Immunodeficiency Flashcards
what are 3 outcomes of an infection?
- resolution
- latent infection
- chronic infection
what is resolution response to infection?
- Normal Immune response
- Pathogen cleared
- Tissue repair
what is latent infection response?
- Normal immune response
- Pathogen controlled (no replication)
- Infection can re-occur
what is chronic infection response?
- Defective immune response (aka: immunodeficiency)
- Pathogen not cleared or controlled
- ongoing viral replication & infection of new cells
what is the major hallmark for immune deficiency?
recurrent infections (especially in young children)
what does SPUR stand for and what is it?
= it’s the things that can be signs of immuno deficiency
Serious infections (unresponsive to oral antibiotics)
Persistent infections (early structural damage & chronic infections)
Unusual infections (unusual organisms & sites)
Recurrent infections (2 or 1 major and recurrent minor infections in 1 year)
what are some less major features that may also suggest primary immmune deficiency?
- Weight loss or failure to thrive
- Severe skin rash (eczema)
- Chronic diarrhoea
- Mouth ulceration
- Unusual autoimmune disease
- Lymphoproliferative disorders (could be precursor to cancer)
- Cancer
- Family history
what is primary immunodeficiency?
quite common - immune dysregulation & autoinflammatory disorders & defects in innate & adaptive immmunity
What response causes most of hypersensitivity diseases?
humoral response (antibody response)
what are common complications of immunodeficeincy?
upper & lower respiratory tract complications
what are polyclonal activators?
like super antigens - non specific way to activate T cells
what do pulmonary complications lead to?
morbidity & mortality
HIV virus attacks what cell type?
immune cells expressing CD4
where does B cell development occur?
in bone marrow through series of developmental stages
once fully mature, what do B cells do?
they exit the bone marrow & circulate around body via blood stream, lymphatics & secondary lymphoid tissues
what happens if B cell defects?
- Increased susceptibility to extracellular pathogens (bacteria, intestinal parasites), also enteroviruses
- Delays in growth and development
- Increased incidence of autoimmune diseases, malignant tumours
what is XLA?
X-linked agammaglobulinemia
- formed by mutation on BTK gene which blocks differentiation & development of pre-B cells
= this means absence or severe reduction in B lymphocytes and Ig’s of all types
how can you diagnose XLA?
measure serum Ig levels or number of peripheral B cells in blood
confirmatory test = DNA sequencing of BTK gene locus
what is treatment of XLA?
Intravenous Immunoglobulin (IVIG) - first case you would prescribe antibiotics for ongoing infections, you can give antibody therapy, if very sick then hemapoetic stem cell therapy to complete replace
what is hyper-IgM (HIGM) syndrome?
caused by a variety of mutations - commonly in CD40L gene (X-linked recessive)
= it means normal number of B lymphocytes, normal or elevated IgM an decreased IgG
= this means defective interactions between B and Tfh cells so CD4 T cells aren’t stimulated so B cells don’t get swapped to different Ig’s
what normally do Tfh hlper cells do?
they bind to and activate and increase expression of co-stimulatory molecules that will interact with CD4 T cells
what is diagnosis of hyper-IgM syndrome?
- Assess serum Ig levels / the B cell numbers in the blood
- Assess CD40L expression on activated T cells
- DNA sequencing of the relevant gene loci (e.g. CD40L, CD40, others)
what is treatment of hyper- IgM syndrome?
- Intravenous Immunoglobulin (IVIG)
- Granulocyte colony stimulating factor (G-CSF) therapy if neutropenia is present
- Hematopoietic stem cell transplantation (bone marrow or cord blood stem cell) where T cell dysfunction is also present (X-linked HIGM)
*in primary immunodeficiency you wouldn’t want to give them vaccine
what are features of T cell immunodeficiency?
- Increased susceptibility to intracellular pathogens (viruses, intracellular bacteria)
- Delays in growth and development
- Death at early age if untreated
- Increased incidence of malignant tumours
what is T cell immunodeficiency?
developmental problem affecting development of thymus so block in T cell development & differentiation
-> Ig deficiencies often present as well since B/T interactions critical important for normal humoral immunity
What is DiGeorge syndrome?
when you don’t have functioning T cell as don’t have functioning thymus
- developmental defect whcih causes facial defects & congenital heart defect
why does T cell functionality drop with age?
thymus shrinks gradually over time
what is X-SCID?
X-linked severe combined immunodeficiency
caused by mutations on the gene encoding IL gamma chain of several cytokine receptors
->causes infections of all types & unusual skin disease - often early infant death if X-SCID not already identified with wider family tree
what is CGD?
chronic granulomatous disease - phagocytotic deficiency
- mutations in gene that code for NADPH oxidase complex components so not effective killing & reduced phagocytotic killing by neutrophils & macrophages
what is secondary immune deficiency?
- common
-often subtle - often involves more than 1 component of immune system
like HIV, measles
what is HIV?
- significant cause of secondary immune response
- high mutation rate
- HIV infects CD4+ cells - CD4 is main target for HIV attachement (which means T cells but also cells like macrophages that present CD4)
CD4 help stabilise reaction between TCR & MHC class 2 with peptide on it - without CD4 then not stable
-over time CD4+ T cells are depleted = progressive immunosuppression
