WK 12- IMMUNE DEFICIENCY Flashcards
What is immunodeficiency
presence of impairment in function of part or parts of the immune system that render the immodeficient individual more susceptible to infectious disease
What are the indicators of underlying immunodeficiency
- A history of repeated infections suggests a diagnosis of immunodeficiency (Particularly when very young)
- Unusual frequency of infections
- Chronic recurrent infection
- Infection in multiple body sites
- Failure of infection to respond to standard antimicrobial therapy (antibiotics work in conjunction with the immune system- if antibiotics fail to work then it could hint at immune system defect)
- Infection with environmental microbes e.g. Aspergillus, yeast (microbes that normally do not cause infection) - Persistent lymphopaenia (low lymphocyte count) or hypogammaglobulinaemia (low plasma gamma globulins and impairment of antibody formation)
- Disease affecting a particular family
- Failure to respond to vaccination (due to being unable to generate memory T and B cells)
What are the two aetiologies which immunodeficiencies are classed into
Primary and Secondary
What are the 7 disorders which come under primary immunodeficiency disease (what cells/functions are affected and deficient)
- predominantly antibody disorders (humoral deficiency- most common)
- predominantly T lymphocyte disorders (most serious- T cells are central to all aspects of immunity)
- combined cellular and Ab deficiencies
- defects in innate immunity
- complement factor deficiencies (can be deficiency in regulatory protein that causes excessive complement activation, can have deficiency in complements themselves)
- congenital defects of phagocyte number and/or function (affect macrophages and PMN cells)
- Other immune regulation
What is gamma globulin
a mixture of blood plasma proteins, mainly immunoglobulins
What are some of the reasons for primary immunodeficiencies
Can be caused by gene defects (ie. brutons) or from cell developmental blocks (ie. blocking the development of phagocytic cells, B cells, T cells, and complement cells through blocking myeloid lineage)
Why are infants more at risk of developing PID
Passively transferred IgG from the mother being to wane at birth and are significantly dropping from 3 months- infants only begin to create their own IgG at around 6 months-year → after the waning and before production of infants own Ab is when immunodeficiency is most likely to occur
Do primary immune deficiencies affect adaptive or innate or both defence mechanisms- but portions of these mechanisms are affected (what cells)
Both
- Adaptive immunity (humoral or cellular)
- Innate host defence mechanisms (complement proteins and cells (phagocytes and NK cells))
How do primary immune deficiencies affect B cells and therefore Abs
Defects in B cell development result apoptosis of the B cell and deficiencies in production of all Ag isotypes
What is the effect of low Ab
inability to clear extracellular bacteria and some viruses (due to Ab being the primary immune response)→ these pt are more susceptible to infections (virus/bacteria) that require Ab to be removed from the body
What are the 3 major B cell defects
- Defects in early B cell developement
- Class-switch recombination defects
- Common variable immunodeficiency
What is a class switch combination defect- how does it cause immunodeficiency- what syndrome does it cause
Mainly caused by T cell defects affecting B cell ability to switch from IgM to other isotypes resulting in increased IgM (can’t isotype switch so stuck with generic IgM) e.g. HyperIgM (occurs in CD40L mutation→ T cells cause isotype switching by communicating with B cells via CD40L:CD40)
What is selective IgA deficiency
- pathogenesis
- symptoms
- tx
- Do not produce IgA, but produce all other Ig isotypes and the functions of T cells, phagocytic cells and complement systems are all normal→ often asymptomatic (as IgM can fill in for IgA)- thought to be related to lack of IL-4, IL-6, IL-7, IL-10, TGF-β, and most recently IL-21 and defects in genetics
- many people with IgA deficiency appear healthy or only have mild gastrointestinal (due to IgA playing a key role in mucosal immunology) /respiratory infections/allergic disorders→recurrent sinus/pulmonary Infections are the most common findings and autoimmune diseases are among the most important clinical manifestations in IgA deficiency
- Mainstay of treatment is treatment of any associated diseases/symptoms (no real necessity to do anything major unless patient is significantly ill)
How do T cell defects cause low Ab
T cells are required to stimulate B cells to produce Ab and also required for Ab class switching -Without T cells you cannot get B cell activation/switching
How do T cells become defunct (what types of defects are possible)(5)
- Defects in antigen receptor gene rearrangement (due to mutation in genes responsible for the rearrangement)
- Defects in signalling from T cell receptors (if signal can not pass through TCR and into nucleus- will cause defect in function)
- Defects in several cytokine receptors on surface of T cells (e.g. IL-2 receptor)
- Genetic defects in thymic development or function that block T cell development (defect in various genes affecting the stroma of the thymus (stromal epithelial cells drive development and progression/selection)
- Deficiencies in MHC expression→ MHC is important for selection in the thymus→ no CD4 or CD8 T cells e.g. Bare lymphocyte syndrome = defective expression of MHC class II
