Cumulative Final deck from Study Guides and Case Studies Flashcards
What are the two major groups of the immune system
Innate immune cells (hours to days)
Adaptive immune cells (days to weeks)
What are the cells in the innate immune system
Neutrophils, mast cells, eosinophils, basophils, macrophages, natural killer cells
What are the immune cells in the adaptive immune system
T cells, B cells
What are the mediators of humoral vs cell-mediated immunity
Humoral: mediated by the blood/B lymphocytes
Cell-mediated: T-lymphocytes (destroy microbes)
What system is the first line of defense for the human body against invaders?
innate
What cells in the immune system are responsible for producing antibodies?
Plasma cells ( B cells)
What is the function of natural killer (NK) cells in the innate immune system?
Kill cells that are infected with viruses or other intracellular pathogens
- Perforin forms pores in membrane, granzymes enter and trigger apoptosis
What are the primary lymphoid organs?
Thymus ( t cells) and Bone marrow ( B cells)
What are the secondary lymphoid organs and what is their main function?
Spleen, Lymph nodes
Where do B cells complete their maturation
Spleen
What is required in T-cell dependent activation of B cells
Co-stimulatory signal required by T helper cell. CD40 on B cells and CD40L on T helper cells. Checks and balance system.
Where do T cells mature before migrating to secondary lymphoid organs?
Thymus
What has PAMPS
Microbial invaders have PAMPS on them and Macrophages have receptors that detect PAMPS
Which cells produce antibodies
Plasma cells
Where do plasma cells mature from
B cells
What are the 2 proteins that make up the B cell’s surface receptor
Two heavy chains and 2 light chains
What are the 2 signals a B cell must recieve for activation
Co-stimulatory signal, BCR engaged signal
Describe the antibody classes, IgM, IgA, IgG, IgE
IgM: First antibody produced, great at activating complement
IgA: Protects mucosal surfaces such as the digestive tract
IgG: Passes from mother to fetus through placenta, long lasting
igE: Involved in allergic reactions and defense against parasites
Which antibody is most abundant in the human body and protects mucosal surfaces
IgA
During class switching, which part of the antibody changes?
Fc (the constant region)
What role does class switching play on the immune response
Change in antibody class allows the immune response to be more specific to the type of infection
Explain the importance of somatic hypermutation
- Somatic hypermutation allows rearranged genes of BCr to increase affinity to cognate antigen
- introduces random mutations into the variable (Fab) region of the B cell receptor.
This process increases the affinity of the antibodies produced, allowing for stronger binding to the antigen.
B cells that produce higher-affinity antibodies are selected to survive and differentiate into plasma cells or memory B cells
True/False - The process of opsonization involves antibodies binding to a pathogen and directly killing it
False- Opsonization involves antibodies binding to a pathogen, but the antibodies do not directly kill the pathogen. Instead, they “tag” the pathogen for destruction by immune cells such as phagocytes, making the pathogen easier for these cells to engulf and destroy.
What are the 2 types of cells that B cells can differentiate into
plasma cells (secrete antibodies) and memory b cells ( long-term immunity)
What region on the antibody determines the class
the Fc region
Which region of the antibody bind to specific antigens
the Fab regions
Which antibody is The most abundant antibody in blood; provides long-term immunity and can cross the placenta.
IgG
Which antibody is Found primarily in secretions. Such as tears, saliva, and mucus, and plays a role in mucosal immunity.
IgA
Which antibody is Involved in allergic reactions and defense against parasites.
IgE
Which antibody does the complement system produce
IgM
Describe the antibodies created in a primary and secondary immune response
The primary immune response occurs where a B cell encounters an antigen for the first time. This response is complement and typically involves the production of the IgM class of antibodies.
The secondary immune response occurs upon subsequent exposure to the same antigen. It is faster, stronger, and mainly involves the production of Ag specific antibodies.
What is the germinal center for B cells after activation
the spleen (undergo further processes to improve the immune response)
Which mutation occurs in the germinal centers, and where does this mutation occur?
Somatic hypermutation, where the Fab region of the B cell receptor gets mutations ( increases affinity of antibodies produced, allows for stronger binding of the antigen)
Which B cells are selected to survive and differentiate into plasma cells or memory b cells after somatic hypermutation
B cells that produce higher- affinity antibodies
Name 3 APC’s
Dendritic cells, macrophages, B cells
Which MHC do T cells recognize
T cells do not recognize MHC I; they recognize antigens only when they are presented by MHC II.
Where do you find MHC1 vs MHC2
MHCI: presents antigens to II
MHC class II presents antigens B & T cells.
Where does the source of the antigen come from for MHC class1 vs class 2?
MHC class 1: Antigens come from intracellular infected cells (i.e. viruses)
MHC class 2: Antigens come from extraceular sources (i.e. bacteria)
MHC class 1 presents to which T cells
CD8 (cytotoxic)
MHC class 2 presents to which cells?
T cell or B cell
Which cells are the key APCs
Dendritic cells ( capture antigens and migrate to the nearest lymph node to present antigens to T cells)
Which MHC class does a dendritic cell express
Dendritic cells express both MHC class I and MHC class II molecules, allowing them to present antigens to both naive T cells and helper T cells.
A “helper T cell(CD4)” is a differentiated T cell that specifically interacts with MHC Class II molecules to activate other immune cells
A Cytotoxic T cell responds to MHC 1 (CD8)
Which signals are required for full activation of T cells
two signals are required: the first signal comes from TCR with the antigen-MHC complex, and the second signal comes from the co-stimulatory molecules (like CD28 that interacts with the B7 on the surface of APCs)
What does a T cell become if it only recieves the first signal from a TCR without co-stimulation?
Anergic- becomes unresponsive and can’t make an immune response
The majority of T cells have what kind of receptors?
Alpha Beta
Can B cells or T cells undergo somatic hypermutation?
Only B cells
Which protein on T cells is critical to receive co-stimulatory signals during activation?
CD 28
What are the 3 things that are required for T cell proliferation
MHC II & Ag bind to TCR
CD40 bind to CD40L
B7 bind to CD28
What do cytotoxic T cells release and why
Perforin and granzyme B → induce apoptosis of infected cell
A t- cell that recognizes its self-antigen will undergo:
apoptosis or anergy
What is the primary function of a T cell receptor (TCR)?
To recognize antigens presented by MHC molecules
Which protein is involved in co-stimulation during T cell activation?
CD28
What is the role of the CD4 molecule on helper T cells?
To bind to MHC Class II molecules and assist in stabilizing the TCR-MHC interaction
What is the primary role of the CD3 complex in T cell activation?
It transmits the activation signal from the T cell receptor to the cell’s nucleus
What is the primary role of the CD40 and CD40 Ligand interaction in T cell signaling?
It helps in the activation and survival of antigen-presenting cells like dendritic cells
What is the primary purpose of IL-2 and IL-2 receptor expression in T cell activation?
To stimulate the proliferation and survival of activated T cells
True/False - Traditional T cells express γδ T cell receptors.
FALSE: Traditional T cells express αβ T cell receptors. γδ T cells are a distinct, less common subset of T cells.
True/False - Naive T cells can be activated without receiving any co-stimulatory signals.
False: Naive T cells require both TCR binding to the antigen-MHC complex and co-stimulatory signals to be fully activated. Without co-stimulatory signals, they become anergic.
True/False - T cell receptors can only recognize ONE antigen.
True- each TCR is specific to one antigen, so each T cell receptor can recognize only one unique antigen-MHC complex
True/False - CD28 is a cytokine that promotes T cell proliferation.
False– CD28 is not a cytokine; it is a co-stimulatory receptor on T cells that binds to CD80/CD86 on APCs, promoting T cell proliferation and survival.
What is the difference between dendritic cells and follicular dendritic cells (origin and function)
Dendritic cells originate from bone marrow and are key antigen-presenting cells that activate T cells.
Follicular dendritic cells (FDCs) are of mesenchymal origin and are primarily involved in presenting antigens to B cells in the germinal centers.
What happens in the dark zone?
B cells undergo rapid proliferation and somatic hypermutation to diversify their antibodies.
What happens in the light zone?
B cells with high-affinity receptors are selected for survival
They can then undergo class switch recombination and differentiation into plasma cells or memory B cells.
How do lymphocytes typically enter lymph nodes?
Lymphocytes enter lymph nodes mainly via high endothelial venules (HEVs) or through the afferent lymphatic vessels.
Where are HEVs found and why are they important? Where are they NOT found?
HEVs are found in secondary lymphoid organs like lymph nodes and Peyer’s patches.
They are important for facilitating the entry of naïve lymphocytes from the bloodstream. HEVs are not found in the spleen.
How do lymphocytes enter the lymph node? (2 ways)
HEVs
Afferent lymphatic vessels
How do antigens enter the lymph node? (2 ways)
Afferent lymphatic vessels
Dendritic cells that capture and present them
What are the 4 major events that have to happen before the adaptive immune system can produce antibodies?
Antigen presentation
B cell activation
T cell co-stimulation
B cell differentiation into plasma cells
Peyer’s patches are examples of what?
Secondary lymphoid organs (found in Gut-associated lymphoid tissue (GALT))
Why is the spleen special as far as B cell activation?
The spleen filters blood, trapping blood-borne antigens and initiating B cell activation.
Why are asplenic patients at risk of infection by encapsulated bacteria? What is an example of this type of bacteria? What kinds of vaccines should an asplenic patient receive?
Asplenic patients are at risk, because the spleen plays a critical role in clearing encapsulated bacteria (Streptococcus pneumoniae). These patients should receive vaccines for encapsulated organisms.
Inducible regulatory T cells (iTregs) produce what?
IL10 and TGF-beta (they help suppress the immune system)
What are the function of IL 10 and TGF B
Regulate the immune responses, preventing excessive inflammation and maintaining tolerance.
What is the role of CTLA-4?
CTLA-4 is an inhibitory receptor on T cells that competes with CD28 for binding to B7, downregulating the immune response. CTLA-4 is upregulated on T cells after activation.
What is PD1 and PDL1 and when is it expressed? What is the function?
PD1 is an inhibitory receptor on T cells, and PDL1 is its ligand, expressed on APCs. Their interactions lead to immune suppression, preventing overactivation.
Which antibody lives the longest
IgG
What is the result of the Fas-FasL interaction?
Triggers apoptosis
Which cytokine subset is primarily involved in defense against viral or bacterial infections, and which cells produce it?
Th1 cells
IFN-y
Which cytokine subset is involved in defense against parasites and bacteria and which cells produce it?
Th2 cells
IL-4
What is the significance of cytokine range being limited to short distances?
Cytokines act over short distances to ensure that the immune response is localized to the site of infection, preventing widespread activation that could cause unnecessary tissue damage.
What are the three main subsets of helper T cells, and what type of invaders do they primarily defend against? What cytokines does each release?
Th1 cells - defend against intracellular pathogens (bacteria, viruses), release IFN-y
Th2 cells - defend against extracellular parasites and some bacteria, release IL-4 and IL-5
Th17 cells - defend against fungal infections and extracellular bacteria, release IL-17
IL-4 function
Promotes class switching to IgE in B cells.
IL 5 function
Stimulates the growth and differentiation of eosinophils..
IL 9 function
Mast cell activation
Il 13 function
Enhances IgE production and contributes to mucus production and airway hyperresponsiveness
Where are IgE receptors found
mast cells and basophils
What is anaphylaxis?
more than one organ system involved & severe inflammatory response to allergen that is life threatening
What lab test can confirm an anaphylaxis reaction?
Tryptase within 2 hours
What type of reaction is anaphylaxis?
type 1 hypersensitivity
What type of cells mediate a type IV hypersensitivity reaction?
CD4+ T cells (Th1 cells) and CD8+ T cells (Cytotoxic T cells)
Type 1 hypersensitivity reactions:
allergic asthma, allergic rhinitis, anaphylaxis, and food allergies.
Type 4 hypersensitivity reactions
contact dermatitis, hypersensitivity pneumonitis, and TB skin test (PPD).
What do most autoimmune disorders result from
failure of the tolerance-inducing mechanism to eliminate self-reactive cells in genetically normal individuals
What does “molecular mimicry” mean and how does it link an infection with the development of an autoimmune disorder?
Protein from Ag mimics protein in body
Name 4 examples of autoimmune diseases.
Type 1 diabetes
plaque psoriasis
Rheumatoid arthritis
lups
what are the Non-infectious vaccines:
“Killed” virus or bacteria
Polio, flu, typhoid
Toxoid vaccines
Acellular vaccines
Subunit vaccines
What are the risks of attenuated vaccines?
The potential for the weakened pathogen to revert to a more virulent form, especially in individuals with weakened immune systems. This could potentially cause disease in those with compromised immunity.
A type I hypersensitivity is a type of allergic reaction that is characterized by the rapid release of what
Histamine, mast cells and basophils releasing other inflamatory mediators, IgE antibodies
What was michael treated with to help his SCN?
recombinant human granulocyte colony-stimulating factor (rhG-CSF), which improved his neutrophil count
When michael underwent genetic testing, it revealed a mutation in which Gene?
ELAINE gene, commonly linked to SCN
How might one differentiate between increased peripheral destruction of neutrophils and decreased production in the bone marrow as a cause of neutropenia?
Need bone marrow examination
- In peripheral distruction, bone marrow has increased production of neutrophils
-In decreased production, there are reduced development of neutrophils
Why are neutrophil transfusions only rarely used in the treatment of SCN?
neutrophils have a short lifespan (about 8 hours)
Why do somatic mutations that truncate the intracytoplasmic tail of the G-CSF receptor cause an increased risk of leukemia?
Mutations in the G-CSF receptor that truncate its intracellular tail impair normal cell signaling and regulation, leading to uncontrolled proliferation of neutrophil precursors.
Neutrophils are especially important for defense against what?
bacteria
Neutrophils are part of which immune system
Innate
Where are neutrophils born
in the bone marrow
How do neutrophils “end” their life?
A neutrophil is able to engulf and kill bacteria and subsequently die via apoptosis
What is the benifit of a bone marrow biopsy in a patient with suspected SCN
A bone marrow biopsy can provide support for the diagnosis of SCN showing problems with maturation of myelocytes.
In the case of Michael, the neutropenia was caused by a mutation in the ELANE gene. This mutation was:
Recessive
What are the encapsulated vaccines that should be administered to people with asplenia?
Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis
Where do pathogens go that enter the body via the gastrointestinal tract?
Lymph nodes
Where do pathogens go that enter the body via the blood?
Spleen
What are the two functions of the spleen?
Filtering blood and producing antibodies
There are two main “flags” by which phagocytes recognize pathogens that are the direct result of immune system activation. What are these “flags”?
Antibodies and complement proteins
What two bacterial infections are most common in people with asplenia?
Streptococcus pneumoniae and Haemophilus influenzae
What long-term treatments are recommended for asplenia?
Immunization and prophylactic antibiotics
A patient with X-linked agammaglobulinema is most susceptible to what types of infections?
Extracellular bacteria
What was the problem with Daisy, the girl with hyper IgM syndrome caused by a mutation in the AID gene?
AID deficiency prevents immunoglobulin class switching, resulting in an excess of IgM and a lack of IgG, IgA, and IgE.
Describe an opportunistic infection?
An infection that occurs when the immune system is compromised, allowing normally harmless microbes to cause disease.
AID plays an important role in various immunological processes. What are they?
Class switching and somatic hypermutation in B cells
Antibody production with increased affinity for antigen during an immune response
Selection of cells with mutations that lead to higher affinity to antibodies
How is hyper IgM syndrome inherited
inherited via a defect in either an autosome or sex chromosome
What does flow cytometry do?
It is commonly used to identify immune cell populations (like B cells, T cells, and natural killer cells) based on the presence of specific surface markers.
Which cell types are involved in asthma?
CD4+ Th2 cells, Mast cells, Eosinophils
Which compounds cause the late-phase of an allergic reaction?
Leukotrienes, Cytokines, Eosinophil products
The main benefit of albuterol treatment is:
Bronchodilation
What occurs in leukotrienes in asthma
Leukotrienes lead to inflammation and smooth muscle constriction.
How does immunotherapy help alleviate allergies in patients like Frank?
Gradually desensitizes the immune system to allergens
How is SCID inherited?
X-linked
What should patients who have SCID not be given?
Administration of vaccines, including rotavirus, varicella and MMR
What is the survival rate of SCID with HCT?
80-90%
how is SCID screened for at birth?
Measurement of TRECs is a way to measure thymopoiesis as TRECs are produced during the maturation process of T lymphocytes.
How was lack of T cell function demonstrated in Martin’s case?
Mitogen testing showed unresponsiveness to PHA, concanavalin and pokeweed
Why do some SCID patients still require immunoglobulin replacement therapy even after a successful bone marrow transplant?
Because B cell function is not restored in all patients
What is the primary function of integrins in leukocytes?
Facilitating cell migration to infection sites
What is most characteristic of Leukocyte Adhesion Deficiency (LAD)?
Elevated white blood cell count
Why do children with LAD experience delayed wound healing, such as delayed umbilical cord separation?
Impaired neutrophil and monocyte migration to the wound site
What role does CD18 play in the pathophysiology of LAD?
It is a component of integrins necessary for leukocyte adhesion and migration
How do patients with LAD typically present in terms of susceptibility to infections?
They have recurrent pyogenic bacterial infections
In the case study of luisa with LAD, why was the Rebuck skin window test used, and what was its significance?
To monitor the migration of immune cells into damaged skin
What is a common oral manifestation of LAD in surviving patients?
Severe Gingivitis
What finding on a newborn exam would concern you for LAD?
Umbilical cord separation delay
What is LAD due to (Which CD is a problem)?
mutations in the ITGB2 gene located on chromosome 21 that encodes for CD18.
Macrophage vs Neutrophil
Macrophages are tissue residents but neutrophils are blood residents. Neutrophils are the first ones to respond to an infection.
Which Co- receptor do CD4 T cells have
MHC2
Which Co-receptor do CD8 T cells have
MHC1
