Exam questions Flashcards
What are example of PAMPs?
PAMPs stand for pathogen asscoiated molecular patterns and examples of them are LPS which are bacterial cell wall components, viral RNA/DNA, flagellin etc
How can the immune cells recognize PAMPs?
With their pattern recognition receptors
What are examples of DAMPs?
DAMPs stand for damage assoicated molecular patterns and are released from damage and stressed cells. Examples include DNA or cytosolic components outside of the cell.
What are the five main ways T cells regulate immune responses?
- They release anti-inflammatory cytokines such as IL-10 and TGF-B which inhibits activation and function of other T-cells
- Cell-to-Cell contact inhibition by sending signals through direct contact to cells inhibintg them
- Metabolic regulation, making the surrounding enviorment less favorable for immune cells depriving it with necessary nutrients, or alter metabolic conditiions making it harder for effector T-cells to grow and function
- Indocution of apoptosis in immune cells
- Modulation of antigen presenting cells (APCs) function so they can’t activate other immune cells like factor T cells
What are the main differences between conventional and unconventional T-cells?
Conventional T-cells like CD4+ and CD8+ recognises antigens presented on MHC molecules. Unconventional T cells recognize antigens without the requirment of MHC molecules and instead respond to broader range of signals such as metabolites, lipids, and other non peptide antigens and act as a bridge between the adaptive and innate immune system
What are 2 examples of cytosolic different PRRs?
NLRs: Are cytosolic or endosome bound receptors thar recognize intracellular pathogens and stress signals and trigger the assembly of inflammasomes that cause the release of IL-1b.
rig like receptors are cytosolic receptors that identifies viral RNA in the cytoplasm and induces interferon production to inhibit viral reproduction.
What are the activation steps of Th cells?
The activation steps of Th cells include TCR-MHC interaction where the TCR receptor binds to a compatible antigen on a MHC molecule, co-stimulation that happens between co-receptors CD28 on T-cell and B7 on APCs and cytokine signaling such as IL-12+IFN-g or TGFb-IL6 which allows for T-cell differentiation so the immune response is appropriate.
Describe the polrarization process of Th cells
Th1 polarizes from IL-12 and produces IFN-g and TNF-a. Th2 proliferates from IL-4 and produces IL-4,IL-5 and IL-13, Th17 proliferates from TGF-B and IL-6 and produces IL17 and IL-22. Tregs proliferate from TGF-B and makes TGF-B and IL-10.
What functions does the 3 most common Th cells have?
Th1 is primarily involved in intracellular pathogens such as viruses and intracellular bacteria. It activates macrophages and CD8+ cells. Th2 is associated with humoral immunity and is effective against parasites, stimulates B cells to produce antibodies especially IgE, activates eosinophils and cause mhistamin release from mast cells and basophils but can also cause allergic responses. Th17 defends against extracellular bacteria and fungi by recruiting neutrophils, stimulate epithelial cells to produce antimicrobal peptides and promotes epithelial proliferation and repair but can cause RA and lead to inflammation and joint damage.
What are the two patyhways of Cytotoxic T cell mediated cell killing?
Perforin-Granzyme pathway
-CTLs release perforin, a protein that forms pores in target cell membranes
-Perforin facilitates entry of granzymes, proteolytic enzymes, into the target cell through these pores.
-Granzymes enter the cytoplasm and activate caspases, initiating apoptosis pathways
-apoptosis leads to programed cell death, preventing release of potentially harmful contents.
Fas-fas Ligand pathway
-CTLs express FasL on their surface
-FasL bind to Fas receptors on the surface of the target cell.
-Binding of FasL activates caspases inside the target cell
-Caspase activation initiates apoptosis
Which cells respond to commensals in the gut and where are they produced?
-Th17 cells is the major group of cells that respond to commensals in the gut.
-Th17 cells are primarly induced in the gut-associated lymphoid tissue (GALT), such as Peyer’s patches and
mesenteric lymph nodes, in response to signals from commensal bacteria.
What effector function of Th17 contribute to homeostasis and how?
The Th17 causes antimicrobal peptides to be produces from epithelial cells by secreting IL-17 and IL-22 and recruits neutrophils to site, IL-22 also promotes epitehlial proliferation and repair which also helps with maintaing homeostasis as it’s harder for pathogens to atatch because the tissue is constantly proliferating
What are the Principles of central and peripheral tolerance:
Central tolerance:
Definition: It’s the mechanism by which potentially self-reactive T cells and B cells are eliminated or rendered nonfunctional during their development in the thymus (T cells) or bone marrow (B cells).
Thymic selection: T cells undergo positive selection for recognition of self-antigens presented by thymic epithelial
cells. Those with strong reactivity to self-antigens undergo negative selection and are eliminated. (need to recognize
but not react(?)).
Bone marrow selection: B cells that strongly react to self-antigens during their development are eliminated or under
go BCR editing to reduce self-reactivity.
Peripheral tolerance:
Definition: Tolerance mechanism that occur in the periphery (outside thymus or bone marrow) t control and suppress
any remaining self-reactive lymphocytes that escaped the central tolerance.
Tregs: Suppress the immune responses and prevent autoimmunity by inhibiting the activation of autoreactive T cells.
Anergy (tolerance induction): Anergy refers to the functional inactivation of potentially self-reactive lymphocytes that
encounter self-antigens without co-stimulatory signals.
Describe late phase allergy “molecular and cellular level”
Late phase is then hours after exposure when eosinophils have had time to be recruited to the site of inflammation from the signaling of Th2 with IL-5. The eosinophils can release toxic proteins that cause inflammation. This can then lead to chronic inflammation with tissue damage etc.
Describe Phagocytosis of pathogens, what receptors and what are the major steps called?
Receptors typically involved in initiation of phagocytosis:
PPRs e.g., TLRs, opsonin receptors and scavenger receptors bind to PAMPs on pathogen surfaces.
Major steps:
-Recognition and attachment: PPRs bind to PAMP
-Engulfment
-Phagolysosome:
-Digestion:
-Exocytosis:
Is NLPR3 part of the innate or adaptive immune response?
-This NLRP3-mediated inflammasome activation serves as a key component of the innate immune system,
How does JAK inhibitors work shortly?
Inhibition:
-JAK inhibitors, such as , interfere with JAK activity, preventing
phosphorylation of STAT proteins
-By inhibiting JAKs, these drugs downregulate the production of pro-inflammatory cytokines and other mediators
involved in immune responses.
How IgA are transported across mucosal surfaces, what consequences for the structure and function of IgA
Plasma cells in the submucosa produce dimeric IgA which are two monomers linked by their J chain. Epithelial cells can express polymeric-Ig receptor which binds to the J chain of the dimer and facilitates transport though the endothelial cells by receptor-mediated endocytosis. It’s transported in vesicles to for example the lumen in the GI tract where the poly-Ig receptor is enzymatically cleaved and IgA is released with a secretory component, that is part of the receptor still bound to it. This protects it from degradation from proteases and enhances stability and function and gives a non-inflammatory protection. IgA is important for mucosal immunity
They are first produced by antibodies as monomers, single units but become monomers when passing the mucosal tissues to work more efficiently called dimers
To get across the mucosal lining IgA binds to a receptor called pIgR found on the cells lining the tissue. They are then transported as a complex through the cells to the surface where the receptor is cut and the secretory component stays attached to IgA.
The secretory component protects IgA from being degraded and allows it to work in harsh environments like the gut.
When they form dimers they can attach better to harmful microbes and blocking these pathogens help maintain balance in gut microbiome.
Immunological Consequences of Glucocorticoid Treatment:
Glucocorticoid treatments inhibits pro-inflammatory signaling of enzymes such as IL-1, IL-6, TNF-a, it inhibits COX-2 which leads to decreased prostaglandin production, prevents leukocyte migration and lysosomal enzyme release, reduces T-cell proliferation, induces apoptosis of lymphocytes, suppresses macrophage activation and inhibits complement activation.
Difference of phagocytic receptors
Function: Phagocytic receptors are specialized in recognizing and facilitating the engulfment of particulate matter,
including pathogens, cell debris, and other foreign particles.
Location: These receptors are typically present on the surface of phagocytic cells, such as macrophages and
neutrophils.
Recognition: Phagocytic receptors recognize specific ligands on the surface of particles targeted for engulfment. This
recognition initiates signaling cascades that lead to the formation of pseudopods, which surround and engulf the
target particle.
Examples: Fc receptors and complement receptors are examples of phagocytic receptors.
In summary, the main difference lies in their primary functions and the types of patterns they recognize. Endocytic
PRRs focus on the recognition of PAMPs to internalize a wide range of pathogens, while phagocytic receptors are
specialized in the recognition and engulfment of particulate matter, including pathogens and other foreign particles.
A1. what the drug consists of and the presumed main mechanism (2p)
Adalimumab (Humira):
B1. why this leads to improvement in a particular immune-mediated disease (2p)
C1. one principal side effect (1p)
- Composition and Mechanism:
- Adalimumab is a monoclonal antibody.
- It targets tumor necrosis factor (TNF), a pro-inflammatory cytokine.
- Mechanism: Adalimumab binds to soluble and membrane-bound TNF, preventing its interaction with TNF
receptors and inhibiting the inflammatory cascade. - Example Disease: Rheumatoid Arthritis (RA): - TNF is a key mediator of inflammation in RA. - By inhibiting TNF,
adalimumab reduces inflammation, joint damage, and alleviates symptoms in RA patients.
Increased Risk of Infections: - Inhibiting TNF may compromise the immune response against infections. - Patients on
adalimumab are monitored for signs of infections, and precautions are taken to minimize the risk.
A2. what the drug consists of and the presumed main mechanism (2p)
Rituximab (Rituxan):
B2. why this leads to improvement in a particular immune-mediated disease (2p)
C2. one principal side effect (1p)
- Composition and Mechanism:
- Rituximab is a chimeric monoclonal antibody.
- It targets CD20, a protein on the surface of B cells.
- Mechanism: Rituximab binds to CD20, leading to B cell depletion through antibody-dependent cellular
cytotoxicity and complement-mediated lysis
Example Disease: Rheumatoid Arthritis (RA) and Non-Hodgkin Lymphoma: - B cells play a role in the pathogenesis
of RA and lymphoma. - Rituximab depletes B cells, reducing autoantibody production in RA and targeting malignant B
cells in lymphoma.
Increased Risk of Infections: - B cell depletion may compromise the immune response, increasing susceptibility to
infections. - Precautions are taken to monitor and manage infections in patients receiving rituximab.
Which is the most abundant immune cell in the brain and what functions does it have under basal states and
during inflammation?
the most abundant immune cell in the brain is the microglia.
Functions under Basal States:
1. Surveillance and Maintenance:
Microglia continuously survey the brain environment, monitoring for abnormalities or potential threats.
They play a crucial role in maintaining the overall health and homeostasis of the central nervous system (CNS).
2. Phagocytosis of Cellular Debris:
Microglia actively engage in phagocytosis, clearing cellular debris, dead neurons, and other waste products to
support tissue maintenance.
3. Neuronal Support:
Microglia contribute to the maintenance of neuronal circuits by providing support and regulating synaptic
connections.
Functions during Inflammation:
1. Immune Response Activation:
In response to injury, infection, or inflammation in the brain, microglia become activated.
They undergo morphological changes and release pro-inflammatory cytokines to initiate and regulate the immune
response.
2. Phagocytosis of Pathogens:
Activated microglia enhance their phagocytic activity to engulf and eliminate pathogens, infected cells, or debris
associated with inflammation.
3. Antigen Presentation:
Microglia can present antigens to T cells, contributing to the adaptive immune response in the brain during
inflammation.
4. Regulation of Inflammatory Responses:
Microglia play a role in modulating the intensity and duration of inflammatory responses in the brain to prevent
excessive damage to healthy tissues.
While microglia are essential for immune surveillance and response in the brain, dysregulation of their activities can
contribute to neuroinflammatory disorders and neurodegenerative diseases.
Question 2 (10 points): T helper (Th) cells are important regulators of immune reactions. They are polarized by
cytokines, and act by secreting cytokines that will lead to activation of other effector cells. Read all questions (a-d)
before you start to write your answer!
d) For one of the three Th subsets, give one example of a cytokine that
* Cytokine to Block: Interleukin-17 (IL-17)
* Disease Setting: Rheumatoid Arthritis (RA)
Rationale: In rheumatoid arthritis, there is excessive inflammation and joint damage. Th17 cells, which produce IL17, play a significant role in promoting inflammation and recruiting immune cells to the joints. Blocking IL-17 or
inhibiting its signaling pathways can be beneficial in RA treatment by reducing the pro-inflammatory response and
mitigating joint destruction. Several therapeutic agents targeting IL-17 or its receptor are used in clinical practice to
manage rheumatoid arthritis and related autoimmune conditions.
Question 5 (4 points): During recent decades, it has become apparent that the brain and the immune system are
not separate entities but can influence each other.
Which are the main routes by which the brain can affect immune cells in the periphery? Shortly describe two such
routes/pathways, including major signaling molecules, and describe how they affect the function of immune cells.
(4p)
The inflammatory reflex regulated the immune response and prevents excessive inflammation through interactions between the vagus nerve, splenic nerve and immune cells. When cytokines, PAMPs and DAMPs are present in peripheral tissues the molecules activate the vagus nerve that send signals to the brainstem. The brain stem has a reflex response that causes the vagus nerve to transmit signals to the celiac ganglion which communicates to the splenic nerve. The splenic nerve is adrenergic and releases norepinephrine onto specialized cholinergic T cells in the spleen. This causes the cholinergic T cells to release acetylcholine which binds to receptors on macrophages and inhibits the production of pro-inflammatory cytokines TNF-a, IL-1B and IL-18.
The HPA axis in the hypothalamus is activated during stress and releases CRH and CRF into the pituitary gland circulation. This causes the pituitary gland to secrete ACTH into the blood stream that acts on the adrenal cortex in the kidneys and cause production and release of cortisol. The peripheral tissue has glucocorticoid receptors that the cortisol acts on. Cortisol suppresses the production of pro-inflammatory cytokines such as TNF-a, IL-1B and IL-6 from macrophages, T cells and dendritic cells. It suppresses T cell proliferation and differentiation, promotes Tregs and reduces activity of innate immune cell. It causes leukocytes to migrate from bloodstream to lymphoid tissues. However during acute stress the immune system is enhanced due to norepinephrine and adrenaline also being released when activating the sympathetic nervous system. Immune cells migrate from bone marrow to peripheral tissue, NK becomes more cytotoxic and pro-inflammatory cytokines are being released.
Describe 2. Autonomic Nervous System (ANS) Pathway - Sympathetic Nervous System (SNS):
signalling pathways and effect
In response to stress the sympathetic nervous system will become more activated and cause SNS fibers to release norepinephrine which acts locally on immune organs such as lymph nodes, spleen, bone marrow etc, The adrenal medulla will also release epinephrine into the blood stream which can binds to adrenergic receptors on immune cells. This causes under acute stress increased mobilization of the neutrophils, monocytes and NK cells to the peripheral tissues and bloodstream. It also enhances the phagocytic activity of macrophages and neutrophils and cause secretion of pro-inflammatory cytokines. Chronic stress however generally makes it less responsive and causes more anti-inflammatory macrophages secreting IL-10, a bias toward Th2 polarization of Th cells, decreased proliferation of CD8+ cells etc.
