TBL 11 Bacteria Flashcards
Lymphocytes and lymph return to the blood via the ______ duct.
thoracic duct
The first line of host defence is the ______ mechanism, which prevent the bacteria/pathogen from infecting the body.
barrier mechanism
The first stage of infection by pathogens involve _______ to the epithelium, followed by local infection and _______ of the epithelium.
adherence and penetration of epithelium
First line of defence:
The ____ acts as a physical barrier and contains antimicrobial peptides.
Skin
First line of defence:
The gastrointestinal tract has (low/high) pH, intestinal motility and intestinal ______ which acts as a biological barrier as it competes with the pathogens for nutrients.
low pH; intestinal motility and intestinal flora
First line of defence:
The neurological tissues have a ______ barrier.
blood-brain barrier
The second line of host defence is the _____ immunity, which helps to clear most infective organisms, and only those with ________ may survive.
Second line of host defence is the innate immunity.
Only those with virulence factors
The innate immunity involves recognition of ______ using pattern recognition receptors which recognise conserved microbial structures such as fimbriae, dsRNA, peptidoglycan.
_____ can also be used as a recognition signal, and this includes inflammation and necrotic cell death.
PAMPs and DAMPs
The third line of defence is the _______ immunity, which is mainly mediated by ___ and ___________.
adaptive immunity; mainly mediated by B and T lymphocytes.
In the presence of _______ released by CD4+ T cells, B cells can switch their antibody class to provide a more specific immune response, and undergo affinity maturation to increase affinity of antibodies.
cytokines
The memory B and T cells formed in response to an infection remain circulating in the _________ and ______, or reside in the ___________, waiting for re-exposure to the same antigen/pathogen.
Memory cells remain circulating in the bloodstream and lymph, or reside in the secondary lymphoid organs.
Memory cells allow for:
1) Faster
2) Stronger
3) More specific
secondary response?
All
Faster - sensitive to antigens
Stronger - more cells
More specific - undergone affinity maturation
Some pathogens are ________. This can be further divided to being on the epithelial surface, or existing in interstitial spaces, blood or lymph.
extracellular
Some pathogens are _________. This can be further divided into cytoplasmic or vesicular.
Intracellular
For extracellular pathogens within the interstitial spaces, blood and lymph, the typical immune response includes:
1.
2.
3.
4.
- Complement activation
- Antibodies
- Neutrophils and macrophages
- Inflammatory reaction
Pro-inflammatory mediators released by macrophages causes the (dilation/contraction) of local small blood vessels and expression of adhesion molecules.
(More/less) white blood cells are produced and enter the bloodstream, then move to the site of infection.
Pro-inflammatory mediators cause the dilation of local small blood vessels. More white blood cells are produced.
Innate immunity causes the (increased/decreased) production of chemokines which attract white blood cells to site of infection via _________.
increased production of chemokines which attract WBCs to the site of infection via chemotaxis.
________ refers to the leakage of plasma proteins, which occurs due to (increased/decreased) vascular permeability.
Plasma exudation; occurs due to increased vascular permeability
Blood clotting may occur in the microvessels to prevent microbial spread in the blood.
-
Th17 cells release cytokine _____, which act on fibroblasts or epithelial cells to secrete neutrophil chemotactic proteins to recruit neutrophils and induce production of ______.
Th17 release cytokine IL-17; induce production of defensins
Large extracellular parasites trigger _______ and _______ responses.
(like allergic reactions)
eosinophils and mast cells
Upon recognition of parasite antigen presented on APCs, ____ cells become activated and secrete cytokines.
IL-4 and IL-13 induce B cell development and differentiation to produce specific anti-parasitic antibody ____ which bind to antigens on the parasite.
Th2 cells; antibody IgE
Parasite:
Cytokine ____, which is produced by Th2 cells, will induce terminal differentiation of eosinophils by binding to CCR3 receptor, causing the eosinophil to express specific Fc receptors which recognise the IgE antibodies on the parasite.
IL-5
Parasite:
Upon binding to the parasite, mast cells release _______, TNF-a and enzymes. _________ release major basic protein, peroxidases and eosinophil cationic protein.
Mast cells release histamine, TNF-a and enzymes.
Eosinophils release…, causing cellular lysis and death of parasite.
The typical immune responses against intracellular pathogens include:
- 2.
- Hyperactivation of macrophages
2. Cytotoxic T cells
For macrophage hyperactivation,
the activated Th_ cells will express CD__ ligand on its surface, which binds to CD__ on the macrophage, and secretes ____, hyperactivating the macrophage.
Activated Th1 cells express CD40 ligand which binds to CD40 on the macrophage, and secretes IFN-y, hyperactivating the macrophage.
If the immune system is unable to destroy the intracellular pathogen, it attempts to wall it off and prevent the infection from spreading via _________ formation.
granuloma formation
Granuloma formation is an (active/passive) process.
Active process; since the constant death of macrophages in the granuloma core require constant turnover by addition of new cells
Viruses often act (intracellularly/extracellularly).
intracellularly
Typical immune response against viruses include: 1. 2. 3. 4.
- Interferons
- NK cells
- Cytotoxic T cells
- Antibodies
_________ help microorganisms to cause disease and may include toxins or mechanisms for adhesion, uptake, mobility, survival and immunomodulation.
Virulence factors
Immune evasion for pathogens:
________ involve pathogens possessing surface structures resembling human molecules, so the immune system mistakes them as “self” and does not attack.
Molecular mimicry
Immune evasion:
Many pathogens have different variations of a single antigen, immune system unable to recognise.
-
Immune evasion:
Some bacteria living on mucosal membranes cleave antibody ___ using ______ (enzyme) to prevent its activity.
Cleave antibody IgA using IgA proteases
_________ contains several pathogenicity islands (SP1/SP2), which encode type III secretion systems used to inject effector molecules into host cells.
Salmonella
___ of Salmonella is used to force macrophages to engulf the bacterium, whereas ___ is used to avoid killing within the macrophage.
SP1 - force macrophage to engulf bacterium
SP2 - avoid macrophage killing
The type III secretion system is encoded for by (SP1/SP2)
SP2
The salmonella bacterium contained within the vacuole can inject different effector molecules into the cytoplasm of the host cell using the type III secretion system to:
- Block the intracellular trafficking of ______ and docking to the phagosome, reducing phagolysomal fusion.
- Block assembly of _________ such that no oxygen radicals are produced and no macrophage killing.
- _________ of MHC class II molecules, tagging them for degradation, causing less antigen presentation by MHC II.
- Block intracellular lysosome trafficking, reducing phagolysosome formation
- Block NADPH oxidase
- Ubiquitination of MHC Class II
Shigella is often ingested with food, and are first taken up by __ cells above the Peyer’s patches in the intestine.
M cells (designed to take up specific antigens from the gut)
______ (bacterium) rapidly escapes from the phagosome into the cytoplasm, evading the macrophage killing.
Shigella
Shigella will replicate and kill the macrophage, becoming released on the ______ surface of the epithelium, leading to massive inflammation induced by macrophages.
Shigella is released on the basolateral surface of the epithelium
Shigella can spread laterally from cell to cell without exposing themselves to the immune system, by inducing ____ polymerisation to propel themselves into the next cell.
actin polymerisation
Actin tail formation
Immunomodulation by microorganisms include:
- Killing of _______ (cells) by leukocidins
- Production of _______ which bind TCRs and MHC molecules in the non-variable regions, linking them together and distorting the T cell response
- Production of VacA toxin and y-glutamyl transferase to inhibit (cell) activation and proliferation by acting on IL-2 and IL-2 receptors
- Induce ____ cells to suppress the immune response
- Killing of neutrophils by leukocidins
- Production of superantigens to distort T cell response
- T cell inhibition
- T reg cell activation
The _______ in the brain regulates the core temperature of the body using temperature sensors to monitor temperature.
hypothalamus
The ________ (POA) and ________ (DMH) are the two important structures in temperature regulation.
Pre-optic area and dorsomedial hypothalamus
The maintenance of body temperature relies on sensing the external environment and responding to it, using warmth and cold sensors.
Warmth sensors are unmyelinated __________, whereas cold sensors are _______ and decreased input from ______.
Warmth sensors: unmyelinated C-fibres
cold sensors:
A-delta fibres and decreased input from C-fibres
The temperature sensation detected by the sensors enter the spinal cord via the _________, which passes signals to the _________ and finally the hypothalamus.
Enter the spinal cord via the A) Lissauer’s tract, which passes signals to the B) lateral spinothalamic tract and finally the C) hypothalamus
Temperature signals from temperature sensors are processed in the ______ and _______
POA and DMH in the hypothalamus
When (warmth/cold) sensors in the skin detect increased skin temperature, afferent signals are sent to the POA and DMH which will transmit efferent signals to effector organs to effect a response:
- Peripheral (vasodilation/vasoconstriction) of skin arterioles to allow greater blood flow to the surface.
- (Constriction/Dilation) of shunt vessels to force blood to move through the surface of arterioles for cooling.
- (Increased/decreased) production of sweat
- Peripheral vasodilation of skin arterioles
- Constriction of shunt vessels
- Increased sweat production
When (warmth/cold) sensors in the skin detect decreased skin temperature, afferent signals are sent to the POA and DMH which will transmit efferent signals to effector organs to effect a response:
- Peripheral (vasoconstriction/vasodilation) of blood arterioles to prevent blood flow to the surface
- (Dilation/constriction) of shunt vessels to allow blood to bypass the surface of arterioles
- __________ of hairs to trap a cushion of heat-insulating air
- Metabolism of ___ to help generate heat
- ________ due to intense muscular spasms to produce heat
Warming up:
- Peripheral vasoconstriction of blood arterioles
- Dilation of shunt vessels
- Piloerection of hairs
- Metabolism of fat
- Shivering
Temperature variation of core body temperature in humans is primarily regulated by the __________ which project into the POA, allowing for circadian modulation of body temperature.
suprachiasmatic nucleus (circadian pacemaker)
Lying down can (increase/decrease) distal skin temperatures, causing a (increase/decrease) in core body temperature.
Lying down can increase distal skin temperatures, causing a decrease in core body temperature.
Melatonin is a sleep-related neurohormone that causes peripheral (vasodilation/vasoconstriction) and radiation of heat causing heat (loss/gain).
Peripheral vasodilation causing heat loss.
A (increase/decrease) in body temperature and its maintenance overnight is integral to a normal circadian rhythm.
decrease
The gold standard for measuring body temperature is to measure the temperature of the blood within the __________.
pulmonary artery
Temperature is generally measured at four peripheral sites:
Oral, tympanic (ear), rectal, axillary
Fever is when body temperature is raised in the presence of an _________.
infective agent
________ fevers are characteristic to TB, abscess, schistosomiasis.
Spiking
_______ (diurnal variation) fevers are characteristic to Kawasaki disease, malaria and amoebiasis.
Remitting
________ fever (i.e. fever for 7 days then 3 days normal) is characteristic to dengue, Legionnaire’s disease.
Saddleback
Longer periodicity fever is characteristic to Pel-Ebstein fever in ________.
lymphoma
Infections lead to the release of ______ that will cause the increased production of _____ which will bind to EP3 receptor within the ___ of the hypothalamus, which signals to the DMH, causing a sympathetic activation of non-shivering thermogenesis.
Infections lead to the release of pyrogens that will cause the increased production of prostaglandin E2 (PGE2), which bind to EP3 receptor within the POA of the hypothalamus, which signals to the DMH.
TLDR:
Pyrogens –> Production of PGE2 –> bind to EP3 receptor in POA —> signals to DMH –> Sympathetic activation of thermogenesis
There are two main endogenous cytokine pyrogens: ___ and ___.
IL-1 and TNF-a
IL-1 and TNF-a enhance breakdown of arachidonic acid into _________, enhancing localised inflammation and induces fever.
prostaglandins