Chapter 16
Genetics of Immunity 2  - Inherited Immune Deficiencies

IV.  Inherited immune deficiencies.

Mutations in genes encoding proteins used in immunity result in impaired immune response.


20 types of inherited immune deficiency

Chronic granulomatous disease: mutation of oxidase enzyme results in neutrophils that cannot kill bacteria.

Severe combined immune deficiency (SCID) impacts both humoral and cellular immunity due to lack of mature B cells and/or T cells.



V.  Human Immunodeficiency Virus (HIV)

HIV or human immunodeficiency virus is an infectious virus entering the body with direct contact of bodily fluids (blood, saliva, semen). 


Virus infects macrophages and later helper T cells.  Virus replicates and bursts out of the helper T cell, killing it.


Loss of helper T cells prevents B cell activation.  Infections occur because the immune system cannot respond.



AIDS or acquired immune deficiency syndrome is the disease resulting from HIV infection.  The term AIDS implies that the immune system impact of HIV infection has progressed to impairment of immune function.


Life cycle of a virus


Viruses are DNA or RNA molecules enclosed in a protein coat called a capsid.


Viruses enter a cell by binding to cell surface receptors. 


Viruses insert their DNA genome into the DNA of the host cells  (RNA viruses make a DNA version of their genome first).


Viruses use enzymes of the host cell to replicated their DNA.

Structure of HIV


Early HIV infection

HIV binds CD4 or CCR5 receptors of helper T cell

The capsid with the HIV RNA enters helper T cell. 

Viral reverse transcriptase creates a DNA copy of the virus which integrates into the host genome.

Viral proteins are made from the viral DNA, new virus is produced and packaged for release.

Released HIV particles can infect new cells.

Late HIV infection

Treatment of HIV infection

Drug therapies have cut the mortality rate from AIDS in half since 1996.


Two reverse transcriptase inhibitors and a protease inhibitor are commonly used.


Reverse transcriptase inhibitors block conversion of the viral RNA into DNA.


The protease inhibitor limits the processing of several viral proteins required for new particle formation.

Resistance to AIDS?

Are some individuals less susceptible to AIDS than others?


People at high risk for HIV infections (individuals with multiple partners or hemophilia) who are not infected more often have a CCR5 receptor gene with a 32-base deletion.  This deletion truncates the protein and prevents localization to the cell surface. 


VI.  Autoimmunity

When the immune system attacks the tissues of an individual’s own body it is called autoimmunity.  Autoantibodies recognize “self” proteins.


Some mechanisms include:

Viruses use host proteins on the viral cell surface.  These host proteins become the target of the immune system which responds as if they are viral proteins.

Thymocytes which recognize “self” antigens survive instead of apoptosing.

Nonself antigen may coincidentally resemble “self” antigens.


An autoimmune disease?

Scleroderma is thought to be an autoimmune disorder.



Fatigue, swollen joints, stiff fingers, hardening of skin, masklike appearance.



VII.  Allergy

Is an immune system response to a non-threatening foreign substance called an allergen?


Size of allergens may determine type of allergic response:

Larger (e.g. grass pollen) -> hay fever

Smaller (e.g. cat dander, dust mites) -> asthma



Asthma is a chronic disease involving contraction of the respiratory airways, inflammation and mucus production in the lungs.  Breathing becomes difficult during an asthma attack.  Some asthma attacks are triggered by allergic reactions.


Allergic response

Humoral and cellular arms respond.  IgE class antibodies are made and bind mast cells. 


Mast cells release allergy mediators like histamine and heparin that cause inflammation, runny eyes and nose, rashes and asthma.


Allergens activate a class of helper T cells which release cytokines.


    Severe allergic reaction throughout the body is called anaphylatic shock and can be life-threatening.

Allergy: initial exposure

Allergy:  second exposure

Treatment of allergies

Corticosteroids enter nuclei of affected cells and suppress activity of cytokine and allergy mediator genes.


Antihistamines block receptors on mast cells that bind IgE antibodies preventing the release of histamine.


Antibodies produced in the laboratory bind IgE blocking contact with mast cells.


Sensitization is the gradual exposure to small amounts of allergens to prevent allergy attacks.  Mechanism is unknown.


A vaccine uses antigens from a pathogen to invoke immunity before an individual has been exposed to the pathogen. 


Antigens are chosen to be harmless alone.


Ability to respond rapidly to subsequent exposure prevents infection to a degree that would cause disease.


Vaccination has been performed from the 11th century China.




VIII.  Immunotherapy

Is medical treatment used to amplify or redirect the immune response.


Monoclonal antibodies  (MAb) are useful for detecting and targeting one particular antigen.  Single B cells recognize a single antigen and make a single or monoclonal of antibody.


Cytokines enhance cellular immunity.  Production of cytokines has been developed for drug treatments. 

Uses of monoclonal antibodies

    Monoclonal antibodies (MAb) are useful for detecting and targeting one particular antigen.


Home pregnancy test strips contain a monoclonal antibody.  If urine contains hCG protein (present only during pregnancy), it binds the Mab and changes the color of the test strip.


Herceptin is a monoclonal antibody based drug.  The monoclonal antibody is used to target breast cancer cells so they are more effectively destroyed.

 A single B cell produces monoclonal antibodies that recognize a specific epitope


VI.  Transplantation

    when organs are moved from one individual to another.


   Types of transplantation are defined by the relationship between the donor and recipient:

Autograft   from one person to self

Isograft      from identical twin

Allograft    from member of same species

Xenograft  from another species



Graft rejection

The immune system reacts to grafted tissue recognized as foreign by trying to destroy it.


Hyperacute rejection reaction is a severe form of graft reaction in which the blood supply to the graft tissue is cut off.


Graft versus host disease occurs in bone marrow transplants.  The immune cells of the grafted bone marrow recognizes the host body as foreign and attacks it.  The transplant rejects the host.

pigs and baboons have been tissue and organ donors for human transplants