Flashcards in Immune System Diseases Deck (40):
Difference between primary and secondary immunodeficiency syndromes?
-Primary = inherited
-Secondary = acquired
What are the 5 major risk groups of adults at high risk of developing AIDS?
-homosexual/bisexual men (50%)
-IV drug users (not homosexual) (20%)
-Recipients of blood and blood components who are not hemophiliacs (1%)
-Heterosexual contacts of members of other high risk groups (20%)
-HIV infection of the newborn (2% under 13 y/o) =placental transmission
What are the two ways in which HIV viral transmission occurs?
-Direct inoculation into the blood vessels by trauma
-infection of dendritic cells or CD4+ cells within the mucosa
Sexual transmission of HIV is _________ by coexisting sexually transmitted diseases especially those associated with genital ulceration.
HIV is a non-transforming human retrovirus belonging to the lentivirus family, meaning:
-it will not transform normal cells into cancer cells
What is the structure of the HIV virus?
-electron dense core surrounded by a lipid envelope derived from host cell membrane
What is contained within the HIV core?
-The major capsid protein p24
-Nucleocapsid protein p7/p9
-Two copies of viral genomic RNA
-The three viral enzymes protease, reverse transcriptase and integrase
Why is research of HIV so complicated?
-there are a butt load of subtypes
What are the two main targets of HIV infection?
Describe the pathogenesis of HIV.
-Profound immune deficiency, primarily cell-mediated immunity
-results from infection and loss of CD4+ T cells and impairments of surviving Th cells
Describe the life cycle of HIV.
Consists of infection of cells, integration of the provirus into the host cell genome, activation of viral replication, and production and release of infectious virus
What does gp120 bind to?
CCR5 & CXCR4
Describe the process of HIV entering a cell.
-gp 120 binds CD4
-gp120 & CD4 binds CCR-5 receptor (on T cell)
-leads to fusion to host cell
Why are naive T cells difficult for HIV to infect?
-they contain an active form of an enzyme that introduces mutations to the HIV genome
-they don't express CCR5 & CXCR4
Can macrophages and dendritic cells also be infected by HIV?
Why can't B cells produce antibodies to HIV
-They don't have the T cells to stimulate them
What are the three phases of the clinical manifestations of HIV?
-An acute retroviral syndrome
-Middle chronic phase
What is the initial clinical presentation of the initial viremia of HIV?
-Acute retroviral syndrome
-3-6 weeks after infection
-nonspecific symptoms including sore throat, myalgias, fever, weight loss, and fatigue similar to the flu
Describe the middle chronic phase of HIV infection.
-In the next phase of the disease lymph nodes and spleen are sites of continuous HIV replication
-during this phase of the disease there are little or no clinical symptoms
-However the infection is killing off T cells and over years the CD4+ T cells drop to insufficient numbers
Describe the AIDS stage of HIV infection.
The final progression is to AIDS, characterized by a breakdown of host defense, a dramatic increase in plasma virus, and severe, life threating disease
Why does it take at least 6 months (of age) for a primary immunodeficiency to show up?
What is the difference between Type I and Type II leukocyte adhesion defects?
Type I: Defect in synthesis of Beta2 chain shared by integrins
Type II: Defects in selectins
What is Chediak-Higashi syndrome?
-defective fusion of phagosomes and lysosomes, resulting in defective phagocytic function and susceptibility to infection
-main abnormalities: neutropenia, defective degranulation, and delayed microbial killing
Why does Chediak-Higashi syndrome result in neutropenia?
-need to phagocytose bacteria to create cytokine signals to attract neutrophils
What is chronic granulomatous disease?
-defects in bacterial killing due to defects in gene encoding components of superozide
What is the most common compelement deficiency?
-deficiency of C2
**many pts have no clinical manifesttions, probs because the alternative pathway is adequate
What does a deficiency in C3 result in?
-susceptibility to serious pyogenic (pus generating) infections
-Increase in incidence of immune complex-mediated glomerulonephitis
What is SCID?
Severe combined immunodeficiency (SCID) represents a constellation of genetically distinct syndromes, all having in common defects in both humoral and cell-mediated immune responses
Why do infants with SCID get a rash after birth?
-maternal T cells that transferred across the placenta attack the fetus
What is the treatment for SCID?
-Bone marrow transplant
**without this, pt will die in first year
Describe X-linked SCID.
-The most common form, accounting for 50-60% of cases and is more common in boys than girls
-The genetic defect is a mutation in the common gamma chain subunit of cytokine receptors in T cells
-As a result of this defect there is a profound defect in the earliest stages of lymphocyte development
What is X-linked agammaglobulinemia?
-characterized by failure of B cell precursors to develop into mature B cells = no antibodies
-Caused by mutation in a cytoplasmic tyrosine kinase called Bruton Tyrosine Kinase (Btk)
-when mutated, pre-B cell receptor cannot deliver signals to nucleus and maturation stops
What is DiGeorge Syndrome?
-DiGeorge sysndrome is a T cell deficiency that results from failure of development of the third and fourth pharyngeal pouches (Thymus)
Why would DiGeorge Syndrome result in tetany?
-Underdeveloped thymus means no calcitonin
-no calcitonin means blood Ca too high
-Causes muscle contraction
What is Common variable immunodeficiency?
-Usually a diagnosis of exclusion
-This relatively frequent but poorly defined entity encompasses a heterogenous group of disorders in which the common feature is hypogammaglobulinema, generally affecting all the antibody classes but sometimes only IgG
What characterizes tissue transplant rejection?
-a process in which T lymphocytes and antibodies produced against graft antigens react against and destroy tissue grafts
-Recognition of graft Alloantigens by T and B lymphocytes
What is the major antigenic difference between a donor and recipient that results i rejection?
What is the direct pathway of allorecognition by T cells in organ transplant?
-T cells of the transplant recipient recognize allogenic (donor) MHC milecules on the surface of APCs in the graft
-It is believed that dendritic cells carried in the donor organs are the most important APCs for initiating the antigraft response, because they not only express high levels of class I and II MHC molecules but also are endowed with costimulatory molecules
What is the indirect pathway of allorecognition by T cells in organ transplant?
-In the indirect pathway, recipient T lymphocytes recognize MHC antigens of the graft donor after they have presented by the recipient’s own APCs
-This process involves the uptake and processing of MHC molecules from the grafted organ by host APCs.