Exam questions

Question 1

What are example of PAMPs?

Answer 1

PAMPs stand for pathogen asscoiated molecular patterns and examples of them are LPS which are bacterial cell wall components, viral RNA/DNA, flagellin etc

Question 2

How can the immune cells recognize PAMPs?

Answer 2

With their toll like receptors

Question 3

What are examples of DAMPs?

Answer 3

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.

Question 4

What are the five main ways T cells regulate immune responses?

Answer 4

1. They release anti-inflammatory cytokines such as IL-10 and TGF-B which inhibits activation and function of other T-cells
2. Cell-to-Cell contact inhibition by sending signals through direct contact to cells inhibintg them
3. 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
4. Indocution of apoptosis in immune cells
5. Modulation of antigen presenting cells (APCs) function so they can’t activate other immune cells like factor T cells

Question 5

What are the main differences between conventional and unconventional T-cells?

Answer 5

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

Question 6

What are 2 examples of cytosolic different PRRs?

Answer 6

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.

Question 7

What are the activation steps of Th cells?

Answer 7

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.

Question 8

Describe the polrarization process of Th cells

Answer 8

The polarization of Th cells are dependent on cytokines. IL-4, STAT4 and T-bet leads to Th1 proliferation. IL-4, STAT6 and GATA3 leads to proliferation to Th2, TGF-b, IL-6, STAT3 and RORgammaT leads to Th17 proliferation and TGFb and Foxp3 leads to Treg differentiation.

Question 9

What functions does the 3 most common Th cells have?

Answer 9

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 but can also cause allergic responses. Th17 defends against extracellular bacteria and fungi by recruiting neutrophils and enhancing barrier functions but can cause RA and lead to inflammation and joint damage.

Question 10

What are the two patyhways of Cytotoxic T cell mediated cell killing?

Answer 10

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

Question 11

Which cells respond to commensals in the gut and where are they produced?

Answer 11

-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.

Question 12

What effector function of Th17 contribute to homeostasis and how?

Answer 12

-(production of IL-17)IL-17 produced by Th17 cells stimulates production of antimicrobial peptides and enhances the
barrier function of epithelial cells, contributing to the control of commensal population and protection against
pathogens-
-(Recruitment of neutrophils) IL-17 recruits neutrophils to mucosal surfaces, aiding in the clearance of pathogogens
without causing excessive inflammation.
-(Tissue repair and maintenance) Th17 cells, through IL-17 and other cytokines, support tissue repair and
maintenance, promoting overall gut health.

Question 13

What are the Principles of central and peripheral tolerance:

Answer 13

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.

Question 14

Describe late phase allergy “molecular and cellular level”

Answer 14

Molecular
-Activated mast cells and basophils release chemokines recruiting other immune cells-
-IL4 and IL-13 from T cells contribute to late-phase respone
Cellular
-Eosinophils, neutrophils and T cells are recruited to the site
-Tissue damage and prolonged inflammation occur.

Question 15

Describe Phagocytosis of pathogens, what receptors and what are the major steps called?

Answer 15

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:

Question 16

Is NLPR3 part of the innate or adaptive immune response?

Answer 16

-This NLRP3-mediated inflammasome activation serves as a key component of the innate immune system,

Question 17

How does JAK inhibitors work shortly?

Answer 17

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.

Question 18

How IgA are transported across mucosal surfaces, what consequences for the structure and function of IgA

Answer 18

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.

Question 19

Immunological Consequences of Glucocorticoid Treatment:

Answer 19

Anti-inflammatory and Immunosuppressive Effects:
Cytokine Modulation: Suppresses the production of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF).
Leukocyte Migration Inhibition: Diminishes the migration of immune cells to sites of inflammation.
Inhibition of Immune Cell Activation:
T and B Cell Suppression: Reduces the activation and proliferation of T and B lymphocytes.
Macrophage Function Impairment: Hampers the activation and function of macrophages.
Resolution of Inflammation:
Vascular Permeability Reduction: Restricts the movement of immune cells, mitigating tissue edema.
Balance Shift in Mediators: Alters the pro-inflammatory and anti-inflammatory mediator equilibrium, fostering
resolution.
Immunosuppression:
Lymphocyte Apoptosis Induction: Triggers apoptosis in lymphocytes, contributing to overall immunosuppression.
Infection Risk: Prolonged use may heighten susceptibility to infections due to compromised immune responses.
Immunosuppression:
Lymphocyte Apoptosis Induction: Triggers apoptosis in lymphocytes, contributing to overall immunosuppression.
Infection Risk: Prolonged use may heighten susceptibility to infections due to compromised immune responses.

Question 20

Difference of phagocytic receptors

Answer 20

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.

Question 21

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)

Answer 21

• 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.

Question 22

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)

Answer 22

• 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.

Question 23

Which is the most abundant immune cell in the brain and what functions does it have under basal states and
during inflammation?

Answer 23

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 24

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)

Answer 24

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 25

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)

Answer 25

Routes by Which the Brain Affects Peripheral Immune Cells:
1. Neuroendocrine Pathway - Hypothalamic-Pituitary-Adrenal (HPA) Axis:
* Overview:
* The HPA axis is a major neuroendocrine pathway involving the hypothalamus, pituitary gland, and adrenal
glands.
* It releases signaling molecules that impact immune cells in the periphery.
* Major Signaling Molecules:
* Cortisol (Glucocorticoids):
* Released by the adrenal glands in response to stress signals.
* Effect on Immune Cells:
* Immunosuppression:
* Cortisol suppresses the immune system by inhibiting pro-inflammatory cytokines.
* It reduces the activity of immune cells, such as T cells and macrophages, thereby dampening the
immune response.

Question 26

Describe 2. Autonomic Nervous System (ANS) Pathway - Sympathetic Nervous System (SNS):
signalling pathways and effect

Answer 26

• Overview:
• The SNS is part of the autonomic nervous system, responsible for the “fight or flight” response.
• Norepinephrine is a key signaling molecule released by sympathetic nerves.
• Major Signaling Molecules:
• Norepinephrine:
• Released by sympathetic nerve terminals.
• Effect on Immune Cells:
• Modulation of Immune Function:
• Norepinephrine can either enhance or suppress immune responses depending on the context.
• It can affect the activity of immune cells, including T cells and macrophages, influencing their function
  in response to immune challenges.
  Impact on Immune Function:
• These neuroendocrine and autonomic pathways play a crucial role in the bidirectional communication
  between the brain and the immune system.
• Stress-related signals and neural inputs can modulate immune responses, impacting inflammation, immune
  cell trafficking, and overall immune function.
• Dysregulation of these pathways has been implicated in various immune-related disorders and chronic
  inflammatory conditions.

Question 27

Question 7 (4 points): Breast-fed infants seem to be protected against SARS-CoV-2 infection, as compared to
nonbreast-fed babies. Explain on a cellular and molecular level how the mucosae of breast-fed infants are
protected against the viral infection. (4p)

Answer 27

Breast-fed infants exhibit enhanced protection against SARS-CoV-2 infection compared to non-breast-fed babies,
attributed to cellular and molecular mechanisms.
Breast milk serves as a vital source of maternal antibodies, predominantly IgA, which actively block viral entry into
mucosal cells.
Additionally, immune cells present in breast milk, including T lymphocytes and macrophages, migrate to mucosal
tissues, releasing cytokines and chemokines that reinforce the antiviral response. The nutrient-rich composition of
breast milk, including bioactive factors like lactoferrin and oligosaccharides, contributes to a healthy mucosal
environment, with lactoferrin exhibiting direct antiviral properties.
Moreover, breastfeeding influences the infant’s gut microbiota, shaping a balanced microbial community that aids in
immune development and defense.
In summary, breastfeeding provides a multifaceted defense strategy, encompassing the transfer of immune
components, modulation of micr

Question 28

Question 1 (7 points): The innate immune system is the first line of defense against microbes. Innate immune cells
react to potential threats upon sensing through innate immune receptors. (7p)
b. Explain why innate immune receptors are located at different sites within the cells. (1p)

c. Describe how innate immunity can shape the subsequent adaptive response and give at least one example. (1p)

Answer 28

Specialization of Recognition:
* Different locations allow innate immune receptors to specialize in recognizing distinct types of pathogens or
danger signals.
* Receptors at the cell surface primarily recognize extracellular pathogens, while those in endosomes and
cytoplasm detect intracellular threats.

How Innate Immunity Shapes the Subsequent Adaptive Response and Example (1p):
* Adaptive Immune Priming:
* Innate immune responses provide signals and cytokines that shape the activation and differentiation of
adaptive immune cells.
* Dendritic cells, activated by innate signals, present antigens to T cells, initiating adaptive immune responses.
* Example:
* Activation of TLRs on dendritic cells by microbial components leads to the upregulation of co-stimulatory
molecules and cytokines.
* This primes naïve T cells and promotes their differentiation into effector T cells, shaping the adaptive immune
response.
Conclusion: Innate immune receptors, including TLRs, NLRs, RLRs, CLRs, and scavenger receptors, play crucial roles in
detecting pathogens and danger signals. Their strategic locations within cells allow for specialized recognition, and
the signals they generate influence the subsequent activation and differentiation of adaptive immune responses, as
exemplified by dendritic cell activation through TLRs.

Question 29

Anakinra (Kineret) is a recombinant version of the human IL-1 receptor antagonist (IL-1Ra) protein. Describe theraputic applications and considerations

Answer 29

Therapeutic Applications:
* Used in conditions like rheumatoid arthritis and autoinflammatory disorders.
* Alleviates symptoms by mitigating excessive IL-1 activity.
Considerations:
* May increase infection risk; monitoring for infections is essential during treatment.

Question 30

Question 5 (4 points): During the recent decades, it has become apparent that the brain and the immune
system are not separate entities but can influence each other. Briefly describe the pathways and consequences
when the activated immune system signals to the brain to induce brainmediated inflammatory symptoms.

Answer 30

This intricate network further involves the trafficking of immune cells into the brain from peripheral tissues. As these
immune cells infiltrate the brain, they release inflammatory molecules, contributing to localized inflammation and
the activation of resident immune cells.
Moreover, immune activation can modulate neurotransmitter systems, impacting the release of key signaling
molecules in the brain. This, in turn, leads to changes in mood, behavior, and cognitive functions.

Question 31

Describe 3 complement pathways:

Answer 31

The complement system consists of three main pathways: the classical pathway, the lectin pathway, and the
alternative pathway. Each pathway is activated by different triggers, such as antigen-antibody complexes for the
classical pathway, microbial carbohydrates for the lectin pathway, and spontaneous hydrolysis of C3 for the
alternative pathway. Despite their distinct activation mechanisms, all three pathways converge at the formation of
the C3 convertase, leading to a common outcome – the activation of the complement cascade, which enhances
immune responses, opsonizes pathogens, and facilitates their clearance.

Question 32

Why mainly IgG transported through the placenta to the baby:?

Answer 32

Neonatal FcR, active transport, IgG has a half-life of 3 weeks. After birth IgA through the milk. IgM babies can make.
Why? IgG is potent and important.

Question 33

2. Is rheumatoid arthritis a type 3 or type 4 hypersensitivity reaction?

Answer 33

Most autoimmune diseases are a bit of 2-4. Some even type 1.
Both Type 3 and 4

Question 34

Describe the Fas-fas Ligand pathway

Answer 34

-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

Question 34

Mechanisms that “turns of” innate immune responses

Answer 34

Feedback inhibition: Downstream products of immune activating signals inhibits the initial signaling pathway to
prevent overstimulation.
Decoy receptors: These receptors compete with functional immune receptors for ligand binding which reduces the
overall signaling strength.
Anti-inflammatory cytokines: For instance, IL-10 released by Tregs will suppress the pro-inflammatory response and
promote resolution of the inflammation.
Negative regulators: Proteins such as SOCS act as breaks on signaling cascades which limits the duration and
intensity of the immune response.

Question 35

What FcRs are:

Answer 35

-FcRs are cell surface receptors that specifically bind the Fc portion of antibodies.
- Various immune cells, such as macrophages, neutrophils, mast cells, NK cells etc express FcRs, but also red blood
cells which are important for the clearance of ICs.
-The ligands for FcRs are the Fc region of antibodies.

Question 36

The function/biological role of FcRs:

Answer 36

Phagocytosis and clearance:
-FcRs on phagocytic cells such as macrophages and neutrophils bind the Fc region of antibodies attached to
pathogens or target cells.
-This interaction enhances the recognition and engulfment of the opsonized particles, facilitating their clearance
from the body.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC):
- FcRs on e.g., NK cells bind to the Fc region of antibodies attached to target cells marked for destruction.
-The binding triggers the release of cytotoxic substances by the NK cells, leading to the lysis of the target cell. This is
important for defense against infected cells and cancer cells.

Question 37

The human major histocompatibility complex (MHC) is located in chromosome 6p21 and contains the human
leukocyte antigen (HLA) genes. A strong association between the HLA region and autoimmune disease has been
established for over fifty years. How can this HLA/MHC-association be of importance for development of
autoimmune diseases? Explain at the molecular and cellular level. (2p)

Answer 37

MHC and HLA are the same thing, named HLA in humans.
-MHC/HLA genes encode for cell surface proteins responsible for antigen-presentation.
- Variability in HLA genes can influence the peptide-binding specificity of HLA molecules, impacting the range of
presented antigens.
- Certain HLA alleles have been strongly associated with susceptibility or resistance to specific autoimmune diseases
- Molecularly, specific HLA alleles may generate HLA gene product that present self-antigens more effectively to T
cells, leading to the activation of autoreactive T cells
- At the cellular level, the HLA/MHC-association influences the efficiency of antigen presentation and subsequent
immune responses, contributing to the development of autoimmune diseases

Question 38

Explain at a molecular and cellular level how oral immunotherapy can reduce symptoms of peanut allergy.

Answer 38

Allergen desensitization and tolerance (Molecular(?)):
-incremental exposure to the allergen promotes desensitization of immune cells to the allergen.
- Alters the immune response, shifting it from an allergic to a more tolerant state.
- Continuous exposure triggers activation of Tregs which play a key role in suppressing the responses to allergens.
Antigen presentation and shift of effector response (cellular (?)):
-dendritic cells in the gut capture and present the allergen to T cells which initiates the immune response.
-repeated response by T cells promotes tolerance
- it also Shifts the balance from pro-allergic Th2 responses to regulatory Th1 responses.
B cell modulation:
-Interaction with B cells producing allergen-specific IgE antibodies.
- Gradual exposure induces a shift towards IgG4 production.
- Alters the antibody profile, reducing the potential for allergic reactions
Mucosal Immune Environment:
- the allergen interacts with GALT
- Fosters an immunosuppressive environment in the gut
- Supports oral tolerance, decreasing the likelihood of adverse reactions.
oral immunotherapy with Palforzia operates by desensitizing the immune system through gradual exposure to
peanut allergens. This process induces molecular and cellular changes, including the activation of regulatory T cells,
modulation of T and B cell responses, and the promotion of an immunosuppressive environment in the gut. These
mechanisms collectively contribute to the reduction of symptoms associated with peanut allergy, allowing patients to
tolerate small amounts of peanuts with only mild reactions.

Question 39

Normal Role for Immune Complexes:

Answer 39

Immune complexes play a crucial role in the clearance of pathogens and debris by facilitating their recognition and
removal by immune cells.
Clearance Mechanisms:
Phagocytosis by Macrophages: Immune complexes are recognized by Fc receptors on macrophages, leading to their
phagocytosis and subsequent degradation.
Renal Clearance: Small immune complexes may undergo filtration in the kidneys and be excreted in the urine.
Erythrocyte Immune Complex Clearance: Immune complexes can associate with erythrocytes, which carry them to
the liver for phagocytosis by Kupffer cells, contributing to clearance.

Question 40

Two mechanisms by which IgG immune complexes together with complement may result in harm to tissues.

Answer 40

IgG immune complexes can activate the complement system, leading to the generation of anaphylatoxins such as C3a
and C5a.
Anaphylatoxins attract and activate inflammatory cells, particularly neutrophils, causing an inflammatory response at
the site of immune complex deposition.
Excessive or chronic inflammation can result in tissue damage, especially in organs where immune complexes
accumulate, such as the kidneys in conditions like immune complex glomerulonephritis.
Complement-Mediated Tissue Damage:
Immune complexes can activate the classical pathway of the complement system, leading to the formation of the
membrane attack complex (MAC).
MAC formation results in the formation of pores in cell membranes, leading to cell lysis.
In tissues where immune complexes deposit, such as blood vessel walls in conditions like systemic lupus
erythematosus (SLE), complement activation and MAC formation can cause damage to endothelial cells, leading to
vasculitis and tissue injury.
OR
Tissue Destruction:
Immune complexes can deposit in tissues, triggering inflammation and recruiting immune cells.
Activation of complement and inflammatory responses can lead to tissue damage.
Autoimmune Pathogenesis:
In autoimmune diseases, the immune system may mistakenly target self-antigens.
Persistent formation of immune complexes against self-antigens can contribute to chronic inflammation and tissue
destruction.

Question 41

Blocking immune complex-Fc receptor interactions to improve autoimmune diseases

Answer 41

Blocking Fc Receptor Activation:
Mechanism: Inhibiting Fc receptor activation prevents immune cell activation in response to immune complexes.
Therapeutic Approach: Monoclonal antibodies targeting Fc receptors or Fc portions of antibodies can interfere with
immune complex binding and subsequent inflammatory responses.
Complement Inhibition:
Mechanism: Immune complexes often activate complement, leading to inflammation.
Therapeutic Approach: Complement inhibitors, such as anti-C5 antibodies or complement regulatory proteins, can
be used to prevent complement activation and tissue damage mediated by immune complexes.

Question 42

Question 6 (4 points): Surface plasmon resonance (SPR) is a phenomenon that can be used to measure the
concentration of biomolecules.
a. What can you learn about an antibody-antigen interaction by doing an SPR-based analysis? Give two examples.
(2p)

b. In order to study antibody-antigen interactions with SPR, either the antibody or the antigen needs to be
immobilized to a surface (a sensor chip), while the other molecule is provided in solution. Why is surface
immobilization necessary? (2p)

Answer 42

Information Learned from SPR-based Analysis of Antibody-Antigen Interaction:
1. Association and Dissociation Kinetics:
* SPR allows the real-time monitoring of the association and dissociation phases of an antibody-antigen
interaction.
* Kinetic information provides insights into the rate at which the molecules bind (association) and separate
(dissociation).
2. Affinity and Binding Strength:
* SPR enables the determination of the binding affinity between an antibody and its antigen.
* Affinity information helps assess the strength of the interaction, providing insights into the stability of the
antibody-antigen complex.

Surface Immobilization in SPR Studies:
Surface plasmon resonance occurs at the surface…
* Maintaining Molecules at the Sensor Surface:
* Surface immobilization is necessary to ensure that either the antibody or the antigen is stably present on the
sensor surface.
* This immobilization allows for the continuous monitoring of binding events without the molecules diffusing
away from the sensor.
surface immobilization in SPR studies is crucial for maintaining molecules at the sensor surface, enhancing sensitivity,
allowing real-time monitoring, and minimizing non-specific interactions, ultimately providing detailed insights into
antibody-antigen interactions.

Question 43

What is an example of a PRR that facilitates phagocytosis?

Answer 43

C-type lectin receptors bind to carbohydrates on pathogens which facilitate phagocytosis and activation of immune responses.

Question 44

What is an example of a PRR that activates a pro-inflammatory signalling cascade?

Answer 44

TLRs: Which stand for toll like receptors, they are membrane bound and recognize microbial components such as LPS. When activated it leads to a pro-inflammatory signaling cascade.

Question 45

Describe the sentisization process in allergies

Answer 45

-Sensitization (initial exposure): APCs present the allergen to Th2 cells →Th2 cells release IL-4 and IL-13 which
promotes B cell differentiation into antibody producing plasma cells → Plasma cells produce allergen-specific IgE
antibodies that bind to FcεRI receptors on mast cells and basophils.

Question 46

Describe early phase allergy response on molecular and cellular level

Answer 46

-Re-exposure to allergen cross-links IgE on mast cells/basophils. This triggers degranulation which releases
mediators such as histamine and prostaglandins. This causes vasodilation, increased vascular permeability, smooth
muscle contraction.
-other mediators that attract more immune cells to the site are also released.

Question 47

What happens in the engulfment step in phagocytosis?

Answer 47

-Engulfment: The phagocyte extends pseudopods to engulf the pathogen, forms the phagosome.

Question 48

What is is formed when the phagocyte has endocytosis the pathogen and what components does it contain to degrade the phagocyte?

Answer 48

Mechanisms inside the phagolysosome
- ROSs are produced and causes oxidative stress in microbial cells.
- NO produced by iNOS has antimicrobial effects
-Enzymes in the phagolysosome, such as lysozyme and proteases degrade microbial components.
- pH Acidification: Acidification of the phagolysosome creates an inhospitable environment for pathogens.

Question 49

What is NLPR3 and what does it do?

Answer 49

It’s an intracellular receptor that when activated upon exposure to PAMP or DAMP initiated signalling event cause conformational changes and it forms into NLRP3 inflammaosme

Question 50

What does the inflammasome consist of and what does it do?

Answer 50

It consists of NLPR3, the adaptor protein ASC and pro-caspasase-1 and facilitates cleavage and activation of caspasase-1

Question 51

What does caspasase-1 do?

Answer 51

Activates pro-inflammatory cytokines such as IL-1B and IL-18 and cause them to be released from the cell which contributes to inflammatory responses and activation of immune cells through pyroptosis which is a form of apoptosis where it releases it’s inflammatory contents.

Question 52

Describe shortly step by step what JAK signalling does

Answer 52

The general MoA of works like this:
1. Cytokines binds their respective receptors on the cell surface.
2. Receptor associated JAKs are activated.
3. The activated JAKs phosphorylate the receptor, creating docking sites for STAT proteins.
4. Phosphorylated STAT proteins (also phosphorylated by JAKs) bind the receptor and forms dimers that
translocate to the nucleus.
5. In the nucleus STAT dimers regulate gene expression of genes involved in inflammation and other immune
responses.

Question 53

What are some examples of names of JAK inhibitors

Answer 53

upadacitinib, baricitinib, and tofacitinib

Question 54

What are some side effects of JAK inhibitors

Answer 54

Side effects:
- JAK inhibitors can suppress the immune response, increasing the risk of infections. Especially herpes zoster.
- Changes in blood cell counts, including anemia, neutropenia, and lymphopenia, may occur.
-May elevate liver enzymes
- There is a potential increased risk of blood clots.
- Rare cases of gastrointestinal perforations have been reported.

Question 55

Glucocorticoids definition

Answer 55

Definition: Glucocorticoids are synthetic drugs designed to emulate the actions of natural corticosteroid hormones.

Question 56

Glucocorticoids purpouse

Answer 56

Purpose: Widely employed for their potent anti-inflammatory and immunosuppressive properties, contributing to
their use in conditions such as allergy and rheumatology.

Question 57

What receptor does glucocorticoids work on?

Answer 57

Receptor Interaction: Glucocorticoids enter cells and bind to cytoplasmic glucocorticoid receptors (GRs).

Question 58

Transcriptional Control of glucocorticoids?

Answer 58

-The glucocorticoid-GR complex translocate to the nucleus, where it acts as a transcription factor.
-This complex inhibits the transcription of pro-inflammatory genes while promoting the synthesis of antiinflammatory proteins like lipocortin-1.
Additional Actions:
Phospholipase A2 Inhibition:
-Reduces arachidonic acid production, leading to decreased synthesis of inflammatory mediators such as
prostaglandins and leukotrienes.
NF-κB Pathway Interference:
-Impairs the activation of NF-κB, a key regulator of immune and inflammatory responses.

Question 59

Describe endocytic PPRs

Answer 59

Function: PRRs are primarily responsible for recognizing specific molecular patterns associated with pathogens,
known as pathogen-associated molecular patterns (PAMPs). These patterns are typically conserved structures
present in various microorganisms.
Location: PRRs are commonly found on the surface of immune cells, such as macrophages and dendritic cells, as well
as on epithelial cells.
Recognition: PRRs recognize a broad range of pathogens based on their PAMPs, triggering internalization of the
pathogen for further processing and immune response activation.
Examples: Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) are examples of endocytic PRRs.

Question 60

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!
a) Which major pro-inflammatory Th subset is mainly needed for clearance (elimination) of:
-Viruses
-Fungi
-Parasites
-Intracellular bacteria

Answer 60

• Viruses Th1 cells
• Fungi Th17 cells
• Parasites Th2 cells
• Intracellular bacteria Th1 cells

Question 61

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!

b) The third signal required for the activation of a naïve Th cell is cytokines. Which specific cytokines are required
for polarization of the naïve Th cells into each of the three major pro-inflammatory Th subsets? (3p)

Answer 61

Cytokines for Polarization of Naïve Th Cells:
* Th1 Polarization: Interleukin-12 (IL-12)
* Th2 Polarization: Interleukin-4 (IL-4)
* Th17 Polarization: Interleukin-6 (IL-6), Transforming Growth Factor-beta (TGF-β)
* Treg (Regulatory T Cell) Polarization: Transforming Growth Factor-beta (TGF-β)

Question 62

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!
​
c) For each of the three pro-inflammatory Th subsets, state at least one cytokine that it secreted upon activation,
and explain briefly what target cell(s) this cytokine activates. (3p)

Answer 62

1. Th1 Subset:
   * Cytokine: Interferon-gamma (IFN-γ)
   * Target Cells: Activates macrophages, enhances antigen presentation, and promotes inflammation.
2. Th2 Subset:
   * Cytokine: Interleukin-4 (IL-4)
   * Target Cells: Stimulates B cells for antibody class switching to IgE, enhances eosinophil activation, and
   promotes humoral immunity.
3. Th17 Subset:
   * Cytokine: Interleukin-17 (IL-17)
   * Target Cells: Activates epithelial cells and fibroblasts, recruits neutrophils, and enhances the immune
   response against extracellular pathogens.

Question 63

Anakinra (Kineret) is a recombinant version of the human IL-1 receptor antagonist (IL-1Ra) protein. Describe their mechanism of action

Answer 63

Mechanism of Action:
* Anakinra is a recombinant IL-1 receptor antagonist (IL-1Ra).
* It competitively inhibits IL-1α and IL-1β from binding to IL-1 receptors, primarily IL-1R1.
Molecular Effects:
* Competitive inhibition prevents IL-1-mediated signaling.
* Blocks inflammatory pathways, reducing production of proinflammatory molecules.

Question 64

Question 5 (4 points): During the recent decades, it has become apparent that the brain and the immune
system are not separate entities but can influence each other. Describe what cytokines are involved in immune and brain interaction

Answer 64

One prominent avenue involves the release of pro-inflammatory cytokines by immune cells. These signaling
molecules, including interleukins such as IL-1, IL-6, and TNF can traverse the blood-brain barrier or stimulate afferent
nerve fibers, effectively communicating with the brain. The consequence is the activation of microglia and astrocytes
within the brain, which, in turn, release additional inflammatory mediators, fostering a neuroinflammatory
environment.

Question 65

Question 5 (4 points): During the recent decades, it has become apparent that the brain and the immune
system are not separate entities but can influence each other. How does the brain and body interact with each other on a more systemic way?

Answer 65

Additionally, the activation of the vagus nerve by the immune system introduces another dimension to this
communication. Signaling through the vagus nerve reaches the brainstem, influencing neuroinflammatory responses. The release of
stress hormones, such as cortisol, in response to immune activation adds another layer to this communication, as
these hormones interact with the hypothalamic-pituitary-adrenal (HPA) axis, regulating immune responses and
modulating inflammatory processes within the brain.
In summary, the bidirectional communication between the immune system and the brain involves a multifaceted
interplay of cytokines, neural pathways, immune cell trafficking, neurotransmitter modulation, and hormonal
responses. Understanding these complex mechanisms provides insights into the broader implications for neurological
and psychiatric conditions influenced by immune activation.

Question 66

Example disease where FcRs are involved (RA):

Answer 66

Antibodies form ICs with autoantigens in the joints. These ICs activate FcRs on immune cells in the synovium of the
joints. This leads to the activation of pro-inflammatory recponses such as cytokine release and recruitment of more
inflammatory cells. During clearance of the antibodies surrounding cells will be “caught in the crossfire”.