Innate immunity (Bowden) Flashcards
Which type of immunity will recognize molecular patterns and which recognize microbial molecules such as antigens
innate- molecular patterns.
Adaptive- specific antigens on microbes
Describe the difference of where the R originate from in innate vs adaptive immunity
innate- germline- limited diversity
encoded by genes produced by somatic recombination of gene segments- greater diversity
Describe the distribution of R in innate and adaptive immunity
innate- nonclonal, identical R on all cells of same lineage
adaptive- clonal, clones of lymphocytes with distinct specificities and R
Which type of immunity can discriminate between self and non self
both
What does IL-3 convert a pluripotent stem cell into
myeloid and lymphoid progenitors
What is IL-7 role in hematopoiesis
commitment to lymphoid lineages (B and T cells), made by BM stromal cells,
What converts a myeloid progenitor cell NOT into a RBC
IL3, GM-CSF, IL1 and IL6
What commits myeloid to megakaryocyte
thrombopoietin and IL-11
what commits myeloid to eosinophil
IL-5
What commits granulocyte-monocyte CFU to neutrophil?
IL-3 GM-CSF and G-CSF
What commits granulocyte-monocyte CFU into monocyte?
IL-3, GM-CSF, M-CSF
What are PMNs
neutrophils, polymorphonucleated because the nucleus has 2-5 lobes
What are the R for neutrophils
IFNgamma, chemokines, TLRs, Complement, Mannose, scavenger, FcR IgG
What leukocyte is first at site of infection and what takes days
neutrophils- hours
macrophages-days
2 types of Macrophages
Inflammatory and Resident
What shape nucleus is in a macrophage
u shaped
R for macrophages
TLRs, Scavengers, N-formyl Met-Leu-Phe, Fc, Complement, Mannose, Integrins, IFNgamma and chemokines
What activates macrophages
phagocytosis, opsonization, ROS, iNOS, Cytokines, GF
What is the role of the N-formylmethionyl R on macrophages
Migration into tissues
What is the role of the mannose R onmacrophages
phagocytosis
What are the rolls of TLRs and Cytokine Rs on macrophages
ROS,iNOS,cytokines TNF and IL-12, Fibroblas growth factors, angiogenic factors, metalloproteinases
How do NK cells work on macrophages?
secrete IFN gamma which activates macrophages
How do macrophages work on NK cells?
secrete IL-12 to activate NK
What principal mediator of ADCC do NK activate
IgG Fc
inhibitory R of NK cells
class I MHC
How do NK cells get into cell to cause apoptosis
granzymes then perforins
What receptors are constitutively active on NK surface
activating and inhibitory
Two types of Mast cells
tissue and mucosal
What stimulates mast cells
direct injury, chemical alcohols, and certain antibiotics, cross linking of IgE R or by activated complement proteins
What is in the immediate release of mast cell granules
histamine, protesases, heparin, TNF
What is made in membrane derived lipid mediators over minutes in mast cells
PGs, leukotrienes,platelet activation factor(PAF)
what cytokines are produced in mast cells
IL- 1 IL3 IL4 IL5 IL6 IL8 and TNF
What causes the differentiation of eosinophils
IL5
What was the original purpose of eosinophils
multicellular parasites, now do everythign
Dendritic cells (APC)
pick up antigen for processing, long dendritic processes. bridge between innate and adaptive
2 types of APCs
conventional and plasmacytoid
Fucntions of epithelia
physical and chemical barrier, normal flora, specialized lymphocytes
functions of mucosal surfaces
removal of particles, rapid pH buffer, mucus/secretions, cilia, normal flora
Defensins characteristics
tiny aa sequences. + charged. widely distributed. B sheets and 6 di-S bonds
Defensins antimicrobial activities
Gram - and + bacteria, fungi(yeasts), parasites, viruses
What are defensins produced by?
neutrophils, lymphocytes, paneth cells, epithelial cells and keratinocytes
PAMPs
Pathogen-associated Molecular Patterns
recognition of microbes
Where PAMPs found
on molecules and structures on a variety of microbes but not self molecules. MAIs and Danger Signal
structures microbes need to survive and infect
LPS(OPS), mannose residues, dsRNA
What are DAMPs
Damage associated Molecular Patterns.
recognize necrosis
What is an example of a DAMP
Alamins
What do DAMPs cause
TLR signaling through NF-kB activation
Increased levels of DAMPs have been assoc with what type of disease?
inflammatory diseases like sepsis, arthritis, atherosclerosis, lupus, crohn’s, cancer
How do we recognize PAMPs and DAMPs? Where are these R encoded?
Pattern Recognition Receptors- germline encoded
What are the signaling pathways of TLRs
NFkB, AP1 IRF3 IRF5
What genes do TLRs upregulate
TNF, IL1b IL6 IL8 and IL12 and e selectin
What is the net result of activated TLR
increase in microbial activity and apoptosis, production of defensins, expression of co-stimulatory molecules
What are NOD Receptors and what do they bind to
Intracellular TLRs, recognize PAMPs no viruses and some bacteria
What is the general cascade of tLR
recruitment of adaptor proteins->recruitment and activation of protein kinases-> activation of transcription factors-> gene transcription and then expression of inflammatory cytokines, chemokines, e selectin etc
What cytokines are major pyrogens
TNF and IL1
primary role of chemokines
increase integrin affinity and chemotaxis
Where is IL12 produced and what does it cause
produced in dendritic cells and macrophages to act on NK and T cells to increase IFNgamma production.
cause T cells to differentiate into T helper cells
Type I IFNs where are they found. and what do they do
alpha:dendritic and macrophages. beta:fibroblasts Causes all cells to increase class I MHC expression and activates NK
Where is IL10 made what what are its affects
macrophages, dendritic cells, T cells inhibits IL12 production and reduces expression of class II MHC molecules
What does IL6 do and where is it produced
causes liver to produce acute phase proteins.
causes B cells to create many ab
made in macrophages endothelial cells and T cells
What does IL 15 do and where is it produced
causes proliferation of NK and T cells, produced by macrophages
Where is IL18 produced and what effect does it have
macrophages
targets: NK cells and T cells and IFNgamma production
What are the mechanisms of immune evasion
resistance to phagocytosis, resitance to ROS in phagocytes, resistance to complement activation, resistance to antimicrobial peptide antibiotics
3 key parts to acute inflammatory response
vasodilation, increased vascular permeability, emigration of leukocytes from bottom into the damaged area
what signaling molecules increase permeability
Histamine, bradykinin, C5a, leukotriene-B4, f-met-leu-phe, platelet-activating factor
What proteins are involved in inflammatory exudate (edema)
clotting proteins, fibrinolytic protein, complement system, kinin cascade
what is the kinin cascade in Edema
vasodilation, increase permeability of blood vessels and stimulates pain receptors
What molecules increase expression of P and E selectins
IL1 and TNF
how to P and E selectine recruit leukocytes
leukocytes bind, dettach and roll until they are slowed down and can react to chemokines. Reaction involves flattening and entering endothelium.
What receptor stops neutrophils from rolling away
ICAM1
What receptor stops macrophages from rolling away
VCAM1
3 possible outcomes of capillary damage
Chronic inflammation, fibrosis or resolution
Leukocyte Adhesion Deficiency LAD
Leukocytes cannot leave the vasculature to migrate to tissues during inflammation/infection
b2 chains of integrins or CD18 deficiency
LAD1 because little to no surface membrane expression of LFA1, Mac1 or gp150/95
what is the inheritance mode of LAD 1
autosomal recessive
Clinical presentation of LAD 1
delayed separation of the umbilical cord and omphalitis
recurrent bacterial infections of skin and mucosa
leukocytosis
periodontitis
impaired wound healing
absent pus formation
