Natural Born Killers: NK cells and CD8+ T Lymphocytes

Question 1

Origin of NK and T cells

Answer 1

• Both arise from common lymphoid progenitor cell

* Both part of the lymphocyte lineage

Question 2

what are NK cells?

Answer 2

Natural killer cells are a subset of innate

lymphoid cells

Question 3

Role of cytotoxic lymphocytes

Answer 3

• We need cytotoxic cells to be able to destroy
• Cells infected with bacteria, viruses or parasites
• Tumour cells
• Lymphocytes scanning a target cell surface need to detect changes in protein production inside that target cell

Question 4

Adaptive immunity – Cytotoxic T Cells (CTL, CD8 T Cells)

Answer 4

• Cytotoxic adaptive immune cells
• Kill virally infected targets
• Kill tumour cells
• Controlled by T cell receptor recognition, with CD8 acting as a co-receptor
• Highly specific

Question 5

Innate – Natural Killer Cells

Answer 5

• Cytotoxic innate immune cells
• Kill virally infected targets
• Kill tumour cells
• Controlled by a balance of signals between different activating and inhibitory receptors on their surface
• Broad specificity for target cells

Question 6

Why do we need more than one type of cytotoxic lymphocyte?

Answer 6

1. To combat infection in the period before a T cell response develops
2. To provide an alternative system when a tumour or infected cells evade Cytotoxic T cell responses
3. To provide an additional mechanism for killing infected targets via antibody
   recognition

Question 7

NK cells and infection

Answer 7

• Low NK cell activity correlates with severe disseminating herpesvirus infections
• NK cell deficiency
• 13 year old girl, overwhelming chickenpox, later developed life-threatening primary HCMV infection, severe HSV
• 4 children, EBV-driven lymphoproliferative disorder, severe respiratory illnesses

Question 8

Role of MHC class I : Antigen Presentation

Answer 8

• Lymphocytes scanning a target cell surface need to
detect changes in protein production inside that
target cell
• MHC class I proteins are found at the cell surface

• Form a structure that presents protein fragments
(peptides) at the cell surface for immune surveillance
• Recognised by CD8+ cytotoxic T cells

Question 9

Intracellular proteins are presented at the cell surface by MHC class I

Answer 9

Proteins expressed within a cell are processed and presented on MHC class I proteins

Samples include ‘normal’, mutated or viral proteins

• Tissue distribution: found on all nucleated cells
• two polypeptides, non-covalently bound:

Question 10

Major Histocompatibility Complex (MHC)

Answer 10

• In humans, proteins are also known as HLA (Human Leucocyte Antigens).
• The human MHC gene complex is located on chromosome 6 and
contains 3 MHC class I proteins and 3 MHC class II proteins
• Highly polymorphic – There are 100s of different genetic variants

Question 11

Why do we have HLA polymorphism?

Answer 11

Pathogens can evolve to evade immune responses

Variation in MHC class I proteins - Multiple genes (e.g. two copies each of HLA-A, B and C) and high genetic variability within these genes may counteract this across 
populations