Cell-mediated adaptive system

L21

Where do T cells mature?

in the thymus

How do t cells bind antigens?

through specific t cell receptors

What are the 2 main subpopulations of t lymphocytes?

• t helper cells (CD4 +ve)

• t cytotoxic cells (CD8 +ve)

What types of molecules do t helper cells produce?

cytokines

What’s the role of t helper cells (CD4 +ve)?

• help b cells make antibodies

• activate macrophages and NK cells

• help dvpt of cytotoxic t cells

What’s the role of t cytotoxic cells (CD8 +ve)?

recognise and kill infected host cells

What’s the structure of TCRs (T lymphocyte receptors)?

very similar to Fab arm of an antibody - alpha and beta chains with variable and constant regions

Is the constant or variable region closest to the t lymphocyte membrane?

constant

What type of antigen do b vs t cells recognise?

soluble, free, native antigens vs cell-associated, processed ones called MHC

What are MHCs?

Major Histocompatibility Proteins - initiate t cell responses

Which chromosome encodes MHC?

chromosome 6

Why are MHCs described as very polymorphic?

many different alleles at each gene locus

What’s the likelihood of two people having the same mhc present on cells?

1 in a million - very individual and specific proteins

On what cells are MHC 1 present? To which cells do they display antigens?

all nucleated cells

to CD8 +ve cytotoxic T cells

On what cells are MHC 2 present? To which cells do they display antigens?

macrophages, dendritic cells, B cells

CD4 +ve helper T cells

Which type of MHC has more limited expression?

MHC II

What are the 2 types of MHC?

1 and 2 displaying antigens to the 2 different types of T cells

How are viral proteins expressed on a cell surface?

virus infected cell has proteosomes in the cytosol which break down viral proteins that are transported to the ER

How do cytotoxic T cells kill infected cells?

via perforins that induce apoptosis

What do cytotoxic T cells recognise antigens?

recognise peptides bound to MHC I

How do helper T cells recognise antigens?

peptide bound to MHC II

Where do peptides bind to MHC II? What does this lead to?

in endosomes

peptides expressed on cell surface

What do activated t helper cells do for b cells and how?

help make antibodies

produce cytokines that activate/regulate other leucocytes

Where are t cells educated and what does that mean?

in the thymus

acquire their receptors

Do t cells that recognise self-MHC survive?

Only T cells that recognise self-MHC but NOT self peptides survive to avoid autoimmune disease

where do t cells migrate to after acquiring their receptors?

peripheral lymphoid tissue

What are some main groups of cytokines?

• interleukins

• interferons (IFNs)

• chemokines

• tumour necrosis factor (TNF)

• colony stimulating factors (CSFs)

How many interleukins exist today and what are they made by?

1 through about 38 - made by T cells

What is the role of interferons?

combat viral infections and activate cells

What is the role of chemokines?

cell mvt or chemotaxis

What’s the role of tumour necrosis factor?

pro-inflammatory, can kill some cells

What’s the role of colony stimulating factors?

leukocyte production

Why are cytokines called hormones of the immune response?

act as chemical messengers, regulating immune responses and inflammation

How big are cytokines on average and what are they involved in?

5 to 20 kD - communication between cells of the immune response

How do cytokines act and where are they produced/do they act?

act by binding to specific receptors on the surface of target cells (cytokine receptors)

produced & act locally

What are biological effects of cytokines binding to cytokine receptors on a target cell?

changes in cell behaviour (mvt and secretion) and gene expression

How did the innate and adaptive immunity relatively evolve?

co-evolve

How do innate responses impact adaptive responses?

initiates it

How do adaptive responses impact innate responses?

augments it

Who led to the eradication of small pox? How?

Edward Jenner

Showed that infection with cowpox was protective against smallpox.

Why does cowpox protect against small pox?

the viruses responsible for both share antigens

Who made the first vaccine?

Edward Jenner in 1796

What are 5 different types of vaccines? And examples of each?

• RNA - moderna sars-cov 2

• Engineered virus - astra zeneca sars cov 2

• attenuated strains - polio

• killed pathogen - polio

• subunit - toxoid like virus spike protein

What are the 2 phases of vaccination that simulate the primary and secondary adaptive immunity phases ?

primary vaccination then booster dose for the “memory“

What’s a risk and a limitation of attenuated strains being used as vaccination?

that they revert + can’t be used in immunocompromised patients

Which major diseases today still don’t have effective vaccines?

malaria, schistosomiasis, TB, HIV/AIDS

Which eradicated disease is resurfacing in the US due to reduced numbers of vaccinations?

measles

How do cytotoxic vs helper t cells act within the adaptive immune system?

specifically kill infected host // control immune responses by making cytokines

Where are t cells recognising self-MHC and foreign peptides selected?

in the thymus

How does vaccination essentially work?

exploits immunological memory to protect against some infectious diseases

true or false: the main role of MHC proteins is to prevent graft rejection

false: their main role is to present antigens to T cells, which is crucial for initiating an adaptive immune response

Which cells can make cytokines and briefly explain what these are

T and B lymphocytes + NK cells + macrophages + dendritic cells

small proteins in the immune system that dictate cell mvt, action etc