Primary Immunodeficiency Flashcards
What are the 2 types of immune system
Innate
Adaptive
What does the immune system start, describe the process
- Danger signals (PAMPs and DAMPs) in the tissue are recognised by antigen presenting cells
- Antigen presenting cells present the antigen to CDT tell cells
- CD4 cells give instructions to b cells
- B cells produce antibodies which act as opsonins and activate complement
What is the role of b cells
Produc antibodies
What are the the types of t cells and what are the functions
Cd4 t cells: produce cytokines to support b cells
Cd8 t cells: cytotoxic cells that destroy virally affected cells and tumour cells
T reg cells: help suppress auto reactive t cells
What is the role of phagocytes
Engulf and destory extracellular pathogens and present antigens
What is the role of complement
Opsonination (c3b)
Immune complex clearance (c1q)
Membrane attack complex
What is the role of nk cells
Destroy virally infected cells and tumour cells
When should we consider immunodeficiency
When we see recurrent infections
Where could the defect be in immunodeficiency
Non immune defect e.g non Anatomical structure problem T cell defect B cell defect Combined defect of t and b cells Innate defect (neutrophils and complement problems) Global defect (signalling molecular and cytokines)
What are the 4rs in the immune response
- Problem in the recognition of pathogen
- Probelm in the response to pathogen
- Problem in the regulation of immune response
- Problem in generation resolution and memory
What makes you think of immunodeficiency
Severe Recurrent invasive infection
Unusual organism or site of infection
Severe recurrent or disproportionate inflammation
Unexplained lymphoproliferation
If a baby has lymphocytes count less than 1 what does this suggest if unless proven otherwise
Severe combined immunodeficiency
Where do normal lymphocytes come from
- Common lymphoid precursor differentiate into b cell, t cell and nk cell precursors
- B cell precursor turn into naive b cells
- T cell precursor turn into t naive cell
- Nk cell precursor turn into nk cells
What can stop this differentiation of lymphocytes from occuring
Genetic disease
What is ADA SCID
Leads to build up toxic metabolite in the common lymphoid precursor that causes it to die. You therefore get negative t, negativ b and negative nk cell SCID.
What does genetic disease that causes tcr rearrangement failure in t cell and b cell precursor lead to
B negative, t negative and nk cell positive SCID
What does t cell lineage specifc loss of survival signals lead to
T cell negative, b cell positive and nk cell positive SCID
Wgat does cell sruvival signal failure in t cell precursor and nk cell lead to
T cell negative, nk cell negative and b cell positive SCID
What is the presentation of SCID
Early onsent of infection that fail to clear
Child fails to thrive
Erythrodemic rash- caused by mothers lymphocytes attacking the baby
Eosiniophillia
Lymphopenia
What is the management of SCID
Initiate prophylactic antifungal, antibiotics, antiviral and IVIG
Strict infection control
No live vaccine or breast feeding
CMV negative and irradiarted blood production to prevent engrafment of lymphocytes
What is the aim of the management of SCID
To get child into a position for bone marrow transplant
What are the function of antibodies
Opsonistation
Antibody dependent cytoxicityt with NK cells
Phagocytosis
Neutralise
Agglutinate pathogen to make them easier to phagocytosis
If there is antibody deficiency what are the types of infections you can get
Pneumonia
Bronchiectesis
Conjunctivitis
Otitis media
What is the characteristic pattern of pathogen that you can get in antibody deficiency
Streptococcal infection
Haemophillus infection
Staphyloccocal infection
Giardiasis, campylobacter, salmonella
What are the genetic causes of antibody deficiency
Brutons tyrosine kinase in boys
X linked agammaglobulinemia
Hyper igm syndrome
What is brutons tyorsine kinase
- Btk is a signalling molecule that helps be cells keep alive as they rearrange from pro b to pre b cells
- Without BTK there is be cell maturation arrest so you are unable to make naive b cells
- No naive b cells means no antibodies
What is x linked agammaglobulinaemia (XLA)
X linked disease where there are absent b cells and undetectable immunoglobulin
What is the treatment of xla
Prophylactic antibiotics
Replacement of immunoglobulin
Respiratory opionin
What is hyperigm syndrome
When b cell development needs to cell help
To swtich from igm to igg what need to happen
- Antigen binds to b cells
- Antigen is internalised and put onot the surface of b cells as MHC
- T cells recognise MHC
- This causes class swtich where igm is switched to igg in b cells
What causes hyper igm syndrome
A deficiency in CD40 ligand on t cells leads to inability to generate the signal needed to class swith so there is high igm
What are the types of neutrophil defects
Defect in the neutrophil number
Defect in neutrophil chemotaxis- the way neutrophils migrate in blood to tissue
Defects in neutrophils killing
What is x linked chronic granulomatous disease
A defect in neutrophil killing
What is the pathogeneis of chronic granulomatous disease
- Failure of the one of the subunit of NADPH complex
- Purpose of the NADPH complex is to produce ROS which then generates a potential difference in the vacuole
- Build up of potential difference causes pottasium influx into the vacuole that causes activation of enzymes to kill of ingested bacteria
- Failure of NADPH complex means you cant kill the bacteria
What is the tratment of chronic granulomatous disease
Prophylactic antibodies
Antifungals
Gene therapy
How does chronic granulomatous disease present
Early onset deep seated infection with catalase positive organism, staph, aspergillus, norcardia, serratia
IBD like diease
What is the complement cascade involved in
Classical pathway via antibody
Mannose binding lectin pathway
Alternative pathway
What do 3 pathways activate
Cause c3 to cleave into c3a and c3b
What does c3 do
Cleave c5
When c5 is cleaved what ahppens
TCC is assembled on the surface of the antigen of the pathogen to help punch a hole through it
What is a deficiency associated with the classical pathway
Lupus like disease
What is a disease associated with the MBL deficiency
Usually asymptomatic
What is a disease associated with the alternative pathway
Neisseria meningitis
What disease is a defect in terminal complement complex (TCC) lead to
Neisseria meningitis
What is common variable of immunodeficiency (CVID)
Hypogammaglobulinemia (low igg, iga,igm): causes recurrent infections such as sinupulmonary
Polyclonocal lymphoproliferation: causes large lymph nodes, spleen
Autoimmunity: causes vitiligo, hypothyroid
Granulomatous disease: gi granulomata
Enteropathies: chronic norovirus, IBD
What is the management of CVID
Immunoglobulin replacement
Prophylactic antibodies
Immunosupresssion
Bone marrow transplant
