Lecture 29. Overview of the Immune System Flashcards
What are the key primary lymphoid organs of the immune system ?
- Thymus
2. Bone marrow
What are the secondary lymphatic tissues ?
Spleen, tonsils, lymph vessels, lymph nodes, skin and liver
Where do B-cells develop ?
Bone marrow
Where do t-cells develop ?
Thymus
What do immune cells use to travel through the body ?
Lymphatic highway system
What are some strategic locations where immune cells may be stored ?
- Ln
- Tonsils
- Peyers patch
- Spleen
What are the phagocytes ?
- Macrophages
- Neutrophils
- Dendritic cells
What do innate leukocytes include ?
- Phagocytes
- Basophils
- Natural killer cells
What is the function of innate leukocytes ?
Identify and eliminate pathogens and are important mediators in the activation of the adaptive immune system
What do natural killer cells go after ?
Tumor cells and viruses
What is the function of perforin ?
Perforates membrane
What is the function of granzyme ?
Degrades membranes
What is the function of natural killer cells ?
Inserts granzymes and perforin into the cells that destroy tem
What is the function of T-cells ?
Destroy foreign or damaged cells
What is the function of helper T-cells ?
Regulate the attack of foreign and damaged cells
What do killer T-cells do ?
Carry out the attack on the foreign or damaged cells
What do B-cells produce ?
Antibodies
What are antibodies specific towards ?
One antigen
What is an antigen ?
A toxic or foreign substance
What happens when the antibody binds to the antigen ?
A signal for other cells and molecules of the immune systems to come and destroy the antigen
What is one of the key differences between the adaptive and innate immune system ?
Innate is rapid, the adaptive immune system takes longer to develop
How is an autoimmune disease caused ?
The body sees its own cells as foreign and attacks them
What are two examples of an immune over reaction ?
- Autoimmune problem
2. Allergic reaction
What are two examples of an immune under reaction ?
- Disease
2. Infection
What is homeostatic inflammation used for ?
A protective response
What happens everyday to the cells of the villi ?
They shed and new ones are made by stem cells in the crypts
What are some results if the immune system in the gut goes wrong ?
- Ulcerative colitis
- Crohns disease
- Coeliac disease
- Food allergy
- Colorectal cancer
How are RNA viruses recognised ?
Via nucleic acid detection
What do RNA viruses drive ?
Interferons
What type of RNAs are innate immune responses most reliant on the detection of ?
dsRNA
What type of virus is covid ?
Positive sense single stranded RNA
What type of RNA does covid generate ?
Double stranded RNA
How does covid replicate ?
The replication of the positive sense ssRNA genome proceeds through double stranded RNA intermediates,
What is the purpose of covid replication in membranous invaginations ?
Avoidance of cellular response to the presence of dsRNA
What is the function of oligo adenylate synthase ?
Activates RNAase L
What is the function of RNAase-L ?
Degrade cytoplasmic RNA
What do RNA viruses try to subvert ?
Recognition via nucleic acid detection
What does CoV mediated antagonism of innate immunity begin with ?
The evasion of PRR sensing
What do ssRNA form during replication ?
dsRNA intermediates
What can dsRNA be detected by in the endosome ?
TLR3
What can dsRNA be detected by in the cytosol ?
- RIG-I
- MDA5
- PKR
What can ssRNA be detected by ?
- TLR7
- TLR8
- RIG-I
- PKR
How can CoVs avoid PRR activation ?
- Avoiding recognition
2. Antagonising PRR action
How do dsRNAs evade PRR ?
dsRNA is shielded by membrane bound compartments that form during viral replication of SARSCoV-1
What is the structure of viral RNA ?
Guanosine-capped and methylated at the 50 end by CoVs nonstructural proteins 10, 13, 14 and
What does the structure of viral RNAs help ?
Look more like self RNA
What helps dsRNA avoid detection by MDA5 ?
An endonuclease that cleaves off poly uridine
What is hypoxemia ?
Not enough oxygen in the circulating blood cells
How does cancer occur ?
When a normal cell goes out of control dividing and these cells express stress markers or produce antigens that normal cells dont produce
What are activatory receptors ?
Stress markers which become activated to kill
What is the function of an activatory receptor ?
How immune cells particularly innate immune cells kill
What does a T-cell need to kill ?
Two signals
What is the function of the first signal of the T-cell ?
Alert the immune cells
What is the function of the second signal in T-cells ?
A costimulatory molecule which gives a boost to activate the T-cell
What is the most important costimulatory signal for a T-cell ?
CD28
What does CD28 do ?
Binds to B7 on the presenting cell
What do immune cells also have ?
Inhibitory receptors
What are inhibitory receptors critical for ?
Autoimmunity
What are two examples of inhibitory receptors ?
- PD1
2. CTLA
What is CTLA4 ?
A checkpoint that binds B7 - in competition with CD28
What does PD bind to ?
PDL
How does cancer hijack the immune system ?
Cancer cells put the receptors for these checkpoints in their surface which inhibits immune response
What does ipilimumab do ?
An antibody which blocks CTLA4
How does the immune system respond to fat ?
Inflammatory response
What happens when fat cells store excess fat ?
They burst and release lipids into the body which is toxic to cells
What is the function of macrophages and fat ?
Engulf the lipids to try clean up and produce cytokines to helpp
What is a characteristic of obesity ?
Inflammation in the dat tissue
What can TNF do ?
Activate JNK signaling
What does the activation of JNK signaling pathway do ?
Phosphorylation of the insulin receptor and leads to insulin resistance
What is the immune system in fat doing in healthy lean people ?
Constantly fighting disorder to maintain homeostasis
What is lean adipose tissue full of ?
Innate T-cells
What are ab T -cells ?
They are CD4 or CD8 positive and recognise antigens presented in the context of MHC
What is special about innate T-cells in fats ?
They recognise lipids
What are iNKT cells rich in ?
Adipose tissue
What is one of the things that iNKT cells do ?
Produce anti-inflammatory cytokine IL-10
What activates iNKT cells ?
Alpha GalCer
What are iNKT important for ?
Thermogenesis
What are microglia ?
Macrophage like cells
What is alzheimers sensed by ?
Microglia
Are the brain and the immune system in constant communication ?
Yes
What are the meninges of the brain packed with ?
Immune cells