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Who is the father of immunology?
Edward Jenner
What is the milkmaid observation?
dairymaids didn’t die from smallpox as much as other people
Who is Louis Pasteur
attenuated pathogens can be used to build immunity against normal pathogens
What did Louis Pasteur study?
Anthrax in sheep
How did Pasteur popularize immunology?
1885 boy bitten by rabid dog and treated with attenuated rabies virus
What is immunology?
is the study of the cells and tissues that mediate
immunity and the investigation of the genes and proteins
underlying their function.
What is immunity?
from the Latin, immunitas “to be exempt from”
What can the immune system be activated against?
foreign substances, altered self molecules/cells or unfortunately even unaltered “self” molecules/cells
What is homeostasis?
a natural state of balance of all organs and the nervous and circulatory systems
What is infection?
the attachment and entry of a pathogen into the host
What is an extracellular pathogen?
pathogens that do not need to enter cells to reproduce
What are examples of extracellular pathogens?
some bacteria, most parasites, fungi
What is an intracellular pathogen?
pathogens that must enter a host cell in order to reproduce (usually via subverting the host’s endogenous processes
What are examples of intracellular pathogens?
viruses, some bacteria, few parasites
What are the 2 mechanisms underlying the immune response?
Cell-mediated immunity and humoral immunity
What is cell-mediated immunity?
depends on the action of cells that destroy or remove unwanted material from the body.
What is humoral immunity?
depends on soluble molecules in the serum of the blood that could eliminate foreign entities
What is an example of humoral immunity?
antibodies
What is an example of both mechanisms of immune response working together?
leukocytes produce cytokines (a signaling molecule)
What are the two types of immune responses?
innate and adaptive
What triggers innate immunity?
recognition of PAMPs and DAMPs
What is a PAMP?
pathogen-associated molecular pattern - a molecular structure on the surfaces of pathogens or cells they have infected
What is a DAMP
damage-associated molecular pattern - host macromolecules that exist when cells are damaged or dying
What are PRMs?
pattern recognition molecules
What are PRMs’ functions?
host proteins expressed by innate leukocytes that recognize PAMPs and DAMPs
Describe memory associated with PRMs
there is no memory - speed and strength of reaction is exact same each time
How is the adaptive immune system triggered?
antigens bind to antigen receptors (with specific recognition)
Describe memory associated with antigen receptors
adaptive leukocytes have memory - speed and strength of adaptive response is increased upon subsequent exposures
What are central elements of innate immunity?
barrier defenses, complement activation, phagocytosis, pattern recognition, inflammation, and target cell lysis
What are barrier defenses?
anatomical (skin), physiological (tears, low pH of stomach acid, vaginal lactic acid)
What is complement activation?
a complex system of enzymes that circulates in the blood in an inactive state
What is phagocytosis?
sophisticated means of engulfing entities - involved in antigen presentation
What are phagocytes?
PRR cells (neutrophils, macrophages, and dendritic cells) that perform phagocytosis
What is pattern recognition?
relies on PRRs to recognize DAMPs and PAMPs
What is inflammation?
PRRs engaged →pro-inflammatory cytokines are produced → localized gathering of cells and molecules necessary to repair tissue damage and clear pathogens
What is target cell lysis?
when cancer cells and cells with intracellular pathogens express DAMPs/PAMPs → target cells are lysed
Which cells carry out target cell lysis?
neutrophils, macrophages, and natural killer cells
What cells are involved in adaptive immunity?
Lymphocytes (B and T cells)
What are characteristics of adaptive immune response?
specificity, division of labor, memory, diversity, tolerance
Specificity
antigen receptors on surfaces of T (TCR) and B (BCR) lymphocytes hinge on the presence of unique molecular shapes of individual pathogens
What types of pathogens do B cells fight and how?
extracellular - antibody mediated clearance
What types of pathogens do Tc cells fight and how?
intracellular - lysis of infected host cells → prevent spread
What types of pathogens do Th cells fight and how?
intracellular and extracellular - secrete cytokines for activation of B and Tc cells and stimulation of innate leukocytes
What is immunological memory?
Enhanced adaptive response mounted upon second and subsequent exposures to pathogens so that signs of clinical illness are mitigated or prevented
What is clonal selection?
only lymphocytes bearing receptors specific for a particular antigen are triggered to respond to a stimulus
What is diversity?
innate immune system has limited capacity for antigen recognition, but adaptive system is limitless
What is the main genetic mechanism that allows wide diversity of adaptive immunity’s response?
somatic recombination - single, random combination of gene segments created in each developing lymphocyte
What does diversity guarantee?
There will be at least one clone expressing a unique receptor sequence for every antigen encountered during host’s life span
What is tolerance?
dealing with lymphocytes and recognizing “self antigens”
What is central tolerance?
eliminates lymphocytes that recognize “self antigens” early in development
What is peripheral tolerance?
functionally silences any lymphocytes that recognize “self antigens” that escaped central tolerance
What is primary immunodeficiency?
an affected individual is born with a genetic defect that impairs his/her ability
to mount innate and/or adaptive immune responses
What is acquired immunodeficiency?
An external factor such as a nutritional imbalance or pathogen may cause the loss of an immune system component.
What is transplant rejection?
the normal attack of a healthy immune system on a foreign tissue transplant meant to preserve life
What is an autoimmune disease?
when the tolerance of an individual's adaptive immune response fails, self tissues are attacked
What is a hypersensitivity?
an immune response that is too strong or long. When an individual’s normal adaptive immune system responds inappropriately to an antigen that is generally harmless, the immune response is manifested clinically as an allergy
What is chronic inflammation?
normal regulation of the inflammatory response is lost and is conducive to the formation of tumors, heart disease or autoimmune diseases
What is hematopoiesis?
The generation of all red and white blood cells
What are hematopoietic stem cells (HSCs)?
multipotent stem cells that create 2 distinct lineages
What are the 2 lineages of cells that arise from HSCs?
myeloid and lymphoid
When are HSCs detected after conception?
3-4 weeks
Where are HSCs found in fetuses?
liver, tibia, femur
Where are HSCs found in adults
axial skeleton: sternum, ribs, vertabrae, pelvis, and skull
Which 3 types of cells are granulocytes in the myeloid lineage?
neutrophils, basophils, and eosinophils
What are granulocytes
they are cells with intracellular granules
What 2 types of cells do not possess granules and use other means to carry out their functions?
monocytes and macrophages
Which cells compose the innate immune system?
granulocytes, monocytes, mast cells, and macrophages
What are the most abundant leukocytes in circulation and constitute majority of cells activated during an inflammatory response?
neutrophils
How many neutrophils in an average adult
over 50 billion
How long is the life-span of a neutrophil?
1-2 days - require constant production by bone marrow
How quickly can neutrophils respond to chemokine gradients?
as early as 30 minutes
What are the functions of neutrophils?
phagocytosis (PRRs of neutrophils bind to DAMPs or PAMPs) → degranulation → pus
What are basophils named for?
dark blue color when stained with hematoxykin
What is the population of leukocytes in the body like?
Present in very low numbers (less than 1% of all leukocytes - reside primarily in blood)
What do basophil granules contain?
substances to sustain inflammatory response
What are the functions of basophils?
Mainly degranulation, some rare phagocytosis
What are eosinophils named for?
the red color the exhibit when dyed with acidic dyes like eosin
What do eosinophil granules contain
highly basic proteins and enzymes that can kill large parasites
Where do eosinophils reside?
connective tissues (4% of all leukocytes)
What is the function of an eosinophil?
degranulation
What are some of the largest cells in the blood circulation?
monocytes
What are the main functions of monocytes?
phagocytosis, secretion of cytokines that promote and regulate inflammation
What do monocytes do in their day to day lives?
patrol blood for 1 day then enter tissues where they can differentiate into macrophages or dendritic cells (DCs)
What cells are several times larger than monocytes?
macrophages
where do macrophages reside?
various tissues around the body
What are kupffer cells?
liver macrophages
What are osteoclasts?
bone macrophages
What are littoral cells?
macrophages in the spleen
How long do macrophages live?
2-4 months
what do macrophages do?
phagocytosis of pathogens and spent cells and secretion of cytokines
What are hperactivated cells?
activated T cells that secrete cytokines that give macrophages additional properties
Can macrophages activate naive T cells?
No
What types of cells are in the lymphoid lineage?
T, B, Natural Killer, and Dendritic cells
What do T and B cells use to recognize pathogens?
Cluster of Differentiation markers (cell surface proteins)
What is cross-reacting
an antigen may be recognized by more than 1 lymphocyte if the shape and property is similar
What can lead to lymphocyte priming?
binding of a specific antigen → activation of a lymphocyte → cell division
What happens after lymphocyte priming?
progeny cells → morphological and functional changes → lymphoblasts within 18-24 hours after antigen perception → effector cells (short lived) and memory cells (long-lived)
What are effector cells of B cells?
plasma cells - secrete antibodies
What are effector cells of Tc cells?
Cytotoxic T Cells (CTL) - target cell cytolysis and cytotoxic cytokine secretion
What are effector cells of Th cells?
effector Th cell - secretes copious cytokines supporting B and Tc responses