intro to immunology

what is a pathogen? what are opportunistic pathogens?
any organism that has the potential to cause disease. microbes that cause disease if they get into the wrong place or cause disease if the body’s defenses are weakened
what things is the immune system involved in besides infectious processes?
transplantation immunity/rejection, autoimmune disorders, (lupus, RA), hypersensitivites such as allergies, contact dermatitis, and possibly tumors
what are some lymphocytes? how are they nucleated?
B, T lymphocytes and NK cells. these are all mononuclear cells.
what are some granulocytes, what is another name for these?
neutrophils, basophils, eosinophils. they are also referred to as polymorphonuclear leukocytes, (PMNs).
what are some mononuclear phagocytes?
neutrophils/eosinophils called macrophages, (if in tissue), monocytes, (if in blood), and dendritic cells, (serve as the best bridge between the innate and aquired immune response)
what are some general molecules, (not cells), that are part of the immune system?
antibodies, (structurally immunoglobulins, antibodies is a functional term as they are secreted products of B lymphocytes in response to a stimulus like antigen), cytokines, (proteins secreted from one cell that influence function of the cell that produced it or other cells, hormone-like) and complements, (proteolytic cascade involved in clearance of many different types of pathogens from the body, effector mechanism, they play immuno-regulatory roles)
what is another name for NK cells?
large granular lymphocyte
what cells secrete antibodies?
B cells
what cells secrete cytokines?
T cells, NK cells, macronuclear phagocytes
what cells secrete complements?
macronuclear phagocytes
what cells secrete inflammatory molecules?
basophils, mast cells, and platelets
what do tissue cells secrete in terms of immune response?
interferons, cytokines
what are PMNs?
polymorphonucler lymphocytes, (as opposed to macronuclear phagocytes). neutrophils, eosinophils, basophils. thes are also called granulocytes.
what cells do all the blood cells involved in immune system originally derive from?
the hematopoietic stem cell
what 3 kinds of progenitor cells come from the hematopoietic stem cell?
the common lymphoid progenitor, common myeloid progenitor, and the common erythroid megakaryocyte progenitor
what does the common lymphoid progenitor give rise to?
B cells, (become plasma cells), T cells, (become effector T cells), and NK cells
what does the common myeloid progenitor give rise to?
the common granulocyte progenitor, the monocyte, (which further gives rise to dentritic cells+macrophages), and mast cells
what does the common granulocyte progenitor give rise to?
neutrophil, eosinophil, basophil
what does the common erythroid megakaryocyte progenitor cell give rise to?
the megakaryocyte, which gives rise to platelets, and erythroblasts, (become RBCs)
what proportion of leukocytes in the blood do neutrophils compose?
what proportion of leukocytes in the blood do eosinophils compose?
1-6% unless parasitic infection or major allergic rxn
what proportion of leukocytes in the blood do basophils compose?
<1% mostly unknown function
what proportion of leukocytes in the blood do monocytes compose?
2-10% (monocytes = mononuclear phagocytes that live in the blood)
what proportion of leukocytes in the blood do lymphocytes compose?
20-50% largely T+B cells, (a small %, ~10 of these are NK cells or large granular lymphocytes)
where do B lymphocytes come from? what is a key function?
b cells come from Bone marrow, they are key players in the (humoral) adaptive immunity
where do T lymphocytes come from? what is a key function?
t cells come from the thymus, they are key players in adaptive immunity, (humoral and CMI, cell mediated). “T cells do everything”
what do B+T cells look like in relation to NK cells?
B+T cells have only a little visible cytoplasm, while NK cells have much more cytoplasm and also have prominent granules, called LGLs
what do NK cells do? what else are they called? what kind of immunity do they mediate?
large granular lymphocytes, or NK cells are prominent cytoxic effectors of innate immunity, particularly with virally infected or tumor cells
what are the most prevalent of the PMNs?
what defines neutrophils in the body? what cell differentiation do neutrophils arise from? why are they called “neutro”phils? what kind of immunity do they mediate?
they are the most prevalent and lethal of the PMNs. they arise from myeloid differentiation. they are important elements of innate immunity. and have prominent “neutral” cytoplasmic granules, (don’t really stain).
what do neutrophils do? what is a common target for their action?
they can capture, engulf and kill microorganisms via reactive substances that kill and enhance inflammation. they form “pus”, (dead+alive neutrophils, dead bacteria). they commonly target bacteria.
why are neutrophils considered polymorphonuclear?
they have irregularly shaped and multi-lobed nuclei, (look like beads on a string)
how quickly can neutrophils be activated?
they can be rapidly mobilized to enter sites of infection. they are the prominent element of an acute inflammatory reaction.
can neutrophils work in anerobic environments?
what is eosinophila indicative of?
allergic rxn or parasitic infection, (such as hemlminth/intestinal parasite)
why are eosinophils named that?
they stain w/eosin, which appears red on an H+E and covers the nucleus which does look like a PMN
how do basophils appear? what is their relative prevalence in the blood? what is known about their function?
they stain with hematoxylin, (appear bluish purple). they are the least abundant of the granulocytes, and little is known about their function.
what are monocytes? what is their size relative to granulocytes? how does their nucleus appear? what are they progenitors of?
they are mononuclear phagocytes that circulate in the blood. they are bigger than granulocytes. their nucleus is distinctively indented, (not like PMNs that appear like “beads on a string”). they are progenitors of the sedentary tissue macrophage.
what are macrophages? how are they named?
macrophages are mononuclear phagocytes that are tissue bound. they are named for the tissue they are differentiated to inhabit. ex: kupfer cells in the liver, langerhans cells in the skin.
how long do macrophages last? what is their appearance characterized by?
they are long lived. they are irregularly shaped cells with extensive cytoplasm and numerous vacuoles.
what do macrophages do generally?
they act as general scavengers that dispose of dead cells and debris via phagocytosis.
what are the specific functions of macrophages concerning the immune system? how do they regulate other cells in the immune system? what is their role concerning innate or aquired immunity?
macrophages process and present antigens to T cells. they express both class I+II MHC, (molecules encoded by the Major Histocompatibility Complex -> members of the immunoglobulin superfamily). they secrete cytokines that regulate other cell types, (neutrophils/other leukocytes), and bridge between innate and aquired immunity, (not as well as dendritic cells)
what is the difference between macrophages and dendritic cells?
dendritic cells have a unique function in initatation of adaptive function in immune responses via picking up antigens in infected tissue and moving them to lymphoid tissue, (T cells). macrophages can’t do this b/c they are stationary.
what differentiation do dendritic cells arise from? what is their morphology?
dendritic cells arise from myeloid differentiation. they have a distinctive star shape, (they are the “stars” of the macrophage monocyte cell)
what is an antibody? where do they come from? what do they do?
an immunoglobulin protein that binds specifically to an antigen. they are produced by plasma cells, (terminally differentiated B cells), IN RESPONSE to infection/immunization. they bind to and neutralize pathogens, (bind to active site/attachment structure), or prepare them for destruction by phagocytes/by complement.
what are cytokines? where do they come from? what do they do?
soluble, hormone-like molecules secreted by immune system cells in a very tightly regulated system, (both cytokine+receptor production). cytokines act on cells by binding to specific receptors and influencing proliferation or activation of a particular function.
what are the 3 major functions of the complement system?
recruitment of inflammatory cells, opsonization of pathogens, (facilitating uptake and killing of pathogens), and perforation of cell membranes
what are the 3 pathways complement that result in complement activation?
the major, (and last), is the classical pathway, alternative, and lectin pathway
what are the two types of immune response?
innate, (natural), and acquired, (specific+adaptive)
what defines the recognition mechanisms of innate immunity?
a fixed rapid response, (within hours), a limited number of specificities, and constant efficacy during response. its effects encompass the time you feel “crappy” when sick.
what defines the recognition mechanisms of aquired immunity?
variable slow response, with numerous highly selective specificities, and it’s efficacy improves during response. it’s effects encompass the time you start to feel better while still sick.
are innate defense mechanisms present prior to pathogen exposure?
are natural immune responses more evolutionarily more primitive?
does innate immunity have memory?
what important role does innate immunity play in defense against microbes?
stimulating adaptive or specific immune response
which is usually more responsible for resolving infections, innate or adaptive?
how long does specific immunity’s memory usually last?
long, sometimes life-long
what are 3 main elements of innate immunity?
mechanical, chemical, and microbiological
what are examples of mechanical innate immunity in the skin, GI, respiratory tract, urogenital tract, and eyes?
overall:epithelial tight junctions. skin:fluid flow, perspiration, skin sloughing GI:fluid flow, mucus, food, saliva RT: flow of fluid/mucus, cilia action+airflow UI:flow of fluid, urine, mucus, sperm eyes:flow of fluid/tears
what are examples of chemical innate immunity in the skin, GI, respiratory tract, urogenital tract, and eyes?
skin:sebum+lactic acid GI:acidity+enzymes RT:lysozyme in nasal secretions UI:vaginal acid, spermine/zinc in sperm eyes:lysozyme in tears
what are examples of microbiological innate immunity in the skin, GI, respiratory tract, urogenital tract, and eyes?
overall:antimicrobial peptides, (defensins). skin:normal flora of the skin GI:normal flora of GI RT:normal flora of RT UI:normal flora of UI eyes:normal flora of eyes
how can antibiotics lead to infections by worse microbial infections?
the colon is colonized by a large number of commensal bacteria and if antibiotics kill enough of them, pathogenic bacteria, (like c dif), gain a foothold and produce toxins that cause mucosal injury, leading to leakage of RBC/WBCs into gut between injured epithelial cells
why do smokers get more RT infections?
their cilia are burned off
what is fever direct result of in terms of the innate immune response? why is it enacted?
fever is a systemic effect of proinflammatory cytokines that act as endogenous pyrogens. bacteria/viruses don’t grow as well at higher temps, but the immune system works better at higher temps. examples of cytokines often involved with fevers: IL-1, Il-6, and TNF-alpha, which act on the hypothalamus (Il = interleukin)
beyond the immune system, what other tissues do cytokines act on? what do they do in terms of metabolic processes? bacterial/viral replication? antigen processing? immune process efficacy?
vascular endothelium, (P selectin), hypothalamus, muscle and fat. they alter metabolic processes to generate heat, decrease bacterial/viral replication, alter leukocyte/lymphocyte migration patterns, enhance antigen processing, and cause specific immune processes to become more potent.
what are cytokines: IL-1, Il-6, and TNF-alpha called collectively?
proinflammatory cytokines
what are the major cellular elements of natural immunity
phagocytes, (mononuclear phagocytes or neutrophils)
how do phagocytes recognize pathogens? do they have antigen receptors?
phagocytes do not have antigen receptors like lymphocytes, but they do recognize pathogen-associated molecular patterns, (PAMPs)
how does direct recognition of pathogens by phagocytes work?
direct recognition involves surface receptors on the phagocyte surface that interact directly with the pathogen such as toll-like receptors, mannose receptors, (which are C-type lectins), and scavenger receptors, (these recognize and mediate uptake of microbes into phagocytes, but can play pathologic role in generation of cholesterol-laden foam cells in atherosclerosis)
how does indirect recognition of pathogens by phagocytes work?
indirect recognition involves phagocytic binding to host proteins that have bound to the pathogen such as antibodies, (via phagocytic Fc receptor), complement, (via phagocytic C3b receptor), +others. these function as opsonins.
what does PAMP stand for? what does a phagocyte use to recognize these?
pathogen associated molecular patterns. phagocytes have PRRs, phagocyte recognition receptors.
what do PRRs on pathogens do?
some pattern recognition receptors signal the prescence of infection and lead to activation of pro-inflammatory signaling pathways/changes in gene transcription
why would genes for MHC and CD80/86 be induced in phagocytes upon stimulation of PRRs?
these gene products regulate adaptive immune responses, MHC is important for presentation of antigen to T cells, and CD80/86 is an important costimulatory molecule for T cells
why would genes for lysozyme be induced in phagocytes upon stimulation of PRRs?
in order to enact direct anti-microbial activity
why would genes for inflammatory cytokines/chemokines be induced in phagocytes upon stimulation of PRRs? which ones might be induced specifically?
genes for cytokines TNF-alpha, IL-1 and IL-8, a chemokine help prepare the body to fight off an infection
what are two results of some PRRs recognizing PAMPs and mediating uptake of microbes into the phagocyte?
their delivery into lysosomal compartments will lead to death of the microbe and antigen processing/presentation to the T cells, (macrophages and dendritic cells)
what are toll-like receptors? when are they important? what happens if the gene for these is mutated? are there several kinds?
a kind of PRR named for a transmembrane protein in flies. these are important during embryogenesis. mutations in the gene for this lead to high susceptibility to infection, (via gram+ bacteria or fungus). there are at least 11 kinds of TLR in mammals
where are TLRs, (toll-like receptors) expressed?
TLRs are expressed more on macrophages, dendritic cells, NK cells, neutrophils, mucosal epithelium, and endothelial cells
what does TLR4 recognize? is binding direct?
TLR4 recognizes bacterial lipopolysaccaride, (LPS), on gram negative bacteria. binding is indirect.
what does TLR6 recognize?
CpG DNA on bacteria/protozoans
what does TLR5 recognize?
flagellin, found on various bacteria
what does TLR3 recognize?
double stranded RNA, something eukaryotic cells don’t have, but viruses do
what do TLRs recognize generally?
anything found on pathogenic prokaryotes that is not found in/on normal eukaryotic cells
what are the 2 main mechanisms for recruitment of leukocytes to the site of infection? do these overlap? is this a function of innate or aquire immunity?
binding adhesion molecules on epithelia and chemoattractants produced in response to infection, these do overlap, (chemokines upregulate adhesion molecules). this is a function of innate immunity
what is recruitment in terms of leukocyte response?
recruitment is a mult-step process involving the adherence of circulating leukocytes to the luminal surface of the endothelium and migration through the vessel wall.
what does recruitment of leukocytes involve in terms of selectins? chemokines?
recruitment of leukocytes includes selectin-mediated rolling of leukocytes in response to endothelium upregulation of P+E selectins in response to microbial infection, (cytokines IL-1 and TNF help bring selectins to the surface). chemokines increase the affinity of leukocyte integrins for selectins, which leads to stable binding.
what is transmigration?
when the leukocyte can break through a hole in the endothelial wall
how does phagocytosis of microbes occur?
the microbe binds to the phagocyte via a mannose receptor, and more receptors bind as the phagocyte “zips” engulfs it, creating a phagosome that is met with a lysozyme filled with destructive enzymes. the microbes can also be killed with ROS and NO
what makes the process of phagocytosis more efficient? what is the killing mechanism largely dependent on?
release of cytokine: IFN-gamma, (interferon), activates the macrophage/neutrophil and increases it’s efficacy. killing of the microbe occurs largely through oxygen-dependent mechanisms, including production of ROS intermediates
why are sites where macrophages/neutrophils are working sometimes even more inflamed?
b/c of their “sloppy” release of microbe-targeted ROSs
what are O2-dependend mechanisms that macrophages and neutrophils use in destruction of microbes? what about mechanisms that facilitated degradation after killing?
lysozyme, lactoferrin, major basic protein. acid hydrolases are used to facilitate degradation after killing. O2 is required for all these mechanisms