First Midterm Flashcards
what is an ideal PRR?
An ideal PRR should be:
- ubiquitous
- able to detect non-self antigen
- rapid and potent
An ideal PAMP is:
- has bacterial lypopolysacc present on many bacteria
- Has mannose glycoproteins
- double stranded RNA
- in methylated cpG RNA
What happens during an inflammation?
Vasodilation
Dec in blood flow velocity
Inc in capillary permeability
Influx of immune cells to appeared tissues
Four signs of inflammation
Redness
Heat
Edema
Pain
Steps in inflammation
Epithelium is breached
Microbe invasion
Resident phagocytes detect microbes
Steps in phagocytosis:
- Expression of surface PRRs
- PRRs detect/engage invading microbes
- Cytoskeleton rearrangement
- Microbe internalization in the phagosomes
- Lysozyme destroy microbes
- Reactive o2/n2 destroy microbe proteins etc
What are cytokines?
Secreted proteins by the macrophages and natural killer cells
Drives the immune and inflammatory response
What is the effect of the cytokines?
Induce protein in the endothelium, inc its adherrence to passing leukocytes
Difference of chemokines from cytokines?
Low molecular weight
What are the effects of chemokines?
Stimulate leukocyte movement and regulate the migration of leuk to the tissues from blood
How does inflammation causes cancer?
Tumor is seen as unhealed wound and inflammation can promote growth through supply of nutrients
Toll like receptor (TLR) cause the release of what?
Release of anti-microbe peptide
Inflammatory cytokines
Other molecules that drive immune response
What is NF-kB?
Nuclear factor-kB: activated in response to TLR + PAMP
- transcription factors that regulate genes involved in immune response
What is I-kB?
Inhibitory of kB: cytoplasmic protein which binds and retains NF-kB in the cytoplasm
Process of transcription of immune genes by the NF-kB?
- I-kB is still bound to NF-kB, retaining it in the cytoplasm in a resting cell
PAMP+TLR = intracell signaling
Proteolytic destrctionof I-kB
nF-kB–>nucleus –> transcription of immune genes
What are adaptor proteins?
Non-enzymatic proteins that assist assembly of signalling complexes which are recruited by PRR upon its PAMP detection
What does TIR mean and what does it do?
Intracellular Toll Interleukin-1 Receptor-1 motif: structural motif that converts pathogen detection to intracellular signalling cascade found at the base of TLR
What does NLS do?
NF-kB in a resting cell is not active (i.e. Inert in the cytosol). NLS allows it to move inside the nucleus to be activated
What critical cellular processes does NF-kB regulate?
Inflammation
Adaptive immunity
Proliferation
Survival
TLR signalling consequences involve what?
Cytokine production
Production of enzymes involved in immune responses
Growth factor production (promotes healing)
Activation of adaptive immune cells
What are the advantages of TLR signalling?
Speed (fast signalling system after PAMP detection)
Economy (limited no of tlr but they detect large # of pathogens)
Amplification (activation of large, systemic responses after a localized detection of microbes)
What is an “oxidative burst”?
Production of ROIs and RNI which digest the microbes after the detection of PAMP by the PRR
What are the multiple contributions of PRR to immune response?
Induction of phagocytosis
Activation of oxidative burst
Recruitment and activation of additional leukocytes
Distinct characteristics of Adaptive Immune Response which differentiate it from the innate?
- Detects vast repertoire of molecules
- Receptors generated by somatic recombination
- Improved “adapted” response after repeat exposure
State the main difference between B cells and T cells:
T cells require antigen presentation by dedicated antigen presenting cells (APCs), while BCR can directly recognize its cognate antigen
What is humoral immunity?
It is directed against EXTRACELLULAR microbes and is mediated by B cells which secretes antibodies that neutralize and eliminate microbes and microbial toxins
What is cellular immunity?
It is directed against intracellular microbes and is mediated by T lymphocytes which activates phagocytes and lymphocytes or kill infected host directly
To activate naive lymphocytes what 2 signals are required?
- Antigen receptor binds to antigen
2. Microbial/innates immune signals
What happens after microbial elimination and once the signal for lymphocyte activation disappears?
They undergo programmed cell death (apoptosis)
What are antibodies?
A secreted BCR after activation of b cells which is released into the circulation and mucosal fluids upon infection. They neutralizes microbes and microbial toxins.
Stop microbes from entering/colonizing host cells.
What are MHCs?
APCs present antigens to T cells on major histocompatibility complex (MHC) class i and class ii molecules
Structure of Class I MHC consists of:
An alpha chain, non covalently bonded to a beta2-microglobulin chain
Where is the polymorphic residues of the Class I MHC located?
Alpha1 and alpha2 domains
Why is it that only CD8+ T lymphocytes respond to Class I MHC?
Because of alpha3 domain which is invariant and contacts only T cell CD8 receptor