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Immunology > Development of Lymphocytes > Flashcards

Development of Lymphocytes Flashcards

1
Q

Name cells of the innate immune system

A
  • Neutrophils
  • Monocytes
  • NK
  • Macrophages
  • Eosinophils
  • Basophils
  • Dendritic cells
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2
Q

Name cells involved in adaptive immunity

A
  • T cells
  • B cells
  • Plasma Cells
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3
Q

What other somatic cells are involved in the immune response?

A

Tissue cells (e.g. endothelial cells) and Platelets

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4
Q

Describe the significance of Lymphocytes

A
  • Very powerful + Diverse
  • Actively dividing homeostatic populations
  • Key to protection against infection and cancer
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5
Q

What is the function of lymphocytes?

A

Lineage:
- T and B cells

Function:
- e.g. helper / cytotoxic / regulatory

Produce:
- Th1: IL-2, IFN-ɣ Th2: IL-4, 5, 6, and 10

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6
Q

What are the 2 key features of adaptive immunity?

A
  • Specificity: targeted

- Memory: rapid response

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7
Q

Describe the specificity of B cells

A

For B cells - one cell, one Ig

  • May class switch (IgM → IgG) but always the same basic Ig receptor
  • May undergo affinity maturation
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8
Q

Describe T cell specificity

A

For T cells - one cell, one TCR
Selection and expansion of that clone

Retention in ‘memory’ of clonal progeny

  • Continues production of antibody (B cells)
  • More rapid specific secondary responses (B and T cells)
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9
Q

Give examples of B cell defect syndromes

A

Congenital agammaglobulinemia
Common variable immunodeficiency
Novel biologics - Rituximab

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10
Q

Name some T cell defects

A

Severe combined immunodeficiency (SCID)
DiGeorge Syndrome
Acquired - HIV / Chemotherapy / Novel biologics

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11
Q

Where do T/ B lymphocytes originate?

A

Both produced from same lymphoid precursor in bone marrow and end up in lymph nodes from where they circulate the body

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12
Q

Where do T cells mature?

A

T cells mature in thymus and recirculate as Th cells (CD4+) and are distributed among lymphoid organs

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13
Q

What is the variable region of TCRs?

A

The variable region of the TCR is the antigen binding site that provides specificity

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14
Q

How are specific lymphocyte receptors formed?

A

Generation of diversity via gene reassortment is a key process

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15
Q

What are the 4 basic approaches of predicting pathogens?

A
  1. Generic recognisable features e.g. TLR, PAMPs
  2. Presence associated with damage e.g. DAMPs
  3. Recurrent pathogens - adaptive immune response
  4. Autoimmunity - non-self recognition
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16
Q

What are the problems with lymphocytes predicting unknown pathogens?

A
  • Delayed response due to a low precursor frequency during primary response
  • May miss pathogen due to lack of specificity
  • Over- or under-assiduous recognition
  • Self recognition
17
Q

How do lymphocytes recognise tumour cells?

A

Still “self”

Express cancer-specific immune targets that are recognisable

18
Q

Outline the peptide-MHC complexes that form on T cells

A

MHC-I plus peptide binds to TCR on CD8 T cells

MHC-II plus peptide binds to TCR on CD4 T cells

19
Q

What is the effect of T cell positive selection in thymus?

A

Positive selection: Lymphocytes must bind MHC or they die

20
Q

What is the result of negative T cell selection in the thymus?

A

Must not bind self peptides

Cells in thymic medulla express tissue specific antigens (colonal, endothelial etc.) if bound to these antigens the cell dies
⇒ Naive T cells

21
Q

Describe B cell positive selection

A

Identifies immature B cells with completed antigen receptor gene rearrangement

Functional membrane Ig molecules (BCR) provide survival signals

22
Q

How does B cell receptor editing occur?

A

If high avidity self-recognition - receptor editing changes BCR specificity

Reactivation of RAG genes produces new Ig light chain

If still reactive, rearranges λ light chains

23
Q

When do B cells undergo negative selection?

A

If still auto-reactive, immature B cells with high-affinity self-recognition die by apoptosis in bone marrow or spleen

24
Q

What is the effect of mature B lymphocyte presence?

A

Once the transition is made to the IgM+ IgD+ mature B cell stage, antigen recognition leads to proliferation and differentiation

25
Q

Where do T cells go after maturation in thymus?

A

Naïve cells recirculate primarily from blood to lymph nodes

26
Q

Outline the T cell memory heterogeneity

A
  • Central memory: TCM
  • Effector memory: ECM
  • Regulatory T cells: Treg
27
Q

Describe the central memory of T cells

A

Central memory (Tcm)

  • CCR7+ and CD62L+
  • Enter Lymph Nodes and recirculate
28
Q

Describe the effector memory of T cells

A 
Effector memory (Tem)
- CCR7- and CD62L-
- Migrate into tissues
- Rapid effector activity
- Cytolytic, cytokines 
(IFg, IL-4, IL-5)
29
Q

Which memory T cells have a higher turnover?

A

Effector memory CD4 T cells have faster turnover than central memory T cells: Tem > Tcm

30
Q

Describe the lifespan of effector memory T cells

A

TEM effector memory cells:

  • Short Lived population
  • Continually replenished
  • Doubling time ~15 days
31
Q

Outline the lifespan of central memory T cells

A

TCM: central memory cells:

  • Turnover at significant rate
  • Doubling time ~48 days
32
Q

Describe the longevity of CD4+ regulatory cells

A

> short lived population
Need continual replenishment
Some originate from CD25- memory T cells

33
Q

How are Treg cells produced?

A

Produced in same lymphocyte activation cascade and are also antigen specific

34
Q

Why are there more memory cells than naive T cells?

A

Memory populations > “naive” pools - population of cells that have previously met pathogen continue to proliferate: makes memory cells a flexible population (continuously changing)

35
Q

Describe the concepts of immunological memory

A
  • Accrued cumulatively over time
  • ‘Stored’ for future use
  • Readily available when required
  • Dynamic process
36
Q

Describe B cell development

A

Activated B cells transform into Plasma cells
“Antibody factories”
also produce CD27+ memory B cells

37
Q

How does immune senescence occur?

A

Lymphocyte function deteriorates with age

  • Both age of the cell and age of the individual
  • Telomere shortening
  • Change in functional attributes
  • Accumulation of CD57+ cells
  • CMV infection a key driver of immune senescence

Immunology (14 decks)

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