Immunology Flashcards
What is the difference between innate and adaptive immunity receptors?
- PRRs bind to PAMPs or DAMPs while TCRs and IGs bind to antigens
- PRRs are encoded in the germline (limited diversity) while TCRs and IGs are a result of somatic recombination (greater diversity)
- We have <100 different types of invariant receptors for innate immunity and 2 types of receptors, each with millions variations, for adaptive immunity
- Non clonal vs clonal
Which are the 4 important characteristics of acquired immunity?
- Diversity
- Specificity
- Memory: each exposure to antigens generates long lived memory cells
- Self tolerance (characteristic also of innate immunity)
Which are the 5 cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
Which are the hallmarks of acute inflammation?
- Infiltration of leukocytes into tissues
- Hyperemia
- Edema
- Increased vascular permeability
What is the cluster of differentiation (CD) number and why is it important?
It is a number that identifies all structurally defined surface molecules and is used in the developmnet of therapeutic antibodies.
What is the role of histamine in inflammation and allergic reactions?
Mast cells’ granules contain histamine, whose release causes visodilation and increased vascular permeability, thus promoting inflammation.
Why are mast cells important in allergic reactions?
They have Fcεri receptors on their surface that, when bound to IgEs, trigger degranulation of the cell and release of histamine in the blood circulation
Which factor triggers the production of granulocytes and macrophages in the bone marrow?
The granulocyte-macrophage colony stimulating factor
Why can neutrophils be defined as polymorphonuclear leukocytes?
Because their nucleus is segmented into 3 to 5 lobules
What are the long lived tissue resident macrophages and when do they develop?
They are a special type of macrophages found in the tissues that develop at birth and have specialized functions
Describe the classical activation process of macrophages.
This process is triggered by microbial molecules and IFN-γ, released by Th1. These macrophages will secrete chemokines such as Il-1, Il-12, and Il-23 that promote inflammation
Describe the alternative activation process of macrophages.
This process is triggered by Il-4 and Il-13, released by Th2. These macrophages secrete Il-10, an anti-inflammatory chemokine, and are involved in tissue repair
What does it mean that dendritic cells are the only professional APCs?
They are able to activate T cells directly, without the need of en effector T cell.
How is the inital activation of naive cells called?
Priming
Which are the marker and the antigen expressed on HSCs?
CD 34 marker and SCA-1 antigen
What is the peculiarity of the medullary thymic epithelial cells?
Thei present self antigens to developing T cells to gurantee selection of the lymphocytes, thus self tolerance
In what consists the Di George syndrome?
It is a genetic mutation that leads to an impaired thymic development and results in a natal defect of T cells.
In which vessel is the lymph coming from the toracic duct collected?
Superior vena cava
What is the role of fibroblastic reticular cells in the lymph nodes?
Form conducts that transport antigens to the T cells populated zones
What is the role of high endothelial venules?
Bring naive T cells, antigens, and APCs into the populated zones
What is the structural difference between the four families of chemokines?
- CC: 2 adjacent cysteine residues
- CXC: 2 cysteine residues divided by 1 aminoacid
- CX3C: 2 cystein residues divided by 3 aminoacids
- C: 1 cysteine residue
What does GPCR stand for?
Guanosine triphosphate binding protein-coupled receptor
What is the function of the atipical chemokine receptors?
Do not ingage in signaling pathways but inhibit or terminate chemokine responses in cells
How do chemokines recruit circulating leukocytes during inflammatory reactions?
- Increasing the leukocytes adhesion to the endothelium
- Creating a chemokine concentration gradient
In what does the process of margination of the leukocytes consist and why is it important?
When the blood flow decreases the leukocytes will tend to move closer to the vessel lining due to their dimension. This facilitates the binding of the selectin ligands to E- and P-selectins found on endothelial cells
Where is the CD31 protein expressed?
On the surfaces of both leukocytes and endothelial cells
What are the E, L, and R motifs of the chemokines and why are they important?
They represent a sequence of glutamic acid, leucine and arginine located before the cysteine. Only the chemokines that present this particular motifs participate in the migration of neutrophils out of the blood vessels.
For how much time does a single T cell normmaly remain into a lymph node?
24 hours
What is the Toll-Il-1 receptor domain needed for?
Signaling
Why does the innate immune system not react against healthy cells?
- Normal host cells do not produce ligands for the surface immune receptors
- Receptors capable of recognizing host antigens are located in intracellular compartments
- Regulatory proteins expressed by healthy cells prevent activation of innate immune responses
What is the role of the N-terminal effector domain in Nod-like receptors?
Recruitment of proteins to form signaling complexes
What does an MyD88 adaptor protein defect result in?
Severe infection by Streptococcus pyogenic pneumoniae
What does ASC stand for?
Apoptosis associated speck like protein containing a CARD
What is pyroptosis?
Is the apoptosis of a cell, led by the formations of pores in the membrane that alter the osmotic equilibrium of the cell
Which cells secrete alpha defensins and where are they located?
Alpha defensins are secreted by paneth cells in the crypts of the small bowel
What is the role o ILC-1,2, and 3?
- Against viruses
- Against helminths
- Intestinal barrier functions
Why are pentraxins called acute phase reactants?
Because they are elevated in blood during acute inflammatory reactions
What is an example of a receptor for opsonins?
High affinity Fc receptor that recognizes and binds to the Fc portion of IgG antibodies, which are the most efficient system of opsonization
What is the two signal hypothesis?
Activation of lymphocytes requires 2 different stimuli:
1. response to an antigen
2. response to innate immune stimuli. Cytokines produced during this process stimulate proliferation and differentiation of lymphocytes
Why are antibodies also called immunoglobulins?
Because in the electrophoresis of the serum most antibodise fall in the third fastest migrating group of globulins, the gamma globulins, and they all have immunity-conferring properties
How many constant regions can heavy chains have?
3-4
Why is antibody fragmentatiton important?
Antibody fragments perform a more efficient penetration of tissue sections, resulting in improved staining in immunohistochemistry (IHC). They also potentially have higher sensitivity in antigen detection in solid phase applications as a result of reduced steric hindrance from large protein epitopes.
What is an antiallotypic antibody?
An antibody able to recognize allotypic determinants of another antibody
What is an antiidiotypic antibody?
An antibody able to recognize idiotypic determinants of another antibody
How long is the half life of IgGs compared to the one of other Igs?
23 days instead of 2-6.
What does polivalency mean?
Is the presence of many epitopes on the same molecule
What is the antibody repertoire?
Is the total collection of antibodies with diverse specificity
Why are adjuvants needed in a vaccine?
Because APCs activity is enhanced by exposure to microbial products, therefore in the case of administration of pure antigens we need to provide for example a killed mycobacteria in order to elicit the immune response.
What do Rag-1 and Rag-2 stand for?
Recombinant activation gene 1 and 2
What is the cause of X-linked agammaglobulineamia?
Mutations in the gene encoding for Bruton’s tyrosine kinase that lead to failure in B celll maturation
On which type of cells is the self peptide-self mhc complex needed for positive selection of Thymocytes expressed?
Cortical thymic epithelial cells
What causes the Autoimmune polyendocrine syndrome?
It is caused by a mutation in the gene encoding AIRE and consists i the impossibility to perform negative selection
What does ICOS stand for?
Inducible costimulator CD278
Which inflammatory diseases are caused by excessive reaction of T helper cells?
- An excessive reaction of Th1 and Th17 cause autoimmune diseases associated with inflammation.
- An excessive reaction of Th2 lead to allergic reactions.
What is the JOB syndrome and what causes it?
It is caused by a mutation in STAT-3 transcription factor that results in defective Th17 development, causing increased susceptibility to cutaneous fungal and bacterial infections
What is the JOB syndrome and what causes it?
It is caused by a mutation in STAT-3 transcription factor that results in defective Th17 development, causing increased susceptibility to cutaneous fungal and bacterial infections
To the pathogenisis of which inflammatory diseases do Th17 cells contribute?
- Psorias
- IBD
- Rheumatoid arthritis
- Multiple sclerosis
What is the peculiarity of HIV infections, regarding CD8 and CD4 T cells?
CD8 CTls are able to kill the cells infected by the virus but this infects and eliminates CD4 Th cells, required for activation of CD8 CTLs.
In fact, AIDS is defined by CD4 count < 200 cells per microL of plasma.
How can the destruction of infected cells cause tissue injury in HBV and HCV?
The infected liver cells are killed by host CTLs, thus causing tissue injury.
What is the hapten-carrier effect?
In this process, a non-immunogenic molecule (hapten) needs to bound to a carrier protein in order to produce an immunogenic effect in a B cell. Once the hapten-protein conjugate complex is recognized, it is phagocytosed and the carrier is trimmed and presented on Class II MHC for antigen recognition by CD4+ T helper cells. Once activated the T helper cell will stimulate the production of anti-hapten antibodies by the B cell.
What does a mutation in the CD40L gene cause?
It causes the X-linked hyper IgM syndrome, characterized by defects in isotype switching, affinity maturation and cell-mediated immunity.
Why during immune responses B cells require antigens with an increasing affinity in order to survive?
Because the amount of available antigens decreases during immune responses
A polymorphism in which gene does result in an increasd susceptibility for systemic lupus erythematosus?
Fc gamma R2B gene polymorphism, which causes an uncontrolled antibody production
Which are the Ig domains recognized by the C1 protein of the complement system at the beginning of the classial pathway?
The Ch2 domain of IgG or the Ch3 domain of IgM.
What is the cause of the autosomal dominant inherited disease called hereditary angioedema?
C1 inhibitor deficiency
What is the cause of paroxysomal nocturnal hemoglobulinuria?
Deficiency of the enzyme required for production of the decay accelerating factor in HSC.
Why CR1, membrane cofactor protein and decay accelerating factor can inhibit complement activation only in host cells?
Because they are produced only by mammalian cells and not by microbes.
What are the anaphylatoxins and what is their function?
They are C3a, C4a, and C5a complement proteins and they are able to cause degranulation of vasoactive and inflammatory products, such as histamine
How are neonatal mammals protected from infections?
Through maternal antibodies transported across the placenta into fetal circulation, and by antibodies found in ingested milk transported across the gut epithelia (transcytosis)
How can microbes evade the complement system?
Either by recruiting host complement regulatory proteins or by producing specific proteins that mimic human complement regulatory proteins.
What are neoantigens?
Self antigens that underwent structural changes or enzymatic modifications caused by cell stress or injury, and therefore it is more difficult for our organism to clear them during central tolerance processes.
