Immunology 3: Adaptive immunity Flashcards

1
Q

Adaptive receptor overview

A

– Antibody (soluble), B cell receptor or T cell receptor

– Formed by rearrangement of genomic segments -> joining of non-contiguous gene segments to make functional receptor -> recombination and junctional processes make diversity or receptors

– Soluble or cell surface receptors

– Huge repertoire of different receptors
-> an individual might express 10^8 different specificities

– Each receptor clonally expressed on very few cells (unless stimulated)

– lymphocyte cells (long lived, self reneweing, fast replicating)

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2
Q

Temporal features of innate and adaptive responses

A

Innate immune system is stimualted first and stimualtes the adaptive immune system (primary infection).

The innate immune system resturns to to basal resting state and the primary immune response should clear the infection.

some adaptive kept at memory state -> faster response upon secondary infection

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3
Q

B/ T cell selection

A

Anticipatory repertoire = random receptor generation in the thymus or the bone marrow leading to populations of niave cells that undergo different levels of selection

Selection:
-> CENTRALLY (thymus/ bone marrow) – avoids overt self-reactivity (auto-immunity)
-> PERIPHERALLY (lymph nodes/ spleen) – controls what is activated (prevents inappropriate activation which takes energy and results in low affinity receptor)

Selection of T cells and memory formation:

Thymic selection: presented with self peptides in the thymus -> can select T molecules w/ correct intermediate level of response when posed w/ self-MHCs (if bind self-peptides too much then killed)

Response: Receptors w/ high affinity for pathogen peptide exceed threshold + activated + replicate (1million cells from 1 cell in a week) -> occurs outside thymus

Memory: some kept in memory state after response = closer to activation threshold + more of them so replicate faster next time

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4
Q

B cell developement and subsets

A

Irreversible early developement in the bone marrow:
- B1: natural antibodies which are T-independent, have no memory, house keeping antiodies
- B2: Classical B cells

Activation in the periphery:
- Following infection niave B2 cells are differentiated in the periphery via dendritic cell antigen presenting to BCR and secondary signals (from T cells)
- IgM is the first antibody that the body produces, and it can be changed by class switching and affinity maturation depending on the antigen present.
- B cells commit to other antibody subtypes (IgA, IgG, IgE)
- Can later develope to form B plasma cells and memory cells

class switch: change in Ig constant region of antibody

Affinity maturation: producing antibodies with increased affinity to pathogen via interaction with T cell

Later activation
- They are activated in the tissue when they encounter an antigen, engulf it, present it to a T helper cell which binds and releases cytokines -> this leads to clonal expansion
- Can occasionally be activated when interact with antigen without T cell binding

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5
Q

Antibody activity mechanisms

A
  • Block function (bind to important molecules on the pathogen)
  • Agglutinate (stick pathogens together)
  • Activate Complement
  • Opsonise (This means Fc can be recognised by receptors on cells)
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6
Q

T cell develeopement and subsets

A

Early developement in thymus:
- Pre T cells differentiate into yd or ab cells
- ab cells become niave CD8+, CD4+ cells or iNKT
- CD4+ can differentiate into natrual CD4+ Treg (regulates immune system)

Later develeopement in the perifery
- Dendritic cell presents antigen to the naive cells on MHCI and MHCII
- Those that have correct receptor bind to MHC and divide
- niave cells differentiate into effector cells depending on the cytokines released (CD4+ can also differentiation into inducible Treg)

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7
Q

Classical T cell types

A

TCRαβ
CD4+ = T helper cells TH (for MHC class II -> external antigens)

Naive T helper cells (Th0) divide and then differentiate into subsets once they receive signal leading to upregulation of TF (reciprocal inhbition) -> reprogramming possible

IGNy from NK or IL-12 -> upregulates T-bet ->Th1 -> activate macrophage via IFNγ - cytokine
IL-4 from PMN -> upregulated Gata3 -> Th2 -> help B cells make antibodies via IL4 interleukin-4 - cytokine

Formation of memeory cells
- fewer memory cells than CD8
- Different CD4+ subset can be formed in primary and secondary infection from memory cells

CD8+ = T cytotoxic cells TC (for MHC class I-> internal antigens)
-> In early activation express a selection of terminal phenotype making a mix of perforin, granzyme A + B, granulysin and IFNγ
-> At terminal activation express all required protein, have cytotoxic capabilities and produce IFNg

Function:
Release granules in immunological synapse:
Perforin: forms a pore in the target membrane by oligomerisation
Granzymes A and B: serine proteases that activate apoptotic pathways
Granulysin: activates apoptosis and has direct antimicrobial effects

Release chemokines that block infection of unifected cells

Lead to transcription supression of latent infections

Formation of memeory cells
EFFECTOR memory – preferentially circulate in tissues and spleen
* Rapidly acquire effector function
* Short lived and rapidly be rapidly depleted

CENTRAL memory – lymph nodes, spleen, bone marrow
* Acquire effector function slower
* Long-lived and Rapid proliferation
* CM pool more resistant to depletion

Persistent viral infections eg. EBV Epstein Barr Virus can cause CD8 T cell exhaustion as deplete pool

TCRγδ
- no evidence of memory formation
- Epithelial or peripheral groups
- Recognise different molecules to ab (e.g. heat shock proteins + inorganic pyrophosphates)
- Protect against infection in early life when ab response not efficient
- Regulate αβ T cells

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8
Q

Non classical

A

iNKT
- invariant NKT cell (non-classical TCRαβ cells)
- no evidence of memory formation
- all have same T cell receptor = no need for memory in these cells
- recognise CD1 (lipid antigens) = non-classical MHC class-I like molecule (not MHC class I)
- Activated early in infection and produce IL-4 which promotes subset differentiation (this is similar to role of NK which make IFNγ)

TCRgd T cells

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