HLA human leukocyte antigen and MHC major histocompatibility complex.

Major histocompatibility complex (MHC) and Human Leukocyte Antigen (HLA) , introduction,it's types and it's role in immune system.

1. MAJOR HISTOCOMPATIBILITY
COMPLEX (MHC)

2. MAJOR HISTOCOMPATIBILITY COMPLEX
(MHC)
* The MHC is a closely linked complex of genesthat govern
production of the major histocompatibility
* In humans, MHC resideson the short armof chromosome 6
*Three genes(HLA-A, HLA-B, HLA-C) codefor
the class I MHCproteins
* Several HLA-D locidetermine the class II MHCproteins i.e.
DP, DQ and DR
*HLA genesare very diverse(polymorphic)
i.e. there are many alleles of the class I and II genes

3. THE HUMAN LEUKOCYTE
ANTIGEN (HLA) SYSTEM
•Essential to immune function: HLA molecules
present peptide antigens to the immune
system (T-cells)
•Important for self versus non-self distinction

4. MAJOR HISTOCOMPATIBILITY
COMPLEX (MHC)
* Between the class I and class II gene loci, there is a third
locus (Class III)
* This locus contains genes encoding tumor necrosis factor,
lymphotoxin and two complement components(C2 and C4)
* Class IIIantigens do not participatein MHC restriction or
graft rejection

5. MHC CLASS I ANTIGENS
* Class I MHC antigensare : HLA-A, HLA-B and HLA-C
*These antigens are glycoproteins found on surfaces of all
nucleated human cells and on platelets
* HLA-A contains24 different antigenic specificities,
HLA-B contains52 andHLA-C contains11
* Class I MHC antigens areinvolved ofMHC restriction of
cell mediated cytotoxicity

6. HLA Class I Monitors Insideof the Cell
CN
CR
Tapasin
Dr. Brian Freed

7. MHC RESTRICTION
* Endogenously processedcytosolic peptidesin virus
infected cells or tumor cells are transported to the surface
of the cells
* They bindto MHC I moleculesto be recognized by
cytotoxic T-cells which then killthese cells
* In other words;
T-cellsare only activatedwhen they recognizeboth antigen
and class I MHC molecules in association

8. MHC CLASS II ANTIGENS
Class II antigens are: HLA-DP, HLA-DQ, HLA-DR antigens
These antigens are glycoproteins found on the surface of
macrophages, B-cells, Dentritic cells, langerhans cells of skin
and activated T cells
HLA-DP contain 6 different antigenic specificities, HLA-DQ
contains 9 and HLA-DR contains 20

9. HLA Class II Monitors Outsideof Cell
DM
monitors
peptide
specificity
for DR
Peptides
Extra-
cellular
Proteins
DM
Dr. Brian Freed

10. MHC CLASS II ANTIGENS
* Helper T-cells recognizeantigens on antigen-
presenting cells onlywhen the antigens are
presentedon the surface of cells in associationwith
class II MHC
* Class II antigens reactwith the CD4molecule on
the helper T-cellswhich secrete cytokines

11. CLASS I MHC AND CLASS II MHC
MHC Class I MHC Class II
Nomenclature
HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ,
HLA-DR
Found on
All nucleated somatic
cells
Macrophages, B-cells,
Dendriticcells,
langerhanscells of skin
and activated T cells
Recognized by
CD8 TC cells CD4 TH cells
Functions
Presentation of Ag to
TCcells leading to
elimination of tumor or
infected host cell
Presentation of Ag to
THcells which secrete
cytokines

12. CLASS I (1.1 MB)
Class II (2.2
Mb)
Class III (0.7 Mb)
Complement
& cytokines

13. HLA-DQB1*0302HLA-DRB1*0401
HLA-DRB1*0401
Allele:
Haplotype:
Genotype:
J. Noble
Gene low high resolution typing
“subtype”=01
HLA-DQB1*0302
HLA-DRB1*0301 DRB1*02
HLA-DRB1*04
HLA-DQB1*0201

14. 32
 



•Binds 8-10mers
•Expressed on most
Nucleated cells
•Presents Cytosolic
Proteins to CD8+ T cells
•Binds 13-25mers
•Expressed on APCs,
Macs, B cells, activated
T cells
•Presents Vesicular
Proteins to CD4+ T cells
Class I Class II
HLA Class I and II Molecules Have a Distinct Structure and Function
BDC

15. Teaching slides: www.barbaradaviscenter.com
Antigen–presenting cells (APCs):
monocytes, macrophages, dendritic cells, B cells

16. Humoral
Versus
Cellular
Immune
Response

17. TRANSPLANTATI
ON
AND
GRAFT
REJECTION

18. TYPES OF GRAFTS
1) Autografts :
The transfer of an individual’s own tissues
from place to place
e.g. Skin grafts(regularly accepted)
2) Isografts :
Transfer of tissuesbetween genetically
identical persons
e.g. Identical twins( accepted permanently)

19. TYPES OF GRAFTS
3) Allografts (homograft):
-Transfer of a graft between genetically different
members of same species
e.g from one human to another
-Rejection occur if donor and recipient are not matched
4) Xenograft (heterograft):
-Transfer of tissues between different species
-Always rejected

20. MECHANISM OF GRAFT
REJECTION
1) Both TH and TC are activated
-TC cellsdestroy graft cells by direct contact
TH cells secrete cytokines that attract and activate
macrophages, NK cells and polymorphs leading to
cellular infiltration and destruction of graft (Type IV)
-B cellsrecognize foreign antigens on the graft and produce
antibodies which bind to graft cells and
. Activate complement causing cell lysis
. Enhance phagocytosis, i.e. opsonization (Type II)
. Lead to ADCC by macrophages, NK,PML
-Immune complex depositionon the vessel walls induce
platelets aggregation and microthrombi leading to
ischemia and necrosis of graft (Type II)

21. TYPES OF GRAFT REJECTION
!) Hyperacute rejection:
-It occurs hoursafter transplantation
-In individual with preformed antibodies either due to -
blood groups incompatibility or previous sensitization
by blood transfusion, previous transplantation
2) Acute Rejection:
-It occurs 10 to 30 daysafter transplantation
-It is mainly T-cell mediated
3) Chronic or late rejection:
-It occurs over a period of months or years
-It may be cell mediated, antibody mediated or both

22. GRAFT VERSUS HOST (GVH)
REACTION
* An immunologically competentgraft is transplanted into an
immunologically suppressedrecipient (host)
* The grafted cellssurvive and reactagainst the host cells
i.einstead of reaction of host against the graft,
the reverse occurs
* GVH reaction is characterized by fever, pancytopenia, weight
loss, rash , diarrhea, hepatsplenomegaly and death