Immunology Flashcards
What effect may cause high doses of corticosteroids on nerve system?
corticosteroid-induced psychosis (hallucinations, confusion)
What is the acute effect of corticosteroids on WBCs? (5)
Incr. neutrophils, decr. basophils, eosinophils, monocytes, lymphocytes
Corticosteroid use –> dec. basophils. Effect? Why?
decreased local inflammatory responses by preventing histamine release.
Corticosteroid use –> dec. eosinophils. Effect? Why
reduced eosinophil count –> decreased mediators release from eosinophils in allergic reactions.
Where corticosteroids redistribute lymphocytes from vessels? (3)
spleen, lymph nodes, bone marrows
When corticosteroid use -T or B lymphocytes decr. more?
T lymphocytes
how corticosteroids decreased lymphocytes?
inhibit Ig synthesis + stimulate lymphocyte apoptosis + redistribute lymphocytes to lymphoid organs
Corticosteroid use –> effect on macrophages?
inhibit peripheral extravasation
What is the effect of corticosteroids on the presentation of the antigen?
presentation is decrease by macrophages and dendritic cells
T-lymphocytes, or thymocytes, are produced in the bone marrow and undergo maturation in the thymus during ……………….
the first trimester of gestation
Procesess of TCR in thymus (4)
beta gene rearragement –> alpha gene rearrgament –> positive selection –> negative selection –> expression of membrane markers and co-stimulatory molecules
What means ,,double negative” T lymphocyte?
Lack of both CD4 and CD8
What is maturation of T lymphocyte?
loss of either CD4 or CD8, because as a result it has to have only one marker
Thymic epithelial cell express …………..
MHC antigens
Thymic epithelial cell express interact with ……… lymphocytes
immature
what happens if lymphocyte in positive selection stage cannot bind thymic receptors?
Are killed or becomes regulatory
What T cells can be activated by dendritic cells?
All types - naive, effector and memory
What’s the different between dendritic and macrophages/pagocytes in regard of MHC II?
Dendritic - express constitutively
Macrophages - inducably
What T cells can be activated by macrophages?
effector and memory [NO NAIVE}
What T cells can be activated by B cells?
All types - naive, effector, memory
How B cells express MHC II?
Constitutively (are always “on”)
What 2 tests measure the function of the complement?
CH50 (total complement)
AH50 (alternative pathway)
Deficiency in the terminal pathway (C3; C5-C9). CH50 and AH50 levels?
Low, low
Lectin complement deficiency? CH50 and AH50 levels?
Normal, normal
Classical cascade deficiency? CH50 and AH50 levels?
Low and normal
Alternative pathway factor B and D deficiency. CH50 and AH50 levels?
Normal, low
What are steps of leukocyte adhesion cascade?
Margination, rolling, activation, tight adhesion, transmigration
What increases expression of endothelial selectins? what step?
cytokines; rolling
What facilitates margination of lymphocytes?
hemoconcentration and decreased wall shear
LAD 2 damage in which lymphocyte adhesion step?
Rolling
What components are on the neutrophils and endothelial cells in the rolling step?
Neutrophils - sialylated carbohydrate groups (Sialyl Lewis X or PSGL-1)
Endothelial cells - L-selectin or E/P-selectin
LAD3 defect, what adhesion step?
Activation
why slow rolling of neutrophils is important?
neutrophils can sample cytokines from inflammed tissue which cause conformational changes in integrins needed for binding.
In which stage neutrophils become firmly attached to the endothelium?
Tight adhesion and crawling
Junction of neutrophils and endothelial cells in tight adhesion and crawling?
Neutrophils - CD18 beta 2 integrins (mac1 and LFA1)
Endothelial - ICAM1
What is CD18 beta 2 integrins (mac1 and LFA1)?
junction molecules on neutrophil to bind ICAM1 and endothelial cell. Tight adhesion and crawling step
Where is found PECAM1?
at the peripheral intercellular junctions of endothelial cells.
LAD 1 defect which step?
Tight adhesion
In rolling stage participate ……………..; in activatio - ……….
cytokines; chemokines
What do cytokines in leukocyte adhesion process?
Induce endothelial expression of selectins
What do chemokines?
lead to integrin activation
Inheritance of LADs?
autosomal recessive
LAD type 1 results from ………
absence of CD18
recurren skin infections without pus + poor wound healing + delayed umbilical deatachment = ?
LAD 1
LAD 1 leads to inability to sinthesize ……….
beta2 integrins Mac1 and LFA1
In LAD 1 are affected …… steps.
tight adhesion and crawling + trasmigration
What is the difference in LAD1 and LAD2 in clinical manifestation?
LAD 1 more severe. LAD2 has no delay in umbilical cord separation and less sever and fewer infections.
What is the similarities and diffecences in LAD1 and LAD3?
same clinical manifestaion: severe recurrent infections, delayed umbilical separation; dif - bleeding complications due to affected beta 3 integrins on patelets.
Which LAD manifest as bleeding?
LAD3
IgG primarily is responsible for …….
recurrent bacterial infections
Ig region that activates complement?
Fc - CH2 (second heavy chain)
Which complement is activated by IgG?
Classical
2 mechanisms of action by IgG?
Complement activation and direct phagocytosis
Direct phagocytosis by IgG. What part of Ig is ligand for phagocytic cell? What part of p.cell binds?
Fc, third heavy chain.
p.cell - Fc receptor (CD16)
Lymph nodes serve as sentinel sites for generation of ……………
the adaptive immune response
What cells display large, unprocessed foreign antigen to draining lymph node?
follicular dendritic cells
Which part of lymph nodes get large, unprocessed antigent?
B cells germinal centers
Who process large antigen to small in lymph node?
B cells
What happens when B cells display small antigen parts to MHC II to naive T?
Naive T cells differentiate to helpers –> secretion of cytokines
What do cytokines produced by T cells in lymph nodes?
promote survival and proliferation of the ANTIGEN SPECIFIC B CELLS –> leads to generation of germian centers.
Why in malignancy there is no pain in lymph nodes?
Because (in case of atypical B cells) proliferation of B cells without antigen stimulation is not assoc. with cytokine release.
What changes (histo) happens in bacterial infection in lymph node?
FORMATION OF GERMINAL CENTERS
Chemotactic agents? (4)
leukotriene B4, 5-HETE, C5a, IL-8
Why there is protein-reach exudate in inflammatory site?
Due to increased vascular permeability
Autoimmune hepatitis. Antibodies?
Smooth muscle cell antibodies
Primary biliary cholangitis. Antibodies?
Antimitochondrial antibodies
What target c-ANCAs?
neutrophil proteinase 3
wegener (granulomatosis with polyangiitis) antibodies?
c-ANCA
What signaling is in interferon pathway?
autocrine/paracrine
What receptors bind interferons on infected cells?
Type I interferon receptors
What happens when interferons reach neighboring cells?
induce transcription of antiviral enzymes
What is the function of antiviral enzymes?
halting protein synthesis of virus
What proteins produce virally infected cells?
RNase L (endonuclease that degrades all RNA in the cell) Protein kinase R (inactivates eIF-2, which inhibits translation initiation)
What do RNase L?
Endonuclease that degrades all RNA in the cell
What do protein kinase R?
Inactivates eIF-2, which inhibits translation initiation
What condition is needed to make active RNase L and Protein kinase R?
double-stranded RNA [viral made]. Must to be, othervise enzymes won’t be active
What forms in the cell of viral replication?
double-stranded RNA
interferons induce expression on the cell surface ………
MHC I
What type interferon in INF gama?
type I
3 functions of interferon gama?
promotes Th1 differentiation
incr. MHC II expression on APC
improves intracellular ability of marcophages
Absence of HLA-DR indicates …..
defective expression of MHC II
MHC I present after antigen …..
cytosolic antigent presented to endoplasmic reticulum
MHC II present after antigen …….
endocytosis with acidified lysosome
How interferon gamma improves antigen presentation?
increases expression of MHC I and II
What enzymes induce apoptosis?
granzymes, perforins
TAP is related to which antigen-presenting receptor?
MHC I
TAP allows to present antigen from …….. to ………
cytosol to ER
Viral infection. MHC I has antigen. What happens next?
Antigen is presented to cytotoxic T cells to TCR and CD8
What part of Ig makes them susceptible to proteases? Which Ig has it?
hinge region;
IgG, IgD, IgA
What is advantages of having hinge region?
Increased flexibility –> Increased avidity (IgA, IgG, IgD)
IgE interacts with the ………. receptor on ……………
Fc epsilon; mast cells
IgG interacts with the ………
receptor on …….. and ……..
Fc gamma; phagocytes/NK cells
IgA interacts with the ……… receptor on …………., ……………, and ………..
Fc alpha; neutrophils, macrophages, and eosinophils.
What helps to IgA and IgM to become multimers? (2)
disulfide bonds between Fc chains and additional amino acid sequence called J chain
What’s the point of hinge region?
flexibility to Fab arms
Longer hinge regions are associated with ……………. Why?
increased antibody avidity; Fab can reach antigens that are farther apart on the bacteria
What Ig do not have hinge?
IgE and IgM
Which Ig is longer?
IgM
Where phagocytic cells bing IgM?
CH4
Hinge region is rich in ………………… and ……….
cysteine and proline
Disadvantage of hinge region?
susceptability to proteases
Affinity vs avidity?
affinity –> stronger single connection; avidity –> bond more antigens
FOXP3 encodes a transcriptional regulator that converts ……………… into ………….
activated CD4 into T reg
What is the function of T reg?
Inhibit immune activation
Expression of FOXP3 drives production of … (3)
it activates cytotoxic T CD 4 and it leads to synthesis of IL-10; TGFbeta
3 functions of IL-10?
inhibits macrophages; downregulates MHC II on APCs; block inflamatory cytokine release from T CD4
2 functions of TGF-beta?
inhibits B-lumphocyte proliferation/activation;
promotes Treg differentiation (eg FOXP3 expression)
FOXP3 –> cytotoxic CD4. Role?
Cytotoxic –> CD4 binds B7 on APC –> less available APC to bind T cells –> less active T cells
Reason if IPEX?
mutation in FOXP3
IPEX manifestation (3)
autoimmune enteritis; eczematous dermatitis; DM1
Inflammatory reaction that occurs shortly after vaccination
reactogenicity
What immune system part is activated in case of acute onset symptoms after immunization?
rapid-onset innate immune response
What drives rapid-onset innate immune response?
pattern recognition receptors on local stromal and local/circulation immune cells (eg marcophages, monocytes, mast cells)
Activated pattern recognition receptions recognize ……………… and it results in ………………………..
eg LPS; release of pyrogenic cytokines
However, manifestations of reactogenicity tend to improve after ……….
24-36 hours after vaccination
Immune checkpoint receptor? What it binds?
CTLA4; CD80/86
MHC I is decreased in …. (2)
Virus-infected and tumor cells
What facilitates granzymes gain access in target cells?
Perforins make holes in the membrane and granzymes via it enters the cell.
Function of perforins?
produce holes in cell membrane
Function of granzymes?
induce cell apoptosis
What is the result of NK cells function on cells?
Target cell undergoes apoptosis.
What surface markers express NK cells?
CD16 and CD56
In athymic patients there is a lack of T lymphocytes, but not ……., because they do not mature in thymus.
NK cells
What activates NK cells? (2)
INF gamma and IL-12
There is antigen in intestinal mucosa. What happens firstly?
B cells move from mesenteric lymph nodes and peyer’s patches to lamina propria uderlying the intestinal mucosa.
Where B cells become fully differentiated in gut?
In lamina propria underlying the intestinal mucose
What bing IgA in mucose after they are synthesized?
pIgR - polymeric immunoglobulin receptor
Where is found pIgR?
basolateral surface of intestinal epithelial cells
What happens to pIgR after IgA is secreted to intestinal lumen?
part is left in endosome where IgA and pIgR was, other part is left attached to IgA and is called secretory component.
Why in hyper IgM syndrome patients are prone to have sinopulmonary recurrent infections?
Lack of IgG –> no opsonization
Why in hyper IgM syndrome patients are prone to have GI infections?
Lack of IgA
Why in hyper IgM syndrome patients fail to thrive?
increased metabolic demands from recurrent infections, as well as nutrient loss from chronic diarrhea
2 functions of ROS?
direct damage to m/o
activate granule proteases
What enzyme is increased in anaphylaxis?
tryptase
triad of dead due to anaphylaxis
Laryngeal edema + hyperinflated lungs + cerebral edema
Why there is hypotension in anaphylaxis?
histamine –> H1 and H2 receptors –> vasodilation
Why there is tachycardia in anaphylxis?
histamine –> H1 and H2 receptors –> inc. catecholamine secretion.
dar bus del hypotension
Why there is bronchoconstriction in anaphyaxis?
Histamine –> H1 receptors
Why there is incr. vascular permeability in anaphylaxis?
Histamine –> H1 receptors
Why there is GI symptoms in anaphylaxis?
Histamine –> H2 receptors –> incr. gastric acid secretion –> contributes symptoms such vomiting, nausea
Why there is pruritus/pain in anaphylaxis?
histamine activate nociceptive receptors
histologic examination of acute serum sickness? (2)
small vessel vasculitis with fibrinoid necrosis and intense neutrophilic infiltration
which complement is decreased in type 3?
C3
why neutropenia may manifest in serum sickness?
serum sickness –> release of C5 = neutrophilic attachement at the site on complex deposition –> neutrophilic marginalization and tissue infiltration
WHy may manifest thrombocytopenia in serum sickness?
active vascular inflmmation –> local platelet consumption –> mild thrombocytopenia
what is the difference between DIC and henoch schonlein purpuros? pathohistology
DIC - fibrin deposits, no vascular inflammation
HSP - may be seen fibrin thrombi, extensive vascular inflammation
