Exam 4 Flashcards
What are hypersensitivity/allergic reactions?
Adaptive immune responses to innocuous environmental antigens
What are allergens?
Antigens that cause allergic reactions
What is IgE involved in?
Defense against parasites and type I hypersensitivity reactions
In developing countries, what do IgE responses do?
Protect against helminth infections
In developing countries, what is the prevalence for allergies?
Low
In developed countries, what are IgE responses responsible for?
Type I hypersensitivity reactions
What are IgE responses directed at in developed countries?
Innocuous environmental antigens
Where are mast cells located?
In association with blood vessels and at epithelial surfaces
What does the primary exposure to an antigen result in?
Activation of Th2 cells and class switching to IgE
What does IgE bind to and do?
Binds to mast cells and sensitizes the mast cell to the allergen
What is the process for activation of IgE mediated type 1 allergic reactions? (4)
First exposure to pollen
Extraction of antigen
Activation of antigen-specific T cells
Production of IgE and its binding to mast cells
What happens due to the fact that mast cells are long lived?
They accrue a diversity of antibodies
What does the cross-linking of mast cell receptors result in?
Degranulation
What do mast cells responses act to? (2)
Physically expel the pathogen
Recruit and activate other effector cells
What are eosinophils home to?
Sites of allergic reactions
When are eosinophils produced in greater numbers?
During immune stimulation
What are 2 effector functions of eosinophils?
Release cytotoxic molecules to damage pathogen
Amplify inflammatory response
What can the response of a sensitized individual to intradermal allergen or inhaled allergen be divided into?
The immediate reaction and the late-phase reaction
What is the immediate reaction due to?
Release of pre-formed mast cell inflammatory mediators
What do edema and reddening of skin result in during the immediate reaction?
Wheal and flare reaction
What do edema and constriction of smooth muscle result in during the immediate reaction?
Airway narrowing
What is the late phase reaction caused by?
Continuous synthesis and release of inflammatory mediators
What happens with edema in late-phase reaction?
Increased area and degree
What happens with airway narrowing in late-phase reaction?
Second phase
What does the symptoms of IgE mediated allergic reactions depend on?
The route of entry of the allergen
What are the 5 types of reactions?
Systemic anaphylaxis Acute urticaria Seasonal rhinoconjunctivitis Asthma Food allergy
What is the route of entry for systemic anaphylaxis?
Intravenous
What is the route of entry for acute urticaria?
Through skin
Systemic
What is the route of entry for seasonal rhinoconjunctivitis?
Contact with conjunctiva of eye and nasal mucosa
What is the route of entry for asthma?
Inhalation leading to contact with mucosal lining of lower airways
What is the route of entry for a food allergy?
Oral
What are features of allergens that promote activation of Th2 cells that drive IgE production?
Allergens are soluble proteins carried on dry particles
Usually derived across mucosal tissue at low dose
Several allergens are proteases
What is allergen capable of on contact with mucus?
Diffusing into mucosal tissue
What do allergens contain?
Peptides that can bind MHC class II
What is predisposition to allergic disease influenced by?
Genetic and environmental factors
What is atopy?
A predisposition to mount IgE responses to environmental allergens
How many people may be atopic?
Up to 40% of European and North American
What is the hygiene hypothesis?
Main candidate environmental factor is changes to exposure of infectious disease in early childhood
What does excess hygiene result in?
Less early exposure to common environmental microbes
What may less early exposure to common environmental microbes do?
May make the body less efficient at producing immune-modulatory responses
How can allergens be directly injected into the blood?
Via insect/animal bites
Can allergens be absorbed into the blood stream?
Yes
What do allergens bind to?
Mast cells in connective tissues around the body that surround blood vessels
What are symptoms of systemic anaphylaxis like?
Mild (such as hives) or fatal (results anaphylactic shock)
What do serious symptoms of systemic anaphylaxis cause?
Loss of blood pressure due to loss of fluid (results in shock)
Constriction of airways and swelling of epiglottis (leads to asphyxiation)
What is allergic rhinitis?
Mild allergic reaction caused by allergens that enter through the nasal mucosa and activate mast cells below the nasal epithelium
What does allergic rhinitis cause?
Local edema
Blocked nasal passages
Increased mucus produciton
What is allergic conjunctivitis?
Allergens enter through the conjunctiva and cause watery inflamed eyes
What is asthma?
An allergic reaction caused by allergens that activate mucosal mast cells in the respiratory tract
What is the acute response to rhinitis and asthma?
Bronchial constriction and an increase in fluid and mucus
What is the chronic response to rhinitis and asthma caused by?
Continued presence of TH2 cells, eosinophils, and other leukocytes
What do allergens do when there is urticaria and angioedema?
Activate mast cells in the skin and cause raised swellings
What is urticaria?
Swelling is at the surface of the skin
What is angiodema?
Swelling is in deeper layers of the skin
With food allergies, what can allergens cause?
Systemic effects and gut reactions
How many people have a food allergy?
Approximately 1-4% of US and European adults
What is the most common food allergy? What percentage does this allergy make up?
Peanut allergy
25%
What does food allergens cause?
Cramps, vomiting, and diarrhea
What are current treatments for allergic disease?
Treat the symptoms or general anti-inflammatory drugs
What is epinephrine used to do?
Prevent anaphylactic shock
How does epinephrine work?
Stimulate reformation of tight junctions and relaxation of smooth muscle
What do antihistamines do?
Relieve symptoms of rhinoconjunctivitis and urticaria
How do antihistamines work?
Block histamine receptor
What corticosteroids do?
Promote dilation of bronchial smooth muscle
What does monoclonal anti-IgE antibody do?
Prevents IgE binding to IgE receptors
What is monoclonal anti-IgE antibody to do?
Control chronic asthma
What is Type II hypersensitivity characterized by?
An IgG antibody response to allergens that have bound to the surface of host cells
What does IgG do in type II hypersensitivity?
Tags the host cells for opsonization and destruction and activates complement
What are type III hypersensitivity response mediated by?
An IgG antibody response to an excess of small soluble antigen that forms antigen:antibody immune complexes
In type III hypersensitivity, where are immune complexes formed?
Throughout the body
In type III hypersensitivity, where do immune complexes deposit?
In blood vessels, lung alveoli, or global
In type III hypersensitivity, what can immune complexes do?
Activate complement resulting in an inflammatory response mediated by C3a and C5a
What are type IV hypersensitivity responses mediated by?
Allergen specific effector T cells
What are type IV reactions also called?
Delayed hypersensitivity reactions
What is an example of type IV hypersensitivity?
Allergic contact dermatitis
What is allergic contact dermatitis caused by?
Direct skin contact with an allergens
What do allergens do in allergic contact dermatitis?
Penetrate the skin and are taken up by antigen presenting cells
What can the allergens in allergic contact dermatitis cause?
Activation of CD4 or CD8 T cells
What does the tuberculin skin test mimic?
A type IV hypersensitivity
Chapter 14 study guide and charts
Chapter 14 study guide and charts
What is an autoimmune response?
An immune response against self-antigens
What are autoantigens?
Self-antigens that trigger an immune response
What does the immune system normally show?
Tolerance to self-antigens
When do autoimmune responses result?
When self-tolerance breaks down
How many mechanisms exist to ensure self-tolerance?
Several
What do the self-tolerance mechanisms effective at collectively?
Preventing autoimmunity
What is a major task of autoimmune responses?
To differentiate self from non-self
What does negative selection select against?
Lymphocytes that are strongly self-reactive
What do lymphocytes that are weakly reactive to self-antigens do?
Escape negative selection
What do many lymphocytes with low self-reactivity recognize?
Foreign antigens
If all weakly self-reactive lymphocytes were eliminated, what would happen?
Immune response would be impaired
What can weakly reactive lymphocytes potentially produce?
Autoimmune disease
When are T-cells activated?
When their receptor binds antigen in the presence of co-stimulation from the antigen presenting cell
When are B-cells activated?
When their receptor binds antigen in the presence of T cell co-stimulation
What are lymphocytes that bind antigen in the absence of co-stimulation signaled to do?
Undergo apoptosis or become anergic
What are some T cells that are strongly self-reactive in the thymus induced become?
Tregs
What are some T cells that bind antigen in the presence of anti-inflammatory cytokines induced to become?
Tregs
What can T cells do?
Inhibit other effector T cells that recognize autoantigens in the same general vicinity
Do Tregs that inhibit other effector cells have to recognize the same antigens?
No
What could self-reactive lymphocytes encounter?
An activated dendritic cells presenting self-antigen and expressing co-stimulatory molecules
What may inflammatory cytokine produced during an infection do?
Activate DCs
What may inflammatory cytokines down-regulate?
Treg responses
What may the autoantigen be a ligand for?
PAMPs
What could autoantigens that are ligands for PAMPs do?
Activate self-reactive B cells if it reaches an unusually high concentration
What do responses of autoimmune disease resemble?
Those that target invading pathogens, but the autoantigens often cannot be removed
Because autoantigens cannot be removed, what are autoimmune disease like?
Chronic
What autoimmune diseases affect a specific organ? (4)
Type I diabetes
Myasthenia gravis
Graves disease
Multiple sclerosis
What autoimmune diseases are systemic?
Rheumatoid arthritis
Systemic lupus erythematosus
What are mechanisms of tissue injury analogous to?
Type II, III, and IV hypersensitivity reactions
What is the autoantigen of autoimmune hemolytic anemia?
Rh blood group antigens
I antigen
What is the consequence of autoimmune hemolytic anemia?
Destruction of red blood cells by complement and phagocytes
Anemia
What is the autoantigen of graves’ disease?
Thyroid-stimulating hormone receptor
What is the consequence of graves’ disease?
Hyperthyroidism
What is the autoantigen of myasthenia gravis?
Acetylcholine receptor
What is the consequence of myasthenia gravis?
Progressive weakness
What is a type II hypersensitivity reaction?
Antibodies against cell surface receptors
In type II hypersensitivity reactions, what does the antibody respond to?
Blood cell surface antigens
In autoimmune hemolytic anemia, what do IgG antibodies against surface antigens trigger?
Cell destruction leading to anemia
What is the autoantigen for systemic lupus erythematosus?
DNA Histones Ribosomes snRNP scRNP
What is a type III hypersensitivity reaction?
Formation of small immune complexes
What is systemic lupus erythematosus?
Chronic IgG production against ubiquitous cellular antigens
In systemic lupus erythematosus, what is a large amount of autoantigen produced by?
Apoptotic cells and damaged tissue
In systemic lupus erythematosus, where are small immune complexes deposited?
In renal glomerulus
In systemic lupus erythematosus, what causes inflammation?
Joints and blood vessels of the skin and other organs
What are 5 examples of Type IV T cell mediated diseases?
Type I diabetes Rheumatoid arthritis Multiple sclerosis Crohn’s disease Psoriasis
What is multiple sclerosis?
T cell mediated response against myelin antigens resulting in destruction of myelin in the central nervous system
What does multiple sclerosis result in?
Progressive muscle weakness
Blindness
Paralysis
What is type I diabetes?
T cell mediated response against B cells in the pancreas resulting in insulin deficiency
What does type I diabetes result in?
High blood sugar
What is rheumatoid arthritis mediated by?
T cells and autoantibodies against antigens in the synovial membrane of joints
What happens in rheumatoid arthritis?
Inflammation spreads to bone and cartilage
What does rheumatoid arthritis result in?
Pain
Reduced function
Disability
What is autoimmune disease thought to result from?
Genetic susceptibility, breakdown in tolerance mechanisms, and environmental triggers
What does a relative risk of autoimmune disease greater than 1 indicate?
Increased susceptibility
What does a relative risk of autoimmune disease less than 1 indicate?
Increased protection
What do family studies of MHC genotypes in type I diabetes show?
Affected siblings inherit the same sets of MHC genes much more often than would be expected if MHC genotype did not influence susceptibility
What modifies susceptibility to rheumatoid arthritis?
Genotype and environmental factors
What do 4 of the DRB1*04 alleles do for rheumatoid arthritis?
Confer susceptibility
What does the DRB1*04:02 allele do for rheumatoid arthritis?
Confers protection
What does smoking do in individuals with the DRB1*04 susceptibility alleles do?
Increases susceptibility significantly
In what gender do more autoimmune disease occur?
Female
What are 4 examples of other genes that can predispose someone to autoimmunity?
Genes that affect autoantigen availability and clearance
Genes that affect apoptosis
Genes involved in signals that control lymphocyte activation
Genes that affect development or function of Tregs
How can infections lead to an autoimmune disease?
By providing an inflammatory environment that promote lymphocyte activation
What is molecular mimicry?
Antibodies produced against a pathogen epitope cross-react with self-peptides
What is an examples of molecular mimcry?
Rheumatic fever
Chapter 16 study guide and charts
Chapter 16 study guide and charts
What is histocompatibility?
Donor and recipient have same antigens
What are alloantigens?
Antigens that differ between members of the same species
What are examples of alloantigens?
MHC molecules
ABO blood antigens
What is an alloreaction?
An immune response against alloantigens
What are alloreactions the major impediment to?
Successful transplantation
What is an autograft?
Transplantation of a tissue from one site to another on the same individual
Why can autograft be performed with 100% success?
Perfect histocompatibility because it is your own tissue
What is an allograft?
Transplant of a tissue from one individual to another
What is the most commonly transplanted tissue?
Blood
In blood transfusions, what must the donor and recipient be matched for?
ABO and Rhesus D antigens
Is MHC matching necessary for blood transfusions?
No
What is the universal blood donor?
Type O Rh-
What is the universal blood acceptor?
Type AB Rh+
What is rejection of solid organ transplants due to?
An immune response to non-self MHC molecules
In solid organ transplantations, what is a long-term outcome better with?
A high level of histocompatibility
What is hyperacute rejection caused by?
Existing antibodies that react with antigens on endothelial cells in blood vessels of the grafted tissue
What can existing antibodies that cause hyperacute rejection arise from?
Pregnancy
Blood transfusions
Previous transplants
When does hyperacute reaction occur?
Within 24 hours of transplantation
What happens to vessels in hyperacute rejection?
They become blocked and damaged leading to tissue death
How can hyperacute reactions be avoided?
By blood typing and performing a cross match test
What is acute rejection mediated by?
T cells recognizing the graft tissue as foreign
What are transplants monitored for and treated with?
Symptoms of acute rejection episodes and treated with immunosuppression
What is acute rejections a major risk factor of?
Chronic rejection
What happens in indirect rejection?
Recipient APCs from the graft present processed antigens to recipient T cells on self MHC molecules
In indirect recognition, what do recipient T cells recognize as foreign?
Donor MHC antigen fragments
What happens in direct rejection?
Donor APCs from the graft present antigens to recipient T cells as MHC:antigen complexes
What do receptor cells do in direct rejection?
Recognize the complex as foreign and direct effector cells against the foreign tissue
What are minor histocompatibility antigens?
Alloantigens of non-MHC molecules
What is chronic rejection caused by?
Chronic injury to the graft
What are risk factors of chronic rejection? (3)
Acute rejection episodes
Pre-graft ischemia
Underlying disease
What is graft versus hot disease?
The converse of acute allograft rejection
What does graft versus hot disease result from?
Donor T cells attacking recipient tissues
In hematopoietic stem cell procedure, why is the recipients bone marrow destroyed?
To reduce the number of recipients HSCs, immunosuppress the recipient, and reduce the number of tumor cells
What does protocol of hematopoietic stem cell procedure do?
Damages dividing host cells
What happens to donor hematopoietic stem cells?
They are infused and re-populate the recipients bone marrow
What are sources of hematopoietic stem cells? (3)
Bone marrow
Peripheral blood
Umbilical cord blood
What is hematopoietic stem cell transplantation used to do?
To treat various diseases
What is mucopolysaccharidosis?
Various deficiencies of lysosomal enzymes
What is Gaucher’s syndrome?
Deficiency of the lysosomal enzyme glucocerebrosidase
What does acute graft versus hot disease primarily affect?
Skin, gut, and liver
What do mature donor T cells do during graft versus hot disease?
Promote engraftment and reconstitute the recipient’s immune system
What happens to immune reconstitution without mature donor T cells?
It is suppressed
What is required for T cell function?
Some MHC histocompatibility
What happens if the donor and recipient have different MHC alleles?
T cells that were positively selected by recipient MHC will not be able to become activated in the periphery by donor MHC
In the correlation between hematopoietic stem cell transplantation outcome and MHC histocompatibility, how do you get the better outcome?
Fewer mismatches
When do you not want fewer mismatches?
In graft versus leukemia
How is allogenic hematopoietic stem cell transplantation usually performed?
Using an identical MHC matched sibiing or unrelated MHC matched donor
What is the chance of an identical MHC match with a sibling?
25%
Chapter 15 study guide and charts
Chapter 15 study guide and charts
What do successful pathogens have to do?
Replicate in the host and be transmitted
What must successful pathogens have?
Ways to evade the host immune system
Are the most virulent pathogens the most successful?
Not necessarily
What must successful hosts have?
An efficient immune response
What are antibodies generated against one subtype like for other subtypes?
No effective against them
What do different strains of a pathogen have?
Different surface antigens
What do the influenza virus surface antigens have?
A high mutation rate
Why are the surface antigens of influenza virus ever changing?
To evade recognition by the immune system
What is antigenic shift?
2 or more different strains combine to form a new subtype
What is antigenic drift?
Mutations occur slowly over time within a strain
How can herpesvirus evade the immune system?
By persisting in a latent form
What is herpesvirus normally controlled by?
The immune system
What can herpesvirus cause when the immune system is compromised?
Recurrent infections
What do herpes simplex virus and chicken pox virus persist in?
Neurons in latent form
What does Epstein Barr virus persist in?
B-cells in latent form
What does Cytomegalovirus persist in?
Lymphocytes, endothelial cells, and macrophages in latent form
What are 4 different viral strategies?
Inhibition of humoral immunity
Inhibition of inflammatory response
Blocking of antigen processing and presentation
Immunosuppression of host
What does S. aureus SSLP7 do to block the effector function of antibodies?
Binds to IgA Fc region and V5 to prevent both effector functionsAlso has a protein that binds Fc region of IgG
What does HIV use as a receptor?
CD4
What does HIV infect?
CD4 T cells macrophages and dendritic cell
What does HIV replicate in?
Activated CD4T cells
What does the outer glycoprotein of HIV have?
A high mutation rate
What can HIV remain hidden from the immune system in?
Naïve T cells
In HIV, what happens when T cells become critically low?
Patients become susceptible to infections normally well controlled by a healthy immune system
Where does Mycobacterium tuberculosis replicate?
In macrophage endosomes
Where does Plasmodium falciparum replicate?
In liver and RBCs which do not have low MHC class I expression
What does Plasmodium falciparum produce?
Adhesion molecules in RBCs to prevent destruction
What does Plasmodium falciparum secrete?
Cytokines that prevent a T memory response from developing
What must happen in order for cancer to occur?
Tumor suppressor genes are tuned off
Oncogenes are turned on
What is cancer caused by?
An accumulation of mutations that result in uncontrolled cell proliferation
What happens in leukemia?
Malignant cells arise in the bone marrow and blood
What are the 2 types of leukemia?
Myeloid and lymphoid
What happens in lymphoma?
Malignant cells arise in the lymphatic system
What happens in myeloma?
Malignant cells arise from plasma cells
Does the immune system normally respond to tumor antigens?
Yes
Are immunosuppressed individuals more or less prone to cancers that the general population?
More prone
What are tumor associated antigens?
Antigens that are also found on normal cells, but at lower concentration
What are tumor specific antigens?
Antigens that are not found on normal cells
What are cancer/testes antigens?
Antigens commonly expressed in tumors that are normally only expressed in the testes and during fetal development
What happens when successful tumors evade the immune system?
Down regulate MHC molecules
Tumor associated antigens are closely related to ‘self-antigens’
What do successful tumors that evade the immune system secrete?
Anti-inflammatory cytokines that promote T cell tolerance
What do successful tumors that evade the immune system produce?
Surface molecules that engage T cell receptors and cause anergy
Chapter 17 study guide and charts
Chapter 17 study guide and charts
