Immunology: Development of Lymphocytes Flashcards Preview

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Flashcards in Immunology: Development of Lymphocytes Deck (28)
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1

Name the immune system cells that are part of the innate immune system

  • Neutrophils  

  • Macrophages  

  • NK Cells  

  • Dendritic cells  

  • Monocytes  

  • Eosinophils  

  • Basophils  

2

Name the immune system cells that are part of the adaptive immune system

  • B cells 
  • T cells 
  • Plasma cells 

3

Why do we have lymphocytes? 

  • Without them, we wouldn't be able to get memory of pathogens, so we won't get a bigger and faster secondary response if we get re-infected 

4

What are some examples of causes of lymphocyte deficiencies/defect syndromes? 

  • B cells 
    • Congenital agammaglobulinaemia - loss of gamma globulin 
    • Common variable disease (CVID)
    • Novel biologics - Rituximab 
  • T cells 
    • Severe combined immunodeficiency 
    • DiGeorge syndrome 
    • Acquired - HIV/Chemotherapy/Novel biologics 

5

What dimensions can we use to define a lymphocyte? 

  • Morphology: White cell; small, large nucleus  
  • Lineage: E.g. T cells and B cells 
  • Function: E.g. Helper / Cytotoxic / Regulatory 
  • Phenotype (what surface markers they express): Usually functional receptors 
  • Specificity: What they target - what antibody do they produce or epitope they recognise 
  • Type of receptor: - Ig class for B cell/ αβ vs γδ for T cells  
  • Differentiation: Immature / mature / senescent 
  • What they produce: E.g. TH1 (IL-2, IFN-γ); TH2 (IL-4, IL-5, IlL-6, IL-10) 

6

What are the 2 key features of adaptive immunity? 

  • Specificity - Targeted response 

  • Memory - Allows for quicker and bigger response if exposed to same antigen again 

7

Explain the specificity of the adaptive immune system 

  • Explained by clonal selection theory - one cell has one specificity 
  • B cells - one cell, produces one Ig 
    • May class switch (IgM -> IgG) but always same basic Ig 

    • May undergo affinity maturation  

  • T cells - one cell, one type of T-cell receptor (TCR)

  • When specific antigen recognised by T cell or B cell (selection) that clone is amplified (expansion) 

  • There's also retention in ‘memory’ of clonal progeny of lymphocytes which means: 

    • Continued production of antibody (B cells) 

    • More rapid specific secondary response (B and T cells) 

8

How is specificity achieved by a lymphocyte? 

  • T-cells - ​Each T-cell has one type of TCR 
  • B-cells - Each B-cell has one Ig (B-cell receptor) 
  • Antigen-binding site of TCR and Ig highly variable 
  • This is because genes that code for TCR or Ig able to shuflle around to produce different combos 
  • Genome can't code for every single code so it has a gene that splices the different bits in 
  • After shuffling, it locks the gene - can't make another receptor type once gene's locked 

9

How do immune system cells recognise pathogens?

  • Looks like a pathogen
    • Has general recognisable features e.g. PAMPs
  • Their presence is associated with damage
    • Danger hypothesis (not only presence of pathogen, but also damage needed for action to take place) 
    • DAMPs (Damage-associated molecular pattern molecules) 
  • Immune system cell recognises antigen and "remembers" that it's associated with damage/disease
    • Basis of adpative immune system (memory) 
  • Non-self recognition 
    • Can lead to autoimmunity 

10

How does the immune system recognise things it hasn't seen yet? 

  • Massive array of possibilties approach 
  • Immune system generates huge diversity of T-cell receptors and Immunglobulins (B-cell receptors) so that one of them is able to identify the foreign body 

11

What are the problems with the "massive array of possibilities approach" to identifying unknown pathogens?

  • Causes a delay in primary immune response to particular pathogen - although massive no. of B and T cells produced only small no. able to recognise each type of pathogen so will take time to recognise it 
  • Over-assidiuous recognition - set up reponse to something that doesn't cause harm 

  • Under-assiduous recognition - might miss something/not set up a correct response 

  • Self-recognition - recognising self as enemy - autoimmune disease  

     

12

Why is recognition of tumour cells by immune system cells difficult? 

  • Tumour cells are still classed as “self” - still express MHC, etc  

  • Instead, the immune cells must look for the expression of cancer-specific immune targets

13

What type of peptide do MHC class I and II present? What receptor and cell type do they bind to? 

  • MHC class I - Presents intracellular peptides, including viral peptides, binds to TCR on CD8 T-cells
  • MHC class II - Presents 

14

What is the significance of MHC class I and II? 

  • MHC class I 
  • All normal cells express MHC class I 
  • In peptide binding cleft of MHC class I cell will put components of the cell to show what it going on inside the cell 
  • If a virus infects a cell then infected cell will place viral peptides on peptide binding cleft of MHC class I 
  • This allows cytotoxic T-cell (CD8+ T-cell) to recognise viral peptides and kill infected cell 
  •  
  • MHC class II
  • Antigen presenting cells (APCs) express MHC class II 
  • When they phagocytose something they'll express the peptides from that thing on MHC class II 
  • CD4+ T-cells recognise those peptides as either "self" or "foreign" 

15

Describe the process of thymic selection

  • Immature T-cells go to the thymus and first undergo positive selection 
  • Positive selection involves these immature T-cells binding to MHC 
  • If they don't bind to MHC then they die by neglect 
  • If they successfully bind to MHC the immature T-cells then go through negative selection 
  • During negative selection cells in thymic medulla express tissue-specific antigens 
  • If the immature T-cels recognise these antigens they are killed and if they don't they survive 
  • By the end of thymic selection you should end up with T-cells sufficiently capable at binding to MHC to recognise organisms, but not capable of recognising self-MHC, so will not cause autoimmune disease 

16

What is the name given to T-cells at the end of thymic selection? 

  • Naïve cells - Haven't been exposed to antigen yet 

17

What happens to T-cells after they go through the thymus? 

  • Naïve cells recirculate - primarily from blood to lymph nodes

18

Describe the process of B cell selection 

  • Positive selection
    • Identifies immature B cells with completed antigen receptor gene rearrangement
    • Functional membrane Ig molecules (BCR) provide survival signals
  • Receptor editing
    • If Ig molecules not functional or show autoreactivity then they go through receptor editing 
    • Editing changes Ig molecule specificity and reactivates RAG genes which produces new Ig light chain
    • These 2 changes allow the cell to express a different (edited) B cell receptor that is not self-reactive
    • If still reactive, rearranges λ light chains
  • Negative selection
    • ​If they still recognise self then they are killed by apoptosis in bone marrow or spleen

19

How can you test for presence of Naïve T cells in the blood? 

  • Deuterium labelled glucose taken by patient
  • T cells are then extracted  
  • Naïve t cells will have little labelling as they are dividing very slowly 

20

What triggers T cell differentiation?

  • Naïve CD4+ or naïve CD8+ T cell encountering an antigen triggers T cell differentiation

21

What cell types can a Naïve T cell differentiate into? 

  • Effector memory cells (TEM) 

  • Central memory cell (TCM) 

  • T regulatory cells  

22

What are some characteristics of effector memory cells? 

  • Short lived population 
  • Continually replinshed 
  • Doubling time about 15 days 

23

What are some characteristics of central memory cells? 

  • Turnover at a significant rate 
  • Doubling time about 48 days 

24

What are some characteristics of regulatory T-cells? 

  • Short-lived population  

  • Need continual replenishment  

  • Some originate from CD25 – memory T cells

  • Ensure immune response doesn’t go overboard

25

What are the basic concepts of immunological memory? 

  • It is accrued cumulatively over time 

  • It's ‘stored’ for future use  

  • Is readily available when required  

  • It's a dynamic process 

26

Where are lymphocytes mainly found? 

  • Lymphatic system  

    • Organised mainly into Lymph Nodes

    • Architecture optimised to facilitate cellular interaction

  • Spleen  

    • Key role is antibody production 

  • Tissues  

27

What cells do activated B cells transform into and what do these cells transform into? 

  • Transform into Plasma cells
  • Plasma cells produce antibodies 
  • Also produce CD27+ memory B cells

28

How does lymphocyte function deteriorate with age? 

  • Both age of the cell and age of the individual affect lymphocyte function 

  • Telomere shortening occurs 

  • Change in functional attributes - cells don’t respond as quickly 

  • Accumulation of CD57+ cells - CD57 is a marker of terminal differentiation on human CD8+ T-cells