Why is immunology important Flashcards
what is Severe combined immunodeficiency (SCID)
- Death early in life in absence of an immune system - e.g. Severe combined immunodeficiency (SCID)
- No lymphocytes due a variety of genetic causes
- Babies with recurrent bacterial/viral/fungal infections
- Sinus infections (sinusitis), oral thrush (mouth yeast infection), skin infections, meningitis, pneumonia, chronic diarrhoea
1:100,000 bebes - bone marrow transplant required
Without a fully functional immune system even commensal/low grade pathogens can kill
how does hiv cause AIDs and what causes death
Untreated, HIV most often turns into AIDS in about 8 to 10 years. Having AIDS= immune system v damaged.
HIV targets CD4 T cells. HIV gets inside the CD4 cell and makes copies of itself. Then, HIV kills the CD4 cell and the new HIV copies find other CD4 cells to get inside and start the cycle again.
- Without a fully functional immune system even commensal/low grade pathogens can kill
- HIV+ individuals who got acquired immune deficiency syndrome (AIDS)
- T cells are critical part of immune system
- HIV infects & kills T cells
- AIDS develops in absence of treatment
Infection with opportunistic pathogens like pneumocystis carinii, cryptosporidium, atypical mycobacteria) - Wasting in AIDS is due to chronic diarrhoea due to infection
what is a monoclonal antibody and how do we grow them
Monoclonal antibodies are checkpoint inhibitors in cancer therapy
Monoclonal antibodies are clones of your body’s antibodies which are made in a lab, these stimulate your immune system. Monoclonal antibodies as therapies are more targeted than some other types of treatments and have been more successful at treating some types of diseases, including some cancers
- An antigen is injected into a mouse.
- mouse naturally produces lymphocytes, which produce antibodies specific to injected antigen.
- Spleen cells, which produce the lymphocytes, are removed from the mouse.
The spleen cells are fused with human cancerous white blood cells called myeloma {cancerous white blood cells used in the formation of monoclonal antibodies} cells to form hybridoma {cells produced when spleen cells that produce antibodies are fused with myeloma cells in the process of making monoclonal antibodies} cells which divide indefinitely.
These hybridoma cells divide and produce millions of monoclonal antibodies specific to the original antigen.
what do we mean when we describe the immune system as distinguishing from self and non-self
Distinguishes components of our own bodies (self) from things that are foreign to us and potentially dangerous (non-self) - and respond to only non-self
how do immune cells use their receptors to recognise foreign molecules (non-self)
- Receptor binds to foreign molecule - antigen/Ag
- Signalling cascade initiated
- Gene transcription changes
- Production of effector molecules - e.g. Antibodies/cytokines
define ‘adaptive immunity’
Adaptive immunity involves specialized immune cells and antibodies that attack and destroy foreign invaders and are able to prevent disease in the future by remembering what those substances look like and mounting a new immune response.
where do immune cells develop?
Immune cells develop in** primary lymphoid tissues**: thymus + bone marrow.
The bone marrow is where innate immune cells + B cells are made. B lymphocytes remain in the marrow to mature, while T cells travel to thymus to further develop.
n.b. secondary lymphoid tissue are areas where immune activation/protective mechanisms get activated (tonsils, lymph nodes, lymphatic vessels, liver, spleen, peyer’s patch on small intestine, appendix)
what is an ‘innate’ immune cell + give some examples
innate/non-specific immunity cells participate in phagocytosis + inflammatory processes. They have a generalised recognition of microbes
e.g.
* NK (natural killer) cells are lymphocytes in same family as T/B cells with same common progenitor
* Monocytes/macrophages - macrophages are monocytes that migrated from bloodstream into any tissue
* Dendritic cells
* Granulocytes - e.g. Neutrophils, basophils, eosinophils
what does the innate immune system do?
1. Provides 1st line of defence - keeps pathogens out/eliminates them quickly
* Body barriers can be part of this - stomach acid, skin, resident macrophages
2. Alerts immune system to presence of pathogen + recruits additional immune cells - called acute inflammation (part of normal immune response)
3. Activates adaptive immune response via antigen presentation
what is the role of IL-8
Interleukin-8 (IL-8) aka CXCL8 is a chemoattractant cytokine produced by a variety of tissue and blood cells. Unlike many other cytokines, it has a distinct target specificity for the neutrophil, with only weak effects on other blood cells. Interleukin-8 attracts and activates neutrophils in inflammatory regions.
What is the role of cytokines e.g. TNFa - tumour necrosis factor alpha
Cytokines (e.g. TNFa) make the endothelium lining blood vessel sticky by upregulating adhesion molecules; so neutrophils loosely adhere and roll along to vessel wall, if/until they get additional signals then get recruited to infection site
Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis.
The monoclonal antibody drug ‘Humira aka adalimumab is used to target TNF alpha
How do neutrophils kill bacteria
*intracellularly
*extracellularly
neutrophils kill bacteria
*Intracellularly: by phagocytosing bacteria and exposing them to performed toxic mediators
* Contain performed granules containing mediators that kill bacteria e.g. free radicals, neutrophil elastase, neutrophil collagenase, myeloperoxidase, gelatinase, anti-bacterial peptides, cytokines
* These mediators are toxic to normal host tissue too - collateral damage
Patients with chronic granulomatous disease (CGD) have a genetic deficiency of NADPH oxidase so less able to kill since there is less ROS (e.g. superoxide radical) produced
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Extracellularly; by engulfing them in NETs (neutrophil extracellular traps) - trap/kill microorganism
Nucleic acid matrixes with high conc of anti-microbial proteins
How do innate immune cells recognise pathogens?
- use PRRs (pattern recognition receptors) to recognise PAMPs (pathogen associated molecular patterns
- PRRs- e.g. toll-like receptors (TLRs)
- PAMPs- structures on microbes but not eukaryotes (humans) e.g. cell wall components, flagellin, viral nucleic acids
what is a TLR + its function? Too much activation of which TLR causes sepsis?
TLRs= toll-like receptors
are an example of pattern recognition receptors (PRR)
- Binding to TLRs leads to cell activation + cytokine production
- Have horseshoe structure which recognises antimicrobial properties
- They recognise different structures
- E.g. TLR-5 recognises flagellin
- E.g. TLR-4 - recognises LPS(lipopolysaccharide)- a major component of gram-ve bacterial cell wall - overwhelming bacterial infection causes too much TLR-4 activation which lead to sepsis !!!
scientific details:
* TLRs activate NF-kappaB and MPK signalling pathways to induce inflammatory cytokine production
* this causes TLR dimerization happens - recruits activation molecules - via signalling cascade, TF get activated leading to production of inflammatory cytokines
NF-kappaB - nuclear factor kappa-light-chain-enhancer of activated B cells - family of TF protein complexes controlling transcription of DNA, cytokine production and cell survival
which cytokine is the driver of T- cell proliferation {to increase in number}
cytokine IL-2 (T cell growth factor) is the driver of T cell proliferation
what is the difference between necrosis and apotosis
+ what is pyroptosis
Apoptosis is an active, programmed process of autonomous cellular dismantling that avoids eliciting inflammation.
Necrosis is a passive, accidental cell death resulting from environmental perturbations with uncontrolled release of inflammatory cellular contents.
pyroptosis is a lytic cell death (disintegration of plasma membrane) caused by microbial infection; that allows the release of potential immunostimulatory molecules.
