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Immunology
the study of resistance to infection
430 BCE
observations of disease and immunity but no understanding as to why
1546
Girolamo Fracastore- basics of germ theory
Germ theory
idea that there are small microorganisms that are able to infect and make us sick
1807-1860s
growing evidence for germ theory in correlation with microscope development
late 1800’s
Koch’s postulates, identifying a microorganism as the causitive agent, early vaccinations (smallpox)
Kochs Postulates
isolate microorganism from disease host, infect healthy host, see if it causes the same disease, isolate the same microorganism
pathogens
causitive agents of a disease, some are opportunistic, a wide variety of types
late 1800s
identified many cellular and molecular components
bacteria
prokaryotic, unicellular, many extracellular, some intracellular
viruses
acellular, always intracellular (portion of life cycle)
fungi
eukaryotic, uni or multicellular, extracellular
parasites
many are helminths (worms), eukaryotic, multicellular, extracellular
protozoans
eukaryotic, uni or multicellular, extracellular
innate immunity
first and second line of defense, born with it, uses commonalities and patterns to recognize groups
innate immunity example
ability to recognize peptidoglycan in cell walls of bacteria is specific to bacteria but general to all bacteria
adaptive immunity
third line of defense, learned/developed after contact with pathogen
first line of defense
mostly physical barriers that can prevent pathogen entry
second line of defense
cells, chemicals, and processes that can immobilize or kill pathogens
humoral immunity
B lymphocytes recognize foreign antigens via B cell receptors, produce and release soluble versions (antibodies) which are released into the blood plasma
bcr’s
b cell receptors, used in adaptive immune response to recognize foreign antigens
antibody
membrane bound immunoglobulins which are secreted by b cells into the blood plasma, many types (IgG, etc) which many different effects
antigen
unique molecular shapes that can be recognized by your immune system
cell mediated immunity
t lymphocytes recognize foreign antigens using t cell receptors, need to have the antigen presented to them by antigen presenting cells using major histocompatibility complex, can differentiate into many different types of t cell effector cells
cytotoxic t cell
excrete chemicals to kill cells nearby
helper t cells
coordinate immune responses
helper t cell example
cytokines (chemical messengers)
tolerance
there is extreme diversity in molecules that the immune system can make and respond to, there are about 10^15-10^18 different molecules that the immune system could make
timeline of immune response
innate immune system works throughout infection, but especially in the first 24 hours, adaptive works 1-14 days
aspects of the first line of defense
integumentary system, respiratory tract, gastrointestinal tract, urogenital tract, microbial antagonism
skin as first line of defense
tightly packed cells, dry, acidic, secrete antimicrobial substances (fatty acids, lactic acid, defensins/peptides, lysozymes), dead cells shed regularly
mucosa as first line of defense
shed regularly (slough), mucous contains proteoglycans (protein and sugar), enzymes, and other glycoproteins which inhibit bacterial growth
microbial antagonism
microbiota compete with potential pathogens for resources
microbiota
collection of organisms which normally inhabit the body, typically do not cause disease (opportunistic pathogens are exception), are commensalistic or mutualistic, some aid in digestion
microbiota and immune development
during fetal development and after birth immune system quickly develops tolerance for these mutualistic and commensalistic species, helps secondary lymphoid tissues and mucosal barriers to develop, humans co evolved with many of these species so disruptions to this process can lead to issues such as inflammatory and autoimmune disease, allergies, diabetes, multiple sclerosis, cancer, and depression)
differentiation
cell becoming more specific, almost always a one way street, done by changing the patterns of gene expression
hematopoiesis
formation of blood cells, all differentiate from hematopoietic stem cells
hematopoietic stem cell
a common stem cell precursor which is found in bone marrow
hematopoietic stem cells split into
lymphoid or myeloid precursor
lymphoid precursor becomes
lymphocytes (b cells, t cells, nk cells)
myeloid precursor becomes
monocytes, granulocytes, megakaryocytes, erythroblasts
erythroblasts become
red blood cells (not leukocytes!)
mega karyocytes become
platelets (not leukocytes!)
granulocytes become
neutrophils, basophils, eosinophils, mast cells
granulocytes
grainy leukocytes, some are polymorphonuclear
monocytes become
macrophages, dendritic cells
leukocytes
white blood cells, nucleated, don’t carry hemoglobin
second line of defense
when pathogens breath the first line, the innate system works to limit and eliminate the infection, uses pathogen recognition (no antigen specific responses), pathogen destruction, and communicate (present) to adaptive system
pattern recognition
by soluble components of the complement system (ch 3), pattern recognition receptors detect pamps, perform phagocytosis (ch 2) and trigger inflammation
pamps
pathogen associated molecular patterns, used by pattern recognition receptors (prr’s)
inflammation
the release of inflammatory molecules or cytokines from innate immune cells, vasodilation and extravasantion, complement system proteins secreted, dendritic cells assist
vasodilation leads to
increased blood flow, decreased rate of blood flow, increased blood vessel permeability (edema)
extravasation
cells from inside blood vessel leave/exit during vasodilation, assisted by decreased blood flow rate, surface molecules triggered/expressed during inflammation, which act as anchors for monocytes and neutrophils
dendritic cells during inflammation
uptake pathogen specific antigens and migrate to secondary lymphoid tissues to interact with the adaptive immune system (eg spleen, lymph nodes, malts, galts)