Sensing Microorganisms - Adaptive Immunity

Question 1

Properties of adaptive sensing?

Answer 1

Can recognise almost any microbial or non mocrobial molecule with high specificity

Adaptable due to somatic recombination of gene segments used to make receptors

Each cell has one unique receptor highly specific for one antigen

Question 2

What is an antigen?

Answer 2

Molecule recognised by adaptive immune cells (T and B cells)

Will either bind T cell receptor or antibody (b cell receptor)

Question 3

What is an epitope?

Answer 3

Precise part of antigen recognised by receptor - one Ag can have multiple epitopes

Question 4

What is a paratope?

Answer 4

Part if antibody or T cell receptor that binds the epitope

Question 5

How does a B lymphocyte (B cell) recognise an antigen and what is its following effector functions?

Answer 5

Produces antibodies, which bind antigens - often ones still on the microbe.

Effector functions:
-Neutralisation of microbe
-Phagocytosis
-complement activation

Question 6

How does a Helper T lymphocyte (Th cell) recognise an antigen and what is its following effector functions

Answer 6

Senses microbial antigen presented by antigen presenting cell APC.

Releases cytokines:
-activation of macrophages
-inflammation
-activation (proliferation and differentiation of) of T and B cells

Question 7

How does a cytotoxic T lymphocyte (CTL) recognise an antigen and what is its following effector functions

Answer 7

Senses antigen expressed on infected cell

Effect: kill infected cell

Question 8

What is the effector mechanism of a regulatory T lymphocyte (Treg cell)?

Answer 8

Suppression of immune response

Question 9

What is the main difference between antigen sensing in B and T cells?

Answer 9

B cells recognise Ag on its own (via antibodies)

T cells only recognise Ag presented to them by Antigen presenting cells (APC)

Question 10

Difference between B and T cell antigen receptors?

Answer 10

B cell receptors:
-Membrane bound AND secreted
-Secreted form has immune effector functions

T cell receptors:
-Only membrane bound (called T cell receptor (TCR))

Question 11

Differences between membrane bound and secreted B cell receptors?

Answer 11

Membrane bound:
-called B cell receptor (BCR) or surface immunoglobulin (sIg)

Secreted:
-called antibody (Ab) or immunoglobulin (Ig)

Question 12

Properties of Ag recognised by T cells?

Answer 12

-Proteins
-linear peptide sequence
-8-25 AAs long
-presented on APC
-proteins have to be broken down into peptides

Question 13

Properties of Ag recognised by B cells

Answer 13

-pretty much anything organic
-native molecule (not processed)
-conformational (can still be linear)
-epitope can cross loops (isn’t continuous, requires proteins conformation in order to be recognised- processing can break up proteins loops and cause epitope to no longer be recognised)

Question 14

What is the structure of an antibody?

Answer 14

Two longer chains in middle are the heavy chains
Two sorter ones at top on the outside are the light chains
Chains joined by disulfide bonds

Upper region (contains light chains ant top half of heavy chains) makes up the antibody binding region (Fab)

Lower region (contains the bottom half of heavy chains) makes up the Fc region - remains constant and allows interaction with other cells

Hinge region in middle allow for flexing💪

Question 15

T cell receptor structure?

Answer 15

Made up of two chains (alpha, equivalent to light chain, and beta, equivalent to heavy chain)

One Ag binding site compared to Ab’s two sites

Question 16

How does the antigen binding region (Fab) of an antibody allow high variation?

Answer 16

Somatic recombination of gene segments (which code for the variable region of the Ab)

Question 17

What is used to recombine variable region gene segments?

Answer 17

VDJ recombinase
Permanently alters the cell’s DNA

Question 18

What is junctional diversity?

Answer 18

Rearrangement of V, D and J segments gives only a few million antibody specifities - not enough

Increased by fact that the segments are not joined perfectly
Can be off by a base or two causing variation

Question 19

What is the second step of junctional diversity?

Answer 19

Addition of nucleotides:

After junctional diversity is created by imperfect alignment of gene segments:

RAG complex cleaves heptamer RSSs from the gene segments to create DNA hairpins

RAG complex then opens up hairpins by nicking one strand of DNA in each hairpin - generating palindromic P nucleotides

N-nucleotides then added by TdT (terminal deoxyribonucleotidyl transferase)

Doesn’t make much sense without lecture 5 diagrams but knowing the words is good ig 🐮

Question 20

Third step of junctional diversity?

Answer 20

Deletion of bases:

After random addition of N nucleotides, unpaired nucleotides are removed by exonuclease

Gaps are then filled in by DNA synthesis and ligation to form coding joint between gene segments

Results in new DNA at borders of gene segments changing the AA sequence and upping variation

Question 21

Fate of B cells with non functional sequence on Ab?

Answer 21

Death by apoptosis
Majority of rearrangements don’t result in functional protein

Question 22

What is allelic exclusion?

Answer 22

VDJ genes on chromosome 14
2 of each chromosome so 2x sets of VDJ genes
2 chances to make a productive rearrangement

Each B cell specific for one Ag
Only room for one Ab on each cell
Thus a successfully rearranged chain will block gene rearrangement on the other chromosome

Question 23

What is clonal expansion?

Answer 23

T/B cell senses antigen and becomes activated
Divide
All daughters have same Ag specificity

Time required to activate and expand Ag specific T/B cells to an effective number makes adaptive response slower

IL-2 cytokine drives T cell clonal expansion

Question 24

What is antigenic variation?

Answer 24

1 or 2 amino acid change in antigen can cause T/B cell to no longer be able to recognise or recognise more slowly :(

Question 25

Different strategies of different microbes to achieve antigenic variation?

Answer 25

Influenza:
Have surface proteins haemagglutin and neuraminidase

Trypanosomes and malaria:
Switch between multiple versions of same molecule

HIV:
High mutation rate
Antigenic variation occurs in the host
Prevents effective adaptive immunity
V difficult to make vaccines

Question 26

What problems are caused by adaptive sensing’s ability to detect almost any organic molecule?

Answer 26

Body is made of them
Also food and other innocuous molecules we’re exposed to

T and B cells can’t tell what they’re recognising
Can lead to allergy and autoimmunity

Question 27

Central tolerance?

Answer 27

Mechanism by which T and B cells capable of recognising self are deleted before they are released systematically to fight infection

T cells removed in Thymus
B cells removed in bone marrow

Not perfect - still possibility for self reactive cells to make it through
Also doesn’t stop recognition of outside innocuous molecules (eg food)

Question 28

How can the adaptive immune system tell if an Ag is from a pathogen?

Answer 28

The innate system can tell if something is a pathogen (PAMPs)
Innate cells (eg DCs) tell T cells whether to respond or not

Question 29

How do Th cells sense antigens?

Answer 29

Antigen presented by MHC class II (expressed by professional APC)
Express CD4 on surface which stabilises class II interactions

Question 30

How do Treg cells sense antigens?

Answer 30

Antigen presented by MHC Class II
(Expressed by professional APC)
Express CD4 on surface to stabilise class II interactions

Question 31

How do CTL sense antigens

Answer 31

Antigen presented by MHC class I (expressed on all nucleated cells)
Express CD8 to stabilise class I interactions

Question 32

Oral tolerance?

Answer 32

The active process by which the immune system does not respond to an orally administered soluble antigen

Question 33

Celiac disease vs food allergies

Answer 33

In celiac Th1 cells produce IFN-gamma
Activated Macrophages and B cell activity

In food allergies Th2 cells produce IL-4
B cell production of IgE, Mast cell activation