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DVM 2 - 1 > Immunology 2 > Flashcards

Immunology 2 Flashcards

1
Q

what determines T helper cell differentiation

A
  • Cytokines in the environment at the time of naïve T cell activation define the differentiation pathway of the T helper cells.
    ○ Cytokines present in environment are dependent on the danger signals PAMPS that bind to the neutrophils
  • The cytokines produced by the T helper cells affect their other cells and is the basis of the T helper cell effector function
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2
Q

Dendritic cells, macrophages and B cells what proteins present

A

Dendritic cells
- Peptides, viral antigens, allergens
- Able to class switch in terms of activation of both CD4 and CD8 cells from outside antigens
Macrophages
- Particulate antigens (larger)
- Intracellular and extracellular phagocytosis
B cells
- Only good at presenting antigens if the antigen is specific to the B cell receptor
- Soluble antigens, toxins and viruses

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3
Q

Steps in activation of Cytotoxic CD8 T cells

A

1) 3 signal activation of naive T cell
2) IL-2 released allowing differentiation into CD8 T cells
3) effector T cell doesn’t require co-stimulation signal just recognition of Ag + MHC -> T cell receptor has already gone through selection to ensure doesn’t recognize self
4) CTL recognised and binds to virus-infected cell
5) Programs target for death inducing DNA fragmentation
6) CTl migrates to new target as the cell just targeted dies via apoptosis

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4
Q

List 3 molecules that are released by CD8 cells and their functions

A

1) cytotoxins - perforins, granzymes -> apoptosis
2) FAS ligand - binds to FAS molecule on target cells -> apoptosis
3) cytokine IFN-γ - directly inhibits viral replication

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5
Q

What are the 2 types of antigens and what can they be recognised by

A

1) TI-1 antigen
- Large antigens that can be recognised by B cells directly
○ Don’t need TH2 cells to activate
2) TD antigen
Needed to be processed by T cell first before can activate B cell

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6
Q

Can T cell receptors recognize MHC molecules from other individuals

A

Need to be from the same individual as T cell receptor also recognises the MCH molecule (self) which varies between individuals

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7
Q

List the 4 steps and the 3 signals that are involved with TH2 activation of B cells

A

1) Antibody (only IgM as haven’t been activated by TH2 cell yet) binds to antigen and brings the antigen in to be processed via MCH class II
2) Activation TH2 cells (previous lecture) then recognises and binds to the MCH class II molecule + antigen complex with accompanying CD4 molecule to stabilise
○ This could also occur via memory T cells - secondary infection mainly occurs
- SIGNAL 1
3) CD40L-CD40 interaction between B cell and Activated TH cell
- SINGAL 2
4) Cytokines released from TH2 cell act on the B cell resulting in differentiation
- SIGNAL 3 - different isotypes produced by the B cell ○ Also clonal expansion

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8
Q

What cytokines leads to the production of IgE, IgG and IgA

A

IL-4 - IgE
IFN-γ > IgG1 & IgG3
TGF β > IgA

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9
Q

What are the 2 types of macrophages, how activated and function

A

1) M1
- Classically activated macrophages - via TH1 cells and DAMPS as described above
- Pro-inflammatory with microbicidal actions such as phagocytosis and killing of bacteria
2) M2
- Alternatively activated macrophages
○ TH2 cytokines IL-13 and IL-4 activate these macrophages
- Function is to terminate inflammation and produce growth factors and enzymes that start the process of tissue repair
○ Can be an issue due to increase fibrous tissue - chronic infections may lead to blockage of airways
- Release anti-inflammatory cytokines such as IL-10 and TGF-β

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10
Q

Describe the 3 main functions of TH1 cells

A

1) Macrophage activation (classic macrophages M1)
- Signals from CD40L and IFN-ƴ activate macrophages
- Macrophages can then
1. kill phagocytosed microbes with substances such as reactive oxygen species, nirtric oxide, lysosomal enzymes
2. secrete TNF, IL-1,2 - pro-inflammatory cytokines
3. increased MCH and costimulatory to activate naïve T cells
2) B cell opsonizing Ab via complement
- IFN-ƴ (as present in environment lead to IgG production in presence of TH2 therefore better at opsonisation)
3) Neutrophil recruitment and activation
- Release TNF to recruit and activate

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11
Q

What are the 4 functions of TH17 cells in inflammation

A
  1. Neutrophil accumulation
  2. Monocyte accumulation
  3. Increased mucus secretion
  4. Release of pro-inflammatory mediators
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12
Q

Where is activation of T and B cells occurring

A

1) Primary activation of T cells within the loose lymphatic tissue - dendritic cells and T cells
○ Usually occurs in secondary lymphoid tissues such as lymph nodes, spleen and Peyer’s patches
2) Germinal centres - B cell activation

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13
Q

What cell presents antigens to activate T cells

A

Dendritic - engulf pathogens within tissues, other proteins and cells then migrate to the lymph node

  • Present to the T cells - generally nothing occurs if no infection
    1. If infection - activation of T cells to the dendritic cells resulting in differentiation into different types of T cells
    2. Proliferation and differentiation of T cells
    3. Migration into the efferent lymph through the lymphatics
    4. Eventually into blood stream as activated T cells
    5. Will move into the tissues where needed as inflammation is occurring at site of infection resulting in innate response producing cytokines that upregulate adhesions molecules on endothelial cells at that point of the circulatory system
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14
Q

Define tolerance and its significance in the immune system

A
  • Specific immune unresponsiveness to an antigen that is induced by previous exposure of lymphocytes to that antigen
    • Significance:
  • Self/non-self-discrimination
    ○ Failure of self-tolerance —-> autoimmunity
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15
Q

What are the 2 main mechanisms of immunological tolerance and features

A

• Central tolerance
- T cell education
• Peripheral tolerance
- Anergy
○ Lymphocytes recognize Ag without adequate co-stimulation (B7/CD28)
- Regulatory lymphocytes (T-cells)
Suppression of lymphocyte activation & effector functions

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16
Q

What is anergy and how used in the immune system

A
  • T cells that are rejected initially during the activation of naive T cells due to the lack of co-stimulatory molecules (B7) on the dendritic cell
  • Cannot be activated again
17
Q

Regulatory T cells what are the 2 functions and what are the 2 forms

A

2 functions
1) Suppress immune response
2) Downregulate response after it has been occurring - once the pathogen has been cleared
○ Preventing inappropriate chronic inflammation
2 forms
1) Require contact with naïve T cells - contact-dependent inhibition of T cell responses
2) Mediated through suppressive cytokines - interleukin 10 and TGF- beta

18
Q

What are the 3 requirements for the development for an autoimmune disease

A

1) Genes - genetic predisposition - specifically certain MCH molecules genes - high affinity for self-peptides so presenting
2) Immune regulation - problem with the 3 levels of defence - central and peripheral tolerance
3) Environment - new antigens expressed the same time as DAMPS present therefore recognise new antigens in the wrong context, bacterial protein could also look similar to antigen of self or cross-react - example below

19
Q

List 2 drugs that that prevent auto-immunity and transplant rejection

A

Cyclosporine: blocks cytokine (IL-2) production by T cells
Corticosteroids: inhibit cytokine secretion by macrophages and reduces inflammation

20
Q

List 4 targets on tumors that the immune system can respond to

A

1) Mutate own proteins that lead to uncontrolled proliferation
- Mutation can be detected by immune system
2) Oncogene -encode for proteins that lead to increase proliferation
- Generally not produced by normal cells
3) Over-express self-proteins
- If express too much can be detected by the immune system
4) Oncogenic viruses - Viruses that create tumours
- Proteins from the viruses that

21
Q

What are 3 ways tumours evade the immune system

A

1) Failure to produce the tumour antigen
- Can no longer be seen by
2) Mutate to not produce MCH class 1 molecule therefore avoid recognition by T cells
- However NK cells can still kill as activated when MCH molecules are missing
3) Secrete cytokines resulting in downregulation of immune response - immunosuppressive proteins

22
Q

List one way vaccination against tumours work

A 
Take plasmid that expresses peptide from tumour and place within dendritic cell, that dendritic cell is then injected into the patient and acts on naïve T cells to activate then against the tumour 
○ As the peptide is being created within the dendritic cell it will be expressed on MCH class I which activates CD8 which are the cytotoxic T cell that have the ability to destroy the tumours
23
Q

What are the 6 features of ideal vaccines

A

1) Affordable worldwide
2) • Heat stable
3) • Effective after a single dose
4) • Applicable to a number of diseases
5) • Administered by mucosal route
6) Suitable for administration early in life

24
Q

what do most vaccines induce

A

immune memory

- increases speed, magnitude, persistence and avidity

25
Q

What occurs with vaccines against hidden antigens

A
  • doesn’t rely on immune memory
    Eg - ticks
    Animal not exposed to antigen during infection - tick doesn’t come into contact with the tick antigen as doesn’t invade just sucks blood
  • No boost of immune response during infection
  • Relies on presence of pre-existing Ab
    • Requirement for regular booster of vaccine to ensure there is a certain level of antibody circulating in the blood
  • Ab levels in serum decline
    Memory is present but is of no use since infection does not result in exposure to antigen
26
Q

What are the 4 different types of vaccines

A

1) live attenuated
2) inactivated
3) recombinant protein
4) DNA

27
Q

What are the advantages and disadvantages of live attenuated vaccines

A
  • Have many of the characteristics of the pathogen
  • Often provides good immunity - generally lifelong protection
  • Some induce disease-like symptoms
  • Can cause disease in immuno-compromised animals - side effects
  • recombination to form a pathological strain
28
Q

Inactivated vaccines advantages and disadvantages

A

Advantages:
- Safe
- Standardized successful technology
• Disadvantages:
- reduced immunogenicity > multiple vaccinations, adjuvants
○ Not good CD8 activation so weaker immune response as peptide from outside the cell therefore rely on cross-presentation to activate which isn’t as effective

29
Q

Recombinant protein vaccine what is it, example advantages and disadvantages

A 
Cloned protein from pathogen
- For example Hepatitis B vaccine
• Advantages:
- Safe
- Standardized successful technology
• Disadvantages:
- Reduced immunogenicity > multiple vaccinations, adjuvants
- Expensive > few veterinary applica1ons
30
Q

Describe how a DNA vaccine works advantages and disadvantages

A

Injection of DNA > animal produces the vaccine
- Fish vaccine is only commercial DNA vaccine
- No purification of protein
- No classical adjuvants
- Can use immuno-modulators incorporated into DNA vaccine
• Advantages:
- Can induce cytotoxic T cell responses - peptide within therefore presented on MCH class I molecule
• Disadvantages:
- Very low level of DNA expression
- Generally not very efficacious
Expensive > few veterinary applications - only really works in fish and mouse

31
Q

What is the difference between antigen and adjuvant

A

Antigen = Adaptive immune response

Adjuvant = Innate immune response

32
Q

vaccine components Antigen and adjuvant structure and function

A

antigen - Specific molecule from pathogen against which immune response is induced
- Need to be neutralising
- Often on surface of pathogen (antibody accessible)
Adjuvant
- Increases immune response to antigen
• Increase in terms of better memory response not necessarily primary response
• Longer term immune response/memory
- Defines TYPE of immune response induced - INNATE cytokines
- no antigenic specific response

33
Q

What is the main criteria in choosing an adjuvant, example of one commonly used and why

A

1) define immune response required
Alum is most widely used
- Good Th2 but poor Th1 adjuvant
○ Strong antibody response and that is all - not any quantifiable cell mediated response

34
Q

List 5 functions of adjuvants

A

1) depot for Ag
2) Induce inflammation
3) target Ag to specific Ag processing pathways
4) increase access of immune system to Ag
5) Activates Toll like receptor (TLR) pathways

35
Q

Mucosal vaccines what are the advantages

A
  • Early destruction of pathogen prevents infection of other organs - induce inflammation at those sites - not well established at this point, easier to destroy and less likely to develop clinical signs
  • Some degree of protection between mucosal surface
    • Vaccination at one mucosal site may protect other mucosal sites - debatable, can depend on relationship at different sites
36
Q

What are 3 ideal goes for vaccine efficacy and which is the main one that is achieved

A

1) Protection from disease symptoms - very hard to achieve, animals still carrier and transmit disease
2) reduction in transmission - main goal
3) sterilising immunity - generally hard to achieve
- pathogen eliminated from animal

37
Q

Effect of vaccination what is the equation involving reproduction rate in herd immunity

A

R* = R0(1-f)
R0 = transmission rate without vaccination
f is proportion of population protected by vaccination
R* = new reproductive rate

DVM 2 - 1 (31 decks)

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