Microbio Week 5 & 6 - Online Lectures (Exam 2) Flashcards
What is the main difference between the immune response triggered by extracellular bacteria versus intracellular bacteria?
T cell-mediated immunity is absolutely required for clearance of intracellular bacteria not extracellular bacteria.
Althouth viruses are obligate intracellular pathogens, the immune response elicited is different compared to intracellular bacteria. Chose the correct statement characterizing the immune response against virus.
Viruses elicit a poor antibody response.
Viruses do not involve CTL-mediated killing of infected cells.
Viruses induce a strong production of IFNα that induces an antiviral state.
Viruses induce a strong production of IFNγ that induces an antiviral state.
Viruses induce eosinophil degranulation.
Viruses induce a strong production of IFNα that induces an antiviral state.
What cells of immune response and outcome are associated with…
Intracellular bacteria
Th1-activation of macrophages
What cells of immune response and outcome are associated with…
Virus
IFNα−inhibition of viral replication
What cells of immune response and outcome are associated with…
Helminths
Th2-eosinophil degranulation
What cells of immune response and outcome are associated with…
Extracellular fungus
Th17-neutrophil recruitment
Which of the following mechanisms describes how autoantibodies can kill self cells in a Type II Hypersensitivity response that results in autoimmune disease?
Autoantibody-mediated opsonization and phagocytosis of self cells.
Destruction of self cells mediated by inflammatory cytokines.
Destruction of self cells via T cell-mediated cytotoxicity.
Autoantibody-mediated immune complex deposition that directly kills self-cells.
Autoantibody-mediated signaling through cell surface receptors induction of abnormal physiologic responses.
Autoantibody-mediated opsonization and phagocytosis of self cells.
What is one of the characteristics of autoimmunity?
Genes are not involved in autoimmunity development.
Male are at greater risk for developing autoimmune diseases.
Immune cells mount an immune response against self-antigens.
Infectious agents play no role in the initiation of autoimmune diseases.
Immune cells mount an immune response against self-antigens.
What is the difference between primary and secondary immunodeficiencies?
Primary = genetic defects
Secondary = non-genetic
Which disease corresponds with defective production of reactive oxygen intermediates by phagocytes?
Chronic granulomatous disease
Which disease corresponds with absent or deficient expression of B2 integrins causing defective leukocyte adhesion-dependent functions?
Leukocyte adhesion deficiency - 1
Which disease has absent or deficient expression of leukocyte ligands for endothelial E or P selectins?
Leukocyte adhesion deficiency - 2
Which disease has defective lysosomal function in neutrophils, macrophages, and dendritic cells?
Chediak-Higashi syndrome
MOA of leukocyte adhesion deficiency - 1
Mutation in gene encoding B chain of B2 integrins -> can’t bind to endothelium
MOA of leukocyte adhesion deficiency - 2
Mutation in gene encoding a protein required for synthesis of sialyl-Lewis X component of E and P selectins
Severed combined immunodeficiency (SCID) affects both ________ and ___________________ immunity
humoral; cell-mediated
(both forms of adaptive immunity)
SCID can occur due to defects in… (4)
Cytokine signaling
Nucleotide salvage pathways
VDJ recombination
Thymic development
Which SCID has decreased T cells but normal or increased B cells?
X-linked SCID
MOA of X-linked SCID
Y cytokine receptor mutation
Defective T cell maturation due to lack of IL-17 signals
Which SCID has a progressive decrease in T and B cells?
Autosomal recessive SCID
MOA of autosomal recessive SCID due to ADA or PNP deficiency
ADA or PNP deficiency leads to accumulation of toxic metabolites
Which SCID has decreased T and B cells and reduced serum Ig?
Autosomal recessive SCID due to other causes
MOA of autosomal recessive SCID due to other causes
Mutations in RAG genes or other genes involved in VDJ recombination or IL-7R signaling
Which antibody deficiencies are due to a pre-B receptor checkpoint defect?
Agammaglobulinemia (X-linked and autosomal recessive forms)
Person who has selective IgA deficiency is deficient in
IgA
Person who has common variable immunodeficiency has decreased ___ cell numbers
B
Describe the X-linked form of Hyper-IgM syndrome
Defect in T helper cell-mediated B cell, macrophage, and dendritic cell activation
Mutation in CD40L
Describe the autosomal recessive form of Hyper-IgM syndrome
Defect in T helper cell-mediated B cell, macrophage, and dendritic cell activation
mutation in CD40
Bare lymphocyte syndrome
Defective MHC Class II expression -> decreased CD4 T cells
If someone has MHC Class I deficiency which cells will be reduced
CD8 T Cells
Wiskott-Aldrich syndrome
Defective T cell activation
DiGeorge syndrome has decreased _____ cells
T
MOA of immunodeficiency caused by HIV
Direct toxic effects of infection on CD4 T cells
Plasma membrane is compromised -> lethal influx of Ca2+
Describe the immune response to HIV
CD8 T cells expand but provide limited protection
CD4 T cells help CD8 T cells
Mechanisms of immune evasion by HIV
High mutation rate
Downregulates Class I expression
Oral manifestations in AID pts receiving treatment
HPV virus
Caries
Any molecule produced in the body that has antigenic properties
Self-antigen
Two main adaptive immune response mediators
T cells
Autoantibodies
Delayed-type hypersensitivity (DTH) response is primarily mediated by __________ cells
Th1 CD4 cells
Which types of hypersensitivity can lead to autoimmune diseases?
Types II, III, and IV
In hemolytic anemia there is destruction of RBC’s.
Which Type II mechanism is responsible?
Complement dependent
What is the target of complement/Fc receptor mechanism (ADCC) in Type II hypersensitivity?
TISSUE self-antigens
Pemphigus vulgaris is a rare skin disorder involving blisters in the mucus membranes.
Which Type II mechanism is responsible?
Auto-antibodies against proteins in epidermis - actual mechanism is unknown
What is the target of autoantibody-mediated alteration of physiological responses?
Receptors
Name an autoimmune disease caused by Type III hypersensitivity
Systemic Lupus erythematosus
What is lupus caused by?
immune complex deposition
-> complexes cause vasculitis, rashes, arthritis
What are the antigens involved in lupus?
nucleic acids, histones, ribosomes
Which cells mediate Type IV hypersensitivity?
T cells
What do T cells recruit to cause tissue destruction in Hashimotos (Type IV)?
Lymphocytes and macrophages
What leads to decreased TH production in Hashimotos (Type IV hypersensitivity)?
Autoantibodies interfere with iodine uptake
What cells target beta cells that produce insulin in Type I diabetes (Type IV hypersensitivity)?
CD8 cells
(CD4 cells are also involved)
What cells infiltrate the brain and spinal cord, causing neurologic dysfunction, in Multiple Sclerosis (Type IV hypersensitivity)?
Activated T cells and macrophages
Causes of autoimmune disease
Genes, immune regulation, environment
Autoimmune diseases are most strongly genetically linked to specific _______ genotypes.
MHC
-> more so MHC Class II
Which environmental factors can play a role in autoimmune disease?
hormones
infection
traumatic injury
T/F: Males are at greater risk of developing most autoimmune diseases
False!! Females are at greater risk
What are some proposed mechanisms for initiation of autoimmunity by trauma or infection? (3)
1) release of sequestered antigen
2) activation/migration of APC in target organ
3) molecular mimicry
Describe the 1st and second “hits” of the pathogenic mechanism of autoimmune disease
1: genetic susceptibility
2: infection, injury
What is the goal of autoimmune disease treatment?
Downregulate autoantigen-specific immune response while allowing protective immune response to be functional
-> this is very difficult to achieve
Therapeutic strategies for autoimmune diseases
Tx with antagonists against pro-inflammatory mediators
(ex: cytokines, chemokines, co-stimulatory molecules, integrins, T/B cell signaling molecules)
What are the following describing?
1) prevents virally-induced tumors by controlling viral infection
2) prevents development of chronic inflammatory environments
3) eliminates tumors directly through immune surveillance theory
Primary roles of the immune system in the prevention of cancer
Some viruses encode _______ that can directly induce tumor development
oncogenes
Examples of viral cancers
HPV
HTLV-1
Epstein Barr virus
Herpes (HHV8)
What is this describing?
Immune system identifies and eliminates early stage cancer before it has the chance to grow
Immune surveillance theory
Why do immune responses frequently fail to prevent growth of tumors? (3)
1) tumors are derived from host cells
2) rapidly growing
3) special mechanisms to evade host immune response
Primary immune responses to tumors (5)
tumor specific CD8 T cells
tumor specific CD4T cells
tumor specific antibodies
NK cells
M1 macrophages
What is the principal mechanism of tumor immunity?
CD8 T cells
CD8 T cell induction requires cross presentation by ____________ cells and frequently requires _______ cell help
dendritic; CD4 T
Tumor specific CD4 T cells produce ____ and ______ to increase Class I expression and activate macrophages
TNF and IFNgamma
NK cells attack cells with decreased
MHC Class I
T/F: M2 macrophages can help with tumor regression.
False! They are bad and enhance tumor progression
Why are tumors bad antigen-presenting cells? (3)
1) reduced immunogenicity
2) no adhesion molecules
3) no co-stimulatoy molecules or MHC Class II molecules
How do tumor cells exhibit reduced immunogenicity?
They can lose their antigens spontaneously or they can lose MHC Class I molecules
How can tumors evade the immune system? (4)
1) attract inhibitory cells
2) express immunosuppressive factors
3) inhibit NK cell activity
4) block antibodies
How do monoclonal antibodies treat cancer?
they can directly eliminate the tumor cells or interfere with tumor growth
Two examples of immune adjuvants
Bacilli Calmette-Guerin
TLR 7 agonist
Two examples of cytokine therapy
IL-2
TNF
both are pretty toxic tho
Examples of prophylactic immune therapy
Vaccines against oncogenic microorganisms
Antibiotic treatment
First FDA approved therapeutic vaccine for prostate cancer
Provenge
Why have immunotherapies not been as effective as we would expect?
Negative regulators of immune response Interference
Examples of negative regulators of immune response (3)
CD4+CD24+ regulatory T cells
CTLA-4
PD-1
What are some of the “new” strategies for tumor immunotherapy?
Down-regulatory regulatory T cells
Inhibit negative signaling by CTLA-1 and PD-1
_____________ blocks negative signaling from CTLA-4
Ipilimumab
______________ blocks negative signaling from PD-1
Nivolumab
