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Path - Immunology > Immune Mod Therapies > Flashcards

Immune Mod Therapies Flashcards

1
Q

What occurs to T cells during and after infection?

A

During infection there is massive T cell expansion

After infection, only some memory cells survive

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2
Q

What are the 3 APCs?

A

Denditic cells
Macrophages
B lymphocytes

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3
Q

What are the traits of memory T cells?

A
  • Longevity
  • Specific pattern of expression of cell surface proteins involved in chemotaxis cell adhesion (to allow cels to rapidly access non-lymphoid tissue)
  • Rapid, robust response to subsequent antigen exposure (lower threshold of activation than naive cells)
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4
Q

What are the traits of memory B cells?

A

Longevity
Pre-formed antibody (high affinity IgG)
rapid robust response to subsequent antigen exposure

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5
Q

What are the aims of a vaccine?

A

MEMORY - generate long lasting response
PROTECTIVE response
no adverse reactions
Practical - one shot, easy storage

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6
Q

What antibody is required to fight off influenza?

A

Antibody against haemagglutiini

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7
Q

what is haemagglutinin?

A

The receptor-binding and membrane-fusion glycoprotein of the influenza virus

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8
Q

What are haemaglutinin antibodies detected with?

A

haemaglutinin antibodies are detected with an haemaglutinin inhibition assay

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9
Q

How does a haemaglutinin inhibition assay work?

A

Normally: red cells clump at the bottom forming a red spot

With virus: Sialic acid receptors on RBC bind to hemaglutinin on virus, causing RBC to haemagluttinate (haemaglutinin makes the cells stick together, causing diffuse coloration across the wall)

With Antibodies: antibodies bind to haemaglutinin prevent this haemagglutionation > RBC clump at bottom forming a red spot

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10
Q

What is BCG a strain of?

A

Of bovine TB

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11
Q

What kind of protection does BCG provide?

A

Some protection to primary infection (20%) > little protection against getting the infection
Protection against active progression to active TB (70%)

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12
Q

How will an individual with the BCG vaccine experience TB?

A

TB infection remains latent and well controlled

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13
Q

What is a Mantoux test?

A

Injection of small amount of liquid tuberculin intradermally
Examine area of infection 48-72 hours after tuberculin injection
Reaction is the area of swelling around the site

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14
Q

What are the types of vaccine you can have?

A

Live attenuated
Inactivated /component
Conjugate / adjuvant

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15
Q

What occurs in a live attenuated vaccine?

A

The live organism is modified to limit pathogenesis

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16
Q

What are examples of live attenuated vaccine

A 
MMR 
BCG
Yellow fever 
Typhoid 
Polio (sabin - oral)
Vaccinia
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17
Q

What are advantages of the live attenuated vaccine?

A

Establishes infection (mild)
Raises broad immune response to multiple antigens (protection to MANY strains)
Activates ALL phases of immune system
Confers LIFELONG immunity

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18
Q

What are examples of inactivated vaccines?

A 
Influenza 
Cholera 
Polio (Salk - injected)
Hep A 
Pertussis 
Rabies
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19
Q

What are examples of toxoid vaccines?

A

Diptheria

Tetanus

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20
Q

What are examples of component vaccines?

A

Hep B
HPV
Influenza

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21
Q

What are disadvantages of the live attenuated vaccine?

A

Storage problems
Possible reversion to virulence > DO NOT give to immunocompromised
Spread to contacts of vaccine who have not consented to vaccine
Spread to immunocompromised/immunosuppressed

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22
Q

What are advantages of inactivated/component vaccines?

A 
No mutation or reversion 
Can be used in immunodeficient patients 
Can lead to elimination of wild-type virus from the community 
Easier storage 
Lower cost
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23
Q

What are disadvantages of inactivated/component vaccines?

A

Do NOT follow normal route of infection
Have poor immunogenicity
May need multiple injections
Require conjugates / adjuvants to enhance effect

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24
Q

What is a conjugate vaccine made up of?

A

Polysaccharide + protein carrier

25
Q

What does the polysaccharide cause?

A

A T cell independent B cell response

26
Q

What are examples of conjugate vaccines?

A

haemophiliac influlenza B
Meningococcus
Pneumococcus

27
Q

What is an adjuvant, and how does it work?

A

Increases the immune response without altering the specificity
Mimic actions of PAMPs on TLR and other PRR

28
Q

What are examples of adjuvant’?

A

Aluminium salt
Lipid (monophosphoryl lipid A)
Freund’s anjuvant

29
Q

What is the most commonly used adjuvant in humans?

A

Aluminium salt

30
Q

What vaccines use aluminium salt as adjuvant?

A

Hep A

Hep B

31
Q

What are theories for the function of aluminium salt?

A

Allow antigens to be slowly released over time, leading to prolonged antigenic stimulation
May induce a mild inflammatory r reaction that promoted development of adaptive immune response
May activate Gr1 IL4 oesinophils to prime naive B cells > antibody response

32
Q

What is an adenovirus vector vaccine?

A

DNA of relevant protein inserted to viral vector to produce a vaccine
This infects cells in vivo

33
Q

What are ISCOMs?

A

mmune-stimulating complexes

These are cage like structures mixed with antigens to enhance cell-mediated immunity

34
Q

What are DNA vaccines?

A

Plasmid containing gene of choice from the pathogen is inserted into a muscle cell
The plasmid does not replicate, but the gene encodes protein that is presented at the cell surface
This mimics the normal action of a virally infected cell and stimulates T cell response

35
Q

What is a disadvantage of DNA vaccine?

A

Plasmid may integrate into host DNA and response to DNA could lead to autoimmune conditions eg SLE

36
Q

What are dendritic cell vaccines used for?

A

FOr tumours where dendritic cell function is compromised

37
Q

How do dendritic cell vaccines work?

A

Take patient’s dendritic cells and load them with a tumour antigen
Reintroduce them to the patient to boost immune response against tumour antigen

38
Q

What is an example fo dendritic cell vaccine / personalised immunotherapY?=

A

PROVENGE - for prostatic cancer

39
Q

How does PROVENGE work?

A

Remove WBC from patient’s bloods
Harvest and incubate APC with recombinant protein PAP-GMCSF
APC is infused back to patient

40
Q

What is the technique for replacement of missing components of the immune system?

A

HAEMATOPOEIC stem cell transplantation

41
Q

What are indications for hfaematopoeic stem cell transplant?

A

Life threatening immunodeficiency e.g. SCID
Haematological malignancy
Offers complete, permanent cure

42
Q

What are antibody replacement therapies?

A

Immunoglobulins can be replaced bu giving human immunoglobulin from pool of >1000 donors
Contains pre-formed IgG to a variety of organisms

43
Q

What are indications for antibody replacement=

A

Primary antibody deficiency (agammaglobulimae, hyper IgM syndrome, common variable immunodeficiency)

Secondary antibody deficiency (CL, multiple myeloma, after BM transplant=

44
Q

When do you give specific immunoglobulin ?

A

Passive immunisation (for post exposure prophylaxis - TETANUS)

45
Q

What are examples of specific immunoglobulin given for passive post exposure immunisation?

A

Hp B
Tetanus
Rabies
Varicella zoster

46
Q

When is Adoptive Cell Transfer of virus specific T cells used?

A

Used for EBV in people who are immunosuppressed to prevent the development of B cell lymphoproliferative disease

47
Q

How does Tumour Infiltrating Lymphocyte T cell therapy work?

A

You remove the tumour from the patient
You stimulate T cells within the tumour with cytokines so that they develop a response to the tumour
You the select and expand the tumour infiltrating lymphocyte and rein fuse into the patient

48
Q

How does TCR therapy work?

A

Take T cells from patient
Insert gene that encodes a specific TCR (against tumour cell antigen)
Reinsert T cells

49
Q

What type of receptors are used in CAR therapy?

A

insert CHIMERIC receptors (both B and T) into T cells

It usually recognises CD19 on B cells and harnesses T cells to kill it

50
Q

What treatment can you use for advanced melanoma?

A

Ipilimumab (Antibody specific to CTLA4)

51
Q

How does Ipilimumab work?

A

Ipilimumab binds to CTLA4, which would normally emit inhibitory signal
This means that CD80 and CD86 must act via CD28
CD28 transmits stimulatory signal
Thereby T cell response is enhanced

52
Q

How do Pembrolizumab / Nivolumab work

A

Normally PD1 transmits an inhibitory signal to T cells
Its ligands PDL1 and PDL2 are present on APCs and tumour cells
If tumour cells express PD ligands they turn off T cells

NIVOLUMAB binds to PD1 > blocks this inhibitory effect > activates T cells

53
Q

What is a risk of using Nivolumab?

A

As they invigorate the immune response, there is a risk of AI disease

54
Q

What is interferon alpha used for?

A

Anjunct to Help B, Hep C, Kaposi, CML, MM

55
Q

What is interferon beta used for?

A

Behcet’s disease, MS

56
Q

What is interferon gamma used for?

A

Chronic Granulomatous disease

57
Q

How does the influenza vaccine built?

A

INACTIVATED vaccine

The vaccine used is a trivalent vaccine. Each injected seasonal influenza vaccine contains three influenza viruses:

  • one influenza type A subtype H3N2 virus strain
  • one influenza type A subtype H1N1 (seasonal) virus strain
  • one influenza type B virus strain
58
Q

What is CAR T Therapy largely being used for

A

for targeting CD19

In ALL, NHL

Path - Immunology (11 decks)

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