Immunology Flashcards
IL 2 is produced primarily by _____
Helper T cells
What is the major growth factor for T lymphocytes (Interleukin ___)
IL2
______ binding to t cell receptors stimulates the secretion of IL2 and the expression of IL2 receptors
Antigen
IL2 promotes growth and differentiation of T and B cells as well as activates ____ and _____ .
Natural killer cells
Monocytes
What are IL2 anticancer effects as treatment for metastaticmelanoma and renal cell carcinoma
IL2 increases natural killer cell and T cell activity
Why is the H. Flu vaccine administered as a capsular polysaccharide from H. Flu conjugated to a tenanous toxoid
Polysacharides only elicit B cell responses which do not elicit memory resulting in short relative duration of immunity
Polysaccharide-protein conjugate vaccine ellicits a B and T cell response –> memory -> longer immunity
Why are polysacharide vaccintions not effective in children <2?
They have immature humoral immunity (polysaccharide capsule rovokes an antibody-mediated immune response)
T-cell dependent antigen stimulates which two effects that increase the efficacy of protein conjugated vaccine compared to polysaccharide capsule vaccines?
T cell dependent stimulation of B lymphotcytes
Production of memory B lymphocutes
Type I (alpha and beta) interferons are synthesized by most human cells in response to _____
Viral infections
Secrete alpha and beta type one interferons bind receptors on __________
Neighboring cells (paracrine and autocrine signaling)
Binding of alpha and beta interferons to interferon I receptors leads to the transcription of what enzymes?
Antiviral enzymes (halt protein synthesis): RNase and protein kinase R
Antiviral enzymes transcribed by alpha and beta interferon activity during viral infections become active only in the presence of ______
Double stranded RNA
Effect of alpha and beta interferons during viral infection:
Supress viral replication by haltingprotein synthesis
Promote apoptosis of infected cells
Each molecule of MHC class I protein consists of __________ and an associated beta 2- microglobulin
Single heavy chain
Each molecule of MHC class I consists of a single heavy chain and an associated _____________
Beta 2 microglobulin
Heavy chains are highly _______ which allows them to present a large variety of antigens
Polymorphic
Viral polypeptides are processed in the host cell and combined with MHC class I in the __________
Endoplasmic reticulum
Structural features of MHC class II include ____ and ______ polypeptide chains
Alpha and beta
MHC class ______ has alpha and beta polypeptide chains
II
MHC class I is found on the surface of what cell type
All nucleated cells
MHC class II is found on what cell type
Antigen presenting cells (B cells, macrophages, dendritic cells, langerhans cells
What type of antigens are presented by MHC class I
Virus and tumor proteins
Where are antigens that are presened on MHC class I molecules processed
Cytoplasm
What antigens are presented on MHC class II molecules
Bacteria
Where are antiges presented on MHC class II molecules processed
They are phagocyosed and digested by lysosomes within which antigen binds to MHC II
Antigen presentation by an MHC class I molecule results in
Apoptosis of hte presenting cell
MHC class I present endogenous antigens to ___ cells
Cytotoxic T cells (CD8)
How do reactive T lymphocytes appear differetly than normal T lymphocytes
reactive are larger
Abundunt cytoplasm
Scalloped edge
Reactive lymphocytes are activated, pathogen-specific _____ and ______that form in response to certain intracellular infections
Cytotoxic T cells
Natural killer cells
Reactive lymphocytes are associated to certain intracelullar infections such as HIV, CMV, and toxoplasmosis but are particularly linked to
Infectious mononucleosis (primary Epstein-Barr virus) (Reactive lymphocytosis is a diagnostic feature of infectious mononucleosis)
Reactive lymphocytes are effector cells that contain cytotoxic granules composed of ____ and _____
Perforin
Granzymes
Function of perforin
Creates holes in the infected cell’s membrane
Granzyme function
Enter the cytoplasm of infected cells and trigger cell death
History of recurren respiratory infections and dextrocardia suggest what diagnosis
Kartagener syndrome (primary ciliary dyskinesia (PCD))
Mode of inheritence for kartagener syndrome
Autosomal recessive
Eukaryotic flagella and ciliar are composed of central core known as the _______
Axoneme
The axoneme of flagella an motile cilia consists of a circular array of microtubule doublets surrounding 2 central microtubules called what kind of arrangement
9 + 2 arrangement
The axoneme of flagella and motile cilia is anchored to the cell by a _______
Basal body
Each microtubule doublet in cilia and flagella have A and B subunits that are connected to adjacent doublets via
Dynein arms
What is the function of dyenin arms?
Contain ATPase that generates energy to slide microtubules past each other –> ciliary movement
Failure of dyenin arm to develop normally can result in ______
Primary ciliary dyskinesia
Ankylosing spondylitis has increased production of what cytokines
Il-17
TNF alpha
Prostaglandins
Ankylosis sonylitis has increased risk with what HLA?
HLA-B27
Pain presentation of ankylosing spondylitis
Back and buttock pain that is relieved with exercise and worse at night
Clinical findings in ankylosing spondlitis
Redced chest expainsino, enthesitis (tenderness at tendon insertion sites), dactylitis (swelling of fingers and toes), anterior uveitis
What is “bridging syndesmophytes”? (A finding in ankylosing spondylitis)
Ossification at vertebral body margins (“bamboo spine”)
Where is ankylosing spondylitis thought to originate from? (Whats the cause)
The gut: defects in mucosal barrier and an abnormal intestinal microbiome –> inflammation
IL-17 mediates an inflammtory response via which cell type
Innate lymphoid cells and helper T cells (Th1, Th17)
IL-17 stimmulates production of which additional inflammatory factors
TNF alpha and prostaglandins
What is the effect of high IL-17, TNF-alpha, and prostaglandings in the joints of someone with ankylosing spondylitis?
Bony erosions and abnormal bone growth
Bone erosion –> subchondral sclerosis –> ankylosis (bony fusion
Treatment for ankylosing spondylitis
NSAIDS (inhibit prostaglandin formation)
Anti-TNF alpha agents (etanercept, infliximab)
Anti-IL-17 agents (secukinumab)
Neoantigens are displayed on MHC class ____ molecules and subsequently recognized by _____ cells
I
Cyotoxic T cells
Over expression of programmed death ligand 1 (PD-L1) on cancer cels surface binds PD-1 receptor on T cells to what result
Supresses T cells ability to induce apoptosis: “T cell exhaustion”
Pembrolizumab mechanism of action
Monoclonal antibody that blocks PD-1 (restores cytotoxic t cell response (disinhibition) in cancers that overepress PD-L1)
Cells and humoral components involved in type I hypersenstivity reactions:
IgE
Basophils
Mast cells
Humoral components and cellular components involved in type II hypersensitivity reactions
IgG and IgM autoantibodies Complement NK cells Eosinophils Neutrophils Macrophages
Goodpasture and autoimmune hemolytic anemia are examples of what type of hypersensitivity reaction?
Type II (cytotoxic)
What humoral and cellular components are involved in type III hypersenesitivity responses
Deposition of antibody-antigen complexes
Complement
Neutrophils
Serum sickness, PSGN, and lupus nephritis are examples of what type of hypersensitivity reaction
Type III (immune complex)
anaphylaxis and allergies are examples of what type of hypersensitivty reaction
Type I (immediate)
Type 4 hypersensitivity reactions include what humoral and cellular components
T Cells
Macrophages
(No humoral components)
Contact dermatitis and tuberculin skin test are examples of what type of hypersensitivity reaction
Type 4 (delayed type)
What changes occur on initial exposure to an allergen in a patient who will eventually develop an allergic response
Antibody class switching to IgE which bind IgE receptors on basophils (blood) and mast cells (tissues)
What changes does a second exposure to an allergen illicit
Allergen interacts with cell bound-specific IgE which crosslik and cause degranulation of mast cells
Major antibody for mucosal immunity:
IgA
Plasma cells synthesize IgA linked by ______
J chain
IgA dimers bind to ________ on basolateral surface of intestinal epihelial cells and undergo transcytosis.
Polymeric immunoglobulin receptor (pIgR)
As the linked IgA dimer is released into the intestinal lumen, a portion of pIgR remains attached to the antibody (called _______ )
Secretory component
Live attenuated vaccines generally produce a ________ immune response than killed vacines by acting as a persistent stimulus that better activates helper and cytotoxic T cells
Stronger
Live attenuated oral vaccine will have a significantly higher IgA response in the __________ than a inactivated injected vaccine
Oropharyngeal and intestinal mucosa
Increase in mucosal IgA offers immune protection where
At site of viral entry by inhibiting attachment to intestinal epithelial cells
Name for the live attenuated oral poliovirus vaccine
Sabin
Name for the inactivated poliovirus vaccine
Salk
In _______________ donor T cells from the graft migrate into host tissues where they recognize host MHC antigens and become sensitized —> CD4 and CD8 donor cell activation —> destruction
Graft versus host disease (GVHD)
Graft versus host disease is a condition that usually occurs after allogeneic bone marrow transplantation but can occur following transplantation of organs rich in ________
Lymphocytes (or transfusion of non irradiated blood)
Patients affected by GVDH are generally severely ______ which allows donor T cells to survive
Immunodeficient (due to primary disease process or result of immunosuppressive therapy)
What organs are most commonly affected by graft versus host disease
Skin (maculopapular rash, especially palms and soles of feet) GI tract (diarrhea, intestinal bleeding, abdominal pain) Liver (abnormal liver function tests)
Sialyl lewis X or PSGL-1 bind what on neutrophils to induce rolling in leukocyte accumulation
L-selectin
Selectins are involved in which phase of leukocyte accumulation
Rolling
Integrins (activated by chmokines) change to high affinity state in which phase of leukocytosis adhesion cascade
Activation
Neutrophils bcome firmlia attached to the endothelium via binding of ________ to ________ on endothelial cells
CD 18 beta 2 integrins (MAC-1 and LFA-1)
Intercellular adhesion molecule 1 (ICAM-1)
Transmigration of the nutrophils is accomplished by squeezing between the cells via integrin attachments and adherence to ______________
Platelet endothelial cell ahesion molecule 1 (PECAM-1)
In ____________ disease leukocytes cannot leave the vasculature to migrate into tissue under conditions of inflamation
Leukocyte adhesion deficiency (LAD)
LAD type 1 is the absence of _______
CD18
In LAD type 1, there is an absence of CD18 which leads ot inability to synthesize _________ , affecting tight adhesion, crawling, and transmigration
Beta 2 integrins: MAC-1 and LFA1
Clinical manisfestation of LAD type 1
Recurrent skin infections without pus formation
Delayed detachment of umbilical cord
Poor wound healing
LAD type 2 is due to impaired fucosylation of sialyated carbohydrates ligands which prevents binding to ______
Selectin
LAD 3 is due to impaired cytokine signaling which prevents ______ activation
Integrin
What in the HBV vaccine generates protective immunity against the virus?
Recombinant HBsAg
How are people with the HBV vaccine immune?
Patient will generate anti-HBs antibodies which bind circulating viral partcles and prevents attachment ot and penetration of hepatocytes
During sensitization to an allergen, the antigen is presented on MHC II which activates what cell type
Helper T cells
During sensitization to an allergen, helper T cells are activated by allergen antigen on MHC II and epithelium release of ______ and _______ to become a Th2 cell
IL-25 and IL-33
Th2 cells secrete what cytokines to induce B cell classs switching to IgE produciton
IL-4, IL-13
Which immune cells are responsible for the destruction of cells with decreased or absent MHC class I proteins on their surface
NK cells
Cells markers on NK cells
CD16 or CD56
Do NOT express CD 4, 8, or3
Do NK cells require the thymus for maturation?
No (present in athymic patients)
Do NK cels have antigen specific activities/require antigen for activation?
No
What cytokines activate NK cells
Interferon gamma and IL-12
Duing a parasitic infection, Th 2 induces eosinophil prolferation via release of what cytokine
IL-5
How are hemilinths destroyed by the immmune system?
Antibody dependent cell mediated cytotoxiity
IgG and igA antibodies coating the helminth bind the Fc receptors on eosinophil cell surface –> degranulation and release of cytotoxic proteins and reactive oxygen intermediates o destroy the paraste
What cyctotoxic protein is released from eosinophils
Major basic protein
What cell contributes to the late phase of a type 1 hypersensitivity reaction
Eosinophils (release prostaglandins, leukotrienes, and cytokines)
How does macrophage response to TB infection change over a few weeks once infected?
Initially the pathogen escapes phaolysosome s in alveoar macrophages
After a few weeks APCs start to display mycrobacterial antigens on MHC II and release IL-12 –> Th1 differentiation –> interferon gamma secretion –> macrophage activation –> fully maturephagolysosomes destroy intracellular bacteria and differentiat e into epitheliooid and langhans giant cells to surround extracellular bacteria forming a granuloma
What is released from APCs to differentiate naive CD4 cells into Th 1 cells
IL-12
What is released from Th1 cells to activate macrophages
Interferon gamma
How do granulomas limit myobacteria proliferation
Their acidic and hypoxic central environment limits proliferation (but usually does not eliminate the infection)
Tuberculin skin test is what type of hypersensitivity reacion
Delayed type/T-cell mediated
Why may some people have a negative tuberculin skin test if they were recently exposed to TB but a positive test a few weeks later
The cell mediated response takes several weeks to form
What is a Ranke complex
Calcified lower lobe nodule and ipsilateral hilar lymph node
Often seen in TB patients even when asymptomatic
Takes several months to form
What tranfusion reactions occur minutes to hours after transfusion
Allergic and acute hemolytic
What causes an allergic transfusion reaction
Preformed antibodies against blood product component
What causes an acute hemolytic transfusion reaction
ABO incompatibility (often clerical error)
How does an allergic transfusion reaction present
Anaphylaxis and urticaria within minutes-hours of transfusion
How does acute hemolytc transfusion reaction present
Fever, flank pain, hemoglobinuria, DIC, positive Coombs test minutes - hours after transfusion
How does a febrile nonhemolytic transfusion reaction present
Fever and chills hours after transfusion
What causes a febrile non hemolytic transfusion reaction
Cytokine accumulation during blood storage
How does a transfusion-related acut lung injury present following a blood transfusion
Respiratory distress and bilateral pulmonary edema hours after trnsfusion
How does delayed hemolytic transfusion reaction present
Often asymptomatic, labratory evidence of hemolytic anemia, and + Coombs test days-weeks following blood transfusion
What is the cause of transfusion related acute lung injury
Donor antileukocyte antibodies
What is the cause of delayed hemolytic transfusion reaction
Anamnestic antibody response
What is required for a patient to have an anamnestic response (delayed hemolytic transfusion reaction) to a blood transfusion
A previous exposure to a foreign minor red blood cell antigen (non-ABO) such as pregnancy, prior blood transfusion, or intravenous drug use
Activation of Fas receptor leads to what?
Extrinsic pathway of apoptosis
Upon binding Fas ligand, Fas receptors trimerize to allow their death domains to form a binding site for ______
Fas-associated death domain
Receptor bound Fas associated death domain (FADD) stimulated activation of __________
Initiator capsoses 8 and 10
Initiation caspases 8 and 10 begin an activaion cascade culminating in the activation of _________
Executioner caspases 3 and 6
Executioner caspases 3 and 6 initiate terminal processesof apoptosis such as:
Cleavage of DNA
Fragmentation of the nucleus
Organelle autodigestion
Plasma membrane blebbing
What cells express Fas receptors
T lymphocytes
Activation-induced cell death is apoptosis of T lymphocytes due to constant presence of what stimulating self-antigens
Fas L
Mutations involving Fas or FasL result in excessive accumulation of ____________ and development of autoimmune diseases such as systemic lupus erythematosus
Autoreactive T-cells
Is parapneumonic effusion fluid in the pleural space exudative or transudative
Exudative
Why do infections and inflammtory tissue injuries cause pleural effusion
They increase vascular permeability (allows protein rich exudates to cross)
What is the most potent chemotactic eicosanoid
Leukotriene B4
Which leukotrienes cause bronchospasms and increas bronchial mucus secretion, playing a large role in asthma pathogenesis
LTC4, LTD4, LTE4
5-HETE (leukotriene precursur), C5a, and IL-8 are all important __________ agents
Chemotactic
What type of necrosis is seen in TB
Granulomas with caseating necrosis
In TB, granuloma with caseating necrosis consist of what cells
Large epithelioid macrophages
The most specific cell surface marker of the monocyte-macrophage cell is _______, which binds to bacterial lipopolysaccharide
CD14
The most specific cell surface marker of the monocyte-macrophage cell lineage is CD14, which binds to bacterial _________
Lipopolysaccharide
The caseating granulomas of tuberculosis are almost alway surrounded by large epitheliod macrophages with __________ cytoplasm
Pale pink granular
Classic features of melanoma: (5)
Asymmetry Border irregularity Color varegation Diameter > 6 mm Evolution over time (A, B, C, D, E)
What is color variegation (common feature of melanoma)
Different colors representing different areas of activity within the tumor
In color variegation in melanoma, what do red areas indicate
Vessel ectasia (dilation) and local inflamaiton
In color variegation in melanoma, what do brown or black areas indicate
Flared areas along the border due to advancing, neoplastic melanocytes
In color variegation in melanoma, what do white and gray areas indicate
Cytotoxic lymphocytes recognize tumor antigens (melan-A) and induce apoptosis –> malignant melanocyte regression
Pembrolizumab mechanism of action
Programmed cell death receptor 1 inhibitor (PD-1 inhibitor)
Tryptase is an enzyme that is relatively specific to _____ cells
Mast
Elevated serum levels of tryptase are oten used to support clinical diagnosis of__________
Anaphylaxis
What is the receptor found on mast cells and basophils that normally binds the Fc portion of circulating IgE, coating the cell with various antigen specific IgE molecules
High affinity IgE receptor (Fc epsillon RI)
Crosslinking of multiple membrane bound IgE antibodies by a multivalent antigen results in ____________, causing degranulation and the release of preformed mediators that initiate an allergic response
Aggregation of the high-affinity IgE receptor
IgE class switching is initiated by ____ and _____ which is released by the Th2 cells
IL-4, IL-13
IgE class switching is initiated by IL-4 and IL-13 which are released from which cells
Th2
Cell mediated adaptive immunity (targetting intracellular pathogens) and type IV (delayed type) hypersensitivity reactions mainly involve Th___ cells
Th1
Excess of what cell type my underli the pathogenesis of asthma
Th2 (relative to Th1)
Th2 secretes IL- 5 which activates _____
Eosinophils
Th2 cells release ____ which activates eosinophils
IL-5
