Exam Questions

(a) It needs to mount antigen responses but also be tolerant against food

(b) It has a large surface area

-> anatomical propertie, no problem

(c) It has other functions besides mounting immune responses (e.g. nutrient absorption)

-> true but not special

(d) It needs to protect from pathogens but also be in symbiosis with the microbiota

(e) The gut epithelium renews itself every few days

-> also there in skin so not only gut

(f) All of the above

(a) Mesenteric lymph nodes

-> außerhalb der Darmwand

(b) The Peyer’s patches

(c) Lamina propria

(d) Isolated lymphoid follicles

(e) Epithelium

(f) Crypts

(a) The IE is an effector site, whereas the LP is an inductive site

-> Both IE and LP are effector sites, where immune cells act, not where they are primed.

(b) The IE contains only specialized lymphocytes with site-specific functional properties

(c) The IE belongs to the mucosa, whereas the LP is in the sub-mucosa

-> both mucosa

(d) The numerous epithelial cells of the IE compartment make it an important innate immune site

(e) Only the stromal cells in the IE compartment are immunologically active

-> In the IE, epithelial cells and IELs are active, but stromal activity is minimal.

-> In the LP, many stromal cell types are immunologically active

(f) The LP contains numerous and diverse immune cell types unlike the IE compartment

(a) Priming of intestinal Th17 responses

-> Th17 responses in the gut are driven mainly by cDC2

(b) Priming of intestinal Th1 responses

(c) Migration from the epithelium to the lamina propria to present antigen

-> pathway cdc1 from LP to mesenteric lymph node

(d) Cross presentation of epithelial derived antigen to CD8+ T cells

(e) Help B cells produce IgA in the isolated lymphoid follicles

-> IgA induction depends on:cDC2, Tfh help…

-> cDC! almost no role in IgA switching

(f) Migration to the mesenteric lymph node to prime Th2 responses

-> Th2 is characteristic for cDC2

(a) DCs will present antigen in the draining mesenteric lymph nodes

(b) DCs will take antigen from lumen and present to lamina propria T cells

-> naive tcells are never primed in the laminate propria

(c) During priming in mesenteric lymph nodes DCs will give gut homing signals to T cells

(d) T cells primed in the Peyer’s patches cross through M cells and end up in the lamina propria

-> M cells transport antigen not T cells

(e) When primed in GALT they will express CCR9 and α4b7

(f) They are specific for the microbiota

-> no,

(a) It is when the microbiota antagonize evading pathogens

(b) It is when the microbiota antagonize autoimmunity

-> only attacs pathogens

(c) There is direct and indirect colonization resistance depending on the mechanisms adopted by the microbiota

(d) Too much colonization resistance leads to dysbiosis

-> the other way around

(e) Some colonization resistance mechanisms may involve the immune system

(f) A colonization resistance mechanism is to eat less fiber so that to limit the intestinal mucous barrier and thus pathogens cannot evade

it

-> the other way around: Weniger Ballaststoffe → Mikrobiota frisst Mucus → Barriere wird dünner → Pathogene leichter

(a) The more diverse microbiota the more Th17 cells we have

-> th17 is dependent on SFB

(b) Different bacteria impact different immune cell lineages

(c) The microbiota is not required for antibody production

-> not it is important

(d) Dysbiosis during early life may pre-dispose to allergies and autoimmunity

(e) Dysbiosis during early life is not an important issue, as long as it is corrected later on

-> not true

(f) By regulating production of biological factors from the epithelium, the microbiota can impact the generation of specific adaptive immunity

(a) Enteropathogenic E. coli (EPEC) is a noninvasive bacterium whereas L. monocytogenes is an invasive bacterium

(b) As a noninvasive bacterium EPEC does not need to attach to the epithelial barrier

-> need to attach

(c) Invasive bacteria like L. monocytogenes can infect the gut mucosa

(d) EPEC is called an attaching and effacing bacterium because it damages the cell membrane of macrophages in which it replicates

-> no calles so because in attache to enterozyten and kills mikrovilli from gut epithel

(e) As an invasive bacterium L. monocytogenes does not need toxins like EPEC

-> need toxin (listeriolysin O)

(f) Experimental evidence suggests that EPEC induces a type 3 whereas L. monocytogenes a type 1 response

(a) Crohn’s disease (CD) and ulcerative colitis (UC) are both types of IBD

(b) The only difference between CD and UC and is the location of the GI tract which they affect

-> no only location also different th profiles, dicontinue/continue…

(c) The microbiota composition is thought to play a critical role in predisposing for IBD

(d) GWAS studies have identified 10 mutations which are the cause of IBD

-> keine allein kausal sonder alle erhöhen risiko

(e) Innate immunity is thought not to be important for IBD

-> fehler im angeboren IS sind hochrelevant

(f) The incidence of IBD in Denmark and worldwide increases and this is largely linked to environmental factors like diet

(a) In CD, our immune system attacks and destroys our gut epithelia due to an antigen-specific

adaptive immune response to gluten

(b) The adaptive immune response is dominated by Th1 cells

(c) The pathogenic response is driven by deamidated gluten peptides

(d) If one expresses the CD-dominant MHC-II molecule HLA-DQ8, they will develop symptoms

-> notwendig aber nicht ausreichend

(e) The response to gluten is strictly adaptive

-> also innate response

(f) Therapies to block transglutaminase are routinely used to treat CD

-> no only diet helps

(a) The skin contains three distinct layers: epidermis, dermis, and hypodermis

(b) Despite its diverse immune cells, the skin is an immune privileged site because of its many important functions (e.g. melanin and sweat production)

-> nope: brain, eye, testicals… IPS

(c) Immune cells are concentrated in the epidermis

-> not immune cells in dermis

(d) The stratum corneum makes the skin a true, almost impenetrable, barrier

(e) The dermis is where the specialized Langerhans cells are found

-> nope epidermis

(f) Sensory neurons in the skin actively regulate immune responses

(a) They are as good at presenting antigen as DCs

-> no prof. Antigen presenting cells, can present but inefficient

(b) Their expression of TLRs is a first line of defense against infection

c) They become corneocytes to form a very tight stratified corneum barrier

(d) They can become specialized to have specific immune roles

-> they can become immunological aktv but no specification

(e) They interact with and regulate local immune cell populations

(f) Underneath the stratum corneum is a 1-cell thick layer of keratinocytes, reminiscent of the gut epithelium

-> nope

(a) The skin barrier breaks at the follicle and allows microbes to penetrate

(b) Contains specialized keratinocytes along its length to provide niches for immune cells

(c) It is a highly immunosuppressive site where few inflammatory responses can take place

-> not not immunosupressive, a lot of immune cells

(d) Its few immune cells are almost all T cells

-> also tregs, dendritic cells, macrophages

(e) Acne is a localized innate response at the hair follicle driven by Propionibacterium acnes

-> also adaptive mechanisms and not enough for making it interesting site

(f) It sustains a balance between effector memory and regulatory T cells

(a) Sensory neurons in the skin connect with the draining lymph nodes and alert the immune system of infections

-> no direct connection to lymph node

(b) Sensory neurons in the skin express receptors that sense infections and alert local immune cell populations

(c) Upon infection or inflammation sensory neurons in the skin produce IL-23, which allows them to interact with DCs and thus initiate adaptive immunity

-> IL 23 is from dendritic cells, macrophages

(d) Infection at one skin site can produce enhanced immunity at a distant site due to the action of sensory neurons

(e) Sensory neurons when activated during inflammation cause direct tissue pathology

-> no direct damage more like itch etc

(a) As for the gut, the skin microbiota is important for the induction of adaptive immune responses

(b) Skin associated lymphoid tissues (SALT) are scattered around the dermis at steady-state similar to ILFs in the gut lamina propria

-> salt is functional concept not structural

(c) A uniform microbiota composition throughout the skin ensures robust immunity at skin sites

-> not uniform, diversity

(d) The microbiota can “probe” the immune system by entering through the barrier at hair follicles and sweat glands

(e) SALT can be seen in certain chronic inflammatory conditions but not in healthy skin

(f) The skin microbiota is associated with common skin conditions such as atopic dermatitis, acne and seborrhoeic dermatitis

(a) Natural Tregs are so called because we all have them and are naturally occurring

-> because they come from Thymus

(b) Induced Tregs differentiate from naïve T cells in the periphery

(c) They can suppress T cells by cytokines or by interfering with DC-T cell interactions

(d) They only suppress T cells of the same antigen specificity

-> not antigen specific

(e) They have the capacity to suppress T cells in a tissue-specific manner

(f) Although they mediate peripheral tolerance, they are generally dispensable since mutations affecting their function or development are harmless

-> not dipensable

(a) Superactivating APCs that present self-peptides

(b) Inducing high concentrations of serum IgG immune complexes, which activate self-reactive anti-IgG expressing B cells

(c) Methylating host DNA so that TLR9 can recognize CpG motifs and activate self-reactive B cells

-> no extra methylating (Eine Infektion führt nicht dazu, dass wir unsere DNA mehr methylieren oder weniger methylieren, um TLR9 zu aktivieren.)

(d) Mimicking self-antigens

(e) Inducing immune cell infiltration at immune-privileged sites

-> not true (brach of immune privilige not break of ignorance)

(f) Engaging TLRs on B cells

-> more support for autoreactive antibodys

(a) Tissue damage can lead to the release of new antigens leading to priming of new self-reactive lymphocytes

(b) Immune-privileged tissues are excluded

-> not excluded

(c) Protein complexes taken up by B cells can lead to the generation of new self-reactive T cells

(d) New self-reactive T cells cannot cause damage because they are ignorant

-> not ignorant

(e) T cell help to B cells can generate further self-reactive B cells

(f) Epitope spreading is an interesting scientific observation but unimportant in disease pathogenesis

-> central elementt of pathogenese

(a) Antibodies can neutralize the TCR of Tregs

-> not true

(b) Activated T cells in the tissue can recruit damaging granulocytes

(c) Antibody mediated complement fixation can lead to tissue inflammation or direct cell killing

(d) Cytokines from T cells and innate cells can lead to remodeling of the local tissue microenvironment

(e) Fc receptors on T cells can recognize antibody coated cells or tissues and become activated in a process known as antibody directed cellular activation

-> Tcells not Fc receptors, they are on nk cells, macrophages…

(f) Auto-antibodies can function as agonists or antagonists of signaling receptors leading to hyper or hypo activation of the targeted receptor

(a) AI diseases can be organ specific or systemic

(b) AI diseases can manifest due to single gene mutations

(c) Although T cells get activated in AI diseases they are not pathogenic

-> often direct pathogenic

(d) Granulocytes and other innate cells are not generally considered pathogenic because they don’t live as long as adaptive lymphocytes and cannot form memory

-> they are pathogenic

(e) Screening for single-nucleotide polymorphisms (SNPs) across the genome is often used as means to help understand what genes are involved in AI pathogenesis and initiation

(f) HLA polymorphisms and the impact of the environment are only important after the disease has started

-> before!

(a) Most inhaled particles are trapped by mucus and swept out of the lungs by cilia on epithelial cells

(b) The vocal cord separates the upper and lower airways and are believed to trap host airway microbiota within the lower airway, creating a highly pro-inflammatory environment in the steady-state lung

-> ther is no differntiation

(c) Nasal-associated lymphoid tissue (NALT) forms following encounter of antigens in the upper airway, while antigens rarely make it to the lungs, and bronchus-associated lymphoid-tissue

(BALT) is thus less often observed

(d) The lungs are drained by cervical lymph nodes

-> false

(e) Alveolar macrophages sit in the airway space of the lung. Here, they sense and readily respond to high oxygen levels

-> they are not reacting to high oxygen level

(a) Alveolar macrophages produce IL-12

-> they try to avoid IL12 to prevent not necessary T cell activation

(b) Interstitial macrophages produce IL-10

(c) Plasma cells produce high levels of IgM

-> no a lot of IgA

(d) IL-10 and TGF-b dampen the activity of most airway immune cells

(e) The regulatory T cell (Treg) is the main T cell subtype in the airways during homeostasis

(a) Pulmonary endocrine cells respond to perturbations in the local milieu, including airway stretching

(b) Airway basal cells differentiate into type 1 alveolar cells

-> they dont differntiate

(c) Goblet cells produce mucus in the upper airways

(d) Clara cells lubricate the airway space in the bronchioles

(e) Brush cells are ciliated and brush mucus out of the lungs and into the oral cavity

-> not ciliated and dont brush mucus

(a) Alveolar macrophages are precursors of interstitial macrophages

-> not precursors (vorläufer)

(b) Alveolar macrophages can differentiate from incoming monocytes

(c) Alveolar macrophages engulf and remove inhaled particles

(d) Alveolar macrophages are part of the second-line defense in the lung

-> part of first line defence, second line: neutrophile, dcs…

(e) Alveolar macrophages clear the airways by removing dead cells

(a) IgA-producing plasma cells

(b) Keratinocytes

-> skin

(c) Alveolar macrophages

-> free in aleveo space

(d) Innate lymphoid cells (ILCs)

(e) Dendritic cells

(a)  Distressed airway epithelium produce alarmins (IL-25, IL-33, TSLP)

(b)  Airway epithelial cells sense dsRNA and produce type I interferon

-> there are more cells who notice dsRNA & doe typ 1 IFN

(c)  Airway Tuft cells sense tissue damage

(d)  Airway dendritic cells sense proteoglycan and produce IL-23

-> its typical in the gut

(e)  Airway dendritic cells interact directly with allergen

(a)  IL-2 induces mucus production by goblet cells

-> induced by IL-13

(b)  IL-4 facilitates isotype switching to IgE

(c)  IL-5 activates eosinophils

(d)  IL-10 activates type 2 innate lymphoid cells (ILC2s)

-> IL-10 anti inflammatory cytokines

-> ILC2 activated through IL-25

(e)  IL-13 induces bronchial hyperreactivity

(a) Upon sensitization, allergen-specific IgA is loaded on FceRI receptors on plasma cells

-> IgE

b) Following allergen and IgE crosslinking, mast cells readily release pre-formed inflammatory mediators

(c) Histamine is released by basophils

(d) After allergen and IgE crosslinking, eosinophils secrete IL-5

-> eosinophile activated thorugh IL5

-> after activation they set free: MDP, ECP not IL 5

(e) At sensitization, allergen-specific IgE is loaded on FceRI receptors on basophils

(a) The infected individual induces more Th2 than Th1 cells

(b)  The infected individual produce auto-antibodies to type I or type III interferons

(c)  The infected individual has excess progenitors of immature monocytes and neutrophils in the blood

(d) The infected individual produces neutralizing anti-ACE2 antibodies

-> wrong

(e)  The infected individual induces anti-hemagglutinin CD8 T cells

-> influenca protein

(a) Granulomas are formed by Th17 cells during M. tuberculosis infection

-> fromed by Th1 cells, macrophages…

(b) M. tuberculosis prevent the fusing of phagosomes and lysosomes in neutrophils

-> blocks phagolysosmal in MACROPHAGES

(c) During M. tuberculosis infection, dendritic cells present decoy antigens to T cells

(d) M. tuberculosis delays the adaptive immune response by 2-8 weeks

(e) Most individuals infected with M. tuberculosis experience a latent infection

(a) Loss-of-function mutations in the transcription factor AIRE prevent MHC class II surface expression

-> AIRE MUtation lead to AI not missing mhcII expression

-> MHCII defect becaue of mutation in CIITA/RFX

(b) Loss-of-function mutations in BAFF and APRIL abolish signaling by the T cell survival factor, IL-7

-> they are important for bcell survival & class change not signaling

(c) Loss-of-function mutations in the common gamma chain prevent differentiation of thymic epithelium

-> mutation lead to x-linked scid, influence lymohcytes not differntiation of tyhmusepithel

(d) Loss-of-function mutations in the transcription factor FOXN1 impair T cell receptor signaling

-> Problem is missing tyhmusarchitecture not signal transmission

(e) Loss-of-function mutations in RAG1 and RAG2 impair VDJ recombination and thereby arrest lymphocyte development

(a) IgG crosses the placenta and babies are born with high maternal IgG levels.

(b) Breastmilk supply the newborn with maternal IgG and IgA.

(c) T cell responses are sufficient to eliminate infections in early life.

-> not antibordy are quit important

(d) Antibody production is dependent on T cell help.

-> right but no reason fo this issue

(e) Deficiency in IgA is often asymptomatic.

(a) Immunodeficiencies are often identified because of recurrent opportunistic infections in early childhood.

(b) Defects in single gene variants cause secondary immunodeficiencies.

-> primary

(c) Pathogens evade specific components of the immune system to cause secondary immunodeficiencies.

-> primary

(d) Most types of primary immunodeficiencies are uncommon, often extremely rare.

(e) Biologics (for example cell depletion) may cause primary immunodeficiencies.

-> no can cause seondary

(a) Some RNA viruses encode different segments of their genome resulting major changes in surface protein expression; a phenomenon known as antigenic shift.

(b) RNA polymerase lack proofreading and RNA viruses have a greater mutation rate.

(c) RNA viruses have dedicated a large proportion of their genome to encode immunoevasions.

-> small genoms, use single mutlifunctional proteins

(d) RNA viruses target the type I and/or type III interferon pathway.

(e) RNA viruses modify peptidoglycan to avoid recognition by NOD receptors on host immune cells.

-> they are in bacteria not virus

(a) Some extracellular bacteria escape from the phagosome into the cytosol.

-> mechanism in intracellular bacteria

(b) Some extracellular bacteria shield or modify their surface peptidoglycan.

(c) Some extracellular bacteria encode proteins that inhibit the complement cascade

(d) Some extracellular bacteria target the type I and/or type III interferon pathway.

-> important for virus not extracellular bacteria

(e) Some extracellular bacteria express variants of lipid A to avoid sensing by TLR4.

(a) p53 induces cell cycle arrest in response to DNA damage

(b) Loss-of-function mutations in TP53 lead to uncontrolled cell proliferation

(c) p53 activates apoptosis when cellular damage is irreparable

(d) p53 mutations are associated with resistance to therapies targeting immune checkpoints

-> main enhanver for resistance : MHC I loss, JAK1/2 mutatiom

(e) p53 activation leads to the inhibition of DNA repair processes

-> not direct, indirect repair gene are regulated trhourhg p53 …

a) Downregulation of major histocompatibility complex (MHC) class I molecules

(b) Presentation of cancer antigens to the cell surface

-> would enhance immune reaction

(c) Enhanced expression of neoantigens to attract immune cells

-> tumor cells reduce neoantigens or change them

d) Recruitment of regulatory T cells (Tregs) to suppress the immune response

(e) Secretion of immunosuppressive factors such as TGF-β and IL-10.

(a) Low expression of immune checkpoint molecules like PD-L1

-> cold tumor propertie

(b) Presence of pro-inflammatory cytokines such as IFN-γ and IL-2

(c) High tumor mutational burden (TMB) leading to neoantigen production

(d) High infiltration of cytotoxic T lymphocytes (CTLs)

(e) Immunologically "cold" stroma with minimal immune cell activity

-> less immune cells no reaction to bad or no reaction to immuntherapie

(a) MHC class I molecules bind peptides derived from intracellular proteins

(b) Peptides presented by MHC class I are typically 8-10 amino acids long

(c) MHC class I molecules require beta-2 microglobulin (B2M) for stable expression on the cell surface

(d) MHC class I molecules present peptides primarily to CD4+ T cells

-> MHC I & CD8+, MHC II & CD4+

(e) The peptide-binding groove of MHC class I is formed by the alpha1 and alpha2 domains

(a) Programmed death-ligand 1 (PD-L1)

(b) Beta-2 microglobulin (B2M)

(c) Transforming growth factor-beta (TGF-β)

(d) Tumor necrosis factor-alpha (TNF-α)

-> Pro inflammatory

(e) Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

(a) Both anti-CTLA4 and anti-PD-1 primarily affect T cells in lymphoid tissues

-> pd1 effect in tumor

(b) Anti-CTLA4 primarily affects T cells in tumor tissues, while anti-PD-1 primarily affects T cells in lymphoid tissues

-> the other way around

(c) Anti-CTLA4 primarily affects T cells in lymphoid tissues, whereas anti-PD-1 primarily affects T cells in peripheral tissues

(d) Anti-CTLA4 and anti-PD-1 primarily affect T cells in peripheral tissues

-> affect in lymph nodes

(e) Anti-CTLA4 primarily affects B cells in the peripheral tissues, while anti-PD-1 primarily affects T cells in the lymphoid tissues

-> t cell molecule

(a) CTLA4 binds to CD28 and blocks the co-stimulatory signals of CD28

-> bind on B7

(b) Blocking CTLA4 inhibits CD28 signaling

-> enhance signaling

(c) CTLA4 wins the competition with CD28 to bind to B7 molecules on APCs

(d) CTLA4 binds to PD-L1 to induce inhibitory signals in T cells

-> PD-L1 bind on PD-1

(e) CTLA4 binds to TCR and block the stimulatory signals of T cell receptor

-> CTLA-4 no direct interatcion with TCR

(a) PD-1 binds to CD28 and activates T cells

-> PD-1 binde PD-L1 or PD-L2 not CD28

(b) PD-1 binds to PD-L1, reducing cytokine production by T cells

(c) PD-1 binds to MHC, reducing cytokine production by T cells

-> task of TCR

(d) PD-L1 binds to CD28, reducing cytokine production by T cells

PD-L1 bind PD-1

(e) PD-1 binds to PD-L1, reducing the proliferation of T cells

a) Prevent cancer cells from evading the immune system by inhibiting the interaction between PD-1 on T-cells and PD-L1 on cancer cells

(b) Directly destroy cancer cells by using monoclonal antibodies against PD-1

-> no direct killing, activate Tcells

(c) Decrease cell proliferation of cancerous cells

-> therapie not direct on tumor cells

(d) Reduce the supply of blood to the tumor by inhibiting angiogenesis

-> task of anti_vegf

(e) Prevent activation of naïve T cells in lymph nodes

-> other way around

(a) To treat a large proportion of patients (more than 80%) who do not benefit from current checkpoint inhibitor therapies.

(b) To treat patients who have a durable response (less than 20% of patients).

-> no especially they are not the problem

(c) To treat a small proportion of patients (less than 20%) who do not benefit from current checkpoint inhibitor therapies

-> group ist big not small

(d) To treat patients after transplantation

-> no main motivation

(e) It is a conspiracy by pharmaceutical companies

(a) Mispairing with endogenous T cell receptor can results in a new TCR which recognizes alternative peptides presented on healthy cells

(b) Cytokine release syndrome (CRS) related to co-infusion of high dose IL-2

-> not main mechanism

(c) Cytokine release syndrome (CRS)

(d) Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS)

-> CAR-T typical

(e) Unintended destruction of healthy tissue due recognition of surface antigens

-> CAR-T typical

(a) They persist longer

(b) They proliferate better

(c) They are less exhausted

-> not main advantage

(d) They are more specific for the targeted antigen

-> specifity maintained thoruhg scFv

(e) They are less likely to cause side effects

-> more likely

(a) T cells derived from blood

-> would be adoptive tcell transfer

(b) High-dose IL2

(c) A tumor biopsy

(d) Lentivirus to introduce a T-cell receptor

-> TCR-T or CAR-T enigneering

(e) T cells obtained from a tumor fragment

(a) A low mutational burden

-> would lead to wore TILS

(b) The tumor should be a solid mass

(c) High infiltration of T cells in the tumor mass

(d) A high mutational burden

(e) The tumor should be not be infiltrated with virus-specific T cells

-> they can be very affectiv

(a) To increase proliferation of the CAR T cells

-> proliferation influenced only from cosimulation domain

(b) To anchor the CAR in the T cell membrane

(c) To provide stability for the CAR and antigen interaction

-> stability mainly from scFv

(d) To provide flexibility for the single chain variable (scFv) to bind the targeted antigen

(e) To provide optimal distance between the T cell and the targeted antigen