Brainscape's Knowledge GenomeTM

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


See full index

Path - Immuno > Immune modulation > Flashcards

Immune modulation Flashcards

1
Q

True/False:

B & T cell Receptor repertoire is entirely genetically encoded

A

False;

there is genetic rearrangement and addition/ deletion of nucleic acids at the receptor site - adds variation

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

List antigen presenting cells?

A

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
3
Q

what are the reactions that occur in 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

  1. will undergo germinal centre reaction and differentiate to T cell dependent IgG/A/E(M) memory and plasma cells
    (so 2 options, T cell dependent and T cell independent manner)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what happens to the clonal expansion of CD4/8 T cells post infection?

A

apoptosis

few survive as memory cells

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

T cell clonal expansion requires which things?

A

CD8 T Cells need:
Cytokines produced by CD4 T helpers

CD4 T Cells need:
Specific Antigen
Cytokines e.g. IL-2 that they self produce

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

why are T memory cells better at responding to re-infection than naive cells?

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
7
Q

how do T helper cells provide help to B cells for expansion and isotype switching?

A

CD40L, cytokines

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

why are B cells better at responding to re-infection?

A

Longevity
Long lived memory B cells and plasma cells

Pre-formed antibody
Circulating high affinity IgG antibodies

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

What do we want from a vaccine?

A

MEMORY - Generate protective, long-lasting immune response

No adverse reactions

Practical considerations – one shot, easy storage, inexpensive…

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

what is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies ?

A

Hemagglutinin

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

For influenza what control the virus load and what provides a protective response?

A

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

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

which antibody confers protection to influenza?

A

Hemaglutinin antibody (IgG to haemaglutinin).

The more you have as a % of titre, the lower you risk of infection.

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

what are the 2 main functions of the BCG vaccine?

A

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
14
Q

The following are examples of which type of vaccine;

MMR
BCG
Yellow fever
Typhoid (oral)
Polio (Sabin oral)
A

Live attenuated vaccines

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

what is the problem with live polio vaccine - Sabin?

A

Possible reversion to virulence (recombination, mutation):

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

very rare but has occurred

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

The following are examples of which type of vaccine;

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

A

Inactivated Vaccines

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

The following are examples of which type of vaccine;

Hepatitis B (HbS antigen), HPV (capsid), Influenza (less commonly used)

A

Component/subunit vaccines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

list some benefits of Inactivated vaccines/ component vaccines

A

No mutation or reversion
Can be used with immunodeficient patients
Storage easier
Lower cost

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

list some disadvantages of Inactivated vaccines/ component vaccines

A

Some components have poor immunogenicity

May need multiple injections

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

The following are examples of which type of vaccine;

Haemophilus Influenzae B
Meningococcus
Pneumococcus (Prevenar)

A

Conjugate vaccines

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

what is the MOA of Conjugate vaccines?

A

Polysaccharide alone induces a B cell response – transient

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the purpose of Adjuvants in vaccines?

A

Adjuvant increases the immune response without altering its specificity

Mimic action of PAMPs

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

which vaccine in use stimulates a braod immune response?

A

live vaccines

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

true/false:

in DNA vaccines, the plasmid is supposed to insert into dna and be replicated?

A

false

not integrated. Gene encodes protein presented at cell surface

25
Q

how are Dendritic cell vaccines utilised?

A

Personalised immunotherapy

26
Q

what are the indiciations for Haematopoietic stem cell transplantation hsct ?

A

Life-threatening primary immunodeficiencies:

 - Severe combined immunodeficiency
  - Leukocyte adhesion defect

Haematological malignancy etc

27
Q

what is the utility of Specific immunoglobulin/Human immunoglobulin?

A

post-exposure prophylaxis (passive immunisation)

28
Q

what is the use of Chimeric antigen receptor T cell therapy (CAR–T cell therapy) ?

A

Used for acute lymphoblastic leukaemia in children

Used for some forms of non-Hodgkin lymphoma

29
Q

how does Chimeric antigen receptor T cell therapy work (CAR–T cell therapy) ?

A

T cells with chimeric receptors targeting CD19
Patient’s own T cells

Genetically engineered to express receptor
targets tumour cell

30
Q

what does Adoptive cell transfer (ACT) – T cells involve?

A

a range of techniques involving:

taking the individuals t cells, whether from peripheral blood or the tumour, expanding the t cell volume, in some cases attaching a chimeric receptor and then putting it back in the blood to help fight disease.

31
Q

what is the use of immune checkpoint inhibitors? what kind of drugs are they usually?

name some examples

A

Usually Antibodies that bind to receptors eg CTLA4 or PD-1 on T cells
Blocks immune checkpoint
Allows T cell activation

Ipilimumab & nivolumab

32
Q

what are complications of immune checkpoint inhibitors?

A

Autoimmunity

33
Q

what are indications of immune checkpoint inhibitors?

A

Advanced / metastatic melanoma!!!

Metastatic renal cell cancer

34
Q

list some indications of different recombinant cytokines

A

Interferon alpha
Hairy cell leukaemia, chronic myeloid leukaemia, multiple myeloma

Interferon beta
Behcet’s

Interferon gamma
Chronic granulomatous disease

Interleukin 2
Renal cell cancer

35
Q

how do corticosteroids work?

A
  1. Via Effects on prostaglandins

A. Corticosteroids inhibit phospholipase A2
- Blocks arachidonic acid and prostaglandin formation and so reduces inflammation

  1. Effect on phagocytes:
    A. Decreased traffic of phagocytes to inflamed tissue
    B. Decreased phagocytosis
    C. Decreased release of proteolytic enzymes
  2. Effects on lymphocyte function
    A. Lymphopenia
    B. Decreased antibody production
    C. Promotes apoptosis
36
Q

which lymphocytes do steroids affect most?

A

Affects CD4+ T cells > CD8+ T cells > B cells

37
Q

what is the MOA of Cyclophosphamide?

indications?

A

Mechanism of action – Alkylating agent
Alkylates guanine base of DNA
Damages DNA and prevents cell replication
Affects B cells > T cells, but at high doses affects all cells with high turnover

Indications:
Vasculitis, Cancer

38
Q

what is the MOA of Azathioprine?

A

Mechanism of action – Anti-metabolite - purine
Metabolised by liver to 6 mercaptopurine
Purine analogue
Interferes with DNA production – inhibits proliferating cells
Affects T cells>B cells

39
Q

what are the side effects of azathioprine?

A
  1. Bone marrow suppression
  2. Hepatotoxicity
    - not common
  3. Infection
    Serious infection less common than with cyclophosphamide
40
Q

What must be done before prescribing azathioprine?

A 
Thiopurine methyltransferase (TPMT) polymorphisms =
Unable to metabolise azathioprine

SO Check TPMT activity or gene variants before treatment if possible; always check full blood count after starting therapy*

41
Q

what is the MOA of Mycophenolate mofetil?

A

Mechanism of action – Anti-metabolite - purine
Blocks de novo guanosine nucleotide synthesis
– prevents replication of DNA
Prevents T>B cell proliferation

42
Q

which drugs are associated with:

Particular risk of herpes virus reactivation
Progressive multifocal leukoencephalopathy (JC virus)

A

Mycophenolate Mofetil

43
Q

what therapy would be suitable in the following cases:

Goodpasture syndrome:
Anti-glomerular basement membrane antibodies

Severe acute myasthenia gravis:
Anti-acetyl choline receptor antibodies

Severe vascular rejection:
Antibodies directed at donor HLA molecules

A

Plasma Exchange

44
Q

how do calcineurin inhibitors work?

name 2

A

Block cytokine transcription, therefore prevent lymphocyte proliferation and effector functions

so by preventing thee cross talk between cytokines and lymphocytes - they are inhibitors of cell signalling

Ciclosporin, Tacrolimus

45
Q

The following are what kind of drugs:

Infliximab, Adalimumab, Certolizumab, Golimumab

A

Anti-TNFa Antibodies

46
Q

what a re some indications of Anti-TNFa Antibodies?

A
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Psoriasis and psoriatic arthritis
  • Inflammatory bowel disease
  • Subcutaneous or intravenous
47
Q

Denosumab Antibody directed against RANK ligand would have what indication?

A

Osteoporosis

48
Q

Treatment options include inhibition of TNF alpha or IL12/23 or IL17A or use of a PD4 blocker or ciclosporin in which condition?

A

Psoriasis

49
Q

a lady taking corticosteroids for SLE begins to experience

general weakness that steadily gets worse, clumsiness and balance issues, sensory loss. what is your dfx?

A

John Cunningham Virus (JCV)

  • Common polyomavirus that can reactivate
  • Infects and destroys oligodendrocytes, causing:
  • Progressive multifocal leukoencephalopathy
50
Q

what happens in GVHD - graft vs host disease? why is it different from graft rejection?

A

The T cells present within the transplanted tissue then attack the recipient’s body’s cells, which leads to GvHD. They produce an excess of cytokines, including TNF-α and interferon-gamma (IFNγ).

This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donor’s immune system’s white blood cells reject the recipient.

51
Q

what causes GVHD - graft vs host disease ?

A

A wide range of host antigens can initiate graft-versus-host-disease, among them the human leukocyte antigens (HLA).

Antigens most responsible for graft loss are HLA-DR (first six months), HLA-B (first two years), and HLA-A (long-term survival).

However, graft-versus-host disease can occur even when HLA-identical siblings are the donors.

This is mediated by minor histocompatibility antigens that can be presented by major histocompatibility complex (MHC)

52
Q

Since T cells are the culprit in GVHD - graft vs host disease, why dont we just destroy all T cells in the graft?

A

They are valuable for engraftment by preventing the recipient’s residual immune system from rejecting the bone marrow graft (host-versus-graft)

53
Q

What is Transfusion-associated GvHD?

How is it prevented?

A

associated with transfusion of un-irradiated blood to immunocompromised recipients, or if HLA is mismatched

is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells eg T cells (including lymphocytes) within

54
Q

what is the Billingham criteria - that must be met in order for GvHD to occur?

A
  1. An immuno-competent graft is administered, with viable and functional immune cells.
  2. The recipient is immunologically different from the donor – histo-incompatible.
  3. The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells
55
Q

what are the time frames for acute and Chronic GvHD?

A

acute 10 - 100 days

chronic > 100 days

56
Q

what are the symptoms of chronic GvHD?

A

Rash on the palms of the hands or the soles of the feet, and the rash can spread and is usually itchy and dry

If severe, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:

Decreased appetite
Diarrhea
Abdominal (belly) cramps
Weight loss
Yellowing of the skin and eyes (jaundice)
Enlarged liver
bacterial infections etc etc

MULTIPLE ORGAN TARGETS - eyes, mouth etc etc

57
Q

what are the symptoms of acute GvHD?

A

The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body.

Other symptoms can include Nausea, vomiting, stomach cramps, diarrhea (watery and sometimes bloody), loss of appetite, jaundice, abdominal pain, and weight loss.

you know which systems/organs are affected by ivx eg bilirubin raised if liver involvement,

Skin GvHD results in a diffuse red maculopapular rash, sometimes in a lacy pattern.

RESTRICTED ORGAN TARGETS - Skin rash, Gut, Liver affected

58
Q

how would you manage GvHD ?

A

immunosuppression of varying degrees

note: immunosuppression increases risk of mortality from infections

59
Q

If we are not looking at time, how else do we differentiate acute vs Chronic GvHD?

A

clinical manifestations - extent of organ involvement

Path - Immuno (11 decks)

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