Lecture 16 Flashcards
(34 cards)
What is the course of typical infection?
- infectious agent colonizes and replicates. innate immune system initiates immediately after detection
- when pathogen antigens presented by DCs to lymphocytes, adaptive initiated. pathogen growth continues but restrained by innate
- effector cells, adaptive act to clear
- when clear, persistent antibody & memory T/B provide protection against reinfection
What factors impact infectivity?
number of pathogens, route of transmission, mode of transmission, stability of agent
What are some host factors?
how thick mucus is, antimicrobial peptides, antibodies…
How do extracellular pathogens spread? Intracellular?
e: lymphatics, bloodstream
i: cell to cell, or release into extracellular fluid, inject adjacent/distant cells, or release toxins
What is a non-specific response? How long does it take?
within minutes to hours
- pathogen-activated innate sensors (epithelial cells) produce cytokines and chemokines
- activate endothelium, to express selectin, chemokines to recruit circulating monocytes and neutrophils to increase phagocytes
- leakiness of inflamed endothelium - influx of complement, mainly via alt and lectin pathway
What is a pathogen specific response? How long does it take?
hours to days
- pathogens activate PAMPS, elicit different patterns of cytokines from sensor
- direct mount against pathogens
How do innate lymphoid cells (ILCs) get activated?
microbial-associated molecular patterns (MAMPs) stimulate distinct cytokine responses from innate sensor cells (DCs, macrophages, epithelial) –> stimulate ILC subsets to product effector cytokines
What do activated ILCs do?
amplify and coordinate local innate response, tailored to specific pathogens
How does the adaptive response get called in?
DCs activate, migrate to lymph nodes
antigen-specific effector T and antibody-secreting B generated by clonal selection
ILC “buy time” for adaptive to mature
What is clonal contraction?
when effector lymphocytes die in days/weeks following resolution of infection
How are ILCs able to respond so rapidly?
don’t need antigenic priming and differentiation, seed barrier tissues before birth and stably populate throughout life
What is the role of natural killer cells? Where are they found?
- circulating in blood
- rapid induction of cytolytic activity
- when armed with IgG bound to their Fc receptors, can kill targets in antigen-specific mode
- killing of host cells that lose expression of MHCI molecules via release of activation restraints on NK by inhibitory receptors that recognize MHCI
What is the role of innate lymphoid cell 1? Where are they found?
- localize at tissues
- clearance of intracellular pathogens through activating macrophages by releasing IFNγ
- macrophages and DCs produce IL-12 and IL-18, rapidly activate ILC1 and heighten killing
What is the role of innate lymphoid cell 2? Where are they found?
- activated by cytokines thymic stromal lymphopoietin (TSLP) which is a STAT5 activating cytokine, as well as IL-33 and IL-25 which are all produced in response to helminths and allergens
- produce IL-5 and IL-13, stimulate mucus production by goblet cells, muscle contraction, facilitate worm expulsion (weep and sweep)
- activate eosinophils, mast, basophils to kill worms
What is the role of innate lymphoid cell 3? Where are they found?
extracellular pathogens and fungi, responsive to IL-1b and IL-13 to produce IL-17 and IL-22
What happens downstream of IL-17?
recruit neutrophils, hematopoietic growth factors, epithelium to produce antimicrobial peptide
What does IL-22 help with?
enhanced barrier integrity
What is the role of innate immunity?
recognize type of pathogens, induce appropriate immune response, initiate adaptive immunity
What T cells augment effector functions of innate immune cells?
effector CD4 T cells
What is sterilizing immunity
sensitive, specific actions of effector T cells and class-switched, affinity-matured antibodies –> complete elimination
How do effector T cells move to sites of infection?
after encounter with antigen, many effector T lose expression of L-selectin, leave lymph node (4-5 days later), express integrin VLA-4 and increased LFA-1 –> these bind to VCAM-1 and ICAM-1 respectively on peripheral vascular endothelium at sites of infection
How do Th1 cells control intracellular pathogens?
through activating macrophages via IFNγ and CD40L
How do activated macrophages produce antimicrobial effectiveness?
induce key lysosomal enzymes to produce microbicidal reactive oxygen and nitrogen species after the fusion of phagosomes and lysosomes
How are granulomas formed?
when intracellular pathogen/its constituents cannot be completely eliminated (like Mycobacterium tuberculosis) –> chronic, low level infection
