dont know (7) Flashcards
L18- Intracellular bacteria evasion?
- Invade non phagocytic cells
- Replicate in epithelial cells
- Many replicate in macrophages
Innate immunity to intracellular bacteria - Autophagy: macrophages or epithelial cells degrade intracellular pthogens.
- Innate sensing (intracellular/cytosolic
sensors) of pamps? - Cell death
Cells can induce:
>Apoptosis
>Necroptosis
>Pyroptosis - Inflammasome
> inflammatory cell death
Can alter phagolysosomal compartment to make it hospitable for bacteria.
Can interfere with ros and ph. Make phagolysosome a vacuole. Some pathogens want to be in cytosol e.g: in epithelial cells.
* Inhibition of phagolysosome formation (Mtb,
Salmonella)
* Resistance to degradation in phagolysosome
(Mtb, Salmonella, Legionella)
* Phagosome escape (Listeria, Shigella)
* Block autophagy (Mtb, Shigella)
* Block cell death (Shigella, Yersinia)
* Inhibition of innate sensing (almost all
viruses and bacteria)
L18- Immunity to viral infection
Inteferon prod by innate immune system. Interferon stimulated gene block viral replication. NK cells kill virus infected cells. Adaptive immunity: B cells produce antibodies that neutralise virus. CD8+ kill infected cells.
Immune evasion:
Inhibition of IFN induction or signaling
(SARS-CoV2) all of them can do this:
Block: signalling pathways of making inteferons and isg? Search this part up
- Inhibition of inflammatory signaling
- Production of immunosuppressive
products, vIL-10 (Epstein-Barr)
- Antigenic variation (Influenza)
- Inhibition of MHC pathway
(Cytomegalovirus, herpes simplex)
- Infection/death of immune cells (HIV)
yersina example ***
T3SS- or injectisome
A major virulence determinant conserved among many virulent bacteria.
Found in pathogens such as Salmonella, Shigella, Yersinia, Pseudomonas, E. coli, Bordetella, Vibrio, and various plant pathogens.
Functions as a ‘molecular needle’ that injects effector proteins (virulence factors) directly into the host cell.
These effector proteins manipulate the host cell’s processes to benefit the pathogen, such as:
Subverting immune responses.
Altering the cytoskeleton for bacterial invasion or survival.
Promoting intracellular replication and spread.
Enteropathogenic Yersinia
- Invades the gut epithelium
- Taken up by macrophages and
migrate to the lymph nodes, liver - Induce apoptosis (death) in
macrophages - Uses effectors of T3SS to
- Block phagocytosis by macrophages
- Block innate signaling and cytokine
expression - Manipulate cell death and inflammation
Yop
Effectors
Invasin
Migration to
MLN, liver
Apoptosis of
macrophages
Inhibition of inflammatory genes
Inhibition of phagocytosisInflammatory
genes
Invasion of epithelial cells
Phagocytosis driven by actin- actin activated by strong gtpases in the rho family.
* Activated by Rho GTPases
* Lead to bacterial death
- Yersinia is an extracellular pathogen
- Blocks its phagocytosis
- Through inhibition of Rho GTPases
No phagocyotsis, no actin, pathogen survives.
Intracellular sensors: inflammasomes recognise that host protein is modified, causes pyroptosis that causes death of pathogen
* Insertion of the Yersinia T3SS and
modification of Rho GTPases are
detected as danger signals
* These lead to activation of
Inflammasomes which induce Pyroptosis
* Pyroptosis = very inflammatory cell
death. IL-1β and IL-18 produced activate
immune response.
* Yersinia has evolved another set of
virulence factors that cleave or
inhibit different inflammasomes
* This prevents pyroptosis and
inflammatory signaling
* Yersinia blocks phagocytosis
* And evades pyroptosis
Yersinia vs Man: detection of Yersinia activities*
Mechanisms of Immune Privilege
Immune privilege: - Eyes
- Placenta and foetus
- Central nervous system
1. Anatomy: physical separation of priveleged locations e.g: bbb
2. Increased regulatory populations
- Regulatory cytokines IL-10, TGFβ
- Regulatory cells Tregs, Bregs, M2 macs
3. Decreased effector populations
- MHC expression
- Complement inhibition
- FasL expression
BRAIN
Anatomy: blood-brain barrier (tight
junctions)
2. Increased regulatory mechanism:
- Soluble: neuropeptides (somatostatin)
- Cells: microglia – anti-inflammatory
macrophages
3. Decreased effector populations, BUT…
evidence of latent virus control:
immunosurveillance
Effector Regulatory
FOETUS
1. Anatomy: uterus + placenta - barrier
2. Increased regulatory mechanism:
- Soluble: IL-10, TGFβ
- Cells: tolerogenic DCs, Tregs
3. Decreased effector populations:
- Complement inhibition
- No MHC-II
- Low MHC-I
L9- Thymus
During embryonic development: have endodermal and ectodermal cells that fuse together to form a thymic anlage. endoderm in the middle (medulla) and ectoderm (cortex) surrounding it, forming the stroma. Form a bilobed organ: the thymus.
No thymus= no t cells.
T cell development takes place in the thymus- a specialised organ where t cell progenitors from the bone marrow migrate to and mature and differentiate.
The thymus is divided in several anatomical locations (top-bottom) subcapsular region, cortex, cortico-medullary junction, medulla. As thymocytes mature they pass from one environment to another.
Thymus function declines with age. Peak in teens and atrophies with age. Older people- smaller thymus. Weight is proportional to the number of t cells that can develop in it. Older people- do not make as many t cells everyday so more prone to infections etc.
L9- TCR link with inflammation?
Activation in periphery with foreign agonist (activating) peptide that mimics self-peptide
In the thymus t cells are selected on self peptides. In peripheral lymph nodes they have viral or bacterial peptides presented by apc. One reason why t cells in the periphery are not attacking self is because:
Pathogens cause inflammation
So tcr can be activated against them because there are accessory molecules upregulating mhc peptides , adhesion molecules holding t cell with apc to get the signal and increase in co stimulatory signals. Inflammation is needed for adaptive immune response- clear innate and adaptive link.
L3- complement definition?
an innate, non cellular component of the is. 750 proteins soluble in plasma, produced in the liver or membrane bound.
L3- Classicial pathway alternative activators?
DNA: AB against DNA form immune complexes with DNA. c1q binds to their fc region.
CRP: (c - reactive protein)
prions: can form immune complexes with antibodies against prions which bind to c1q
(info from chatgpt must fact-check)
L3- MBL activation?
masp 1 +2 (mbl-associated serine proteins) are activated when mbl or ficolins bind to pathogen surfaces. masp-2 cleaves c4 +v2 complement proteins to c4bc2a- c3 convertase.
MBL: MBL (Pattern recognition receptor): binds to mannose +other sugars on pathogen surface called PAMPS which are absent on healthy cells but may be found in bacteria, fungi and viruses.
MBL in the collecti-ns family. MBL and collections 10, 11 and 12 bind to oligosaccharides and lipids on the pathogen surface.
FICOLINS:
a prr that bind to N-acetylglucosamine (a sugar in bacterial cell walls) ficolins and mbl are both involved in the lectin pathway
