dont know (10) Flashcards
L1- cells of the innate immune system along with descriptions?
(PHAGOCYTE) monocytes- monocytes from the blood mature into macrophages in tissues. Required for phagocytosis, cytokine production, tissue homeostasis, bacterial. (P) Dendritic- Antigen uptake in the periphery for antigen presenting cells. needed for cytokine production (P) neutrophil- circulate in blood, migrate quickly in inflammation for phagocytosis + bacterial. (DEGRANULATING EFFECTOR CELL) basophil- anti parasitic and allergic reactions (DEC) mast cells- in tissues. release granules e.g: histamine. inflammation + allergy (DEC) eosinophils- kill AB coated parasites by secreting granules.
L1- organs of the immune system?
primary lymphoid organs: develop immature immune cells in the thymus and bone marrow. secondary lymphoid organs: where mature immune cells are exposed to antigens: lymph nodes (drain from tissue) + spleen (drain ag from blood), MALT (drain ag from gut). antigens are picked up by dendritic cells or carried in lymphatic fluid, to the secondary lymphoid organs. tertiary lymphoid organs: where IR occurs. SPLEEN: has B, T, macrophages. initiate innate and adaptive response. MALT: peyers patches, appendix, tonsils. gen of B cells producing igA AB ( good for viruses esp for mucosal infections) lymph nodes: site of maturation and differentiation of adaptive immune response.
L1- what cells would be involved in fighting off viruses vs helminths?
VIRUS: NK, Th, Dendritic, macrophages PARASITES: Eosinophils, Basophils, Mast cells, Th,B cells, ILCs. *B cells produce antibodies, particularly IgE, in response to helminths (parasitic worms). These antibodies bind to the parasites and help recruit immune cells like eosinophils and mast cells, which release toxic substances to kill or expel the parasite
L2- How does the skin, respiratory tract, GI, tears, sweat, saliva and microbiome prevent entry?
SKIN: dry, outer, protective layer. Hard for pathogens to penetrate. Fatty acid production inhibits microbes on the skin.
RESPIRATORY TRACT: cells are tightly joined. Tight junctions act as a physical barrier by sealing gaps between cells so pathogens cannot enter. Cillia clear debris. Mucus contains antimicrobial substances (AB and enzymes) to neutralise and destroy microbes. Trapped pathogens are moved by cillia towards the throat to be coughed out or swallowed.
GI: peristalsis. Moves trapped pathogens through the digestive system. Mechanical defense so pathogens cannot stick to the intestinal wall. Produces HCL so low PH to hydrolysed bacteria.
SWEAT,TEARS,SALIVA: contain lysozyme to destroy the bacterial cell wall.
MICROBIOME: microbial competition with pathogens for space and nutrients so prevent microbe growth.
L2- 2 examples of specific microbes?
SKIN- staphyllococcus aureus
GI TRACT- Lactobacilli: produce lactic acid for low PH and competes with bacteria
L2-examples of PRRs? AND TLR WITH LIGANDS
TOLL-LIKE RECEPTOR: present on immune cells like macrophages, dendritic cells, neutrophils, mast cells, some t cells and b cells. membrane-bound on csm and vesicular membranes.
COLLECTINS: proteins in solution. have a collagen-like region- interacts with effector parts of immune system and lectin region- binds to sugar molecules on surface of pathogen e.g: mannose by mannan-binding lectin.
THESE ARE EXTRACELLULAR PRRS
INTRACELLULAR: NOD-LIKE RECEPTORS, RIG- LIKE RECEPTORS CYTOSYLIC DNA SENSORS.
TLR-4: ligand= LPS (gram negative bacteria) on macrophages, mast cells, eosinophils, apc.
TLR-5: flagellin (bacteria)
TLR-9: DNA with methylated CPG (bacteria and herpes viruses)
TLR-3: double stranded RNA (viruses), poly 1:C
TLR-1: TLR-2 heterodimer and TLR-2: TLR-6 heterodimer: lipo mannans (mycobacteria), lipoproteins, lipoteichoic acid (gram positive bacteria), cell wall beta glucans in bacteria and fungi, zymosan.
L2- killing mechanisms?
REACTIVE O2 INTERMEDIATES (NEUTROPHILS): following phagocytosis there is an increase in o2 uptake called respiratory burst. NADPH oxidase assembles onto the phagocytic membrane. O2 is reduced by NADPH oxidase into toxic OH- radicals. Toxic Hypochlorite radicals are are rapidly converted to harmless compounds tp not harm the host. Causes DNA damage and alterations in bacterial membranes so bacteria are unable to replicate and cellular processes are disrupted.
MACROPHAGES: liver, lung, gi tract, spleen. long lived.
REACTIVE NITROGEN INTERMEDIATES: catalysed by inducible nitric oxide synthetase (INOS, NOS2) induced by cytokines and bacterial components. INOS is an enzyme that produces NO from L-arginine (L-arginine plus inos gives you no plus L-Citrulline). Inferion gamma (IFN-Y) upregulates INOS. IFN-Y is cytokine by T and NK cells that activate macrophages and promote adaptive immunity. bind to receptors on immune cells to increase INOS expression. causes DNA damage and alterations in bacterial membranes.
L2- What signals does the innate IS use to activate the adaptive immune system?
FIRST SIGNAL- presentation of an antigen (a peptide) on the surface of a pathogen bound to a MHC (major histocompatibility complex). Those peptides are generated from the degradation of those pathogens. MHC binds to TCR of a naive T cell.
COSTIMULATORY SIGNAL: Co stimulatory molecules are upregulated upon signalling by NF-KB- generated by recognition of the pathogen by a PRR. Forms a co stimulatory signal to convert the naive T cell to a effector T cell.
L15- cytokines vs hormones?
Cytokines are the way in which
the immune system
communicates.
Analogous to hormones of the immune
system.
Produced by a cell usually following a stimulus, travel and bind to a receptor on a target cell and elicit a immunological response.
Diverse group of small proteins (5-
25KDa).
Secreted by a wide range of cells, both
immune cells and non-immune cells
(epithelial cells secrete IL-1, IL-8, IL-6,
TGFb, Stromal cells of bone marrow
secrete growth factors).
Cytokines can be exquisitely sensitive:
* hormones circulate in nanomolar (10 -9 M)
concentrations and usually vary by less than
one order of magnitude.
* In contrast, cytokines (such as IL-6) circulate in
picomolar (10 -12 M) concentrations and can
increase up to 1,000-fold during trauma or
infection. great capacity for changing the magnitude of their response.
Hormones are secreted by specific glands!
Cytokines are secreted by MANY
DIFERENT cells
cytokine families?
Tend to be grouped either functionally or structurally:
interleukins e.g. IL-1, 2, 3… 36, also
includes erythropoietin (EPO) and thrombopoietin. have an alpha chain bundle structure?
inteferons: Structurally diverse and
grouped into type I: IFN a,b,(k,d,e,t) ,and type II: IFN-gamma. Tend to “interfere” with viral replication.
Chemokines: group of cytokines that direct
cell movement. 4 subfamilies classified by the arrangement of their cysteine bonds into CC, CXC, CX3C groups. Contain 2/4 cysteine residues in a conserved
Structural location.Chemokines are divided into four groups depending on the number of cysteines and their spacing (arrangement)
Colony stimulating factors (CSF): secreted
glycoproteins that act upon haematopoietic cells to regulate proliferation and differentiation, G-CSF, M-CSF, GM-CSF
Tumour necrosis Factors (TNF): Primarily
transmembrane, surface proteins. TNF-a, b but also CD40L, FASL, CD30L. bound to cell surface. cleaved and released upon infection.
Growth factors (GF): cytokines that direct
proliferation (and differentiation) e.g. TGF-β,
VEGF
L15- Functional Classification of
Cytokines
5 main groups
Immunoregulatory: IL-2, IFNg, TGFb, IL-4, IL-12, IL-15
Pro-inflammatory: TNFa, IL-1a, IL-6, IL-17, IL-23
Anti-inflammatory: IL-10, IL-1receptor antagonist, IL-4
Chemotactic: IL-8 (CXCL8), MCP-1 (CCL2),
RANTES (CCL5)
Haematopoietic: GM-CSF, M-CSF, IL-5, IL-3, IL-7
L8- antimicrobial peptides produced by neutrophils?
alpha-defensives/ human neutrophil peptides (HNPs), primarily HNP-1, HNP-2, HNP-3, and HNP-4.. present in azurophilic granules. Cationic (positively charged and) bind to negativley charged lipid membrane, or negatviely charged backbones of dna and rna. form pores in membrane.
ll-37 also a small cationic peptide.
Neutrophils elestase: cleaves bacterial virulence factors and outer membrane proteins. this is a proteolytic enzyme.
calprotectin: alters bacterial growth by sequestering magnesium and zinc, depriving microbes. a metal chelator protein.
lactoferrin- a metal chelator protein. alters bacterial growth by binding to iron.
