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MSc Sommer 2021 > Immunologie 2 > Flashcards

Immunologie 2 Flashcards

1
Q

What is atopy?

A

A predisposition to become IgE-sensitized to environmental allergens

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2
Q

Name 5 different forms of IgE-mediated allergic reactions.

A
  • systemic anaphylaxis
  • acute urticaria
  • seasonal rhinoconjuctivitis (hay fever)
  • asthma
  • food allergy
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3
Q

Systemic anaphylaxis

Name 2 common stimuli, route of entry, clinical symptoms

A
  1. Drugs, venoms, food (e.g. peanuts), serum
  2. Intravenous – directly or following absorption into the blood after oral intake
  3. edema, increased vascular permeability, death
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4
Q

Acute urticaria

Name 2 common stimuli, route of entry, clinical symptoms

A
  1. Post-viral, animal hair, bee stings, allergy testing
  2. Through the skin, systemic
  3. local increase in blood flow and vascular permeability, edema
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5
Q

Seasonal rhinoconjuctivitis (hay fever):

Name 2 common stimuli, route of entry, clinical symptoms

A
  1. Pollens, dust-mite feces
  2. Contact with conjunctiva of eye and nasal mucosa
  3. edema of conjuctiva and nasal mucosa, sneezing
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6
Q

Asthma:

Name 2 common stimuli, route of entry, clinical symptoms

A
  1. Dander, pollens, dust-mite feces
  2. Inhalation leading to contact with mucosal lining of lower airways
  3. bronchial constriction, increased mucus production, airway inflammation, bronchial hyperreactivity
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7
Q

Food allergy:

Name 2 common stimuli, route of entry, clinical symptoms

A
  1. Peanuts, tree nuts, shellfish, milk, eggs, soy, wheat
  2. oral
  3. vomiting, diarrhea, itching, hives, rarely anaphylaxis
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8
Q

What type of immune response is mandatory for developing an IgE mediated allergic disease?

A
  • The cytokine responses are type 2 immune responses.
  • Differentiation of naïve T cells to the Th2 phenotype; then Th2 secretes cytokines IL-4, IL-5, IL-13, and co-stimulatory signals stimulate B cells to class switch and produce IgE.
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9
Q

At which sites in the body is most of IgE localized?

A

Predominantly in the linings of the tissues where mast cells are found: skin, mucosal, and submucosal tissues

Note: the mast cells are already covered by the IgE, and the release of granule content is triggered by antigen binding to these IgE antibodies.

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10
Q

Which functional feature do papain and Der p1 have in common and how is it related to allergy propagation?

A
  • They are both enzymatic allergens (they bind to B cells, engage IgE molecules of B cells and promote B cell response); both cysteine proteases. They break barriers so they can go through the skin or mucosa. Then they can be taken up by DCs which then migrate to the lymph node and prime Th2 cells.
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11
Q

Many (not all) inhaled allergens share following features. Explain shortly how they relate to their allergenic properties:

  • Protein, often with carbohydrate side chains
  • Low dose
  • Low molecular weight
  • Highly soluble
  • Stable
  • Contains peptides binding to host MHC class II Molecules
A
  • Protein, often with carbohydrate side chains
    • Protein antigens induce T-cell responses
  • Low dose
    • Favors activation of IL-4-producing CD4+ T cells
  • Low molecular weight
    • Allergen can diffuse out of particles into the mucosa
  • Highly soluble
    • Allergen can be readily eluted/dissolved from particles
  • Stable
    • Allergen can survive/remain effective in desiccated/dried particle
  • Contains peptides binding to host MHC class II Molecules
    • Required for T-cell priming/activation of T cells at first contact
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12
Q

Explain shortly why it makes sense that genetic polymorphism of IL-13, IL-33, FcεR are linked to susceptibility to Asthma?

A

IL-13 favors CD4+ T cell differentiation into Th2 cells; Th2 cytokines help stimulate B cells to switch to IgE production.

IL-33 (and IL-13) can be produced by activated mast cells and damaged or injured epithelial cells, and contributes to amplification of the Th2 response. IL-33 acts directly on Th2 cells via IL-33 receptors.

Fcε​R is an IgE receptor found on mast cells (FcεRI = high affinity IgE receptor). Soluble IgE binds to the FcεR on the mast cell; Antigen binding to IgE cross-links the receptors, causing release of chemical mediators from mast cells.

  • IgE-mediated allergic disease
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13
Q

How can allergy to non-peptide allergens such as Penicillin be linked to MHC polymorphism?

A

Some drugs can interact with specific HLA alleles in a way that changes the structure of peptide antigens bound in the groove of the HLA molecule -> altered peptides -> autoimmune-type response

Particular peptide:MHC combinations favor a Th2 response -> allergy

Certain MHC allele products can bind the peptide and others cannot. So this is how it is linked to MHC polymorphism.

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14
Q

Name the term, which describes the function of a drug such as penicillin in terms of inducing a B-cell response.

A

Involved in hapten-carrier response

Penicillin can bind to various proteins which then makes it able to bind to the B cell receptor

Antigen specific B cell presents to peptide specific helper T cell

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15
Q

What is desensitization and how might it work?

A
  • Immunotherapy to restore a patient’s ability to tolerate exposure to an allergen.

The allergen is injected in tiny amounts and is increased over subsequent injections.

  1. The IgE antibody response is changed over time to an IgG dominated response.
  2. Desensitization also seems to induce Treg cells that secrete IL-10 and/or TGF-β which skews the response away from IgE production.

This works really well with wasp venom as well as bee venom.

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16
Q

What exactly does an allergen in triggering IgE mediated activation of mast cells (keep it simple)? Name the receptor to which it binds.

A
  • A multivalent allergen binding to IgE which is already bound to Fcε receptors of mast cells causes cross-linking of the Fcε receptors.
  • This induces mast cells to release inflammatory lipid mediators, cytokines, and chemokines.
  • FcεRI is the high-affinity IgE receptor on mast cells.
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17
Q

Which compounds are immediately released after triggering the IgE receptor of mast cells and where have they been stored?

A

Tryptase, chymase, cathepsin G, carboxypeptidase, histamine, heparin, some TNF-α – stored in preformed granules inside the mast cell.

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18
Q

Which cells are recruited by Prostaglandin D2?

A

Th2 cells, eosinophils, and basophils

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19
Q

What is the physiological role of eosinophils and which protein compound released by them triggers degranulation of mast cells and basophils?

A
  • Defense against parasites (helminths).
    • Release toxic granule proteins and free radicals to kill microorganisms and parasites
    • Synthesize chemical mediators to amplify the inflammatory response, activate epithelial cells, recruite and activate more eosinophils and leukocytes (Production of prostaglandins and leukotrienes)
  • They may also play a role in restoring tissue homeostasis after infection and tissue damage
  • major basic protein
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20
Q

Which phase of allergy is affected by antihistamines and which phase by glucocorticoids?

A

The immediate phase/immediate response is affected by antihistamines (because the immediate phase is caused by histamine, prostaglandins, and other preformed or rapidly synthesized mediators released by mast cells).

The late phase is affected by glucocorticoids (the late phase is cause by factors which result in vasodilation, vascular leakage, edema, recruitment of eos, basos, monos, and lymphs).

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21
Q

Explain the term “endotype” with respect to asthma.

A

Endotypes are various different phenotypic subtypes of asthma characterized by differences in the nature of the inflammatory cell infiltrates present in the airways, and in the molecular signature of inflammatory mediators that can be recovered from the airways.

This can also lead to differences in patients’ responsiveness to different therapies.

Common endotypes include:

  • common allergic asthma – Th2 cells, eos, basos – most common
  • exercise-induced asthma
  • neutrophil-predominant asthma
  • steroid-resistant asthma – Th17 cells, neutrophils
  • eosinophil-predominant asthma is another one
  • allergic bronchopulmonary aspergillosis (ABPA) is another one – Th17 cells
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22
Q

What are the major effector molecules in Arthus reaction and serum sickness?

A
  • Antibodies forming immune complexes
  • Fc receptors (FcγIII) on leukocytes
  • complement - C5a and C3a
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23
Q

Differentiate between Arthus reaction and serum sickness?

A

Serum sickness – response against foreign immunoglobulins, formation of immune complexes which then activates complement which then causes damage.

Immune complexes localize in certain areas.

Arthus reaction has preformed IgG against the allergen, thats why it may appear in booster vaccines.

Serum sicknes develops IgG after antigen is introduced to the body. So for serum sickness: normal immune response development

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24
Q

Which antigen (molecule) classes induces delayed type hypersensitivity, and which contact sensitivity?

A

DTH –proteins: insect venoms, mycobacterial proteins

Contact – haptens, small metal ions

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25
Q

Which are the target molecules in induction of nickel allergy.

i) in terms of the T-cell response to divalent cations
ii) induction of a proinflammatory signal, which is needed to develop the reaction.

A
  1. The divalent cations can alter the conformation or the peptide binding of MHC class II molecules, which provokes a T cell response
  2. Can bind to receptor TLR-4 to produce a pro-inflammatory signal
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26
Q

Which food protein causes Celiac disease?

A

Gluten (probably more specifically α-gliadin found in gluten)

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27
Q

Please explain the role of Transglutaminase in development of Celiac disease.

A

The enzyme transglutaminase deamidates the gluten protein gliadin enabling it to bind strongly to HLA-DQ2.

-> activation of gliadin-specific CD4+ T cells -> secrete IFN-γ in lamina propria -> intestinal inflammatory response

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28
Q

Give an example for a hypersensitivity:

A
  • Immediate - Type I – allergic rhinitis, allergic asthma
    • IgE mediated, Th2
  • Antibody mediated - Type II – penicillin allergy
    • takes longer to appear than immediate hypersensitivity. Is due to binding of soluble IgG bound to surfaces.
  • Type III – serum sickness
    • IgG mediated by immune complexes
  • Type IV (Th1/Th17/CTL) mediated – contact dermatitis to poison ivy, tuberculin reaction
    • delayed type hypersensitivity. Classic is tuberculin reaction. Appears later, not immediate. Cell mediated.
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29
Q

What is sensitization?

A

involves class switching to IgE production on 1st contact with an allergen

Induction of Type II cytokine producing T cells induces class switch

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30
Q

What is an ‘autologous’, ‘syngeneic’, allogeneic’ and ‘xenogeneic’ graft?

A
  • Autologous graft: graft transplanted from one individual to the same individual (self)
  • Syngeneic graft: graft transplanted between to genetically identical individuals
  • Allogeneic graft: graft transplanted between 2 genetically different individual of same species
  • Xenogeneic graft: graft transplanted between individuals of different species
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31
Q

Please fill in the following table indicating as to which graft will be accepted and which rejected!

A

see picture

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32
Q

Will an animal of strain x accept a graft from strain y after prior transplantation of a graft from strain x?

A

No

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33
Q

An animal of strain x receives a skin allograft from strain z which is rejected within 3 days. Has this animal had a previous skin allograft and if yes of which strain?

A
  • Yes, this is a 2nd set rejection. The animal had a previous allograft from strain z/same strain as the 1st time.
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34
Q

In humans, will a child accept a skin graft from one of its parents?

A
  • No, in humans, the child only inherits half of the HLA genes from each parent, so the other half of the HLA molecules would be foreign.

In these experimental mice, they are inbred and homozygous for these alleles, whereas humans are heterozygous.

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35
Q

After transplantation of a kidney, which molecules are responsible for direct versus indirect allorecognition by the recipient’s T cells?

A

see picture

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36
Q

Are the peptides presented by donor MHC molecules in a solid organ graft ‘self’ or ‘foreign’ to the host?

A

foreign

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37
Q

What are the frequencies of cells specific for a foreign peptide in the context of self-MHC molecules versus a foreign MHC molecule plus foreign peptide among naïve CD4+ T cells?

A
  • 1 to 10% of an individual’s T cells will directly recognize an allogeneic/foreign MHC molecule
  • Only 1 in 105 or 106 T cells recognize a microbial peptide displayed by self-MHC molecules.
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38
Q

Up to how many alleles are there for a given HLA molecule in the human population?

A
  • Over 10,000 total; more than 3,000 for HLA-B (ch. 6, p 124)
  • Definitely several thousand. This is the most polymorphic locus in the genome.
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39
Q

Are alloantigens also indirectly presented to CD8+ T cells and if yes by what mechanism?

A
  • Yes, by cross-presentation (cross-priming). Host dendritic cells ingest proteins of graft cells, deliver the proteins to the cytoplasm where they are processed by proteasomes, and then the peptides are presented on class I MHC molecules.
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40
Q

If indirect allostimulation of recipient CD8+ T cells occurred, would these cells lyse donor cells and if not why?

A
  • No, because CD8+ CTLS generated by indirect recognition of allogeneic MHC are restricted to recognition of peptides from these allogeneic MHC molecules bound to recipient (self) MHC molecules. The donor cells do not express recipient MHC molecules, so the CTLs will not be able to lyse them.
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41
Q

What is an allogeneic mixed leukocyte reaction (allo-MLR)?

A
  • An in vitro reaction of alloreactive T cells from one individual against MHC antigens on blood cells from another individual. The MLR involves proliferation of and cytokine secretion by both CD4 + and CD8 + T cells.
    • This is widely used in vitro readout to study alloreactivity of T cells
    • Can also use this to check for reactivity between recipient T cells and donor MHC molecules
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42
Q

Please indicate the mechanisms of graft rejection?

A

see picture

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43
Q

Why does the binding of preformed antibodies cause greater damage to a xeno than to an allograft?

A

They activate complement, and complement regulatory proteins made by xeno cells cannot interact with human complement proteins, so they cannot limit the extent of injury induced by the human complement system.

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44
Q

May a human individual with blood group A receive a blood transfusion from a donor with blood group 0 and if yes, why?

A

Yes, because Group 0 donor red blood cells do not contain A nor B antigens. The blood group A individual will have preformed anti-B IgM but will not react to 0 blood which has no B antigen present.

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45
Q

Please name the mechanism of action of immunosuppressants Cyclosporine and Tacrolimus used to prevent allograft rejection.

A
  • Inhibits Calcineurin-dependent NFAT activation and thus transcription of T cell genes encoding cytokines such as IL-2. This blocks IL-2 dependent proliferation and differentiation of T cells.
    • Cyclosporine, Tacrolimus
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46
Q

Which cells cause Graft-Versus-Host-Disease?

A

Donor T cells

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47
Q

Which tumours preferentially occur in patients receiving prolonged immunosuppressive therapy after allotransplantation?

A

Virus-associated tumors such as uterine cervical carcinoma (associated with HPV) and lymphomas (associated with EBV).

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48
Q

Please name the main classes of tumour antigens.

A
  • Neoantigens, produced by mutated genes in different tumor cell clones
  • Products of oncogenic viruses
  • Overexpressed cellular proteins/self antigens
    • May be silenced in normal cells; may be expressed at abnormally high levels; may be expressed by more cells
    • De-repressed expression – e.g. cancer/testes antigens
      • Normally methylated
      • During cancer, gets demethylated and can cause T cell reaction
    • Strong overexpression of oncogenic protein due to gene amplification – e.g. HER2/neu in breast carcinomas
    • Increased # of cells expressing tissue-specific protein – e.g. tyrosinase in melanomas
  • Others
    • Oncofetal antigens
      • AFP – comes up in hepatic carcinoma. Can be used as a tumor marker. Genes not strongly expressed in adults but only in fetal life, so there is not tolerance mechanisms in adults
      • CEA is also a fetal antigen
    • Altered glycolipid and glycoprotein antigens
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49
Q

Which cells are the main mediators of anti-tumor immunity?

A

T cells, especially CD8+ CTLs; and CD4+ Th1 cells to maintain the response

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50
Q

How do tumors manage to escape anti-tumor immunity?

A
  • Active inhibition of antitumor immune responses by production of immunosuppressive proteins
  • Expression of inhibitory cell surface proteins
  • Loss of immune-stimulating tumor antigens/neoantigens
  • Mutations in MHC genes or genes needed for antigen processing, leading to lack of T cell recognition of the tumor
  • Induction of regulatory T cells
  • Stimulation of macrophages to go from pro-inflammatory to anti-inflammatory phenotype
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51
Q

What is a checkpoint inhibitor?

A
  • A method of inhibiting immune checkpoints.
    • Immune checkpoints are blocks in immune responses.
    • CTLA-4 is expressed on regulatory T cells which blocks and removes B7 on APCs -> costimulation signals through B7-CD28 binding are blocked -> T cell response is blocked
    • PD-1 on antigen-activated T cells interacts with PD-L1 on tumor cells -> inhibits signals from TCR coreceptor complex, CD28, and other costimulatory receptors -> inactivation of T cells
  • Checkpoint inhibitors block PD-1, PD-L1, or CTLA-4 -> removes T cell inhibition -> allows anti-tumor T cell response to resume
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52
Q

Which approaches are employed for active therapeutic vaccinations against cancer?

A
  • Identify tumor-specific mutations, mutated HLA-binding peptides, and T cells from the patient that are neoantigen-specific
    • Use proinflammatory molecules such as CpG DNA, dsRNA mimics, and cytokines to enhance the number of activated dendritic cells at the vaccination site
  • DC-based: Purify dendritic cells from the patient, incubate with tumor antigens, and inject back into the patient
  • DNA vaccines and viral vectors encoding tumor antigens which are synthesized in the cytosol of dendritic cells, for example, and can then be presented via class I MHC to CD8+ T cells to induce CTL response
    • Need an inflammatory component to drive T cell response
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53
Q

What is a CAR T cell?

A
  • Chimeric antigen receptor T cell; genetically engineered TCR with tumor antigen-specific binding sites and having cytoplasmic tails containing both TCR signaling and costimulatory receptor signaling domains.
    • Thus no costimulation is needed to activate the T cell
    • You will always get a response from the CAR T cell, but if the tumor cells mutate and lose that antigen, you lose the response
54
Q

What are the modes of action of therapeutic monoclonal antibodies directly binding to tumor cells?

A
  • Engaging host effector mechanisms to kill the tumor cells, such as NK cell-mediated cytotoxicity, complement-mediated lysis, and complement- or Fc- receptor-mediated phagocytosis by macrophages – bind to cell surfaces
  • Interference with growth factor receptor signaling necessary for tumor growth and survival – bind to growth factor receptors
  • Targeting host T cells to the tumor cell via bispecific T cell engagers (BiTEs)
    • Can engage host T cells to attack tumor cells with no need for the T cell itself to be antigen-specific
  • Linking chemotherapy drug or radioisotope to the antibody brings that toxin directly to the tumor cell (immunotoxins)
55
Q

What is meant by the ‘Graft-versus-Leukemia Effect’?

A
  • T cells (and NK cells, though they are more rare, and they do not induce GvHD) from the donor recognize the recipient’s leukemia cells as foreign and attack it.
    • Pivotal for successful BMT
    • Oldest form of cellular therapy that we have – 2nd line therapy after tx with classical chemo and irradiation failure
    • Trying to balance between GvL and GvHD
56
Q

Which of the following immunomodulators has a similar mechanism to azathioprine?

What class of drug is it?

  1. Cyclophosphamide
  2. Mycophenolate
  3. Abatacept
  4. Rapamycin
A

Mycophenolate

  • intercalating agent
  • intercalates with DNA and blocks DNA synthesis after it is processed, metabolized
57
Q

Match the following immunomodulating antibodies with their respective mechanism of action:

  1. Natalizumab
  2. Rituximab
  3. Muromomab
  4. Tocilizumab
A
  1. Natalizumab – inhibits cell migration by blocking VLA-4
  2. Rituximab – depletion of B cells by targeting CD19
  3. Muromomab – prevents allograph rejection by targeting the CD3 complex, which inhibits T-cell receptor signaling
  4. Tocilizumab – Anti-IL-6-receptor
58
Q
  1. True or false – chimeric antigen receptor (CAR) T cells are cells that have been retrovirally transduced with a tumor-specific T-cell receptor in order to treat a leukemia.
A

False - Because it is not a T cell receptor actually.

It is a chimeric/fusion receptor which includes intracellular signaling for activation and co-stimulation.

59
Q

Which statement is false?

  1. The vaccine Provenge is prepared using the patient’s own antigen-dendrititc cells to induce therapeutic anti-tumor T-cell responses.
  2. Clinical trials of vaccines against HPV-16 and HPV-18 (associated with 70% of cervical cancers) were 100% effective in preventing cancers caused by these viruses.
  3. Cell-based cancer vaccines can use the patient’s tumor as a source of antigens. In order to enhance immunogenecity these can be mixed with adjuvants such as CpG, which binds to TLR-7.
A
  1. is false b/c CpG binds to TLR-9.
60
Q

Which of the following treatments against cancer is a checkpoint blockade therapy? (One or more may apply.)

  1. Ipilimumab – anti-CTLA-4 antibody
  2. Trastuzumab - anti-HER2/neu antibody
  3. Rituximab - anti-CD20 antibody
  4. Pembrolizumab – anti-PD-1 antibody
  5. Sipuleucei-T - patient’s dendritic cells culture with prostatic acid phosphatase tumor antigen and GM-CSF and reinfused into patient
A
  1. Ipilimumab – anti-CTLA-4 antibody
  2. x
  3. x
  4. Pembrolizumab – anti-PD-1 antibody
    1. PD-1 is a sign of exhaustion on CD8 T cells. They stop working. This is an immune checkpoint to prevent over-active immune response. If you block PD-L1 (which is upregulated on the tumor cells sometimes), you reactivate the T cell so it can kill the tumor.
    2. This drug is more safe than the anti-CTLA-4
  5. x
61
Q
  1. True or False: Chimeric antigen receptor (CAR) T cells can recognize other target molecules besides peptide:MHC complexes.
A

True

  • Use of CAR allows the T cell to recognize almost any molecule regardless of presentation (kind of like an antibody)
62
Q
  1. Match the vaccines of the organism with the type of vaccine
    1. C. diptheriae
    2. H. flu B
    3. MMR
    4. BCG
    5. Influenza A
    6. Sabin polio vaccine
A
  1. C. diptheriae – toxin based
  2. H. flu B – conjugate polysaccharide
  3. MMR – live-attenuated
  4. BCG – live-attenuated
  5. Influenza A – killed
  6. Sabin polio vaccine – live-attenuated
63
Q

Fill in the blanks.

Vaccines have exhibited many phenomena that are beneficial and can be exploited. For example, when an antibody response againsta a bacterial polysaccharide is desired, it is conjugated to a protein to exploit the phenomonon of _______, thus ensuring T-dependent antibody responses. In addition, vaccines may protect against different subtypes of virus, as in the case of influenza, a phenomenon called ___________. When enough people in a population are vaccinated, _______ immunity is achieved, where even unvaccinated individuals are indirectly protected from infection.

A

linked recognition

heterosubtypic

herd

64
Q

Explain the three main drawbacks of peptide-based vaccines.

A
  1. The peptide may not bind to all MHC molecules present in the population due to MHC diversity/polymorphism.
  2. Could induce tolerance if loaded onto cells other than dendritic cells.
  3. Requires cross-presentation in specific DC types to load the peptides into MHC class I molecules for presentation to CD8+ T cells.
65
Q

True or False: all routes of vaccination successfully elicit virtually identical immune responses.

A

False

66
Q

Match the adjuvant to the immune receptor it stimulates

  1. Alum
  2. Freund’s complete adjuvant
  3. LPS
  4. DNA
  5. Imiquimod
A
  1. Alum – NLRP3
  2. Freund’s complete adjuvant – NOD2
  3. LPS – TLR-4
  4. DNA – TLR-9
  5. Imiquimod – TLR-7/8
67
Q

Name one “drug” which can block signal 1.

Define signal 1 and outline the mode of action of the drug.

A
  • Signal 1 is antigen recognition by a lymphocyte receptor (TCR or BCR).
  • Drug: β-interferon
    • binds to HLA molecules and block antigen presentation
  • Drug: muromomab
    • CD3 mAb blocks TCR signaling
68
Q

Name one “drug” which can block signal 2.

Define signal 2 and outline the mode of action of the drug.

A

Signal 2: co-stimulation of a T cell / danger signal -> B7 on DCs interact with CD28 on the T cell.

Drug: Abatacept - a CTLA-4 IgG, binds to B7 which blocks interaction with CD28.

69
Q

Name one “drug” which can block signal 3.

Define signal 3 and outline the mode of action of the drug.

A
  • Signal 3: further activation/clonal expansion of the T cell for example by upregulation of high-affinity IL-2 receptor and production of more IL-2, and cytokine release by activated APCs
  • drug: Cyclosporin A and Tacrolimus inhibit activation of calcineurin which in turn cannot phosphorylate the transcription factor NFAT, and thus NFAT is not translocated into the nucleus where it would normally increase expression of IL-2 and other cytokines.
70
Q

By what can you recognize how far an antibody is humanized? Any idea, why antibodies need to be humanized?

A

Antibodies need to be humanized to reduce immune responses to the non-human portion of the antibodies b/c this causes immune complexes to form and causes serum sickness or even anaphylaxis.

The ending of the mAb name tells you if it is humanized: -zumab = humanized

71
Q

There are two famous drugs which interfere with migration / homing of lymphocytes. Can you name them and / or the target molecule and describe what step of migration they block.

A
  • Fingolimod
    • target = sphingosine-1 phosphate receptor
    • blocks lymphocyte trafficking out of lymphoid tissues
  • Natalizumab
    • target = VLA-4 integrin
    • blocks leukocyte migration into the CNS
72
Q

What is a bacterial superantigen and how does it activate T cells?

A

what? Certain bacterial toxins which activate many more clones of T cells than conventional antigens -> large amounts of cytokines are produced -> systemic inflammatory syndrome

how? Binds to class II MHC molecules outside the peptide-binding groove and to TCRs on all T cells which express certain TCR Vβ gene family chains, ex: Vβ 8

73
Q

What are the 3 effector mechanisms how T cells can respond to extracellular bacteria?

A
  1. T cell mediated (Th1) antibody production via secretion of various cytokines - IFN-γ -> IgG
  2. Th1 macrophage activation via IFN-γ and TNFα secretion leads to phagocytosis and bacterial killing
  3. Th17 inflammatory response / recruitment of neutrophils and monocytes– due to secretion of IL-17, TNF, and other cytokines

(Th2 – eosinophil activation – not typically for extracellular bacteria)

74
Q

What are the 5 effector mechanisms how antibodies and complement can respond to extracellular bacteria?

A
  • a) neutralization via antibodies – IgG, IgM, IgA
  • b) opsonization by antibodies -> Fc receptor-mediated phagocytosis – IgG1 and IgG3
  • c) complement activation -> phagocytosis of C3b-coated bacteria
  • d) complement activation -> inflammation / inflammatory response – C3a, C5a - anaphylotoxins
  • e) complement activation -> lysis of microbe – IgM, IgG1, IgG3
75
Q

How do ILC1 and NK cells cooperate with macrophages to promote innate immunity after infection?

A
  1. stimulated DCs and macrophages secrete IL-12 and IL-15 which activate NK cells and ILC1 cells to produce IFN-γ
  2. activated NK cells and ILC1 cells then secrete IFN-γ (and TNF for ILC1 cells) -> macrophage activation to clear intracellular pathogens
76
Q

Give two examples for toxin-releasing bacteria where the toxoids are used as vaccines?

A
  1. Clostridium tetani
  2. Corynebacterium diphtheriae

(and Cholera but the vaccine efficacy is poor, and Cholera is easily treated)

77
Q

How does bacterial LPS induce septic shock?

A
  • LPS recognized by TLR4.
  • LPS activates macrophages which produce cytokines TNF and IL-6 and prostaglandins and NO in large amounts. (TNF inhibits myocardial contractility and vascular smooth muscle tone, -> leaky vessels -> NO causes the blood vessels to widen, resulting in a marked decrease in blood pressure, or shock.)
  • LPS is called endotoxin b/c they circulate through the body, we have macrophages in all organs, they phagocytose the bacteria and release proinflammatory cytokines systemically.
78
Q

How do CD4+ and CD8+ T cells cooperate with macrophages to kill phagosomal and cytoplasmic microbes?

A
  • Phagosomal – CD4+ Th1 cells recognize peptide antigen presented by MHC class II; they produce IFN-γ and express CD40L -> this activates macrophages which have phagocytosed a microbe to destroy the microbes in their phagosomes
  • Cytoplasmic – CD8+ T cells recognize antigen presented by MHC class I on the macrophage and they kill the infected cell
79
Q

Which T Helper cell subset is induced by fungal infections and what are the cytokines polarizing them?

A

Subset – CD4+ Th17

Polarizing cytokines – IL-23, IL-6, IL-1, TGF-β

80
Q

What is a major pathogen structure by fungi?

A
  • β-glucans on the surface are recognized by C type lectins on macrophages and DCs
  • Mannose recognized by mannose receptor
  • (Hyphae or capsules are used by various fungi as virulence mechanisms)
81
Q

What is the function of type I interferons?

A

To inhibit viral replication in both infected and neighboring uninfected cells (and systemically via type I interferons produced by plasmacytoid DCs) -> induces the anti-viral state in both

82
Q

How do NK cells recognize virus-infected cells?

A

They recognize the absence of MHC class I on the surface of infected cells. MHC class I acts as an inhibitory marker for the NK cell which has been activated via another receptor.

(And maybe activating NK cell ligands)

83
Q

What are the major adaptive immune mechanisms against viruses?

A
  1. extracellular – antibodies block virus attachment and entry into host cells; they may also opsonize the virus and promote clearance by phagocytes -> protection against infection and prevention of cell to cell spread
  2. intracellular – CD8+ CTLs kill infected cells -> eradication of established infection or sometimes latency is established
84
Q

How do Th1 and Th2 immune responses influence Leishmania infection?

A
  • Th1 – produce IFN-γ which activates macrophages (M1) to destroy intracellular parasites - > clearance of Leishmania. In mouse models, the black mouse develops Th1 response, clears the Leishmania.
  • Th2 – produce cytokines like IL-4, IL-10, IL-13 which inhibit classical macrophage activation -> increased parasite survival. White Balbc mouse only develop Th2 responses -> M2 macrophages -> which is not adequate and the mouse does not respond and it dies.

Humans have both responses so this neither clears the infection nor lets it over-grow.

DCs produce IL-12 in one mouse but not the other. In humans it is more balanced. IL-12 -> Th1.

IL-4 can come from basophils and mast cells and other innate cells -> Th2, esp when DCs are not producing IL-12 in response to the pathogen.

85
Q

How do Trypanosoma evade an immune response?

A

Continuous antigenic variation of surface glycoproteins (VSG coat)

86
Q

Name three effector mechanisms of antibody-mediated autoimmune disease.

A
  • Opsonization -> phagocytosis: opsonization by antibodies or activation of complement which then opsonizes. Fc receptor is bound, as well as complement receptor. Both lead to phagocytosis.
  • Inflammation: complement activation -> C3a and C5a -> recruit neutrophils (which release lysosomal enzymes and ROS) and macrophages (Fc receptor- and/or complement-mediated inflammation)
  • Abnormal cellular functions: antibodies bind to normal cellular receptors or proteins and interfere with their function – myasthenia gravis -> dysfunction between nerve and muscle
87
Q

What is the pathomechanism behind Myasthenia gravis?

A
  • Antibodies specific for the nicotinic acetylcholine receptor on the muscle cells inhibits binding of neurotransmitter acetylcholine -> down modulates receptors -> causes functional abnormalities
88
Q

Why is SLE a systemic disorder?

A
  • Immune complexes of antibodies+nuclear antigens (DNA, nucleoproteins, and others) are formed which deposit in small arteries and capillaries of renal glomeruli, skin, and other tissues throughout the body.
  • These immune complexes migrate rather than forming and staying on a localized tissue.
89
Q

What are the mediators of delayed-type hypersensitivity?

A
  • Antigen for which the individual is sensitized
  • CD4+ T cells
  • Neutrophils
  • Monocytes –> granuloma formation
  • fibrinogen -> fibrin -> induration
  • in some cases also eosinophils or CD8+ T cells
90
Q

Describe the pathogenesis of type 1 diabetes mellitus?

A
  • Destruction of more than 90% of the insulin-producing β cells of the the islets of Langerhans in the pancreas results in loss of insulin production -> hyperglycemia + ketoacidosis
    • Inflammation induced by CD4+ T cells reacting against islet antigens including insulin
    • CTL-mediated lysis of islet cells
    • Local production of TNF and IL-1 -> damages islet cells
    • Anti-islet and anti-insulin antibodies
91
Q

How do pathogenic T cells enter the CNS in EAE/MS? How can this be inhibited?

A
  • They are activated in the periphery, then ->
  • Via the integrin VLA-4 on the T cell binding to its ligand, vascular cell adhesion molecule VCAM-1/CD106 on the endothelium
  • Anti-VLA-4 antibody administration - Natalizumab
92
Q

Which genes show the strongest associations with autoimmune diseases?

A
  • HLA genes
    • Different MHC class I or II molecules can present certain self-peptides so not everyone is susceptible
93
Q

Which HLA alleles are highly associated with type 1 diabetes mellitus?

A
  • HLA-DR3 or DR4 or both
94
Q

Besides susceptibility genes, external triggers are discussed to induce autoimmunity. List three of them.

A
  • Viral or bacterial infection – inflammatory milleu
  • Ultraviolet (UV) irradiation - modification of self-proteins
  • Smoking – modification of self-proteins
  • Nonmicrobial environmental antigens such as drugs
95
Q

Intravenous application of large doses of IgG has beneficial effects in some autoimmune diseases.

What might be the mechanism behind that?

A
  • Maybe IgG binds to the inhibitory Fc receptor FcγRIIB on B lymphocytes and DCs, thus attenuating autoantibody production and inflammatory responses.
  • It may also compete with pathogenic IgG antibodies for the neonatal Fc receptor FcRn, reducing the half-life of the pathogenic IgG.
96
Q

Name two examples of cytokine antagonists.

A
  • Soluble receptors / antibodies against
    • IL-1
    • TNF
    • IFN-α
    • IL-6
    • JAK inhibitors
97
Q

Depletion of B cells with CD20-specific antibodies has been shown to modulate disease activity of MS and Rheumatoid arthritis. How can this beneficial effect be explained?

A
  • Possibly due to the role of B cells acting as APCs to activate T cells – these are T cell-mediated diseases. So if you reduce the number of B cells specific for the antigens to which the pathogenic T cells are reacting, you may reduce that activation and alleviate disease symptoms.
98
Q

Describe the pathogenesis of Rheumatoid arthritis.

A
  • There is a breakdown of tolerance to self-antigens, due to genetic susceptibility and environmental factors.
  • Modification / Possibly citrullination of self-proteins -> modified epitopes/neoantigens in patients with HLA alleles capable of presenting the epitopes -> T cell and antibody response.
  • In the joints -> also cytokine release and recruitment of leukocytes -> synovial cells produce collagenases and other enzymes -> destruction of bone and cartilage.
  • Formation of tertiary lymphoid structures in the joint which may maintain and propagate the immune reaction.
99
Q

What does CCP stand for?

A
  • Cyclic citrullinated peptide – anti-CCP antibodies are a diagnostic marker for RA
100
Q

What type of hypersensitivity response is acetylcholine disruption?

A

Type II antibody-mediated hypersensitivity disease

101
Q

What is the classical example of delayed type hypersensitivity?

A
  • Tuberculin antigen injected into skin causes local inflammation 24-48 hrs later if the patient was previously exposed to or immunized against TB.
  • Also chronic DTH causes granulomas.
102
Q

How is MS induced, and what is its pathogenesis?

A
  • maybe a viral infection activates self myelin–reactive T cells by the phenomenon of molecular mimicry
  • Self-tolerance may fail because of the inheritance of susceptibility genes.
  • Th1 and Th17 CD4 + T cells react against self myelin antigens, -> inflammation with activation of macrophages around nerves in the brain and spinal cord, destruction of the myelin, abnormalities in nerve conduction, and neurologic deficits.
103
Q

Give an example of an antibody-mediated autoimmune disease.

A
  • Myasthenia gravis
  • Grave’s disease
  • autoimmune thrombocytopenic purpura
104
Q

How is SLE induced, and what is its pathogenesis?

A
  • There is a breakdown of tolerance to self-antigens
    • due to genetic susceptibility: inheritance of HLA-DR3 or HLA-DR4 or both
    • and environmental factors such as UV irradiation -> apoptotic death of cells and release of nuclear antigens.
  • Defective clearance of apoptotic bodies -> increased nuclear antigens -> antinuclear antibody, antigen-antibody complexes -> endocytosis and TLR engagement in endosomes -> stimulation of B cells and pDCs (IFNa) -> persistent high level antinuclear IgG production
  • Deposition of antigen-antibody complexes in arteries and capillaries systemically -> glomerulonephritis, vasculitis, arthritis
105
Q

What is the difference between primary and secondary immunodeficiency?

A
  • PID is inherited - via mutations in genes
  • SID is acquired - resulting from other diseases or secondary to environmental factors, or adverse event of medical intervention
106
Q

tell me about NFkB

A
  • it’s a transcription factor activated by TLR signaling
  • CD40 signals activate it (during classical Th1 macrophage activation)
  • FcεRI cross-linking lead to nuclear translocation of NFkB to stimulate expression of several cytokines by mast cells
107
Q

What are some factors leading to secondary immunodeficiency?

A
  • malnutrition
  • hematopoietic tumors - leukemia, lymphoma
  • lack of a spleen
  • drug therapy - for cancer, autoimmunity, organ transplant
  • viral infection - HIV
108
Q

Briefly explain the missing self theory of NK cell activation (sketch is sufficient).

A

The ability of NK cells to become activated by host cells that lack class I MHC.

109
Q

Assign a TH1 or TH2 immune response.

  • Type I allergy
  • IFNγ
  • DTH
  • IgE class switch
  • Granuloma
  • Macrophage activation
  • IL-4
  • Worm infection
  • Eosinophil activation
A
  • Type I allergy - Th2
  • IFNγ - Th1
  • DTH - Th1
  • IgE class switch - Th2
  • Granuloma - Th1
  • Macrophage activation - Th1
  • IL-4 - Th2
  • Worm infection - Th2
  • Eosinophil activation - Th2
110
Q

What defects can you expect in the composition of (1-4) peripheral lymphocytes and (5) in lymphocyte function / disease in mice or humans with the following genetic defects. Justify in key words.

  1. Beta-2-Microglobulin
  2. RAG-1 or RAG-2
  3. Cμ
  4. TCRβ
  5. CD95/CD95L (FAS, FASL)
A
  1. Beta-2-Microglobulin - no MHC class I expression -> no CD8+ response
  2. RAG-1 or RAG-2 - no mature antigen receptors - no peripheral B or T cells
  3. Cμ - no IgM expression on B cells
  4. TCRβ - no alpha beta TCRs - reduced T cells
  5. CD95/CD95L (FAS, FASL) - no FAS/FASL induced apoptosis signal from CTLs to infected cells (extrinsic pathway of apoptosis)
111
Q

Which diseases contribute to the development of the following components of the immune system or defects of the immune system?

  • IL-4
  • immune complexes
  • IgE
  • defects in IL-12 signal transduction
  • mast cells
A

Systemic Lupus Erythremodes (SLE): immune complexes

Type I allergy (immediate): IL-4, IgE, mast cells

Mycobacterial infections: defects in IL-12 signal transduction

112
Q

What effects do you expect on the composition of peripheral lymphocytes and lymphocyte function, if any, disease in the event of deletion / inactivation of the common γ-chain locus?

A
  • X-linked SCID
    • impaired development of T cells (impaired IL-7 receptor) and NK cells (impaired IL-15 receptor)
    • reduced numbers of mature T cells and NK cells
    • -> lack of T cell help for antibody production
  • The most common form of SCID is XSCID caused by mutations in the
    X-linked IL2RG gene (encoding the IL-2R common g chain)
113
Q

What defects can you expect in the composition of (a-d) peripheral lymphocytes and (e) in lymphocyte function / disease in mice or humans with the following genetic defects. Justify in key words.

a) TAP
b) MHC Klasse I
c) MHC Klasse II
d) RAG 1 oder RAG 2
e) CD40

A
  • TAP - failure to express MHC class I
    • diminished development and activation of CD8+ T cells
  • MHC Klasse I -
    • decreased CD8+ T cell numbers and function
  • MHC Klasse II - Bare Lymphocyte Syndrome
    • defective positive selection of T cells in thymus
    • reduction of mature CD4+ T cells in periphery
  • RAG 1 oder RAG 2
    • reduced or absent T and B cells due to failed V(D)J recombination
  • CD40
    • defective Th cell activation of B cells, macrophages, and DCs
    • defective class switching (X-linked hyper IgM), somatic mutation, germinal center formation
    • defective cell-mediated immunity
114
Q

Which cytokines are essential for the following reactions or which intensify them?

  1. IL-4
  2. IFNγ
  3. IL-12
  4. IL-5
  • Defense against intracellular parasites
  • Hypersensitivity reaction type I
  • Hypersensitivity reaction type IV (DTH)
  • Class change to IgE
  • Eosinophil activation
A
  1. IL-4 - Class change to IgE (Th2)
    • Hypersensitivity reaction type I (Immediate)
  2. IFNγ - Hypersensitivity reaction type IV DTH (Th1)
    • Defense against intracellular parasites
  3. IL-12 - Hypersensitivity reaction type IV DTH (Th1)
  4. IL-5 - Eosinophil activation (Th2)
    • Hypersensitivity reaction type I (Immediate)
115
Q

Paradoxically, some primary immunodeficiencies (PIDs) show moderate to severe signs of autoimmunity, such as autoimmune hemolytic anemia (AIHA) and lymphoproliferation. Please explain how immunodeficiency could cause autoimmunity and name a few concrete examples (with short molecular explanations).

A
  • Attenuation of some regulatory mechanisms can cause autoimmunity
    • Dysfunction of immune responses to pathogens (causing immunodeficiency)
    • Loss of (peripheral) tolerance (causing autoimmunity)
116
Q

In early life, PIDs affect boys roughly five times more often compared to girls in a similar age. In adults, the male-to-female ratio of newly diagnosed PIDs is, however, close to 1. Explain why this is the case.

A
  • Many inherited gene defects causing severe PID are X-linked recessive. Males have only 1 X chromosome (XY) resulting in what looks like a homozygous phenotype for that mutation. If a female has the mutation on only 1 X chromosome (XX), she is heterozygous/carrier.
  • genes that cause a later (and less severe) onset of PIDs are often non-X-linked and affect females and males in a similar frequency.
117
Q

Please name a few examples of PIDs that have a higher prevalence in males compared to females

A

X-linked severe PIDS:

  • Mutations in IL2RG => XSCID, Defective T cell development
  • Mutations in IKKG => NEMO deficiency, ectodermal dysplasia with immunodeficiency
  • Mutations in CD40LG => hyper IgM syndrome due to ‘help-less’ B cells
  • Mutations in BTK => XLA, Defective B cells development, agammaglobulinemia
  • Mutations in FOXP3 => IPEX syndrome, loss of Treg cells & autoimmunity => Immunodeficiency
118
Q

Severe combined immunodeficiency (SCID) was diagnosed in the past sometimes unexpectedly when babies were vaccinated, e.g. with BCG. Please explain why immunization revealed SCID in earlier times.

A
  • Often a vaccine would be given before the PID diagnosis was made early in life
  • In case the immune system does not function properly (such as in PIDs) the attenuated vaccine pathogen is not eliminated and causes symptoms similar to those of the infections they should prevent.
  • In the case of BCG, babies with SCID would develop infections with the live attentuated M. bovis in the BCG vaccine.
  • MMR
  • BCG
  • VZV
119
Q

NEMO is not only a clown fish in a Disney movie. What else is NEMO and why is relevant for the immune system?

A
  • kinase: NFκB essential modulator protein
    • An essential component of intracellular signaling downstream of TLRs, CD40 which leads to NFκB activation
  • Mutations in IKKgamma cause X-linked recessive NEMO deficiency syndrome -> hyper-IgM syndrome due to impaired CD40-CD40L signaling
    • Impaired B cell class switching
    • Impaired TLR and IL-1 receptor family signaling
    • Susceptibility to pyogenic infections
    • ectodermal dysplasia
120
Q

PID are usually rare or very rare diseases. However, the most prevalent PID is the IgA deficiency syndrome with a prevalence of up to 0.1% (that is, 1,200 people in Würzburg). Most affected people, however, do not even know that they have a PID. Why?

A
  • Because the immune deficiency is relatively mild, and these patients are asymptomatic (unless they have an associated defect in one of the IgG subclasses).
  • compensatory effect of other immunoglobulin isotypes (IgG, IgM, IgE) and adapted cellular defense mechanisms because these patients have usually no defects in T cells, B cells and myeloid cells except the absence of IgA
  • IgA-deficient patients have generally a higher susceptibility for
    (chronic) infections, like sinusitis, bronchitis, pneumonia and gastrointestinal infection.
121
Q

What are the causes of the following PIDs? Identify the affected gene, the kind of heredity and the cellular/molecular mechanism(s) that cause(s) PID:

XMEN syndrome

A

XMEN syndrome

  • X-linked immunodeficiency
  • magnesium defects
  • EBV infection, neoplasia
  • Gene = MAGT1 (magnesium transporter protein­)
  • free magnesium is not transported during T cell and NK cell activation -> defective intracellular signaling
  • defective NK cell and CTL function
122
Q

In research labs, immunodeficient mice are a valuable tool to study the function of the immune system. Name a few commonly used immunodeficient and/or lymphopenic mouse lines.

A
  • Nude mice
    • Mutation in the gene FOXN1
    • Lack of thymic function, no normal T cell development
    • Studying effect of thymic epithelium and thymic function on T cell and B cell development and function
  • • Rag1–/– or Rag2–/–: (No B and T cells)
  • • Cd3e–/– (No T cells)
  • • Rag2–/–Il2rg–/– (No immune cells at all)
  • • NOD/SCID (Mutation in the DNA-dependent kinase Prkdc, lymphocyte defects, diabetic)
123
Q

Name one PID each that affects predominantly/exclusively the following cell types:

  • Treg cells
A
  • IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome
    • mutations in the FOXP3 gene cause defective Treg development
  • Treg cells – Wiskott-Aldrich syndrome (WAS)
    • impaired T cell activation responses and Treg dysfunction
    • due to defective WASp gene
124
Q

Name one PID each that affects predominantly/exclusively the following cell types:

  • B cells
A
  • B cells – X linked agammaglobulinemia (XLA)
    • No B cells, no immunoglobulins
    • due to loss of BTK tyrosine kinase
  • Hyper IgM syndromes
    • NEMO deficiency, CD40L deficiency, AID deficiency
125
Q

Name one PID each that affects predominantly/exclusively the following cell types:

  • Th17 cells
A
  • Th17 cells – Hyper-IgE syndrome (Job’s syndrome)
    • Block in Th17 cell differentiation, elevated IgE
    • due to defective STAT3
  • IL17A and IL17F deficiency
126
Q

Please explain the possible function of MICA in development of Celiac disease.

A
  • Gluten peptides activate mucosal epithelial cells to express MIC molecules.
  • IELs recognize the MIC proteins via NKG2D receptor (important receptor for NK cells, gdT cells, CD8 cells).
  • This recognition + co-stimulator IL-1 activates the IELs to kill the MIC-bearing cells -> destruction of the gut epithelium.
127
Q

Please name the mechanism of action of immunosuppressants Sirolimus or Rapamycin used to prevent allograft rejection.

A
  • Binding and inhibition of mTOR prevents translation of cell survival and proliferation proteins. This blocks effector T cell proliferation, and may have an suppressive effect on DCs and antibody-mediated rejection.
  • Sirolimus/Rapamycin
128
Q

Please name the mechanism of action of immunosuppressant Mycophenolate mofetil/MMF used to prevent allograft rejection.

A
  • Blocking of inosine monophosphate dehydrogenase activity blocks de novo synthesis of guanine nucleotides, upon which proliferating lymphocytes are particularly dependent. This suppresses the lymphocyte response to the allograft.
  • Mycophenolate mofetil/MMF
129
Q

Name a few concrete examples (with short molecular explanations) of how immunodeficiency could cause autoimmunity.

A
  • Hypermorphic mutations in RAG (Omenn syndrome) => Perturbed development of T cells and Treg cells
  • Mutations in AIRE => defective selection of T cells (and Tregs) during thymic development
  • Mutations in STIM1 or ORAI1 genes => Important for Ca2+ signaling in both Teff and Treg cells
  • Mutations in FAS or FASL genes => (ALPS) defective contraction of T cells, loss of peripheral tolerance
  • Mutations in FOXP3 (IPEX syndrome) => Loss of Treg cells & autoimmunity => Immunodeficiency
130
Q

What are the causes of the following PIDs? Identify the affected gene, the kind of heredity and the cellular/molecular mechanism(s) that cause(s) PID:

Bloom syndrome

A
  • Bloom syndrome: Defects in the BLM gene that encodes a helicase required for DNA repair.
  • Cells with BLM mutations show chromosomal instability causing defects in the immune system and a predisposition for cancer.
  • autosomal recessive
  • Because genetic instability occurs during the TCR and BCR rearrangements and germinal center reactions, T and B cells primarily affected
131
Q

What are the causes of the following PIDs? Identify the affected gene, the kind of heredity and the cellular/molecular mechanism(s) that cause(s) PID:

CRAC channelopathy

A

CRAC channelopathy

  • Gene = STIM1 or ORAI1
  • Autosomal recessive
  • Defective CRAC channel -> defect in influx of extracellular calcium
  • Defective T and B cell function
  • recurrent and life-threatening infections with viral, bacterial and fungal pathogens
  • autoimmunity (defective Treg cells)
  • ectodermal dysplasia (brittle hair and nails,
    amelogenesis imperfecta)
  • myopathy (muscle weakness)
132
Q

Can you think of any experiment that require immunodeficient mouse strains?

A
  • Tumor biology (e.g. human xenografts)
  • Transplantation/transfusion biology (e.g. adoptive immune cell transfer experiments)
  • Immune tolerance studies (e.g. absence of regulatory cells)
  • BM and (hematopoietic) stem cell transplantation experiments
  • effects of immune cell subsets in non-immune diseases (e.g. myocardial infarction, metabolic syndrome, neurodegeneration)

MSc Sommer 2021 (3 decks)

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