Immunology Exam 3 Part 1 Flashcards
describe the barriers of the GI, lungs, and oral cavity
GI: simple columnar epithelium, microvilli, goblet cells
lungs: pseudostratified columnar epithelium, cilia, goblet cells
oral cavity: non-keratinized stratified squamous epithelium
what are the types of mucosa associated lymphoid tissues (MALTs)? are they primary or secondary lymphoid organs?
gut-associated
nasal associated
bronchus associated
secondary
describe gut associated lymphoid tissue
components: peyer’s patches, isolated lymphoid follicles
regional lymph nodes: mesenteric/iliac
describe nasal associated lymphoid tissue
components: tonsils, isolated lymphoid follicles
regional lymph nodes: cervical
describe bronchus associated lymphoid tissue
components: inducible in most species
regional lymph nodes: peribronchial/mediastinal
describe the function of M cells, goblet cells, and paneth cells in GI barrier
M cells facilitate transcytosis of antigens across enterocytes to present to immune cells
Goblet cells = mucins/mucous
paneth cells = antimicrobial proteins
most important anitbody for mucousal immunity
IgA
what is an inductive site vs an effector site
inductive site is a secondary lymphoid tissue where immune response is initiated (e.g. peyer’s patches (GALT), mesenteric lymph nodes, tonsils (NALT), BALT, peripheral lymph nodes)
effector sites are everywhere else (SI, LI, glands, bone marrow, cervix, inflamed non mucosal tissue)
what are the six types of antigen sampling methods
- paracellular transport across tight junctions
- apoptosis-dependent transfer
- antigen capture by transepithelial dendrites (TED)
- transcytosis (bulk & receptor mediated transport across M cells)
- FcRn-dependent transport
- uptake via goblet cells
what are involved in tolerance
anti-inflam cytokines like IL10 and TGF-beta
innate lymphocyte cells
Treg lymphocytes
IgA producing B cells
fibroblasts
what are involved in inflammation
proinflam cytoines like IL6 and IL1-beta
Th1, Th2, Th17
how is IgA transported to mucosal surfaces
- IgA J-chain binds to plgR on basolateral face of epithelial cell
- endocytosis of IgA
- transcytosis of IgA to apical face of epithelial cell
- release of IgA dimer at apical face
what are IgA effector mechanisms
-bind/neutralize pathogens/toxins on gut surface or internalized in endosomes
-export toxins/pathogens to apical surface while being secreted
-bind to Dectin-1 on M cell to allow transport of antigen to dendritic cell or any APC
describe the difference in serum IgA and mucosal IgA
serum IgA = pentamer
mucosal IgA = dimer
what are intraepithelial lymphocytes (IELs)? what are there effector mechanisms?
CD8+ cytotoxic T cells in the epithelial lining of the gut
- once virus infected mucousal epithelial cell, IELs will kill infected epithelial cell via perforin/granzymes and Fas-dependent pathways (apoptosis)
list the main effector mechanisms of mucosal immunity
memory T cells
natural effector/regulatory cells
mucins/mucous
IgA
antimicrobial peptides (AMPs)
distinctive microbiota
what is the difference between a mucosal and parenteral vaccine
parenteral - given elsewhere in the body other than mouth or alimentary canal, mainly systemic immunity
mucosal - given mouth/nasal cavity/alimentary canal; mucosal and systemic immunity
where do B cell originate in avians compared to mammals
Bursa not Bone Marrow
do birds have lymph nodes?
no lymph nodes, but build lymph node aggregates in areas of infection
what immunoglobulins do avians have
IgM, IgY, IgA
do NOT have IgD or IgE
how does the IgY chain in avians differ from IgG in mammals
IgY H-chain is longer, 5 domains, and no hinge region
what are heterophils?
avian equivalent to neutrophils
what are the differences in thrombocytes between mammals and avians
avian thrombocytes are phagocytic (reason why you do not what to drain abcesses)
do avian species have a simpler or more complex immune system? why?
simpler
lay eggs
how are the bursa in avians and thymus in mammals similar
both regress with sexual maturity
describe the difference in avian MHC complexes
minimal essential MHC
only 2 class I genes & 2 class IIbeta
usually only one is expressed making it harder to fight off intracellular pathogens
how to avian species generate antibodies compared to mammals
gene conversion
random recombination of pseudogene V sequences and rearranged sequences occur within bursa
what are avians primary lymphoid organs and function
Bursa - B cell production
Thymus - T cells
what are avian secondary lymphoid organs
spleen
harderian gland
cecal tonsils
peyer’s patches
meckel’s diverticulum
other (islet of lymphoid tissue or microbiota)
function of the harderian gland
IgA producing plasma cells, also some IgM and IgY
why is the spleen more critical in avians than mammals
site of progenitor B cell lymphopoiesis
site of interaction between lymphoid and nonlymphoid cells so due to avians lack of lymphatics, spleen is more critical
function of cecal tonsils
B and T cell production
function of peyer’s patches
B and T cell production
function of meckle’s diverticulum. what is it?
role unclear
remnant of yolk sac found 1/2way down small intestine
IgM producing B cells 2 weeks post hatch
IgA and IgY producing B/T cells 2-4 months post hatch
what is meant by seasonality?
what factors influence this?
energy-expensive processes (e.g. immune system) need to be timed appropriately to maximize fitness
factors: photoperiod, food, weather, temp, reproduction, growth, molting, migration, change in disease/parasite pressure
describe the immunity of invertebrates
rely exclusively on innate immune mechanism
describe invertebrates physical barriers
chitinous exoskeleton
antibacterial proteins
mucus
what are the 6 types of invertebrates innate immune defenses
phagocytosis
cytokines
protease cascade (melanin - wound healing)
TLR & other PRR
antimicrobial peptides (defensins, lectins, lysozymes)
RNA interference
how does invertebrate phagocytosis differ from mammals
- hemocytes and coelomyocytes as phagocytic cells rather than dendritic cells, macrophages, etc.
-cytokine-like (e.g. IL-1-like) molecules that activate phagocytic cells & promote phagocytosis
how do we know invertebrates have cytokine-like molecules
LPS stimulation of mollusk hemocytes resulted in the release of other mediators
function of Melanin in invertbrates
antibacterial properties (antimicrobial activity, wound healing, pigmentation)
what is Spatzle?
how does this differ from mammals?
protein ligand that indirectly activates TLR after pathogen recognition via PAMPS
mammals use direct recognition of pathogens with PAMPS
what is the dicer enzyme
degrades dsRNA into small fragments so they can bind to RISC complex
aids in the RNA interference mechanism to prevent viruses from replicating within infected cells
what adaptive immunity does an invertebrate have
Ig-like molecules, such as Dscam (down syndrome cell adhesion molecule) which has similar structure/function to Ab
- opsonization = enhances phagocytosis by hemocytes
what are the first vertebrates to utilize adaptive immune system
jawed fish
how do cyclostomes (jawless) immunity differ from mammals
innate?
adaptive?
innate
-antimicrobial proteins and complement factors
-monocyte-like cells & lymphocyte-like cells
adaptive
no recombination for antibodies or TCR, so they synthesize variable lymphocyte receptors (VLRs) by gene conversion (similar to birds) rather than Ab or TCR
(VLRA, VLRB, VLRC similar to mammalian TCR and BCR adaptive immunity)
describe jawed fish innate immunity
toll like receptors (TLR)
granulocytes, macrophages, lymphocytes, NK cells
lysozymes, lectins, defensins, APP, complement, eicosanoids, cytokines, chemokines
describe differences between jawed fish and mammalian immunity
NO bone marrow or lymph nodes
less diverse gene arrangement due to less gene segments
predominantly IgM (variable structures in diff species)
describe jawed fish adaptive (humoral) response
what cells does the thymus, kidney and spleen make
rely on complement mediated lysis, no opsonization
antibodies found in most tissues including egg yolk
response is seasonally dependent and affected by social interactions (similar to birds)
Thymus makes T cells
Kidney makes B cells
Spleen makes B
intestinal lymphoid tissue (hindgut) makes B cells
RAG recombinase for gene rearrangment
MHC I and II
why is graft rejection lower in cartilaginous fish than mammals
they have less diversity in their gene segments
describe key components of amphibian immune system
antimicorbiral peptides in skin
complement most efficient at low temps
Ab & TCR gene rearrangment
complex changes associated with individual growth impact immune development/function
urodele immune system
no bone marrow
do have thymus = T cells
kidney = B cells
red/white pulp not separate in spleen = B cells
monomeric IgM
slow graft rejection
memory at least 90 days
anuran immune system
bone marrow = B cells
thymus = T cells
lymphnode-like structures
circulating T and B cells
IgM
NK cells & cytotoxic-T cell-like
IgM and IgY most important (5 isotypes)
functional T cell receptors
MHC I and II
monotreme immune system
antimicrobial peptides/complement
gene rearrangment
spleen, thymus, GALT
NO lymph nodes, but do have lymphoid nodules
IgG predominates (8 isotypes)
unique IgO
marsupials immune system
what is unique about the opossum
antimicrobial peptides/complement
gene rearrangment
4 isotypes (IgM, IgG, IgE, IgA)
opossum has early 𝝁TCR chain expressed early provide protection during first few days of life
first species to produce IgG
monotremes
what is the purpose of fevers?
how do ectotherms achieve this?
vertebrates respond to antigens fast and more intensely at high temps
ectotherms “heat seek” because they are immunosuppressed/helper T cells sensitive at low temps
how does hibernation affect the immune system
hibernation = immunosuppressed
metabolic depression “torpor” when the body temp drops can affect blood leukocyte #, complement levels, phagocytosis, cytokine production, T cell proliferation and antibody synthesis
fasting can also affect immune function
Describe differences between the uterine environment and the environment an animal encounters after birth
Uterine environments are sterile whereas the environment an animal encounters after birth has increased risk of pathogens, but those help develop immunity
Compare times of gestation, development of lymphoid organs, and circulation of blood lymphocytes in different species
foals have the longest gestation, time for lymphoid organs to develop and time for blood lymphocytes to circulate, then calves, then puppies
List important components of the innate immune system of newborns
antimicrobial molecules (defensins, lactoferrin, surfactant proteins, lysozyme)
TLR
NK cells
neutrophils (weaker)
macrophages (gradually become better)
commensal organisms
Theorize why a Th2 response is favored in mammalian mothers during pregnancy
reduce risk for fetal rejections
Th2
- IL-4,5 for parasitic pathogens
- activates eosinophils and B cell switch to IgE or IgA
- dampens IFN-gamma
- immunosuppresses Th1 for less inflammatory responses which protects fetus from rejections
Diagram differences in four types of placenta and indicate how this affects transfer of antibodies to the fetus
- hemochorial placenta: humans/primates, maternal IgG direct transfer
- endotheliochorial placenta: dogs/cats, 5-10% of IgG direct transfer
- epitheliochorial placenta: horses/pigs, no transfer of Ig across placenta, dependent on colostrum
- synepitheliochorial placenta: ruminants, no transfer of Ig across placenta, dependent on colostrum
what is passive immunity
immune support from mother (antibodies, complement, lymphocytes) passed through placenta or colostrum
absorption of IgG protects against neonatal septicemia
Indicate how intestinal microflora effect functions of immune system
exposure to complex mix of PAMPS
DC present microbial antigen to CD4+ T cells
balance Th1 vs Th2
Describe differences in the neonate intestine that allow for absorption of colostrum
low protease activity
open gut for 6-8 hours postpartum
specialized enterocytes with FcRn receptors on brush border - bind Ig and transport them
when is permeability of enterocytes maximized for colostrum absorption
6-8 hours after birth, declines rapidly at 24 hours when specialized enterocytes are replaced by mature cells that increase digestion of proteins not absorption
List nutritional and immune components of colostrum
electrolytes, carbs, fats, proteins (80% protein = Ig)
IgG and IgA
complement
pro-inflam cytokines
lymphocytes
trypsin inhibitors
Define failure of passive transfer.
What is a common sign of failure of passive transfer?
what can this lead to?
failure of Ab to be passed to neonates
no protein in urine or serum
leads to infection
what maternal factors lead to failure of passive transfer?
colostrum quality
poor mothering
loss of colostrum before birth
poor health
parity (more than one offspring)
low pathogen exposure
what neonatal factors lead to failure of passive transfer?
premature birth
health of intestine (improper GI development)
failure to nurse
predominant Ig in cattle colostrum
IgG
predominant Ig in horses and pigs colostrum
IgG
predominant Ig in dogs colostrum
IgA
predominant Ig in cats colostrum
IgG
predominant Ig in primates colostrum
IgA
Know how to determine if a neonate has received adequate colostrum
- proteinuria - protein in urine due to immature glomerulus
- serum IgG assessment 18-24 hours after birth
- foals >800 adequate
- calves total protein 5.8-6.3 ideal
Indicate how to treat failure of passive transfer in neonates < 24 h old as compared to neonates > 24 h of age.
< 24hours - before gut closure, tubing w/ colostrum
> 24 hours - after gut closure, IV plasma administration
Discuss how maternal antibodies protect neonates and interfere with vaccination of neonates
protect neonates via transfer of IgA and IgG
can suppress neonates immune response and cause disease = infections or alloimmune conditions (autoimmune diseases)
interfere with vaccination of neonates because maternal Ab last 4-6 months (horses) and about 8 weeks (dogs) and will neutralize Ag and inhibit B cell response by masking Ag
in what order does immune cell development occur in the fetus
thymus first
then spleen, lymphnodes and bone marrow
what would high IgG at birth indicate
intrauterine infection
what is the importance of mucosal epithelial cells in mucosal immunity
turnover frequently
uptake nutrients
TLR & NOD receptors which stimulate production of antimicrobial peptides & proinflam cytokines
