Chapter 9

IMMUNOLOGYChapter 9: Failures of the Body’s Defenses

So, we have talked about how our body wins….. what about when our body looses. Do the organisms win, or does the body fail?

What are the mechanisms that the organisms can use to overcome the body’s defenses.?

The body’s defenses against infection can also fail because of inherited deficiencies of the immune system.

HIV- this is a combination of the firs two components. How the pathogen out smarts the immune system and how the body’s defenses can fail.

Evasion and subversion of the immune system by pathogens.             The immune response to any pathogen involves complex molecular and cellular interactions between the pathogen and its host and any stage in this interaction could be targeted by a pathogen and used for its own benefit. The systematic study of pathogen genomes reveals that most, if not all, pathogens have means of escaping or subverting immune defenses and that some of them have many genes devoted to this purpose.

Genetic variation within some species of pathogen prevents effective long-term immunity.             Serotypes….. different coatings, capsules, for Streptococcus pneumoniae.Over 90 different serotypes.

Mutation and recombination allow influenza virus to escape from immunity.             Some viruses display genetic variation.             Epidemics- pass throughout the community quickly, and then passes.             Antigenic drift.  RNA viruses..             DNA and RNA viruses. RNA viruses are notoriously error prone and generates many point mutations.            Pandemic –  world-wide epidemic with lots of deaths and a general combination between avian and human strains.  Antigenic shift……..

Trypanosomes use gene rearrangement to change their surface antigens.             Mutation and recombination are not the only means by which pathogens can change the face they present to the immune system.  Actual gene rearrangement on the protozoa’s surface, African sleeping sickness. Protozoa alone has more than 1000 genes encoding variable surface glycoproteins.

Trypanosomes….. variants, immune response to dominant strain and then moves onto the next dominant one….. continued immune response,,, continued inflammatory response,  contined tissue damage and expanded disease state.   Malaria,,, similar.

Salmonella typhimurium and Neisseria gonorrhoeae; The hosts’ immune response places pressure on the dominant type and another one is ready to take its place. 

Herpes viruses persist in human hosts by hiding from the immune response.             To terminate an established viral infection, infected cells must be killed by cytotoxic CD8 T cells.   Latency = dormant state, virus enters a dormant state within human cells, one in which they neither replicate nor generate enough virus derived peptides to signal their presence to cytotoxic T cells.

Three types of disease latent examples.Cold sores- Herpes simplexChicken pox – Shingles = Herpes varicella zoster.Epstein-Barr virus ( EBV).  Mononucleosis 

Certain pathogens sabotage or subvert immune defense mechanisms.             Once they are ingested rather than being degraded by the lyzosomes they fuse and protect themselves within the cell’s mechanisms.

 Bacterial superantigens stimulate a massive but ineffective T-cell response. Staphylococcus enterotoxins = toxic shock syndrome. Superantigens.   2-20% of the circulating CD4 cells can be involved. This = a massive production and release of cytokines particularly IL-1, IL-2 and TNF = systemic shock.

Immune responses can contribute to disease.            Pathology of the disease.  If the infection ends up somewhere critical = hepatic vein or portal, the immune response to it can be fatal. Liver flukes….. cysts or eggs hatching.

            Immune responses to pathogens can themselves be a significant cause of pathology.

INHERITED IMMUNODEFICIENCY DISEASES.

            Inherited defects in genes for components of the immune system cause immunodeficiency diseases. These reveal themselves by enhanced susceptibility to infection. Not really a disease until 1950s. Antibiotics keeps people alive longer. Childhood deaths.             These diseases are due to a defect in a particular protein or glycoprotein, and the precise symptoms depend on the role of that component in the immune response.

Most inherited immunodeficiency diseases are caused by recessive gene defects. Again nothing before 1950. Recessive defects in autosomal genes, genes on chromosomes other than the sex ones. They need to inherit the gene from EACH parent. Heterozygous for the defect are carriers.

X-linked men versus women.

Antibody deficiency leads to an inability to clear extracellular bacteria.             Lots of examples. For a particular protein or you can have a genetic defect can also cause deficiency in a particular isotype or class of antibody. Inherited deficiency in type IgA , 1 in 800.

            Diminished antibody production also results from inherited defects in T-cell help.

Defects in complement components impair antibody responses and cause the accumulation of immune complexes.             Keep in mind that complement enhances the work of antibodies. SO if you have a defect in antibody production or with complement, it impacts the other component.

Defects  in phagocytes result in enhanced susceptibility to bacterial infection.             Phagocytosis by macrophages and neutrophils is the principal method by which the immune system destroys bacteria and other microorganisms. Any defect that compromises phagocyte activity will , therefore, have a profound effect on the capacity to clear infections. Adhesion molecules. Deficiency keeps the phagocytes from migrating to where they are needed.               They may “eat” just fine, but they can’t produce the super oxidase radicals that are found in the vacuoles.

Defects in T-cell function result in severe combined immune deficiencies.             Whereas B cells contribute only to the antibody response, T cells function in all aspects of adaptive immunity.  T – cell function  defects have a greater effect on the immune’s system to respond to infection. (SCID) = severe combined immune deficiency. Our case of Alexander and Tatiana……. TAP I or TAP II. 

            Some inherited immunodeficiencies lead to specific disease susceptibilities.             Certain diseases are just unique for a specific problem.

Hematopoietic stem cell transplantation is used to correct genetic defects of the immune system.

            GENE therapy…….             Bone marrow transplants = HLA types.

ACQUIRED IMMUNE DEFICIENCY SYNDROME.

            AIDS. HIV. CD4 cells.

HIV is a retrovirus that causes slowly progressing disease.When HIV infects a cell, the RNA genome is first copied into a complementary DNA by reverse transcriptase. The viral integrase then integrates the complimentary DNA into the genome of the host cell to form a provirus.

HIV infects CD4 T cells, macrophages and dendritic cells.

Some people have a well-defined inherent resistance to AIDS they are deficient in the viral coreceptor CCR5.

Genetic deficiency of the CCR5 co-receptor for HIV confers resistance to infection.

HIV escapes the immune response and develops resistance to antiviral drugs by rapid mutation.  The presence of variant viruses increases the difficulty of terminating the infection by immune mechanisms.  The high mutation rate of HIV greatly complicates the task of developing a vaccine against it. It also limits the effectiveness of antiviral drugs. Combination therapy.

            Clinical latency is a period of active infection and renewal of CD4 cells.

HIV infection leads to immunodeficiency and death from opportunistic infections.             Opportunistic infections. A hierarchy of infections. What comes first….. what comes over and over again.

Make sure you know the summary on Pages 306-307.

Excellent study questions…….. in both chapters 8, 9.Work on for your test.