphocytes
- Plasma Cells
Epithelium
- Defensins
- Physical barriers - ex. tight junctions and desmosomes
- Junctional complexes
Respond to Specific Antigens or Pathogens
- Self vs Non- Self Recognition
- Infection
- The host must first survive long enogh to develop a specific response
- The host then develops highly specific mediators against the pathogen - immune effector cells: binds to the epitope of an antigen that it hasent seen before or been tolerized
- Generates long term immuntity to protect against reinfection
- Vaccination
Vaccination
When vaccinated the host generates long lived immune effector cells which generate long term memory for rapid response to re-exposure
Features of Innate Immunity
- Immediate to form
- Usually lasting a short period
- Not highly specific
- Involves phagocytosis
- Secrtion of pro-inflamitory cytokines
- Can develop into chronic inflamation if unregulated
Innate immune cells have pattern recognition receptors to classes of pathogens, recognixing repetative products of the microbe however does not provide protection against an individual microbe
Features of Adaptive Immunity
- Slower to form - taking days
- Lasts longer
- Specific for antigens of the challenfe
- Requires cytokines ore cell diferentiation
- Can yeild cell mediated or humoral specific immunity
- Can cause autoimmune disease if unregulated
The specific receptors of adaptive immunity are B cell receptors (Ig) and T cell recetors (TCR)
Cells Involved in Innate Immunity
- Macrophages
- Neutrophils
- Eosinophils
- Basophils
- Mast Cells
- Dendritic Cells
- NK Cells
- NK T Cells
- B1 B Cells
- Marginal Zone B Cells
Cells Involved in Adaptive Immunity
- T Cells
- B Cells
- Antigen Presenting Cells
Monocytes
Function: A mononuclear phagocytic leukocyte that circulates briefly in the blood before migrating into tissues where it becomes a macrophage or dendrtitic cell
Cell Type: Innate
Receptors: PRRs, TLRs, FC receptor
Tissue localization: Circulating in tissues
Cell Population Turnover: High turnover
Macrophages
Function: Phagocytosis, proinflamitory rcytokine release, and chemokine release, can activate T cells through antigenpresentation
Cell Type: Innate
Receptors: PRRs, TLRs
Tissue localization: Macrophages can be found circulating in the blood or localized in tissue (intestine, alveolar, microglia, osteoclasts, kupffer, histiocytes)
Cell Population Turnover: Long Lived
Neutrophils
Function: Phacocytosis, proinflamitory cytokine release, chemokines - generally the first cells to arrive at a site of inflamation
Cell Type: Innate
Receptors: PRRs, TLRs, IgG, IgM, Fc Receptor
Tissue localization: Produced by hematopoesis in the bone marrow where they are released into the peripherial blood and circulate before migrating into tisses
Cell Population Turnover: High turnover - lasting only a few days
Eosinophils
Function: Motile phogocytic cells that can release toxic granules, cytokines, and chemokines - involved in parasitic infection and allergic reaction
Cell Type: Innate
Receptors: PRRs, IgE
Tissue localization: Migrate from the blood into tissues (speciffically in the gut)
Cell Population Turnover: High turnover
Basophils
Function: Non phagocytic granulocytes that release cytotoxic granules, cytokines, and chemokines, playing a major role in the allergic response
Cell Type: Innate
Receptors: PRRs, IgE
Tissue localization: Circulating in the blood
Cell Population Turnover: High turnover
Mast Cells
Function: Release cytotoxic granules that contain histamine, cytokine and chemokine release, important in the development of allergies
Cell Type: Innate
Receptors: PRRs, IgE
Tissue localization: Formed in the bone marrow by hematopoesis and released into the blood as undifferentiated cells which do not differentate untill they enter the tissues
Cell Population Turnover: High turnover
Dendritic Cells
Function: Arise from monocytes and process antigen material and present it on the surface to other cells of the immmune system - act as messangers between the innate and the adaptive immune system
Cell Type: Innate
Receptors: PRRs, TLRs, and Fc Receptors
Tissue localization: Migrate from the bloodstream into tissues, moving through lymph to lymph nodes, and back into the blood stream - often found below the epithelium
Cell Population Turnover: Long lived
NK Cells
Function: Large granular lymphocytes that display cytotoxic activity agains tumor cells and cells infected with some viruses - cytotoxic contact and release of cytokines
Cell Type: Innate
Receptors: NK Receptors - recognized the reduction of MHC class 1 molecules or unsusual surface antigen on cells
Tissue localization: Made in the bone marrow, and found in the blood and liver
Cell Population Turnover: High turnover
NK T Cells
Function: Rapid response to antigen or TLR secreeting cytokines needed to support antibody production of B cells and expansion of cytotoxic T cells, can kill target cell
Cell Type: Innate
Receptors: NK receptors, TCR
Tissue localization: Develop in the bone marrow and migrate to the thymus, then circulate in the blood
Cell Population Turnover: High turnover
B1 B Cells
Function: Limited BCR repertoire, fast responder to specific antigen stimulus or TLR
Cell Type: Adaptive - innate like function
Receptors: BCR (Ig)
Tissue localization: Found mostly in the peritoneum
Cell Population Turnover: Long lived (exsists in adult but were made in fetal life)
B2 B Cells
Function: Mature B Cells (90%) Synthesis and display of membrane bound Immunoglobulin, which serve as a receptor for antibody
*When a naive B cell encounters antigen that matches its membrane bound antibody, the cell divides rapidly and its progeny diffentiate into plasma cells and memory B cells
Cell Type: Adaptive
Receptors: B Cell Receptor (Ig)
Tissue localization: Blood, spleen, lymph nodes
Cell Population Turnover: Long lived
Marginal Zone B Cells
Function: 1st responder, rapid response to antigen stimulus or TLR
Cell Type: Adaptive, but innate like function
Receptors: BCR, IgG
Tissue localization: Marginal zone of the spleen (where the red pulp meets the white pulp), near the entering blood
Cell Population Turnover: Long lived
CD 4 T Cells
Function: T helper cells, release T cell cytokines essential in B cell antibody class switching and in the activation and growth of cytotoxic T cells, and maximizing the bactericidal activity of phagocytes such as macrophages
Cell Type: Adaptive
Receptors: TCR recognizing MHC class 2
Tissue localization: Maturation occurs in the thymus
Cell Population Turnover: Long lived
CD8 T Cells
Function: Cytotoxic T cells, kills infected cells
Cell Type: Addaptive
Receptors: TCR recognizing MHC Class 1
Tissue localization: Maturation occurs within the thymus
Cell Population Turnover: Long lived
Antigen Presenting Cells
Dendritic cells, macrophages, B cells
Process antigen from invading pathogen and present it on the surface of the cell in the context of a MHC class 1 or class 2 molecule
Viruses: MHC class 1
Bacteria: MHC class 2
Lymphoid Immune Cells
- Established in lymphoid tissues in late fetal life, and after birth
- Relatively long lived - up to decades
- B Cells and T Cells
- Decreases with age
- Cells of the adaptive immine system
Myeloid Immune Cells
- High turnover throughout life
- Drawn from the blood to sights of injury
- High cheotaxic response
- Essential for defense against bacteria
- Bone marrow derived
- Cells of the innate immune system
Lymph
- Interstitial fluid derived from blood plasma that contains a variety of small and large molecules, lymphocytes, and other cells
- Circulates through the lymphatic vessels
- Becasue of the small diameter of cappilary vessles, osmotic pressure is high, causing fluid to leak out. The fluid is collected by the lymohatic and returned to the blood through the thoracic duct
Lymphatics
Thin walled vesseles through which the fluid and cells of the lymphatic system move through the lyph nodes and ultimately into the thoracic duct where it joins the bloodstream
Unidirectional flow into larger vessels, then ducts
Primary Lymphoid Organs
Organs in which lymphocyte precursors mature into antigenetically committed, immunocompetent cells.
- Bone Marrow - B Cell Maturation
- Thymus - T Cell Maturation
Secondary Lymphoid Organs
Organs in which matture ummuno competent lymphocytes encounter trapped antigens and are activated into effector cells
- Lymph Nodes
- Tonsil
- Apendix
- Pyer’s Patches
- Spleen (The spleen is not on the lympoid circut, and instead filters blood)
Lymphocytes
A mononuclear cell that mediates humoral or cell mediated immunity
- T Lymphocytes: a lymphocyte that matures in the thymus and exprexess a T-cell receptor that can bind antigen
- B Lymphocytes: a lymphocyte that matures in the bone marrow and expresses membrane bound antibody. After interacting with antigen it differentiates into antibody secreting plasma cells and memory cells
High Endothelial Venules
- An area of a cappilary venule that is composed of specialized cells with a cubodial shape that allows lymphocytes to migrate from the blood and enter various lympoid organ
- Lymphocytes bind to special adhesion molecules which allow for migration into the lymph node
- Antigenic stimulation can increase the migration of lymphocytes through the HEV 10 fold resulting in visible swelling of the node
Continuous Capilaries
The smallest of the bodies blood vessels that has an endothelial layer 1 cell thick which provide an uninterrupted lining, and only allow small molecules, like water and ions to diffuse through tight junctions
Discontinuous Capillaries
Large diameter, tortuous vessels. Discontinuous endothelial layer and basal lamina and macrophages outside vessel wall. Found in major exchange sites such as liver, spleen, and bone marrow.
Pathway of Lymph
- Lymphocytes are located into the lymphatic
- Lymph enters the afferent lymphatic which percolates under the capsule and through the cortex
- Lymph filters and flows through the medulla and exits the lymph node through the efferent lymphatic
Cells can also enther the lymph node through the High Endothelial Venule (HEV) at the T cell area where lymphocytes from the blood bind and are removed from the blood.
How do B and T Cells find their correct compartments once they exit the vlood or lymph into the lymph node?
B cells and T cells have specific receptors that respond to specific chemokines
B cells localizes to the B cell follicle due to CXCL13 chemokine located in the follicle
T cells localize to the T cell area due to CCL19/21 in the T cell area.
For the cells to leave their specialized areas, the receptors for the chemokine are downregulated and the cells can escape back into the blood through the thoracic duct
