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Times we want the immune system activated:
Infectious agents, tumors, dead/damaged cells
Times we DON’T want the immune system activated:
Harmless/innocuous substances, other body, own body
Definition of Immunity
A state of protection against foreign pathogens or substances
Hallmarks of adaptive immunity
Antigenic specificity, diversity of players, immunologic memory, self/non-self recognition
Clonal Selection
Stem cells in the bone marrow develop into mature B/T cells, then go to the peripheral lymphoid tissue. The B/T cell then recognizes and binds to an antigen, activating the cell
Clonal Expansion
The activated B/T cell proliferates, creating many more copies of itself. Those cells then differentiate into memory cells, plasma cells that create antibodies (from B cells), and helper and sometimes cytotoxic T cells (from T cells).
Antigen
The substance that interacts with an immune response- smallpox after a person has been infected with cowpox
Immunogen
A substance that triggers an immune response AND interacts with the immune response- Cowpox
Humoral Immunity
Adaptive, production of antibodies (B cells), effective against extracellular infections
Cell-mediated Immunity
Adaptive, production of helper T cells and (sometimes) cytotoxic T cells, effective against intracellular infections
Cells involved in Innate Immunity
Granulocytic (neutrophils, basophils, and eosinophils), Mononuclear cells (monocytes and macrophages), Lymphoid cells (Natural killer cells), mast cells, and dendritic cells.
Cells involved in Adaptive Immunity
T and B lymphocytes
Soluble Mediators in Innate Immunity
Complement proteins, and antimicrobial peptides
Soluble mediators in Adaptive Immunity
antibodies
What does innate immunity recognize?
Pathogen broad patterns (PAMPs)
What does adaptive immunity recognize?
Specific epitopes
How are receptor encoded in innate immunity?
Germline (inherited from parents)
How are receptors encoded in adaptive immunity?
Rearranged gene segmentsWh
What does innate immunity do in response to an antigen?
Engulf and destroy, reduce inflammation
What does adaptive immunity do in response to an antigen?
Produce antibodies, kill infected cells
Hematopoiesis
The formation and development of cellular components of blood (RBCs and WBCs).
Hematopoietic Stem Cells
All blood cells differentiate from these, and they can differentiate into more HSCs, Myeloid progenitor cells, or Lymphoid progenitor cells.
Location of hematopoiesis
Depends on the age/state of development of the individual, but is typically in the liver prenatally and in the bone marrow as an adult.
What increases the rate of hematopoiesis
Infections
What decreases the rate of hematopoiesis
antibiotics, steroids, immunosuppressants, and radiationCE
Cells that arise from myeloid progenitors
Neutrophils, basophils, eosinophils, monocytes, macrophages, mast cells and dendritic cells
Cells that arise from lymphoid progenitors
B lymphocytes, helper T cells, cytotoxic T cells and dendritic cells
Granulocytic cells
Neutrophils, basophils, eosinophils (all innate)
Mononuclear cells
Monocytes and macrophages (all innate)
Lymphoid cells
B lymphocytes, T lymphocytes and Natural Killer cells (all adaptive except for NK cells)
Neutrophil
Granulocytic, myeloid, innate, located in blood.
Phagocytic, has a multi-lobed nucleus, first to arrive at inflamed tissue, contains granules filled with degradative enzymes and antimicrobials to ingest and destroy captured cell.
Eosinophil
Granulocytic, myeloid, innate, located in blood.
Defends against helminths and other parasites that are too big for neutrophils to ingest, cytoplasmic granules are released when cells are activated
Basophils
Granulocytic, myeloid, innate, located in blood.
Same response as eosinophils (respond to parasites too big for neutrophils and release cytoplasmic granules upon activation), but also play a role in allergic responses bc histamines are present in they cytoplasmic granules.
Mast Cells
Myeloid, innate, located in skin, connective tissue, and mucosal epithelial tissue.
Differentiates in tissues, and has cytoplasmic granules filled with histamines and proteases. Protects internal surfaces from pathogens (especially parasitic worms), and plays an important role in allergies
Monocytes
Mononuclear, myeloid, innate, located in blood.
Phagocytic to some extent, but not nearly as much as macrophages and neutrophils. Migrates into tissues where they they differentiate into macrophages.
Macrophage
Mononuclear, myeloid, innate, located in almost all tissues
Extremely long lived (as opposed to neutrophils), phagocytic, antigen processing and presentation to T cells (serves as a bridge!). Able to clear dead cells and cell debris, as well as orchestrates immune responses to activate and recruit other immune cells.
Phagocytic Cells
Mostly neutrophils and macrophages, though monocytes too to a small extent.
Differ in location (neutrophils in blood, macrophages in tissues), life span (neutrophils are short-lived while macrophages are long-lived), and extra abilities (macrophages can scavenge dead cells from the body).
Dendritic Cells
Myeloid AND lymphoid, innate (bridge between innate and adaptive), and located under the skin, below mucosa, and in tissues- all areas likely to come in contact with the outside world.
Perform phagocytosis and pinocytosis (drinking lymph around them looking for pathogens), and are the most potent antigen-presenting cells for activating naive T cells.
B lymphocytes (B cells)
lymphoid cell, lymphoid progenitor, adaptive, mature in bone marrow but circulate in blood, lymph ad secondary lymphoid sites.
Have cell surface receptor for antigens, and differentiate into plasma cells (that secrete antibodies), and memory cells.
T lymphocytes
Lymphoid cell, lymphoid progenitor, adaptive, arise in bone marrow, mature in thymus, and circulate in blood, lymph, and secondary lymphoid sites.
Have cell surface receptors, and are divided into helper T cells (that display CD4 protein) and cytotoxic T cells (that display CD8 protein).
Helper T cells
Express CD4 protein on their surface along with their T cell receptors. Secrete cytokines that play roles in activating other immune cells
Cytotoxic T cells
Display CD8 protein on their surface along with their T cell receptors. Can directly lyse the target cell.
Natural killer cells
lymphoid, innate, blood
Nonspecifically cytotoxic against tumor cells and cells infected with viruses, even though they lack an Ag specific receptor. Can directly lyse the target cell just like cytotoxic t cells, only in a much less specific way.
What cells can originate from both myeloid and lymphoid?
Dendritic cells
What cell types play as a bridge between innate and adaptive immunity?
Dendritic cells and macrophages- both act as a professional antigen-presenting cell
What cells are not granulocytes but contain granules?
Natural killer cells and mast cells
What cells have antigen-specific receptors?
T lymphocytes and By lymphocytes
Which cells predominantly circulate in blood?
neutrophils (highest percentage), eosinophils, basophils, monocytes, natural killer cells, b and t lymphocytes
What cells are NOT circulated in blood?
mast cells, macrophages (tissues), and dendritic cells (tissues)
Which cells can be found in healthy tissue?
Mast cells, macrophages, and dendritic cells
What cells can be found in infected tissues?
Neutrophils (first responders), basophils, eosinophils, monocytes.
Anatomical Barriers
Skin and mucous membranes
Physiological Barriers
Fatty acids in sebum, acidic pH in stomach, lysozyme, lactoferrins, surfactant proteins, AMPs (defensins and cathelicidins), S-100 proteins
Skin
Tight epithelial cells, shedding of dead cells, dry salty acidic surface
Mucous membranes
Tight epithelium, sweeping cilia, mucus secretion, natural flushing by tears, urine, peristalsis in GI
Lysozyme
Found in tears, saliva, and mucosal secretions. Degrades peptidoglycan in cell walls without distinguishing between good and bad mcirobes
Lactoferrins
Found in milk, mucosal secretions in intestine, respiratory, and urigenital tract.
Binds to all the free iron in the body, slowing down the growth of the pathogen to let the immune system catch up
S-100 protein
Found in skin, and mucosal/glandular secretions.
Disrupts membranes, killing cells
Surfactant proteins
Found in secretions of the respiratory tract.
Coats bacterial cells, promoting recognition and phagocytosis
Defensins (an AMP)
Found in skin and mucosal epithelia.
Disrupts membranes of bacteria, fungi, protozoa, and disables viruses
Cathelicidins (an AMP)
Found in mucosal epithelia.
Disrupts membranes of only bacteria
AMPs and Complement Proteins
Function as booth immediate innate and early induced innate because they can be produced constitutively or in the presence of a pathogen.
Secreted by epithelial cells and stored in neutrophil granules