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BDS1 Pathology > Adaptive Immunity - T cells > Flashcards

Adaptive Immunity - T cells Flashcards

1
Q

What does the adaptive immune response consist of?

A

Cell-mediated responses and antibody (humoral) responses - these are carried out by T and B cells

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2
Q

What do T cells drive in adaptive immunity?

A

Cell-mediated immunity - it involves the action of macrophages, NK cells and antigen-specific cytotoxic T-lymphocytes

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3
Q

What do B cells drive in adaptive immunity?

A

Drive humoral immunity and produce antibodies

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4
Q

What is a key feature of the adaptive immune system?

A

Immunological memory - whereby each pathogen is ‘remembered’ by a signature T cell receptor and/or B cell receptor

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5
Q

What are the 4 stages to adaptive immunity?

A
  1. Establishment of infection
  2. Induction of adaptive response
  3. Adaptive immune response
  4. Immunological memory
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6
Q

What are the 3 main receptors of active immunity?

A

3 main molecules that are involved in recognition of foreign antigen by adaptive immune response:

  1. T cell receptor
  2. B cell receptor
  3. Major histocompatibility complex

Multiple genes encoding each allows the development of a repertoire of receptors with specificity for wide range of antigens

  • TLR - just has 1 gene
  • B cell receptor -
  • overtime multiple genes that encode 3 major constituents
  • can pick and choose what genes it wants
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7
Q

What are the 2 classifications of T cells?

A
  • CD4+ (helper cells)

- CD8+ (cytotoxic cells)

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8
Q

What is ‘cluster of differentiation’ in T cells?

A

Cell surface markers involved in signalling

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9
Q

What is major compatibility complex in T cells?

A

Cell surface markers involved in signalling - molecules flagged for presenting antigen

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10
Q

CD8+ is a co-receptor that binds to what?

A

MHC class 1

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11
Q

CD4+ is a co-receptor tat binds to what?

A

MHC class 2

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12
Q

What is used to help anchor the T-cell receptor so it can get a tight signalling complex with the antigen?

A

CD8+/CD4+ and CD3

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13
Q

CD3 is a co-receptor. What is it involved in the activation of?

A

CD4+ and CD8+ cells

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14
Q

What is the function of Gamma-delta T cells?

A
  • Only 5% in humans

- Little known about functions

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15
Q

How many antigens does each T cell have specificity for?

A

only 1

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16
Q

T cell receptors contain alpha and beta chains - how many genes code for each of the 2 polypeptide chains?

A

Multiple genes

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17
Q

What 2 regions are each alpha and beta chain made up of in a T cell receptor?

A
  • Constant region

- Varied region

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18
Q

To make an alpha chain there are 2 gene segments which encode the variable region of the chain. What are these?

A
  • V (variable)

- J (joining)

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19
Q

To make a beta chain there are 3 gene segments which encode the variable region of the chain. What are these?

A
  • V (variable)
  • D (diversity)
  • J (joining)
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20
Q

To generate diversity in alpha and beta chains of T cell receptors, how are genes re-arranged?

A

By somatic recombination (mutation)

  • Has the ability to pick from lots of genes
  • Making alpha chains - picks one V gene and one J gene
  • Making beta chains - picks one V gene, one J gene and one D gene
  • Can pick one gene from a variety of genes
  • By picking and choosing different genes you can produce a unique protein
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21
Q

How many combinations are there for V(D)J in the variant region of the beta chain of a T cell receptor?

A

Approx. 3x10^11

22
Q

The protein structure of a T cell receptor is different to accommodate specific antigens. How is the structure different?

A

Specific antigen binding sites

23
Q

What is the process of thymic education?

A
  • Pre-thymic T cells enter the thymus. Cells are CD8 and CD4 positive (low expression). TCR genes are also rearranged (low expression)
  • As the cells mature, they move into the cortex where they adhere to cortical epithelial cells. TCR’s on their surface interact with the MHC molecules on the epithelial cells (positive selection)
  • Cells that are not selected are subject to apoptosis and are phagocytosed by macrophages
  • Thymocytes then migrate into cortex and expression of CD3, CD4/CD8 and TCR increases
  • TCR’s with self-reactivity are deleted because of contact with autoantigens presented by dendritic cells and macrophages (negative selection)
  • Cells that express CD4 or CD8 appear and migrate to the periphery
24
Q

What is the simplified process of thymic education?

A
  1. Can they bind to MCH class 1 or 2 (not just what they bind to but how strongly they bind) - called positive selection (if can’t bind to 1 or 2 they are disposed of by apoptosis then phagocytosis)
  2. Have T-cell receptor that can bind to infinite number of antigens - what happens next is where dendritic cells show T cell lots of different self-antigens. If T cell binds to one of self-antigens T cell is processed for cell death - negative selection
  3. Then moved to medulla - fully educated T cells - most will go to lymph nodes and can spread around the body
25
Q

Even when T cells leave the thymus after thymic education why is it still defined as a ‘naïve’ T cell?

A

As it has still not been exposed to a foreign antigen

26
Q

Where can T cells be found?

A
  • They circulate in the blood and lymphatics
  • Some T cells find their way to lymph nodes (secondary lymphoid organs) and remain
  • Even though they have been ‘educated’ they are still ‘naive’ cells
27
Q

Lymph nodes are ‘garrisons’ of immune cells. What does this mean?

A

Lymph nodes store ‘troops’ (immune cells) in anticipation of an immune reaction

28
Q

What cells do lymph nodes contain?

A
  • T cells
  • B cells
  • Dendritic cells
29
Q

How are T cells activated by dendritic cells?

A
  • Immature dendritic cells take up and process antigen in the epidermis
  • Once taken up the antigen they migrate to lymph nodes and differentiate along the way
  • Mature dendritic cells have co-stimulatory activity and can prime naïve T cells
  • They can also transfer antigen to other dendritic cells resident in the lymph node
30
Q

What are dendritic cells?

A

Antigen presenting cells

31
Q

What do dendritic cells do once they are activated?

A
  • They leave tissue and during migration they differentiate. Stop processing antigen and the MHC: antigen migrates to cell surface
  • Once they arrive at the lymph noted they express high levels of MHCII: antigen
32
Q

What is ‘priming’ of a T cell?

A

The activation and differentiation of a naïve T cell

33
Q

What are the 3 signals involved in the ‘priming’ of naïve CD4+ T cells?

A
  • Signal 1 - Need T cell receptor that recognises antigen - Dendritic cell (APC) presents antigen on MHC class II to T cell receptor on naïve T cell (CD4 also binds to MCHII) this causes ACTIVATION
  • Signal 2 - APC as its moving into lymph node will start expressing a lot of CD80/CD86 (needs further anchoring through this binding) By these binding to CD28 - Co-stimulatory molecules engage so CD28 binds to CD80/CD86 which is a signal for survival and clonal expansion of T cells (signal 1 but no signal 2 leads to ANERGY)
  • Signal 3 - T cell is exposed to cytokines (determines what type T cell will become by which cytokine has been produced) - Want T cell to become right type of T cell for the pathogen that is present (DIFFERENTIATION INTO SUBSETS OF EFFECTOR T CELLS) - after this the T cell will start to divide to produce many copies of itself
34
Q

What is the definition of anergy?

A

Absence of the normal immune response to a particular antigen or allergen

35
Q

What will determine what types of Specialised cell a naïve T cell will become?

A

Cytokines released by antigen presenting cells

36
Q

Once a naïve T cell encounters presented antigen it undergoes expansion. What is meant by expansion?

A

It produces lots more of itself (many copies)

37
Q

What are memory T cells and what can the allow?

A
  • T cells that become long lasting in the body (they have a life span of over 20 years)
  • They allow a faster and larger immune response to a secondary exposure to an antigen
38
Q

What are the roles of Th1 cells?

A
  • Numerous roles in supporting cellular immunity
  • Linked to innate immunity and heighten ongoing responses in tissues
  • Key role in supporting macrophage function
  • Good at going back to front line and supporting innate immunity
39
Q

What are the roles of Th17 cells?

A
  • Play a role in host defence against pathogens
  • Multiple roles in dictating immune responses
  • Support innate immunity
40
Q

Why are Th17 cells called this?

A

Because they express IL-17

41
Q

What are the roles of Th2 cells?

A
  • Major role in supporting humoral (antibody) immunity
  • Activates mast cells and eosinophils. Protect against parasitic infections but also major role in allergy and hypersensitivity reactions
  • Little innate immunity involvement
42
Q

Where are Thf cells found?

A

Found in secondary lymphoid organs in B cell zone (not T cell zone)

43
Q

What are the functions of Thf cells?

A
  • Helps support B cell responses

- Promotes B cell activation and the formation of antibody producing plasma cells

44
Q

What are Treg cells?

A

Regulatory T cells

45
Q

What are the functions of Treg cells?

A
  • Immune suppression (provide balance)
  • Key modes of action:
  • Release inhibitory cytokines
  • Induce active T cells to undergo apoptosis
  • Inhibit dendritic cell maturation and function
46
Q

How are cytotoxic CD8+ T cells activated?

A

By antigen presentation on MHC class I presented to TCR

47
Q

What are CD8+ T cells also known as?

A

Cytotoxic T cells

48
Q

What are the functions of cytotoxic T cells?

A
  • Induce host cells to undergo apoptosis (programmed cell death)
  • With apoptosis all contents of the cell are kept inside so there is no further unwanted signalling
  • Cytotoxic T cells release contents of granules in direct fashion (granzyme/perforin)
  • Perforin produces pore in cells
  • Granzyme targets apoptotic signalling pathways
49
Q

What is the function of perforin?

A

Directs contents through cell wall (unknown mechanism)

50
Q

What is the function of granzyme?

A

Once in cell, granzyme targets apoptotic signalling pathways:

  • Caspase- 3
  • Disrupts mitochondrial membrane releasing cytochrome c
51
Q

What are the functions of perforin and granzyme inducing apoptosis?

A

Perforin facilitates granzyme entry into infected cell. Once in cell granzyme induces apoptosis

BDS1 Pathology (14 decks)

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