The Major Histocompatibility Complex Flashcards Preview

Physiology Term 2 > The Major Histocompatibility Complex > Flashcards

Flashcards in The Major Histocompatibility Complex Deck (20):
1

What is the MHC?

Family of membrane protein complexes that participate in the immune response, encoded by specific set of genes

Play a role in foreign tissue rejection= Important in differentiating between self and non self

Every nucleated cell of the body has MHC on its membrane

Immune identity + Present peptides to T cells

2

What do MHC proteins do?

Combine with fragments of antigens that have been digested within the cell

MHC-Antigen complex --> Inserted into cell membrane= Antigen is visible on extracellular surface

Free antigen in ECF cannot bind to unoccupied MHC receptors on cell surface

Vital for presentation of antigen to T cells

3

What is histocompatibility?

Histo= Tissue compatibility= Skin grafts are a measure of tissue matching
Major and minor

Minor: Some genetic loci were found to influence skin graft acceptance but were not dominant= Some influence on whether or not the material is accepted as self or non self
Example: H-Y= Associates with Y chromosome, only in males

Major: Genetic loci have significant effect= Difference in MHC= Will have the biggest influence on whether or not the material is self or non self
Major= Cluster together in the genome

Man: HLA= Major

4

What does allogeneic mean?

Grafts from someone with differences at various loci= Graft rejection

Graft= Piece of living tissue that is transplanted

5

What does syngeneic mean?

If alleles of MHC are matched between individuals, graft is usually accepted

E.g. identical twin

6

What does autologous mean?

Grafts coming from the individual themselves

7

What do T cells recognise?

Recognise antigens as peptides= NOT AS PROTEINS
Antigenic peptides have to be presented to T cell receptors by MHC molecules
Function of MHC molecules= Presenting peptides to T cells or else T cells will not 'see' them

T cell receptors have curves corresponding to shape of MHC molecule and peptide= Binds strongly to MHC and peptide combination presented

B cells= Do not need MHC to 'see' antigen

8

What are class I MHC molecules? What is their structure?

Found in all nucleated human cells, encode class I molecules that are expressed on surfaces of all nucleated cells as 2 polypeptide chains

Viruses or bacteria invade the cells, they are digested into peptide fragments and loaded onto MHC-1 'platforms'

Present peptides derived from intracellular, cytosolic proteins

9

What is the structure of class I MHC molecules?

Molecule has heavy chain and light chain + 4 globular domains= 3 on heavy chain, 1 on beta2- microglobulin

Light chain: beta-2 micro globulin= Not coded by MHC, not very polymorphic= could be identical in many people

Heavy chain: Is very polymorphic, could be very different between individuals

Member of immunoglobulin supergene family member= 90 amino acids + intrachain disulphide bond

10

What is some of the features of the peptide binding groove?

The heavy chain= Forms 'binding groove' for peptides
When class I molecule is synthesised, it is able to interact with and bind certain kinds of peptides

Function of H-chain= Binding with peptides non-covalently
B2-microglobulin= Stabilises the molecule and permit it to be displayed on cell surface

Only 1 peptide can bind

Peptide is buried in the molecule

11

What is Class II MHC?

Found primarily on the antigen presenting cells e.g. macrophages, B lymphocytes, and dendritic cells
Immune cell= Engulfs and digests an antigen= Fragments are returned to the immune cell membrane combined with MHC-II proteins

Helper T cells encounters antigen presenting cell- MHC-II
Result: Helper T cell responds by secreting cytokines= Enhance immune response

Encode structural glycoproteins found on B cells, APC

12

What is the structure of Class II MHC?

4 globular domains=
2 heavy chains each with 2 globular domains + bound together as transmembrane proteins
Similar to class I structure

Alpha helices form edge of peptide binding grooves

PEPTIDE BINDING IS MUCH LOOSER: Groove is much wider than for Class I and the peptide stretches out more

Both chains form the peptide binding groove + longer and can overhang peptide binding groove

Peptide is longer and can overhang peptide binding groove

13

What are the loci for MHC Class I genes?

3 types of genes:
1) HLA-A
2)HLA-B
3)HLA-C

14

What are the loci for MHC Class II genes?

1) HLA-DP
2)HLA-DQ
3)HLA-DR

15

What is the polymorphic property of MHC cells?

MHC shows tremendous variation between individuals

Genetic diversity= Single locus but multiple alleles in population, the more alleles for single locus, the greater the polymorphism
Polymorphism= Genetic variation

Many genes coding for MHC molecules= Many alternative forms of genes for each subregion of MHC

Each MHC locus can encode for a very large number of different allelic forms= 6 different loci

Humans= locks is found on chromosome and encodes HLA (Human Leukocyte Antigens)

Combinations of many different allelic forms which are codiminatly expressed= Chances of 2 individuals having completely identical set of alleles is very small

BASICALLY: Huge number of alleles (variations of genes) which people inherit from parents

16

What is Polygenic diversity?

Have lots of different copies of genes which fulfil the same role= Generates some diversity

MHC= Polymorphic + Polygenic diversity
Multiple loci (positions of genes) which fulfil the same role, and for every one of loci there are many different alleles present

17

What is co-dominant?

All alleles for the classes do not get suppressed e.g. the 3 different loci for class I, there are 2 alleles for each (one from mum, one from dad) = Everyone has 6 copies of MHC Class I heavy chain genomes

All 6 gets expressed= 6 possible variants of the heavy chains on cell surface

Number of closely linked genes= Close together

18

How are the MHC inherited?

Low meiotic recombination= Does not shuffle around as much= Will just be inherited as haplotype

The combination of encoded alleles at each of the loci within the MHC on the same chromosomes

Genes within MHC are closely linked, haplotypes are usually inherited intact

Heterozygous human: Inherits one paternal and one maternal haplotype, each containing 3 Class-I and three class II loci

GENOMIC PACK

19

How does MHC fit into immune system as whole?

Repository for us to be able to identify immune differences
Tend to select mates with different immune system to us

20

What are the differences between Class I MHC and Class II MHC?

Class I MHC= Expressed on almost all tissues= If you have nucleus, will most likely have class I MHC
Highly expressed on hematopoietic tissues (blood cells)
-Class I MHC carries peptides form proteins produced within cell itself

Class II expression= much more restricted= Only on antigen-presenting cells e.g. B cells, Macrophages, Langerhans Cells
-Class II MHC= carries peptide from proteins OUTSIDE cell

CD8 T cell= Co receptor for Class I MHC= Kill virally infected cells

CD4 T cell= Co receptor for Class II MHC= Designed to give help to B cells to produce antibody to extracellular antigens