PREPARED BY MOHAMED MERGHANI

1. Genetics of Immunity

2. Objectives :
Revision about the immune system components.
MHCs and some of it’s associated diseases .
Some of the inherited immunodeficiencies.
Rhesus factor .
RNA vaccine.

3. Cells of immune system :

4. Levels of immune protection :

5.  Located on chromosome 6 in the human
1. Class I: expressed on the cell surface of all nucleated cells except sperm.
2. Class II: found primarily on APCs such as monocytes/macrophages and B cells
3. Class III: physiologic roles (TNF and complement proteins).
 They (I & II) are extremely polymorphic
 In humans the MHC is also called HLA (human leucocyte antigen)
 There are three class I loci in the human, called HLA-A, HLA-B and
HLA-C.
 There are three class II MHC loci in the human MHC, called DP, DQ and DR.
!! What is the role of HLA ?

6. MHC Polymorphism :
 Multiple allele for each locus: MHC genes are one of the most
polymorphic genes known. For example: class I MHC region in humans,
there are 240 alleles for HLA-A. 470 alleles for HLA-B and 110 alleles for HLA-C.
 The MHC class I region of any individual would have one of the allele from each HLA-A,
Band C allele bank. So, there are total 240 x 470 x 110 number of theoretical combinations
possible for class I MHC region.
 These alleles encode for products that vary from one another by 5- 10% of their DNA
sequence. Similar polymorphism also exists for alleles of class II DP, DQ and DR loci.
 Codominant expression: MHC genes are expressed in codominant form.

7. Some HLA-Associated Diseases:

8. Inherited Immunodeficiencies

9. Disorders of Innate Immunity :
Chronic granulomatous disease (CGD):
 This is the best known example of a disorder of phagocytic function,
 and follows either an X-linked or an autosomal recessive inheritance. It results
from an inability of phagocytes to kill ingested microbes
 due to defects in the NADPH oxidase enzyme complex which generates the so-
called microbicidal ‘respiratory burst’ .
 CGD is therefore associated with recurrent bacterial or fungal infections
 Treatment Childhood mortality was high until the advent of supportive treatment
and prophylactic antibiotics.
Bone marrow transplant has been successful, as well as transplantation of
peripheral blood stem cells from an HLA identical sibling.

10. Humoral Immunodeficiencies :
Bruton-type agammaglobulinemia :
Males with this X-linked immunodefciency usually develop multiple
recurrent bacterial infections of the respiratory tract and skin after the
first few months of life, having been protected initially by placentally
transferred maternal IgG.
 The disorder has been shown to result from mutations in a tyrosine
kinase specific to B cells (Btk) that result in loss of the signal for B
cells to differentiate to mature antibody-producing plasma cells.
 Treatment of life-threatening infections with antibiotics and the use
of prophylactic intravenous immunoglobulin.

11. Cellular Immunodeficiencies :
DiGeorge syndrome ( Thymus aplasia ): results from a congenital
defect in thymic development leading to defect in T-cell maturation.
• infants are extremely vulnerable to viral, fungal, intracellular bacterial
and protozoan infections
•The Genetic defect: in 90% of cases, there occurs a deletion affecting
chromosome 22q11 which leads to developmental malformation
affecting the lower parts pharyngeal region in embryonic life.
• illnesses, in addition to the thymic defects, there may be associated:
• Parathyroid gland hypoplasia resulting in neonatal tetany .
• anomalies of the heart and the great vessels.
• Treatment: thymus transplantation has been found to be successful in
restoration of immune function

12. Combined immunodeficiency :
Severe combined immunodefciency :(SCID)
 an increased susceptibility to both viral and bacterial infections
because of profoundly abnormal humoral and cell-mediated
immunity.
 Common to all forms of SCID is the absence of T cell–mediated
cellular immunity from defective T-cell development.
 Presentation is in infants with recurrent, persistent, opportunistic
infections by many organisms, including Candida albicans,
Pneumocystis carinii, and CMV.

13. ..cont
 SCID is genetically heterogeneous and can be inherited as either an X-linked or
autosomal recessive disorder.
 The X-linked form (SCIDX1) is the most common form of SCID in males,
accounting for 50% to 60% overall, and has been shown to be due to mutations in
the γ chain of the cytokine receptor for IL-2 (IL2RG ).
 In approximately one-third to one-half of children with SCID that is not X-
linked, inheritance is autosomal recessive (SCID1).

15. Rhesus Factor :
 is a protein found in the outer surface of the RBCs .
 RH locus of human genome which is located on chromosome 1 , consisting
of two genes RHD and RHCE .
 in case of deletion of the gene from the genotype the phenotype is Rh D –
and if the gene is present the phenotype is Rh D +.
 the presence of the Rh trait is dominant .
 83 % of human population are Rh D + .

16. hemolytic disease of the newborn (HDN):-
(erythroblastosis fetalis )
 this disease occur when the mother is Rh D – pregnant with a Rh D+ fetus and at
the delivery some of the fetal blood may cross the placenta and cause in
recognition of the protein as an antigens and production of IgG antibodies in the
mother .
 at later pregnancy with a Rh D+ fetus ; HDN is caused by a maternal IgG
antibody response to the antigens expressed on fetal red blood cells. Maternal
anti-Rh IgG antibodies cross the placenta, This can result in opsonisation of the
red blood cells and their phagocytosis and destruction in the liver or spleen.

17. RNA vaccine or mRNA vaccine :
 is a new type of vaccine that inserts fragments of mRNA into human cells in order
to reprogram them to produce pathogen antigens (e.g. viral protein spikes or
cancer antigens).
 The mRNA molecule is usually held in a drug delivery vehicle, such as lipid
nanoparticles…. WHY ??
 before 2020, mRNA was only considered a theoretical possibility for effective use
in humans.
 As of November 2020, there were two novel mRNA vaccines awaiting emergency
use authorization as potential COVID-19 vaccines, MRNA-1273 from Moderna,
and BNT162b2 from a BioNTech/Pfizer partnership .

18. How mRNA vaccine work :

19. Any Questions ?