Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PathY5 > Immune modulating therapies > Flashcards

Immune modulating therapies Flashcards

1
Q

How can we boost the immune system?

A

Vaccination
Replacement of missing components
Cytokine therapy
Blocking immune checkpoints

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do we vaccinate against in kids?

A

Diphtheria
Tetanus
Pertussis
Polio
Haem Infl B
Pneum C
Men B
Men C
Rotavirus
MMR
Flu
HPV
Men ACWY
BCG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which vx are travel vx?

A

Hepatitis B
BCG
Chicken pox
Hepatitis A
Typhoid
Yellow fever
Rabies
Cholera

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What do we vx the old against?

A

Pneum PPV
Flu
Shingles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is immune memory in the context of measles?

A

Infection was ‘remembered’ and individuals were ‘protected’ 65 years later
Feature of the adaptive immune response

History:
In 1781 an epidemic of measles occurred on the Faroe Islands

No further outbreaks of measles until 1846 when a major outbreak affected more than ¾ of the population

None of those who had measles in 1781 got the disease again

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the adaptive immune response

A

Adaptive Immune Response
B cells and T cells

Wide repertoire of antigen receptors
Receptor repertoire is not entirely genetically encoded
Genes for segments of receptors are rearranged and nucleic acids deleted/added at the sites of rearrangement almost randomly
Potential to create in order of 1011 to 1012 receptors
Autoreactive cells are likely to be generated
Mechanisms must exist to delete or tolerise these autoreactive cells

Exquisite specificity
able to discriminate between very small differences in molecular structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are APCs?

A

APCs are cells that can present peptides to T lymphocytes to initiate an acquired immune response

These cells include:
Dendritic cell
Macrophage
B lymphocyte

Macrophages include Langerhans cells, mesangial cells,
Kupffer cells, osteoclasts, microglia etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Clonal expansion following exposure to antigen?

A

T cells with appropriate specificity will proliferate and differentiate into effector cells (cytokine secreting, cytotoxic)
B cells with appropriate specificity will proliferate and
differentiate to T cell independent (IgM) (memory and) plasma cells
undergo germinal centre reaction and differentiate to T cell dependent IgG/A/E(M) memory and plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Immunological memory?

A

Following infection, residual pool of specific cells with enhanced capacity to respond if re-infection occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do we respond to EBV?

A

High frequency of CD8+
T cells specific for single
epitopes from EBV in
humans with primary EBV
infection and acute
Infectious mononucleosis

Fall in frequency of
EBV specific CD8+
T cells following
resolution of primary
infection

CD4+ T cells from patients with primary and persistent EBV infection respond to a lysate preparation of EBV proteins by
expressing IFN-gamma

The frequency
of CD4+ T cells
specific for EBV
falls following
primary infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the CD8 T cell response?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the CD4 T cell response?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the CD4 subsets and what do they do?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is T cell memory?

A

Longevity

Memory T cells are maintained for a long time without antigen by continual low-level proliferation in response to cytokines

Different pattern of expression of cell surface proteins involved in chemotaxis cell adhesion

These allow memory cells to access non-lymphoid tissues, the sites of microbial entry.

Rapid, robust response to subsequent antigen exposure

There are more memory cells

These cells are more easily activated than naïve cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the B cell response?

A

Activated B cells enter the follicles, proliferate, and displace resting cells. They form germinal centers and differentiate into both plasma cells that form antibody and long-lived memory B cells. Those B cells synthesizing antibodies provide defense against microorganisms, including bacteria and viruses.

It is specific to the antigen they have been exposed to.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the features of B cell memory?

A

Longevity

Long lived memory B cells and plasma cells

Rapid, robust response to subsequent antigen exposure

There are more memory cells

These cells are more easily activated than naïve cells

Pre-formed antibody

Circulating high affinity IgG antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do we want from a vaccine?

A
  1. Generate protective, long-lasting immune response
  2. No adverse reactions
  3. Single shot
  4. Easy storage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

In influenza how does the Vx protect?

A

For influenza although CD8 T cells control the virus load it is antibody which provides a protective response

Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the Haemagglutination inhibition assay?

A

Sialic acid receptors on RBC bind to haemagluttinin of influenza virus to ‘haemagluttinate’

Reaction inhibited by antibodies to haemagluttin

Plate with RBC + virus, Add serum from patients 1 - 8 (Dilution of serum)

Clear correlation between resistance to infection and levels of IgG antibody to haemagglutinin (HA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does the BCG confer protection?

A

BCG – bacilli Calmette-Guerin

Attenuated, strain of bovine tuberculosis

Protects against primary infection (19-27%)

Protects against progression to active TB (71%)

T cell response is important in protection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the Mantoux test?

A
  • Inject 0.1 ml of 5 tuberculin units of liquid tuberculin intradermally.
  • The tuberculin used in the Mantoux skin test is also known as purified protein derivative, or PPD.
  • The patient’s arm is examined 48 to 72 hours after the tuberculin is injected.
  • The reaction is an area of induration (swelling that can be felt) around the site of the injection.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does response maintenace work in influenza and TB?

A

Influenza

Antibody protection begins within 7 days after immunization. Protection can last for approximately 6 months or longer in the general population.

TB

Protection in the UK after BCG lasts about 10-15 years.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the types of vaccines?

A

Live vaccines

Inactivated/Component/Conjugate vaccines

+ Adjuvants to increase immunogenicity

DNA vaccines

Dendritic cell vaccines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are live attenuated vaccine examples?

A

MMR

BCG

Yellow fever

Typhoid (oral)

Polio (Sabin oral)

Vaccinia

Use a live but modified organism to induce an immune response but limit pathogenesis (avoid in immunocompromised)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the advantages of live vaccines?

A

Establishes infection – ideally mild symptoms

Raises broad immune response to multiple antigens – more likely to protect against different strains

Activates all phases of immune system. T cells, B cells – with local IgA, humoral IgG

Often confer lifelong immunity after one dose

26
Q

What are the disadvantages of live vaccines?

A

Storage problems

Possible reversion to virulence (recombination, mutation).

Vaccine associated paralytic poliomyelitis (VAPP, ca. 1: 750,000 recipients)

Spread to contacts

Spread to contacts of vaccinee who have not consented to be vaccinated

Spread to immunosuppressed/immunodeficient patients

27
Q

Which vaccines are inactivated/ component?

A

Inactivated Vaccines

Influenza, Cholera, Bubonic plague, Polio (Salk), Hepatitis A, Pertussis, Rabies.

Toxoids (inactivated toxins)

Diphtheria, Tetanus.

Component/subunit vaccines

Hepatitis B (HbS antigen), HPV (capsid), Influenza (haemagglutinin, neuraminidase).

28
Q

What are the advantages of Inactivated vaccines/ component vaccines?

A

No mutation or reversion

Can be used with immunodeficient patients

Can lead to elimination of wild type virus from the community

Storage easier

Lower cost

29
Q

What are the disadvantages of Inactivated vaccines/ component vaccines?

A

Often do not follow normal route of infection

Some components have poor immunogenicity

May need multiple injections

May require conjugate protein carrier or adjuvants to enhance immunogenicity

30
Q

What is a conjugate vaccines?

A

Polysaccharide plus protein carrier

Polysaccharide alone induces a T cell independent B cell response – transient

Addition of protein carrier promotes T cell immunity which enhances the B cell/antibody response

31
Q

Give examples of conjugate vaccines?

A

Haemophilus Influenzae B

Meningococcus

Pneumococcus

32
Q

What is an adjuvant?

A

Adjuvant increases the immune response without altering its specificity

Mimic action of PAMPs (pathogen associated molecular patterns) on TLR (toll-like receptors) and other PRR (pattern recognition receptors)

33
Q

Give examples of adjuvants

A

Aluminium salts (humans)

Lipids – monophosphoryl lipid A (humans)

Oils -Freund’s adjuvant (animals)

ISCOMS

CpG DNA

34
Q

What is Alum?

A

Primary adjuvant utilized in humans – safe and effective

Mechanism not fully elucidated

Alum may allow antigens to be slowly released, prolonging the immune stimulation

Alums induce a mild inflammatory reaction that will then promote development of adaptive immune response

Alum activates Gr1+ IL4+ eosinophils to help prime naïve B cells leading to antibody response

Used in many vaccines including hepatitis A, hepatitis B, Hib

35
Q

What is ISCOMs?

A
  • Immune stimulating complexes
  • Cage-like structure composed of Quillaja saponins, cholesterol, phospholipids, and protein
  • Mixed with antigen to provide multimeric presentation with built-in adjuvant
  • Enhance cell mediated immune response
  • Experimental ISCOMS – induce protective immunity to viruses, parasites, bacteria in several species
36
Q

What is CpG?

A

·”CpG” stands for cytosine and guanine separated by a phosphate which links the two nucleotides together in DNA

Stimulatory DNA; TCC ATG ACG TTC

·Adjuvant activity is linked to DNA motifs that are rich in CpG dinucleotides which should be unmethylated

·

·CpG motifs bind via pattern recognition receptors (TLR-9).

37
Q

What are DNA vaccines?

A

Plasmid containing gene of choice

(Easy to produce in quantity, very stable easy to store)

Insertion into muscle cell

(several copies)

No replication of the plasmid. Gene encodes protein presented at cell surface

38
Q

What are pros and cons for DNA vaccines?

A

Advantages

Mimics a virally infected cell

Stimulates T cell responses

Disadvantages

Possible plasmid integration into host DNA

Possible response to DNA could lead to autoimmune diseases such as SLE

39
Q

What are dendritic cell vaccines?

A

Acquired defects in DC maturation and function associated with some malignancy suggests a rationale for using ex vivo–generated DC pulsed with tumour antigens as vaccines

Need to find antigens that clearly mark the cancer cells as different from host cells

40
Q

How can we replace missing components in the immune system?

A

Haematopoietic stem cell transplantation

Indications

• Life-threatening primary immunodeficiencies

–Severe combined immunodeficiency

–Leukocyte adhesion defect

•Haematological malignancy etc

Offers potential for complete and permanent cure

41
Q

What is antibody replacecment?

A

Human normal immunoglobulin

Prepared from pools of >1000 donors

Contains preformed IgG antibody to a wide range of unspecified organisms

Blood product:

  • Donors screened for Hep B, Hep C and HIV
  • Further treated to kill any live virus

Administration

•IV or SC

42
Q

What is indications for antibody replacement therapy?

A

Primary antibody deficiency

X linked agammaglobulinaemia

X linked hyper IgM syndrome

Common variable immune deficiency

Secondary antibody deficiency

Haematological malignancies

  • Chronic lymphocytic leukaemia
  • Multiple myeloma

After bone marrow transplantation

43
Q

What are some specific immunoglobulins in use?

A

Human immunoglobulin used for post-exposure prophylaxis (passive immunisation)

Derived from plasma donors with high titres of

IgG antibodies to specific pathogens

  • Hepatitis B immunoglobulin - Bites, needles, sex
  • Tetanus immunoglobulin - IVIG for suspected in UK
  • Rabies immunoglobulin - potential exposure
  • Varicella Zoster immunoglobulin - <20wks women or aciclovir CI
44
Q

How do we replace T cells?

A

Autologous T cells expanded in vitro and then re-infused

Donor (HLA matched) T cells expanded in vitro and then infused

‘Banks’ of HLA matched, virus specific T cells being developed

45
Q

Who should we replace T cells for?

A

Immunosuppression results in failure to control infection with persistent viruses – CMV, EBV

Patients develop CMV pneumonitis, retinitis…..

Patients develop EBV related B cell lymphoproliferative disease

46
Q

What is the aim of recombinant cytokines?

A

Modify immune response

47
Q

What is the clinical use of IFN alpha, alpha 2, gamma and IL2?

A
48
Q

How does Blocking immune checkpoints - Ipilimumab
Antibody specific for CTLA4?

A

Action

  • Antibody binds to CTLA4
  • Blocks immune checkpoint
  • Allows T cell activation

Indications

  • Advanced melanoma
49
Q

How does Blocking immune checkpoints –
Pembrolizumab and Nivolumab
Antibodies specific for PD-1 work?

A

-

Action

  • Antibody binds to PD-1
  • Blocks immune checkpoint
  • Allows T cell activation

Indications and dosing

  • Advanced melanoma
50
Q

Match them up:

  1. BCG vaccination
  2. Bone marrow transplantation
  3. IFN gamma
  4. EBV-specific CD8 T cells
  5. Human normal immunoglobulin
  6. Pembrolizumab (anti-PD1)
  7. Varicella zoster immunoglobulin

A. Post-transplant lymphoproliferative disorder

B. Reduce risk of TB infection

C. X linked hyper IgM syndrome

D. X linked SCID

E. Chronic granulomatous disease

F. Immunosuppressed VZ seronegative individual after chicken pox exposure

G. Metastatic melanoma

A

You’re on your own for this one man.

51
Q

What are mRNA vaccines?

A

f

52
Q

What are adenovirus vaccines?

A

v

53
Q

What are dendritic cell vaccines?

A

x

54
Q

How do we use Virus specific T cell therapy in EBV?

A

This may be indicated for adneoviruse/ EBV lymphoproliferative disorders

55
Q

What is TIL?

A

T cells infused back after IV expansion

56
Q

What is TCR and CAR T therapy?

A
57
Q

What is CAR T?

A

Good for ALL and NHL

Less successful in solid tumours

T cell with chimeric receptors to CD 19 using pts own T cells which are genetically engineered in vitro.

58
Q

What is anti CTLA4 antibody?

A

Ab binds to CTLA4, blocks immun checkpoint and allows T cell activation

Used for advanced melanoma

But may cause auto immunity

59
Q

What is PD-1 Ab?

A

Binds to PD 1, blocks checkpoint and allows T cell activation

Used in advanced melanoma and metastatic renal cell cancer

May cause autoimmunity

60
Q

The purpose of vaccination is to stimulate and enhance immunological memory. Which cells mediate immunological memory?

Neutrophils

B and T lymphocytes

Platelets

Eosinophils

Macrophages

A

B and T lymphocytes

61
Q

Which of the following vaccines should not be given to an immunosuppressed individual?

BCG- bacilli Calmette-Guerin

Diphtheria toxoid

Quadrivalent inactived influenza vaccine

Polio (Salk - injected)

Pfizer Covid mRNA vaccine

A

BCG- bacilli Calmette-Guerin

62
Q

A 23 year old has metastatic melanoma. which of the following may reduce disease progressoin?

BCG vaccination

Bone marrow transplantation

CAR-T cells with specificity for CD19

Nivolumab, an antibody specific for programmed death 1 (PD1)

Normal human immunoglobulin

A

Nivolumab, an antibody specific for programmed death 1 (PD1)

PathY5 (98 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions