WK 9- IMMUNE RESPONSES IN INFECTION Flashcards
What are the 6 examples of virulence factors that allow bacterial colonisation to occur
- Evade adaptive immunity
- Resist innate immunity
- Compete for resources (like iron)
- Invade host cells
- Contact host cells
- Resist physical removal (through things such as adhesion pili which allow bacteria to cling to epithelium)
What is an endotoxin
Endotoxins are released only when the bacteria dies-> they are present on the walls of gram negative bacteria and include complex polysaccharides/LPS
What is an exotoxin- give one example
Exotoxins are toxic molecules secreted by invading pathogens-> act to disrupt host cells through destroying the cell or damaging the cell membrane, interfering with inhibitory neurons, or being a superantigen (staph aureus)
How do endotoxins elicit an immune response
LPS (endotoxin-PAMP) will bind to TLR4 (PRR) on macrophages/DC->the binding causes release of cytokines- IL-1, IL-6, CXCL8 (IL-8, recruits neutrophils), TNF-a, NO-> this causes fever/acidosis/complement activation/DIC-> can lead to multiple organ system failure and death
What are the 4 enzymes released by bacteria that act as virulence factors- how do they act as virulence factors
- Collagenase: breaks fown collagen in the ECM- allowing bacteria to move into tissues
- Hyaluronidase; degrades hyaluronic acid that forms the tight junction between cells- allows bacteria to pass
- Coagulase: produces clotting and allows the organism to grow within the clot- bacteria then produce kinases that degrade the clot and allow organism to escape
- Elastase; assist in invading tissues
What cell is most vital in killing intracellular pathogens- how is it acitvated
Macrophage activation is most vital in killing intracelullar pathogens-> activate the macrophage through release of IFN-g and CD40L produced by Th1 cells-> causes macrophage to ‘kickstart’ and kill pathogens living in intracellular vesicles
What cell releases the cytokines important for macrophage activation
Th1 cells
What are the innate mechanisms by which the body fight extracellular bacteria
- phagocytosis
- complement activation
- inflamm response initiated by PAMPs causing massive cytokine release
What are the adaptive ways in which the body fights extracellular bacteria
ANTIBODIES-> antibodies are key in removing extracellular bacteria-> cause MAC and opsonisation
What are the innate mechanisms by which the body fights intracellular bacteria
- Macrophage activation through Th1 activation
- Phagocytosis of infected cells
- NK cell activity
What are the adaptive mechanisms by which the body kills intracellular bacteria
- CTL induced lysing of infected cells
- CD8 cell activation
- Th2 releasing IL-2 to cause cells to move from the BM
- Thelper cell signals- CD40l and IFN-g
What are the mechanisms by which the bacteria can evade innate immunity
- Inhibit phagocytosis (eg. capsules)
- Prevent acidification of a phagosome and niche
- Escape from the phagosome to the cytosol
- Kill phagocytes and leukocytes
- Formation of fibrin clot that the bacteria can hide and proliferate in- then will release kinins that degrade the clot and allow bacteria to escape (extracellular)
- prevent Ig binding, opsonisation and complement action (capsules)
What are the mechanisms by which bacteria can evade adaptive immunity
- resistance to antibodies (capsules- prevent binding- extracellular bacteria)
- Interfering with cytokine secretion
- Interfering with antigen presentation (particularly used by intracellular bacteria)
- Inhibit B and T cell function
- Change surface proteins and induce expression of immunosuppressive cytokines
How do intracellular bacteria evade the immune system
- resistance to antimicrobial peptides
- inhibition of PAMP signalling
- antigenic variation
- inhibition of fusion of phagosome and lysosome
- survival within phagolysosome
- escape from phagosome
How do extracellular bacteria evade immune system
- resistance to antimicrobial peptides
- inhibition of PAMP signalling
- antigenic variation
- Inhibition of ROS
- Inhibition of opsonisation
What is the function of CD8T cells in protective immunity
These cells are vital in establishing the protective immunity against intracellular bacteria and viruses-> achieve this through differentiating into cytotoxic T cells and binding/killing cells expressing MHC1
What histological feature allows TB to remain latent in the lungs
Granulomas-> wall off and trap the TB bacterium in the lungs-> when the pt is exposed to immunosuppression, the granuloma can ‘break down’ and release the bacteria, leading to a secondary infection
What ways does TB evade immune system
- inhibition of phagosome/lysosome function
- inhibition of acidification
- escape from phagosome
- resistance to lysosomal enzymes
- resistance to oxidative killing
- TLR2 induces anti-inflamm cytokines (IL-10)
Who are at risk of TB
HIV-AIDS sufferers, immunosuppressed, those living in low SES conditions
Are antibodies effective in killing TB
No- T cells are most important, humoral immunity (antibodies) show no effect on TB
What is the pathogenesis of TB
- Primary infection is usually by inhalation of micro-droplets containing M. tuberculosis
- No known exotoxins, endotoxin, or proteolytic enzymes, but resistant to macrophage killing
- Host control of intracellular bacilli is dependent on cellular immunity: CD4 T cells, macrophages, cytokines (esp. Th1)- antibodies play no role
- Tissue destruction results from “excessive” cellular immune response (macrophage-derived proteases
What is the role of CD4T cells in TB
-Th1 are the most important; T cell responses correlate inversely with disease progression (high T cell= low disease progression)-> CD4T cells act to rid the bacterium through cytokine release that promotes killing by macrophages
What is a ghon complex
Calcified tuberculous caseating granulomas
What is type 1 immunity - what do they target
monocytes and macrophage function that are enhanced by TH1 cells, group 1 ILC1 (innate lymphoid cell), opsonising IgG isotypes–> macrophage response to intracellular bacteria viruses and protozoa
What is type 2 immunity- what do they target
-eosinophils, basophils and mast cell function enhanced by Th2, Group 2 ILC (ILC2), IgE and IgG4–> induced by helminths and allergens
What is type 3 immunity- what do they target
neutrophil function enhanced by Th17 cells, group 3 ILC3, Opsonising IgG isotypes associated-> respond to extracellular bacteria and fungi
What role does IL-4 play in type-2 immunity
IL-4 plays crucial role in coordinating the functions of
many other immune and non-immune cells during
Type 2 immune response
What are innate lymphoid cells
-immune cells that belong to the lymphoid lineage but do not express antigenspecific receptors but display attributes directly analogous to the adaptive T helper effector cells, Th1, Th2, Th17
-activated by innate sensor cells (macrophages)
-ILCs co-ordinate local immune responses better tailored to particular pathogen
-Cytokines produced by ILCs help guide development of naïve CD4 T cells into CD4 subsets
NK cells are one type of ILC
How is hepatitis A transmitted
faecal-oral transmission
How is hepatitis B transmitted
blood or body fluid
How is hepatitis C transmitted
blood or body fluid
What types of hepatitis can lead to cirrhosis and hepatocellular carcinoma
Type B and C- C is more likely to promote liver cancer than B
Is hepatitis caused by a bacteria or a virus
virus
What immune evasion techniques do helminths possess
- Shedding of surface antigens
- Protease production to neutralise anti-parasite immune components e.g. degrade immunoglobulins
- Adsorbing host antigens – masking parasite antigens
- Regulation of host functions–> suppression of certain cell types –neutrophils, macrophages, skewing and suppressing of Th responses, neutralise respiratory burst by producing antioxidants, use of host cytokines as growth factors
Why is getting hepatitis at a young age associated with bad prognosis
The earlier you get hepatisis- the more likely you are to develop chronicity and hepatocellular carcinoma
-this is why vaccines are important
