Innate immunity Flashcards
Tell me the roles of the immune system
- Defence (of host) against threat of disease by pathogenic infectious organisms (pathogen)
- IS complexity due to range of organisms encountered – evolved to deal with many challenges
- IS protects against tumours (some)
- Vaccines offer exciting new hopes for infections and cancer therapy
- Chronic immune responses can cause disease, for example sepsis, autoimmunity, Type-2 Diabetes
Cells of the immune system stem from the hematopoietic stem cell tell me the two lineage of the cells and what cells are produced via these two routes?

The immune system has many specialized cell types, all which work together to fight
infection and disease. This infographic introduces the cellular players of the immune
system and illustrates how they are activated against pathogens.
All immune cells are derived from a common progenitor known as what?
Tell me about this cell?
All immune cells are derived from a common progenitor known as the hematopoietic stem cell (HSC).
The HSC develops into two progenitor types: lymphoid and myeloid.
Most lymphoid cells contribute to adaptive immunity
while most myeloid cells contribute to innate immunity.
Tell me the properties of innate immunity?
What does this branch into and what are these branches involved in?

Tell me the properties of adaptive immunity?
What does this branch into and what are these branches involved in?

Adaptive vs innate immunity

Lecture 1 LO
- Describe the importance of innate immunity in our defence against pathogens
- Describe the different roles of innate immune cells and proteins
- Give examples of immune defence mechanisms that are used in the innate immune response and inflammation
- (Phagocytosis, complement system, toll like receptors, neutrophil recruitment)
Whats the two step process of the immune system?
The immune system: infection of the human body by pathogenic microorganisms such as bacteria, viruses, parasites or fungi triggers the immune response. It occurs in a two-step process: innate (1st) and adaptive immunity (2nd)
Innate immunity is the immediate response to infection, tell me about the 3 things its involved in and how it carries them out?
- Awareness – detection of pathogens to signal their presence
- Immediate response – resident tissue cells/factors and the recruitment of cells from the blood – chemical signals generated
- Signals sent to the acquired response for provision of immunity-long lasting - the desired response of vaccination
Tell me about the nonspecific host defences

What is inflammation?
A complex biological response to harmful stimuli like pathogens or injury
Tell me about edema and extravasation linking with inflammation?
What is each of these?
- Fluids can leak from the blood vessels and collect in the tissues (edema)
- Leukocytes will also begin to exit from blood vessels to investigate the local tissue in a process known as extravasation
What are the signs of inflammation?

When a foreign body such as a pin penetrates the skin, what is the response that is generated?

Innate vs adaptive immune system diagram

Which of the following are unique characteristics or components of the innate―but not adaptive―immune system? (Select all that apply.)
a. immune “memory”
b. natural killer cells
c. phagocytosis
d. specificity
C
Tell me about the discovery of Toll like receptors?
The discovery of the TLR
- Immune response has to start with sensing ‘danger’ Medzhitov and Janeway (1997)
Several approaches failed to find receptors that bound pathogens.
- 1985: Christiane Nusslein-Volhard identified Toll genes (Toll = cool, weird) Drosophila melangaster important gene in embryogenesis in establishing the dorsal-ventral axis
- 1996: Jules Hoffman finds that Toll has a role in the fly’s immunity to fungal infection-
- 1997: year later they reasoned that genes related to Toll exist in vertebrates
Give an example of a pathogen recognition receptor (PRR) and a pathogen associated molecular pattern (PAMP) and how they work together to produce a response.
Tell me about the responses

- Example: TLR4 (PRR): LPS from bacteria (PAMP)
- Recognition of PAMP initiates various innate responses:
- Chemokines/cytokines to recruit cells
- Phagocytosis of pathogens
- Lysis of pathogens by antimicrobial peptides

Tell me about some of the roles of interferons and cytokines

Toll-like receptors trigger an intracellular signalling cascade
Tell me the steps to TLR signalling
- MyD88 – Myeloid differentiation primary response gene (88) a universal TIR adaptor (except TLR3) MyD88 interacts via a TIR domain
- MyD88 promotes association of IRAK1 & 4 kinases (interleukin-1 receptor-associated kinase)
- IRAK4 phosphorylates IRAK1 creating a docking site for TRAF6 (TNF-receptor-associated factor 6)
- TRAF-6-IRAK1 dimer complex dissociates
- Complexes with TAK1 (+other proteins) (TGF-beta activated kinase 1) causing kinase activation
- TAK1 is pivotal as it activates both NFkappaB and Map kinase pathways
- Increased transcription of target genes
- TAK1 activates IKK which phosphorylates IkappaB causing activation of NFkappaB

When LPS binds to TLR4, tell me the onset effects?

TLR activation in macrophages results in what?
oxidative burst (phagocytosis) and inflammatory cytokine/ chemokine release
TLR activation in dendritic cells results in what?
TLR activation in dendritic cells results in maturation, antigen presentation, and cytokine production- bridge to adaptive immunity
TLRs on the cell surface and endosomes for defence against a wide range of pathogens




























