Immunity to Infectious Diseases-1 Flashcards
(28 cards)
What are the 4 major categories of human pathogens?
- viruses
- bacteria
- fungi
- parasites
What is the importance of barriers and vectors in infectious diseases?
- pathogens must breach host physical/ chemical barriers to cause infection > innate immunity
- vectors (intermediate hosts)- organisms that help infectious agents circumvent host barriers by carrying infection from one organism to another
What are some host barriers to infectious disease?
- epithelial surfaces of body > skin/ GI tract/ respiratory tract/ reproductive tract > monitored by barrier immune systems
- normal commensal flora at mucosal surfaces completely inhibit binding of pathogens to host cells
How do most vectors work?
- intermediate hosts help infectious agents circumvent host barriers by carrying infection from one organism to another
- most are blood-sucking anthropods > ticks/ fleas/ flies/ mosquitos
- breach natural barriers like skin with their bite
What are 3 strategies pathogens have evolved to escape immune destruction?
- growing within host cells
- expressing molecules similar to host cell membrane molecules
- continual variation in surface antigens
What happens when a pathogen breaches a host?
- encounters responders of innate immunity
- innate mechanisms lead to initiation of adaptive mechanisms > cause final eradication of pathogen/ memory response
What are 3 examples of a pathogen breaching a host and encountering innate immunity?
- bacterial LPS (PAMP) stimulates macrophages to produce cytokines IL-1/ IL-6 > activate phagocytosis
- peptidoglycan on bacterial cell walls activates complement pathway > opsonization/ phagocytosis/ lysis
- viruses induce production of interferons > antiviral response
What is an example of a way to introduce a barrier to infection in a vector?
- introducing barriers to infection in intermediate hosts can disrupt the life cycle of certain infectious diseases
- ex) virus transmitted by mosquito bite
> engineer mosquitos resistant to virus/ release them wild
What is the link between location and immune effector mechanism?
- entry site/ ultimate location of an infectious agent in body determines what immune tools available/ best suited for pathogen detection/ elimination
What are the different entry points for infection?
- contact (eye)
- wound/ anthropod bite (skin)
- mucosal surfaces
> ingestion (GI tract)
> inhalation (respiratory tract)
> sexual exposure (urogenital/ reproductive tracts)
How do most infectious agents enter the body?
- mucosal routes > GI/ respiratory/ urogenital tracts
How are mucosal/ barrier infections typically controlled?
TH2 response
What cells sense pathogens via PRRs?
- epithelial cells
- APCs (macrophages/ DCs)
What is the response to helminths (parasitic worms)?
TH2 response > IL-4/ IL-5/ IL-13 cytokines
What immune effectors deal with pathogens in the GI tract?
- antimicrobial proteins secreted by epithelial cells
- innate lymphoid cells (ILCs)
- MALT
What does the TH2 response involve?
- how most barrier (surface)/ mucosal infections controlled
- activation of ILC-2s
- TH2 specific cytokines > IL-4/ IL-5/ IL-13
- IgE capable of recognizing surface epitopes of pathogen
> cells with high-affinity IgE receptor > basophils/ eosinophils/ mast cells - dimeric IgA at mucosal surfaces > neutralization (blocks pathogen binding to epithelial cells) > passive, so prevents dysbiosis from chronic inflammation
What happens after pathogens breach epithelial barriers?
- enter interstitial fluid (extracellular > can remain local/ spread through body via circulatory/ lymphatic systems
- all pathogens that breach epithelial barriers will be found in extracellular space for all least part of their lifetime in host
- some can enter host cells (intracellular)
What are the immune mediators in extracellular spaces?
- PRRs on phagocytic cells
- complement system
- antimicrobial compounds
- cytokines > activate immune cells
- IgG/ IgM/ mIgA antibodies
- TFH/ TH17/ TH2 cells
What is one reason intracellular pathogens are most difficult to find/ destroy?
- antibodies can not enter cells
What are the immune mediators for infectious organisms within intracellular vesicles?
- TH1 response > DTH
- TH1 cytokine IFNγ activates macrophages to digest vesicle-bound agents (bacteria/ parasites)
What is an example of an infectious organism that enters intracellular vesicles?
Mycobacterium
- includes agent that causes tuberculosis
What are the immune mediators for infectious organisms within the cytosol?
- all viruses/ some parasitic agents enter cytosol > TH1 response/ CTLs
- can be detected by cytosolic PRRs > NLRs/ RLRs
> leads to cytokine secretion/ inflammasome activation
> ultimately induces cytotoxic cells that can kill infected host cells (NK cells/ CTLs) - NK cells kill infected host cells > detect cell-surface changes (signs of infection) ex-decreased MHC I expression > ADCC
- CTLs are primary adaptive mediators of infected cell killing
What is required for the eradication of cytosolic infections?
- strong/ comprehensive cell-mediated immunity
> TH1 CD4+ T cells that can license DCs for cross-presentation
> cytotoxic CD8+ T cells (CTLs)
What are the 2 major types of barrier immune systems to the microbiome?
- Tolerogenic > response to commensal bacteria (homeostasis)
- Inflammatory > response to pathogenic microorganisms
