Immunology: Case Studies 1 Flashcards
What is the immune role of the thymus?
A)NK cell development and selection
B) B lymphocyte development and selection
C) T lymphocyte development and selection
D) Monocyte development and selection
E) Neutrophil development and selection
C) T lymphocyte development and selection
Patient with digeorge syndrome
Numerous severe viral infections and fungal infections
cleft pallette
wide separated low ears
NO THYMIC SHADOW
Development if T cells in the thymus
Double negative T cells do not express CD4 or 8
What best describes T lymphocyte selection in the thymus> After TCR rearrangement comes
A) only negative selection of TLR
b) only positive selection of MHC
c) positive selection and negative selection os TLR
d) positive selection on TLR; negative selection on MHC
e) positive and negative selection on MHC
e) positive and negative selection on MHC
TLR is toll like receptor. They are involved in sensing a pathogen. Dont play a role in T cell development
Positive selction of T cells
Double positive thymocytes
If receptor binds self MHC class I it will be a CD8 T cell
If binds self peptide MHC class II it will become CD4T cell
Negative selection happens to get rid of. cells that react to strongly to self peptides/antigen
If binding affinity high, will not be viable
Negative selection of T cells to kill off cells with high affinity for self antigen
moderate or low binding affinity and cell lives
high affinigty (tight binding) and cell dies
Blue part is produce TCR and then positive selction
orange part is nagative selection
Mature self-restricted, slef tolerant, single positive CD4 or CD8 T cells leqave the thymus in blood vessels
What are the main effector functions of T lymphocytes
a) CD4 cytotoxic ; CD8 secrete cytokines
b) CD4 pagocytic; CD8 secrete cytokines
c) CD4 secrete cytokines; CD8 cytotoxic
d) CD4 secrete cytokines; CD8 pagocytic
c) CD4 secrete cytokines; CD8 cytotoxic
Helper T cell secreting cytokines after microbial antigen presentation by APC which activates macrophages, inflammation, and activation (priliferation and differentiation) of T and B lymphocytes
cytotoxic T lymphocyte
Infected cell expressing microbial antigen
Ag presentation by MHC class I, then killing of infected cell
The child with digeorge has no detectable thymus (ie no T cells). What innate defense mechanisms are still present to kill viruses?
a) IFN-α and IFN-ß; natural killer (NK) cells
b) phagocytic cells; B lymphocytes
c) pagocytic cells; CD8 lymphocytes
d) Interleukin-2 (IL-2); eosinophils
a) IFN-α and IFN-ß; natural killer (NK) cells
IFN are antiviral
NK cells recognise and kill infected cells these cells have downregulated MHC class I
Can not be B. phagocytic cells usually not viral killers
B lymphocytes are part of the adaptive immune response, not innate. They also need helper T cells to class switch and activate B cells
IFN-α and IFN-ß
action against viruses
classificiation
Antiviral activity
activation of NK cells
inhibits viral replicaiton
Innate
NK cells
action against viruses:
Classification:
Lysis of infected cells
innate
CD4 T cell
action against viruses:
classification
Produce cytokines to help B cells and CD8 T cells
Adaptive
CD8 T cell
action against viruses:
classification
Lysis of infected cell; produce cytokines to help NK cells become cytotoxic
adaptive
B cell
Action against viruses
Classification
Produce antibody; neutralization, opsonization for ADCC
ADCC = antibody dependent cellular cytotoxicity. The lysis of an infected cell
Adaptive
DiGeorge
22q11
THYMUS DOES NOT DEVELOP
Bare lymphocyte syndrome
Child with history of bacterial, viral, and fingal infections
long episodes of D
Bare lymphocyte syndrome lab tests
CBC and differential: normal total number of neutrophils, monocytes, lymphocytes, eosinophils, and basophils
Antibody titers for immunization antigens were negligible
Nitroblue tetrazolium (NBT) test showed normal respiratory bursts after phagocytosis (ie phagocytes can kill)
Bare lymphocyte syndrome
Based on the infection history and lack of antibody responses, where do you suspect the defect to be?
Natural killer (NK) cells
Lymphocytes
Neutrophils
Eosinophils
Lymphocytes
What antibodies do
Which cell population helps B cells make antibody?
NK cells
CD4 lymphocytes
CD8 lymphocytes
Macrophages
CD4 lymphocytes
Bare lymphocyte syndrome
Flow cytometry shows severe CD4 lymphopenia. Where do suspect the defect?
Complement proteins expression
MHC class I expression
MHC class II expression
TLR expression
MHC class II expression
Why would lack of MHC II mean no CD4 cells? Posisive selection
None can come out of the thymus to periphery
No CD4 cells = No B cell help
BLS is a rare autosomal disorder caused by genes that control expresison of what
MHC class II.
MHC class II is not expressed on APCs
Tx: IV immunoglobulin, bone marrow transplant
In addition to B cells, what other immune cells express MHC class II
a) dendritic cells and macrophages
b) NK cells and neutrophils
c) basophils and eosinophils
d) CD4 and CD8 lymphocytes
a) dendritic cells and macrophages
Which cell surface molecule is responsible for presenting viral antigen derived from virus infecting a cell?
CD4
CD8
MHC class I
MHC class II
TLR
MHC Class I
Protein being synthesized endogenously.
MHC Class I
In humans, what are the MHC genes known as?
H-2
B
HLA
ABO
ABD
HLA
Which type of antigen is processed for presentation by MHC molecules?
polysaccharides
nucleic acid
protein
glycolipid
carbohydrates
PROTEIN
Development of protection in a primary adaptive immune response to a T dependent antigen takes approximately how much time?
30-120 mins
6-24 hours
1-4 days
1-3 weeks
2-6 months
1-3 weeks
Increase in memory cells after priming means that the secondary response is fater and greater
LAD-1
Leukocyte adhesion deficiency
8 year old F with recurrant necrotic infections to the arms and legs.
LAD-1 Lab tests
CBC diff: normal
Complement levels and function: normal
Nitroblue tetrazolium (NBT) test: normal
Serum Ig (total levels) : normal
Antibody titers for vaccine antigens: normal
What cell type is rapidly recruited to the site of a bacterial infection in the skin?
eoinophils
neutrophils
basophils
NK cells
Neutrophils
What role do neutrophils play in an immune response against a pathogen?
a) antigen presentation to CD4 lymphocytes
b) induce B lymphocytes to make antibody
c) phagocytose and kill foreign pathogens
d) activate NK cells
c) phagocytose and kill foreign pathogens
Neutrophil function and what they express
Neutrophils stored in bone marrow and are released when needed to fight infection
They travel to and enter the infected tissue wher they engulf and kill bacteria. They die in the tissue and are engulphed and degraded by macrophages
Neutrophils express receptors for many bacterial and fungal constituents
Neutrophils bind bacteria, engulf them, and destroy them with the toxic components of the neutrophil granules
Neutrophils were prominent in the patient’s blood and were functional, but were not observed at the site of the infection. What molecule is most likely defective?
pattern recognition receptor
complement
MHC class I
Integrins
INTEGRINS
The child has been diagnosed with leukocyte adhesion deficiency 1 (LAD-1) due to the defect in CD18 (a component of beta-2 integrin/LFA-1
If you look at the picture, you can see that LFA-1 is important in binding and rolling for neutrophil adhesion and entering into tissue.
Thus cell can not get into tissue and can not fight infection
LAD 2
Trafficking defect due to defects in carbohydrates present on the leukocyte cell surface
Carbohydrates are the ligands for P selectin and E selectin
Cell rolloing to slow down the leukocyte does not occur
What is one immune function of the spleen
a) capture lymphatic borne antigen
b) capture blood borne antigen
c) capture mucosal associated antigen
b) capture blood borne antigen
lymphatic borne antigen is captured in the LN
What is the function of the red pulp?
Remove aged or abnormal RBCs
Activate eosinophils
Generate antibodies
Activate NK cells
Remove aged or abnormal RBCs
(white pulp is analogous to LNs)
Howell-Jolly bodies in blood smear. Inclusions are formed by the retention of nuclear remnants in red cells which are usually removed by spleen
What is the function of the white pulp?
Mast cell activation
Secrete complement factors
Interactions between B and T lymphocytes
Activate NK cells
Interactions between B and T lymphocytes
Ways antibodies eliminate pathogens
neutralization
opsonization
Neutralization
Ab binds to pathogen in a way that inhibits pathogen growth, replication, or interaction with human cells; Ab binds to toxin to inhibit activity
Opsonization
coating of pathogen with Ab/ Ab+ complement for efficient phagocytosis
Ways that Abs eliminate pathogens
neutralization and opsonization
Most common and rapidly progressing infections after splenectomy are
streptococcus pneumoniae and haemophilus influenzae
Encapsulated pathogens that can enter the bloodstream
eliminated by innate and adaptive immune respinses in the spleen
Asplenic patients are given what as treatment
antibiotic prophylaxis
Complex immunodeficiency
31 year old F with nasal perforation and ulcerated brown-violet skin lesions
Hx TB
Complex immunodeficiency labs
Leukocytes : normal
Lymphocytes: normal
T cells (CD3+): Normal
CD4 T cells: Normal
CD8 T cells: Absent (αß)
CD4- CD8- γδ T cells: High
B cells: normal
IgG: Low
Other Ig: Normal
Note γδ T cells are a specialized calss of T cells that are not selected in the thymus and are not MHC restricted. They are resident to epithelial surfaces.
Complex immunodeficiency
Where do you suspect the defect?
B lymphocyte development and selection
T lymphocyte development and selection
Monocyte development and selection
Neutrophil development and selection
T lymphocyte development and selection
What mechanism of genetic recombination occurs in developing T lymphocytes that leads to the generation of the TCR
somatic hypermutation
somatic recombination
allele polymorphism
affinity maturation
Somatic recombination
AKA VDJ recomb.
Somatic hypermutation is the mutagenesis of B cells
Affinity maturation happens due to somatic hypermutation
Complex immunodeficiency
Where do you suspect the defect?
MHC class I
MHC class II
RAG
CD3
MHC class I
In complex immunodeficiency you do not have MHC class I and this can not self bind. Can not get CD8 cells bc of this.
Complex immunodeficiency labs
FcRn (brambell receptor)
CD-1 expression
FcRn (brambell receptor): ABSENT
CD-1 expression: ABSENT
FcRn AKA
FcRB (brambell receptor)
What does FcRn (FcRB) do?
It helps increase the half life of IgG molecules
Responsible for maternofetal trandfer of IgG and normal IgG and albumin half-life
Defective FcRn
Low IgG
FcRB carries IgG acrosss endothelium into extracellular spaces
Complex immunodeficiency:
Why the dysfunction in:
MHC class I
FcRn/FcRB
CD1
They all share the ß2-microglobulin as part of their structure
Where do MHC class I molecules bind peptide?
Endosome compartment
Golgi apparatus
Endoplasmic reticulum
Cytosol
Endoplasmic reticulum
MHC Class I pathway
Notice that TAP loads peptides onto MHC Class I.
TAP deficiency can also lead to lack of MHC class I expression
Mutations in TAP are the most common cause of MHC Class I deficiencies
What cells express MHC class I?
Only DC, B cells, macrophages
All nucleated cells, but not DCs, B cells, macrophages
All nucleated cells
All nucleated cells
Proteins processed by the endogenous vs the exogenous pathway
Endogenous- MHC class I expressed on nucleated cells Presents viral and tumor antigens
Exogenous- MHC class II expressed on limited number of cells (mainly DCs, macrophages, B cells) Presents viral, bacterial,fungal, and environmental antigens
The pt with complex immunodeficiency was diagnosed with
B-2 microglobulin
Hypogammaglobulinemia and hypoalbuminemia due to lack of expression of FcRn/FcRB
Deficiency in clearing extracellular pathogens
No CD8 Tc cells in blood due to no MHC class I expression deficiency in clearing intracellular pathogens
