Immunopathology Flashcards
What are the principle factors in the development of autoimmunity?
The inheritance of susceptibility genes and environmental triggers, such as infections.
What is autoimmunity?
An immune response against self antigens.
How do susceptible genes contribute?
Interfere with the pathways of self-tolerance and lead to the persistence of self-reactive T and B lymphocytes.
How does environmental stimuli contribute?
May result in the activation of these self-reactive lymphocytes.
Why is little known about the etiology of human autoimmune diseases?
Three factors: autoimmune diseases in humans are usually heterogeneous and multifactorial; the self antigens that are the inducers and targets of the autoimmune reactions often are unknown; and the disease may manifest clinically long after the autoimmune reactions have been initiated.
Most autoimmune diseases are polygenic and are associated with multiple gene loci, the most important of which are the MHC genes. True or False?
True.
How was autoimmunity considered gene related?
Because if an autoimmune disease develops in one of two twins than it is more likely to develop in the other twin than in an unrelated member of the general population. This increased incidence is greater among monozygotic (identical) twins than among dizygotic twins.
Many autoimmune diseases in humans and inbred animals are linked to particular MHC alleles. True or False?
True.
What is the “relative risk”?
When the incidence of a particular autoimmune disease often is greater among individuals who inherit a particular HLA allele than in the general population.
The HLA allele is not, by itself, the cause of the disease. True or False.
True.
How are some tissues injured?
Infections also may injure tissues and release antigens that normally are sequestered from the immune system. For instance, some sequestered antigens (e.g. In the testis and eye) normally are not “seen” by the immune system and are ignored. Release of these antigens (e.g by trauma or infection) may initiate an autoimmune reaction against the tissue.
Define hypersensitivity.
Immune responses that cause tissue injury and the diseases caused by these reactions are called hypersensitivity diseases or immune-mediated inflammatory diseases.
How do they arise?
Hypersensitivity reactions may arise from uncontrolled or abnormal responses to foreign antigens or autoimmune responses against self antigens.
How is it classified?
According to the mechanism of tissue injury.
Describe type I hypersensitivity.
Caused by the production of IgE antibody against environmental antigens or drugs (allergens), sensitisation of mast cells by the IgE, and degranulation of these mast cells on subsequent encounter with the allergen.
Describe type II hypersensitivity.
Antibodies against cell and tissue antigens may cause tissue injury and disease.
Describe type III hypersensitivity.
Antibodies may bind to circulating antigens to form immune complexes, which deposit in vessels and cause tissue injury. Injury is mainly due to inflammation.
Describe type IV hypersensitivity.
T cell mediated diseases or by killing of host cells by CD8+ CTLs.
What is the morphology of a HIV particle?
Has an outer envelope of lipid penetrated by 72 glycoprotein spikes. The inner surface of the virus lipid envelope is lined by a matrix protein (p17). There are also abundant cellular proteins, notably MHC class I and class II antigens in the lipid envelope. A cone shaped protein core contains the diploid RNA.
Retroviruses possess a defining enzyme, reverse transcriptase (RT), which uses the viral RNA as a template for making a DNA copy, which then integrates into the chromosome of the host cell and there serves either as a basis for viral replication or as an oncogene. True or False?
True.
How many phases of HIV disease are there?
- Acute, chronic, AIDs
Describe the acute stage.
The acute phase lasts for about 12 weeks after initial infection and is characterised by a sharp drop in CD4 T-cells, a spike in viral load, and the first immune responses.
Describe the chronic stage.
The chronic phase can last many years and shows very low viral loads and reduced (but not catastrophic) T-cell counts. The immune system manages to suppress the infection fairly efficiently during this phase.
Describe the AIDS stage.
The AIDS phase is defined by a drop in CD4 T-cells to a dangerously low level. At this point, the immune system is overwhelmed and the viral load shoots up and the patient suffers from wasting, neurological impairment, malignancies and the opportunistic infections that would normally not be a problem. This phase is fatal in the abscence of drug therapy.
What is the purpose of antiretroviral therapy?
To extend the chronic phase indefinitely whereby copies of viral RNA are reduced and CD4 lymphocytes levels are raised. This can restore immune function, leading to clearing of opportunistic infection and dramatic health improvement.
What are the symptoms of AIDS?
Extreme fatigue Persistent diarrhoea High fever Pneumonia Dementia
Name a few opportunistic infections associated with AIDS.
Herpes Influenza TB Candida Strep pneumonia Kaposi sarcoma
What are the methods used for diagnosis?
Detection of antibodies by ELISA
Viral RNA detection by RT-PCR
What is the prognosis?
Without drug therapy, individual will die within a year.
Most will progress to AIDS within 10 years of HIV infection.
