Immunology Flashcards
Primary immune deficiency
inherited cause of immune compramise
Secondary immune deficiency
due to any other cause e.g. infection (HIV), malignancy, mmalnutrition, drugs (steroids)
Physiological immune deficiency
- neonates
- pregnancy
- old age
Constitutive physical barriers of the immune system (3)
- commensal bacteria
- mucous surfaces
- epithelial barrier
Deficiency of epithelial barrier?
Burns - high risk of infection
Deficiency of mucosal barriers?
- organs affected (2)
- genetic risk factor
IgA deficiency
- lungs, GI tracts - recurrent infections
- caucasian population
Deficiency of commensal bacteria?
- when
- common infections (2)
- after broad spectrum Abx
1) candida albicans
2) C.diff
Cells of innate immune system (7)
- Macrophages
- neutrophils
- eosinophils
- monocytes
- basophils
- NK cells
- dendritic cells
How the innate immune system works (7)
- Innate immune cells are produced in bone marrow, and circulate in blood to be able to migrate to tissues
- cytokines and chemokines detect site of infection and activate endothelium
- Toll-like and Mannose recpetors detect pathogen at infection site
- PAMPs recognise pathogen by responding to proteins on their bacterial sugars
- Fc receptors recognise immune complexes
- inflammatory chemokines and cytokines recruit phagocyte by
a) increasing vascular permeability
b) attracting phagocytes - Oxidative and Non-oxidative killing of pathogen
Oxidative Killing
mediated by reactive oxygen species (superoxides and hydrogen peroxide) generated by action of the NADPH oxidase complex
Non-oxidative killing
mediated by bacteriocidal enzymes such as lysozyme
the lysosome and phagocyte come together to form a phagolysosome
Opsonisation
- what
- mediators
“making the pathogen tasty”
binding of pathogen and phagocyte in order to kill pathogen
facilitated by opsonin
mediated by antibodies, Fc receptors and acute phase proteins e.g. CRP
Common bacterial pathogens in recurrent infections? (2)
- staph aureus
2. mycobacteria
Common fungal pathogens in recurrent infections? (2)
- C.albicans
2. Aspergillus
Types of phagocyte deficiency (3)
- recruitment of phagocytes
- find & catch organism
- kill organism
Reticular Dysgenesis
- what
- inheritance pattern
- enzyme mutation
- lab findings
- outcome
- Severe form of Severe Combined Immunodeficiency (SCID)
- failure of stem cells to differentiate down myeloid/lymphoid lineage leading to a complete absence of granulocytes
- autosomal recessive
- adenylate kinase 2 (AK2)
- absolute deficiency in neutrophils, leukocytes, monocytes, platelets
- fatal without BMT
Kostmann Syndrome
- what
- inheritance pattern
- mutation
- Nitroblue test of oxidative killing (NBT)
- neutrophil count
- leukocyte adhesion markers
- severe congenital neutropenia
- autosomal recessive
- HAX1 protein
- NBT neg
- absent neutrophil count
- leukocyte adhesion markers NORM
Cyclic Neutropenia
- what
- inheritance pattern
- mutation
- cyclic neutropenia every 4-6weeks
- autosomal dominant
- neutrophil elastase ELA-2
Leukocyte Adhesion Deficiency LAD1
- what
- mutation
- presentation
- lab findings
- treatment
- failure to express leukocyte adhesion markers therefore neutrophils are unable to get to site of infection
- B-2 integrin subunit of CD18 in LAD1
- Neonatal bacterial infection
- HIGH neutrophil count
- bone marrow transplant
LAD2
- rare
- associated with
a) growth restriction
b) mental retardation
Chronic Granulomatous Disease
- pathophysiology (5)
- investigation
- inheritance pattern
- deficiency in NADPH oxidase
- inability to generate oxygen free radical s
- excessive inflammation due to high neutrophil/macrophage recruitment
- granuloma formation
- lymphadenopathy + hepatosplenomegaly
- Nitroblue test of oxidative killing (NBT) - abnormal
Dihydrorhodamine test - abnormal - x-linked
IFN gamma receptor deficiency
- what
- cytokines involved
- outcome
- defect of interaction between macrophages and other cells (T cells)
- IL12 & IFNgamma
- susceptibility to mycobacterial infections, salmonella, TB and GBS
Common infections associated with chronic Granulomatous Disease (7)
PLACESS Pseudomonas Listeria Asperigillus Candida E coli Staph aureus Serratia
Inflammatory cytokines (4)
IL-1
IL-12
TNF
IL-6
Non-inflammatory cytokines (2)
IL-10
TGF-beta
Neutrophil
Polymorphonuclear cells capable of phagocytosing pathogens and killing by oxidative and non-oxidative mechanisms
NKC
Lymphocytes that express inhibitory receptors capable of recognising HLA class I molecules and have cytotoxic capacity
Dendritic Cell
Immature cells are adapted for pathogen recognition and uptake whilst mature cells are adapted for antigen presentation to prime T cells
Macrophage
Derived from monocytes and resident in peripheral tissues
Complement Classical Pathway
- which proteins?
- main protein and function
- dependant on?
- causes
- C1, C2, C4
- C1 provides binding site on Ab
- immune response
- formation of immune complexes Ab/antigen
MBL Pathway
- which proteins
- protein function
- causes
- MBL
- MBL direct binding to microbial carbohydrates
- links in classical pathway via C2, C4
Complement Alternative Pathway
- which proteins?
- protein function
- factors involved
- C3
- C3 directly binds to bacterial cell wall
- B, I , P
C3
Cleavage of this protein may be triggered via the classical, MBL or alternative pathways
C1
Binding of immune complexes to this protein triggers the classical pathway of complement activation
C9
Part of the final common pathway resulting in the generation of the membrane attack complex
MBL
Binds to microbial surface carbohydrates to activate the complement cascade in an immune complex independent manner
Classical pathway deficiency
- common protein affected
- association
- why
- test
- C2
- SLE
- Classical pathway is repsonsible fro removing immune complexes, these build up in SLE in skin, joints, kidneys
- CH50
MBL deficiency
- common or rare?
- significant when?
- very common (30%)
- significant is another immune impairment present e.g. chemo/HIV
Alternative pathway deficiency
- common factor involved
- susceptible to infections caused by which microbes? (4)
- test
- Factor B
- ENCAPSULATED bacteria
1. N menigitides
2. Strep pneumoniae
3. H influenzae
4. GBS - AP50
Terminal Pathway Deficiency
- what
- why
- associations (2)
- susceptible to infections? (4)
- tests
- lack of C3, 5, 6, 7, 8, 9 so severe susceptibility to bacterial infections
- cannot form MAC to kill bacteria
- glomerulonephritis
- connective tissue disease
- glomerulonephritis
- ENCAPSULATED bacteria
1. N menigitides
2. Strep pneumoniae
3. H influenzae
4. GBS - CH50 & AP50
Membranoproliferative nephritis and bacterial infections
C3 deficiency with presence of nephritic factor
Meningococcus meningitis with family history of sibling dying of same condition aged 6
C9 deficiency
Severe childhood onset SLE with normal levels of C3 and C4
C1q deficiency
Recurrent infections when receiving chemotherapy but previously well
MBL deficiency
Characteristics of the adaptive immune system (4)
- wide repertoire of antigen receptors
- specificity
- clonal expansion
- immunological memory
Primary lymphoid tissues (2)
- Bone marrow
2. Thymus
Secondary lymphoid tissue (3)
1, Lymph nodes
- MALT
- Spleen
Where does B cell maturation occur?
Bone marrow
Where does T cell maturation occur?
Thymus
T Cell Maturation (5)
- arise from haemopoetic stem cells
- exported as immature cells to the THYMUS
- Mature T lymphocytes leave thymus and enter circulation
- Reside in secondary lymphoid tissue
- T cell receptor interacts with HLA molecule on APC
Which HLA Class do CD4+ T cells interact with?
Class II
Which HLA Class so CD8+ T cells interact with?
Class I
Three types of T Cell tolerance ?
- Low affinity for HLA - to avoid inadequate reactivity
- Intermediate affinity for HLA - positive selection for 10% cells
- High affinity for HLA - to avoid autoreactivity
CD4+ T Cell subsets (5)
- Th1
- Th17
- Treg
- TFh
- Th2
Th1 (2)
- Help CD8 T cells and macrophages
2. Subset of cells that express CD4 and secrete IFN gamma and IL-2
Th17
Help neutrophil recruitment
Enhance generation autoantibodies
Treg (2)
- Regulate IL-10/TGF beta expressing
2. Subset of lymphocytes that express Foxp3 and CD25
TFh (2)
- Support the germinal centre on the lymph node
- Play an important role in promoting germinal centre reactions and differentiation of B cells into IgG and IgA secreting plasma cells
Th2
T helper cells
CD8+ T cells (5)
- cytotoxic T cells
- recognise HLA Class I peptides
- kill cells directly
- produce cytokines INFgamma and TNFalpha
- important defence against viral infections & tumours
CD8+ T Cells
Express receptors that recognise peptides usually derived from intracellular proteins and expressed on HLA class I molecules
Antigen encounter in germinal centre of LN (4)
- CD4+ T cell is primed by dendritic cell
- CD4+ T cell helps IgM B cell differentiation
- B cell proliferation
- Isotype switching to IgG, IgE, IgA
What area of the immunoglobulin recognises the antigen?
Fab antigen binding region on both the heavy and light chain
What is the effector area of the immunoglobulin?
Fc region of the heavy chain
Antibody function (3)
- identification of toxins and pathogens - Fab
- Interaction with other immune cells to remove pathogens - Fc
- Defence against bacteria
B Cell Memory (4)
- reduced time between antigen exposure and antibody production
- increased titre of antibody produced
- IgG antibodies dominate
- can be independant of CD4+ T cells
Pre B Cells
Exist within the bone marrow and develop from haematopoietic stem cells
IgA
Divalent antibody present within mucous which helps provide a constitutive barrier to infection
IgG secreting plasma cells
Cell dependent on the presence of CD4 T cell help for generation
IgM secreting plasma cells
Are generated rapidly following antigen recognition and are not dependent on CD4 T cell help
Common infections in Lymphocyte deficiencies
- bacterial (2)
- fungal (2)
- viral
- malignancy
Bacterial 1) mycoplasma 2) salmonella Fungal 1) Pneumocystis 2) Crytosporidium Viral - CMV Early malignancy
Age of presentation of SCID and WHY?
> 3/12
Prior to this protected by maternal IgG that CAN cross placenta
Most common form of SCID?
Mutation?
Pathogenesis (4)
X-linked
IL-2 receptor
1. IL-2 receptor shared by numerous interleukins
2. Inability to respond to cytokines
3. T Cell and NK cell development is arrested
4. Formation of immature B cells
Di George syndrome
- what
- symptoms
- chromosomal abnormality
- laboratory findings
- developmental defect of pharyngeal pouch C- cardiac abnormalities A- abnormal facies T - thymic aplasia C- cleft palate H - hypocalcemia 22 - 22q11.2 deletion - reduced numbers of T cells due to thymic immaturity