The Human Immune Response (MODULE 6A &6B) Flashcards
Which of the following best describes the meaning of the word “innate” based on its medical word parts?
Relating to the immune system
Acquired through experience
Born within or inborn
Occurring outside the body
Born within or inborn
Which of the following best describes the meaning of “prostaglandin” based on its medical word parts?
A substance that promotes stomach acid production
A type of protein found in the adrenal gland
An enzyme that breaks down fats in the digestive system
A hormone-like compound that regulates various bodily processes
A hormone-like compound that regulates various bodily processes
Based on the medical word parts of “histamine,” which of the following most accurately describes its meaning?
A substance that causes tissue damage
A hormone produced by the pituitary gland
A protein found in mast cells
An amine compound playing a role in the immune process
An amine compound playing a role in the immune process
Which of the following best describes the mechanism of action of a pyrogen in the human body?
Inhibits the hypothalamic thermoregulatory center
Directly increases metabolic rate in peripheral tissues
Stimulates the hypothalamic heat-sensing neurons
Activates the innate immune system to induce fever
Activates the innate immune system to induce fever
Which of the following best describes the meaning of “epitope” based on its medical word parts?
A specific site on an antigen
A protein that causes inflammation
A substance that produces antibodies
A type of white blood cell
A specific site on an antigen
Overview of the Body’s Defences. *possibly draw out this chart on slide 3
Innate -
Aka: First line of defense; nonspecific
Status at time of birth: ready and functional
Time to become active: minutes
Immunologic Memory: no
Adaptive -
Aka: Second line of defense; specific; acquired
Status at time of birth: ready to develop in response to encounters with microbes
Time to become active: days
Immunologic Memory: yes
Major Components of Innate and Adaptive Immunity
Innate Immunity • Passive barriers:
o Physical barriers
o Chemical barriers
o Microbiome • Complement • Inflammation • Phagocytosis • Non-phagocytic killing
Adaptive Immunity • Cell-mediated immune response
(cytotoxic) • Humoral immune response
(antibodies)
*Even though we discuss each of these major functions separately, they are intertwined and collaborate with each other – there are not separate, independently functioning ‘lines of defense’
Physical Defenses of Nonspecific Innate Immunity are?
Cellular barriers -
EX: Skin, mucous membranes,
Function: Deny entry to pathogens
endothelial cells
Mechanical defenses -
EX: Shedding of skin cells, mucociliary, sweeping, peristalsis, flushing potential sites of infection
action of urine and tears
Function:Remove pathogens from potential sites of infection
Microbiome -
EX: Resident bacteria of the skin, Compete with pathogens upper respiratory tract, gastro-
intestinal tract, and genitourinary tract.
Function: Compete with pathogens for cellular binding sites and nutrients
Physical Barriers: Cellular Barriers
Overview:
- Prevent pathogens from reaching
susceptible tissues
• Skin, mucous membranes, epithelial cells
• Tight junctions between cells:
o Complementary proteins in cell membrane of
adjacent cells
o Most commonly: One is a glycoprotein and the
complementary protein a lectin with a specific
binding site for the oligosaccharide of the
glycoprotein
Chemical Barriers
- Sebaceous glands in dermis sebum (oil) seals hair follicle pore
and sweat glands
• Lipases from skin microbiome bacteria leads to release of fatty
acids from sebum oil mildly acid environment adverse for many
pathogens
• Salt from sweat also produces adverse growth conditions
• Stomach acid is detrimental for many microorganisms
• Lysozyme in tears and mucus in esophagus breaks down
peptidoglycan in bacterial cell wall
• Antimicrobial peptides: class of nonspecific cell-derived mediators with broad-spectrum antimicrobial properties
T or F
Without a cell wall bacteria cells are not viable
T
What are the jobs of regulatory compounds in plasma protein mediators?
Regulatory compounds act in small numbers and have strong effects, often through cascading mechanisms (e.g., the blood clotting cascade)
What percentage do regulatory proteins make up in the plasma of blood?
<1%
What are the three major groups fo F plasma protiens mediators?
- Acute-phase proteins
- Complement protiens
- Cytokines
Acute-phase protiens are a class of ____________ mediators.
Antimicrobial
What plasma protein mediator is primarily produced in the liver?
Acute-phase proteins
Name examples of acute-phase proteins.
C-reactive protein and Serum amyloid A - Coats bacteria (opsonization) -> phagocytosis
Ferritin and Transferrin - Bind and sequester iron -> inhibits (or slows down) growth *Inhibit Iron
Fibrinogen - Involved in blood clot formation -> traps bacterial pathogens
Mannose-binding lectin - Activation of complement cascade (‘lectin pathway’)
Discuss the overview of the complement system. (Plasma protein mediators) What is it?
Group of plasma proteins (>30 proteins, including C1-C9)
• Some are present as inactive precursors that get activated
when the cascade gets triggered (3 possible triggers)
• Contributes to innate defense
• Connects innate and adaptive immunity
Name and describe the three ways of complement activation.
Alternative Pathway:
How it gets Triggered - presence of invading microbe
Depends on - self-decay of inactive C3; if it does not bind to microbes, C3b gets lysed
Classical Pathway:
How it gets Triggered - Presence of antibody-antigen complex (immune complex)
Depends on - Up regulation of adaptive immunity (humoral immunity)
Lectin Pathway:
How it gets Triggered - Lectins binding to mannose containing microbial surface structure
Depends on - From liver and other cells and macrophages (involved in inflammation)
T or F
It takes days for the up-regulation of adaptive immunity
T
Tied to classical pathway - up regulation of adaptive immunity (humoral immunity)
Three Outcomes of Complement Activation are?
Inflammation increase:
Responsible Complement protein - C3a, C4a, C5a
Consequences - Inflammation attracts phagocytic cells
Opsonization:
Responsible Complement protein - C3b
Consequences - Attracts phagocytic cells
Formation of membrane attack complex (MAC):
Responsible Complement protein - C5b
Consequences - Creates holes in membranes
**Look at the complement system on slide 18 and understand process *Look at PPT
Cytokines Overview:
- Soluble proteins • Act as communication signals between cells
o Originate from certain cells
o Bind to receptor of other cells • Three important classes:
o Interleukins
o Chemokines
o Interferons
Pro-Inflammatory Mediators are?
• Histamine (derived from amino acid histidine)
o Released by mast cells (and basophils)
o Leads to vasodilation (inflammation) and effects related to hypersensitivity
• Eicosanoids (from omega-6 fatty acid arachidonic acid)
o Released by mast cells in vicinity of damaged cells and by damaged cells (if
viable)
o Leukotrienes: similar effects as histamine, but stronger o Prostaglandins: cause pain, make blood vessels leaky; promote fever
• Bradykinin (short polypeptide)
o Makes blood vessels leaky leukocytes and fluid leave blood vessels
o Causes edema
o Activation can be triggered when blood clotting cascade is triggered or upon
contact of the inactive form with foreign surfaces (metal, glass,…)
The Inflammatory Response can be what three inflammations?
• Acute inflammation: Cascade of chemical mediators and cellular
responses in case of damage or stress to cells (more on this in
physiology/pathology modules)
-> recruitment of cellular defenses to eliminate pathogens, remove
damaged and dead cells
-> initiates repair mechanisms
• Excessive inflammation: -> tissue damage, even death
• Chronic inflammation: Prolonged inflammation (longer than several
weeks) due to various reasons (see pathology module)
Look at and understand the inflammatory response step by step. **ppt and slides 25-28
A cut penetrates the epidermis barrier; bacteria invade
Damaged cells and mast cells release histamine, prostaglandins, leukotrienes (shown in green)
Histamine, prostaglandins and leukotrienes lead to vasodilation and increase the permeability of the vessels redness (erythema) and heat
Neutrophils and macrophages squeeze through the walls of the vessels
Blood clot forms (bradykinin activated extended vasodilation) More phagocytes migrate to the site and devour bacteria
Accumulation of damaged tissue and leukocytes forms pus
Eventually, undifferentiated stem cells repair the damaged tissue. The blood clot is absorbed/falls off. Fibroblasts produce new collagen to repair the extracellular matrix
Increased permeability allows antimicrobial chemicals and clotting proteins to seep into damaged tissue but also results in swelling, pressure on nerve endings, and pain.
Fever Overview: What is it? How does it function?
• Systemic response (acute
inflammation is a local response to a
site of infection) • Overall increase in body temperature,
triggered by pyrogens = biomolecules
that alter the ‘thermostat’ setting in the
hypothalamus
• Effects of higher body temperature:
o Slows bacterial growth (moves away from
optimal T of growth) o Enhanced iron-sequestration o Faster phagocytosis
Look at overview diagram on slide 29 (possibly draw)
Pathogen Recognition by Nonspecific WBCs
How do these nonspecific WBC actually recognize pathogens?
- Opsonization by antibodies, C3b, lectins, C-reactive protein 2. Recognition of molecular structures common to many groups of
pathogens, called ‘pathogen-associated molecular patterns’ or
PAMPs
o Examples of PAMPs:
NORTHWESTERN HEALTH SCIENCES UNIVERSITY | nwhealth.edu 30
Peptidoglycan (bacterial cell wall)
Lipopolysaccharide (outer membrane of Gram-negative bacteria)
Flagellin (protein in flagella)
Lipopeptides (common for many bacteria)
Viral DNA or RNA
How does WBC recognition happen?
Pathogen Recognition
• Pattern Recognition Receptors
(PRRs), among them toll-like
receptors (TLRs) are located on
surface of phagocytic cells and in
membranes if intracellular
compartments
• Upon binding between a PAMP
and a complementary PRR, the
phagocytic cell becomes
activated
What is phagocytosis and what is the process of this?
• Leads to degradation of foreign particles, damaged cells,
and dead cells into building blocks and waste products
• Leads to the removal of extracellular pathogens and
fragments of pathogens
• Leukocytes with major phagocytic activity:
o Neutrophils (approx. 60% of all leukocytes in blood)
Have a short life span (a few days)—’hallmark’ leukocyte of acute inflammation
o Macrophages (derived from monocytes)
Have a longer life span (months or even longer)—’hallmark’ immune cell
o Dendritic cells
Derived from monocytes, embedded in skin and mucous membranes
—technically perform endocytosis
What are the two non phagocytic killing mechanisms?
• Eosinophils: Attack parasitic helminths
o Attach to their surface and secrete toxins that weaken or kill helminths
o High eosinophil count (eosinophilia) indicative of helminthic infection
• Natural killer (NK) lymphocytes: Recognize virus-infected cells
o Induce virus-infected cells to undergo apoptosis
o Enhanced activity when cell-mediated immune response ramped up
Leukocyte Analysis for Diagnosis would include?
• High leukocyte count: Bacterial infection (due to high
neutrophil activity)—> Can help to determine whether to prescribe antibiotics
• High lymphocyte count: Viral infection —> Can help to determine whether to prescribe antibiotics
• High eosinophil count: Parasitic worm infection or allergic reaction
Be able to explain and describe***
Innate vs adaptive immunity • Passive barriers (physical, chemical, and microbiome) • Plasma protein mediators
o Acute phase proteins
o Complement
o Cytokines • Acute inflammation and Fever
o Pro-inflammatory mediators • Cells of the immune system
o Focus: innate cells
o Phagocytosis
o Non-phagocytic killing
NORTHWESTERN
Match the descriptions or features with the correct type of immunity.
Immunologic memory
Acquired
Nonspecific
Takes days to become active
Innate or adaptive
Adaptive
Adaptive
Innate
Adaptive
Plasma protein mediators make up the majority of proteins in plasma.
True
False
F
Which of the following describes opsonization?
lysis of pathogens
coating to mark for destruction
holes in the envelope of viruses
communication between leukocytes
Coating to mark for destruction
Match each complement fragment with the correct outcome (answers can be chosen multiple times).
C3a
C3b
C5a
C5b
Either:
Inflammation
Binding to pathogen surface to mark for destruction
Or formation of MAC (membrane attach complex)
Inflammation - C3a
Binding to pathogen surface to mark for destruction -C3b
Inflammation - C5a
Formation of MAC (membrane attach complex) - C5b
Which sign/symptom of inflammation is most closely associated with the effects of histamine and leukotrienes?
Heat
Pain
Edema (swelling)
Erythema (redness)
Erythema (redness)
Eicosanoids are derived from ________________.
bradykinin
C3a and C5a
histamine
polyunsaturated fatty acids
Polyunsaturated fatty acids
Interferons are released in the case of _______________ infections.
viral
protozoal
helminthic
fungal
bacterial
Viral
In helminthic infections, the _________________ count is typically elevated.
monocyte
lymphocyte
basophil
eosinophil
leukocyte
Eosinophil
Nat/o
Born
Medi/o
Born
Complet/o
To fill up
Opson/o
Food/Sauce
Amin/o
Amine
Ped/o
Foot/to walk
Red
Erythr/o
Pry/o
Fire/heat
Humor/o
Bodily fluids
Top/o
Place/location
Agglutin/o
Glue/stick together
Prost-
Prostate
Dia-
Through/across
-ator
One who does/
An agent that performs an action
-ment
Rest/action
-ema
Condition/state of
-gen
Producing
Cytokines
cyto- From the Greek word kytos- meaning cavity or cell
kin- From the Greek word kinesis, meaning movement
The term cytokine combines these elements to describe proteins involved in cell signaling and movement. Cytokines are small secreted proteins that play crucial roles in cell-to-cell communication, particularly in immune responses and inflammation
Bradykinin
brady- meaning slow
kin- meaning motion or to move
The term bradykinin combines these elements to describe a peptide that causes slow movement or contraction of smooth muscles. This name reflects its physiological effects, particularly its role in vasodilation and inflammation
Differentiate B and T lymphocytes.
B -
- From lymphoid stem cell
- Mature in the bone marrow
- Differentiate into (plama cells: antibodies: target extra-cellular pathogens and toxins); memory B cells
- Humoral immunity
T -
- From lymphoid stem cell
- Mature in thymus
- Differentiate into T cells with various regulatory functions (T helper, T regulatory); cytotoxic T cells: target intracellular pathogens, cancer cells; memory T cells
- Humoral and cellular immunity
Where do B lymphocytes mature?
Bone marrow
Where do T lymphocytes mature?
Thymus
T or F
Cytotoxic T cells target cancer cells and extra-cellular pathogens
F,
Cytotoxic T cells target cancer cells and intra-cellular pathogens
Give me a brief overview of antigens.
Pathogen-specific molecular structures; unique to a specific
pathogen
– Play role in stimulating humoral and cellular immunity
– Can be:
*Protiens
*Carbohydrates
—>best suited (complex and unique 3-D structures)
*Lipids
*Nucleic Acids
—> Less antigenic, often in the form of conjugates (combined with protein or carbohydrate)
What are epitopes?
Portions of antigens
– Smaller exposed region on surface of an antigen
– A large, complex protein may have hundreds of epitopes – Each unique epitope can only be bound by a specific antibody
What are Haptens?
– Small molecules that cannot be antigenic by themselves but
as a component of a conjugate
– Not associated with pathogens but responsible for some allergic reactions
– Antibodies produced against the small molecule will bind to free hapten (‘free’ epitope)
Antibodies are also called what?
Immunoglobulins
Antibodies consist of four polypeptides. What are these?
Two pair are the same —> heavy chain
Two lighter chains that are associating with the area of the variable region where the binding of the antigen is happening
What is the Fc region of an antibody responsible for?
Upregulation of complement, attraction of phagocytic cells (opsonization through antibodies), and attraction of NK and cytotoxic T cells.
Antibody-Antigen Interactions:
What two processes have a direct effects on pathogen/toxin?
Neutralization - reduces the ability to have an effect on the host. Complete coverage of a pathogen/bacterium/virus/toxins. This blocks the pathogen from interacting with the host structures.
Agglutination - Bundling/ or gunking up the pathogen. So immobilization and then again through the formation of these larger its less possible for the organism to do harm to the host.
Antibody-Antigen Interactions:
What two processes have a indirect effects on pathogen/toxin?
Opsonization - similar to neutralization, however this case involves the covering of the microorganism with antibodies attracts phagocytic cells which recognize the Fc region. Through that it recognizes that there is a foreign particle that they have to take action against another.
Antibody-dependent cellular cytotoxicity - natural killer cells will find citrus infected cells and through the binding to the Fc region will target those cells for self-destruction through apoptosis.
Activation of complement ‘classical pathway’ - this activation of complement is also facilitated in the classical pathway through the presence of antibody antigen complexes.
Draw out Antibody classes on slide 13*****
What antibody class crosses the placenta?
IgG monomer antibody
- no other antibody crosses the placenta
Mast cells and basophils are involved with binding of the Fc region in the?
A. IgA
B. IgD
C. IgE
D. IgM
C
What antibody is most reaching and consequential?
IgG
80% found in serum
What are the two MHC (Major Histocompatibility Complex) molecules?
What are their roles?
MHC Class 1
- Found in all uncleared body cells
- Internal molecules are partially degraded and presented at the surface of cells.
- Plays a major role in self-tolerance (Meaning: there is a way for the immune system to distinguish between self and foreign)
- Immune system is alerted if cell is ‘abnormal’, not healthy (intracellular pathogens; tumor cells)
MHC Class 2 - Only found in macrophages, dendritic cells, and B-lymphocytes, or B cells
*Both have an antigen binding cleft
How does self-tolerance work?
– Structure of epitope-binding sites in B and T-cell receptors
are randomly formed (randomized amino acid sequence)
—> some receptors bind to autoantigens (autoimmunity) – To prevent immune response against autoantigens, body
eliminates self-reactive lymphocytes through ‘clonal deletion’
—> triggers B- and T-cells that are binding to our own antigens to undergo apoptosis
T or F
Cells of the innate immune system only recognize pathogen associated molecular patterns, not unique structures
T
T or F
B-lymphocytes are antigen presenting cells, but functions differently
T
Overview of Antigen-Presenting Cells (APCs)
- Macrophages, dendritic cells, B lymphocytes
- Have MHC II (in addition to MHC I)
- Antigen-presentation in lymph nodes
- Upregulation of adaptive immunity of adaptive immunity
– Macrophages, dendritic cells: Part of the adaptive immune response; Recognize pathogens through PAMPs; Phagocytes that ingest and kill pathogens - B lymphocytes: Part of the adaptive immune response; Recognize specific epitopes with B cell receptors (IgD and IgM); More on this type of antigen-presentation in the humoral immune response lesson
Watch and understand animation of antigen processing and presention videos** TAKE SCREENSHOTS
Cell-Mediated immunity is also referred to as _______ _______.
Cellular immunity
Draw and understand table on slide 22!!! T lymphocytes
What are the three types of T Lyphocytes?
What are their activations?
And function?
- Helper T cells (Th cells)
Surface CD Molecules: CD4
Activation: APCs presenting antigens bound to MHC II
Function: Orchestrate adaptive immunity; Activation of macrophages and NK cells
- Regulatory T cells (Treg cells)
Surface CD Molecules: CD4
Activation: APCs presenting antigens bound to MHC II
Function: Involved in self-tolerance and prevention of autoimmunity
- Cytotoxic T Cells (Tc cells)
Surface CD Molecules: CD8
Activation: APCs or infected cells presenting antigens bound to MHC I
Functions: Destroy cells infected with intracellular pathogens
T Cell Resceptors (TCR)
Antigen-binding site is ________-_______.
Epitope-specific
*antigen must be bound to MHC I or II
__ million unique epitope binding site
25
Discuss the process of activation/differentiation of the Helper T Cells. *also go back and rewatch the video explaining this
- Also called Th cells and CD4+
lymphocytes
– MHC II presents to T cells that
have CD4 membrane complex – Successful binding between
presented epitope and T cell
receptor triggers clonal
proliferation and differentiation
What is the function of Helper T Cells (Th 1 lyphocytes & Th 2 Lymphocytes)
Th 1 - CELL-MEDIATED IMMUNITY
Lymphocytes • Secrete IL-2 • Activation and differentiation of CD8
lymphocytes to form cytotoxic T cells • Stimulation of macrophages and
neutrophils • Stimulation of NK cells
Th 2 - HUMORAL IMMUNITY
• Secrete IL-4 • Activation and differentiation of B
lymphocytes —> antibody production • Regulate what type of antibody class
is produced
Activation and Differentiation of Cytotoxin T Cells happens where?
Lymph nodes
Watch video on lecture explanation and draw slide 26***
What are the 4 main points of activation and differentiation of Cytotoxic T Cells formation?
- Antigen presentation
- Th differentiation
- Clonal Expasion - memory T Cells
- Self-stimulation - Active Tc Cells
T or F
MHC I is present in all nucleated cells
T
What are perforin?
Complex pores in the process of cytotoxic I Cell Activity
Active _____ lymphocytes leave lymph nodes to find pathogen-infected cells in the infected tissue
Tc lymphocytes
Inactive apoptptic enzymes are/do what?
What are they? (Two types of protein molecules)
Precursor enzymes that initiate destruction of virus infected cell
Perforin - forms complex pore for granzyme to travel through
Granzyme - activate apoptotic enzymes leading to apoptosis
B Cell Receptors
- IgD and monomeric IgM – Each naïve mature cell has approx. 100’000 copies of BCRs in CM, all with the exact same epitope binding site – Variability in epitope binding sites through genetic rearrangement
What is humoral immunity?
Immunity mediated by antibodies secreted by highly differentiated B lymphocytes, called plasma cells
B Cell Production and Maturation
- Derived from lymphoblasts – Stay in bone marrow for maturation – Clonal deletion or negative selection eliminates self-reactive B cells – Final maturation steps happen in spleen: Naïve mature B cells
Humoral Immunity T Cell-Independent Activation of B Cells
– T-independent antigens are large with
a repetitive structure
(polysaccharides, capsules,
lipopolysaccharides) – Cross-linking with repeating subunits
and BCRs serves as the trigger for
the activation of the B cell
** Slide 32 diagram
Humoral Immunity Plasma Cells
– Majority of cells produced during B
cell proliferation – Highly differentiated, single-purpose
cell: production of antibodies – During differentiation, BCRs
disappear – Cells short-lived (a few days-weeks) – Half-life of IgG in blood: approx. 21
days
What results from Humoral Immunity: T Cell-Dependent Activation of B Cells?
Antibodies and Memory B Cells
– Typical for free protein antigens (e.g.
exotoxins, or partially degraded
proteins presented via MHC II) – Proteins associated with pathogens – B cell with matching BCR ingests
antigen and presents to CD4+ cells
via MHC II; somewhat of a
confirmation process – IL-4 from Th2 stimulates B cell to
undergo clonal expansion and for
cells to differentiate into plasma
cells – Some of the cells will become
memory B cells
Explain the effects of immunologic memory. What is primary and secondary immune response?
Building of antibodies after a primary exposure to antigens over 10-20 days then secondary antigen exposure influx of IgG and IgM.
After the first exposure there is a lag period in which the exposed person serum does not contain any detectable antibodies. After several days, the concentration of antibodies slowly rises, followed by a gradual decline. This is the primary response.
**Come back and add
Write out Summary parts and what you know from the unit*
– Elements of adaptive immunity
– Specificity
– Memory
– B and T lymphocytes
– Antigens and antibodies – MHC and antigen-presenting cells
– For upregulation of adaptive immunity – Cell-mediated immunity
– Types of T lymphocytes
– Targets cells infected with intracellular pathogens – Humoral immunity
– T-independent and T-dependent
– Plasma cells
– Primary and secondary immune response
Antibodies are _______________.
carbohydrates
lipids
nucleoties
proteins
Proteins
B cells mature into naive B cells in ________________.
lymph nodes
the serum
the bone marrow
The bone marrow
Match the statement about antibody function with the correct class of antibodies
Most abundant antibody in the serum
Associated with allergic reactions
Conveyed to infants through breast milk
Appears first in a primary immune response
IgM
IgA
IgG
Most abundant antibody in the serum - IgG
Associated with allergic reactions - IgE
Conveyed to infants through breast milk - IgA
Appears first in a primary immune response - IgM
Match the function with the correct cytokine
Promotes humoral immunity
Promotes cellular immunity
Stimulates macrophages and neutrophils
Promotes antigen-presentation
IL-12
IL-4
IL-6
IL-2
IL-8
Promotes humoral immunity - IL-4
Promotes cellular immunity - IL-2
Stimulates macrophages and neutrophils - IL-2
Promotes antigen-presentation- IL-12
Which of the following is NOT a so-called antigen-presenting cell?
T lymphocyte
macrophage
dendritic cell
B lymphocyte
T lymphocyte
The function of MHC (major histocompatibility complex) is to
upregulate the humoral immune response.
recognize antigens.
present antigen fragments to T cells.
break down antigens.
Present antigen fragments to T cells
Which type of antibody can pass through the placenta?
IgE
IgA
IgM
IgD
IgG
IgG
***Look over slide 41 and draw out scenarios of acquired immunity
Active artificially acquired immunity is?
Immunization through administration of antigens
Passive artificially acquired immunity is?
Immunotherapy through administration of antibodies
What is herd immunity?
Occurs if there is only a small number of susceptible individuals in a population —> protection for individuals who cannot get vaccinated
What are the classes of vaccines? (Describe each)
***Stop- pick up on slide 46
– Live attenuated
– Inactivated
– Subunit; Conjugated
– Toxoid
– Nucleic acid
Patients may find themselves in the following four scenarios. Choose the correct type of acquired immunity that is a consequence of each scenario.
Influenza vaccine
Anti-hepatitis B serum
RSV (respiratory syncytial virus) infection
IgG in newborn’s blood
Articical, passive
Artificial, active
Natural, passive
Natural, active
Influenza vaccine - artificial, active
Anti-hepatitis B serum - artificial, passive
RSV (respiratory syncytial virus) infection - natural,
active
IgG in newborn’s blood - natural, passive
DNA vaccines …
A. lead to the expression of an antigen in the recipient of the vaccine.
B. have been commonly and successfully used in humans for the last 20 years.
C. lead to the recipient of the vaccine producing antibodies against that DNA.
D. contain antibody-encoding DNA
A
Which type of vaccine typically requires the least number of booster shots?
A. Subunit
B. Inactivated
C. Live attenuated
D. Toxoid
C
Which of the following is the least stable class of vaccines?
Toxoid
Inactivated
Live attenuated
Subunit
Live attenuated
The relatively weak immune response generated by subunit vaccines is ________________ immunity.
cellular
passive
humoral
innate
Humoral
Antisera (plural of antiserum) often lead to hypersensitivity (allergic reactions), as they contain many different types of antibodies. With monoclonal antibodies the risk of hypersensitivity is much reduced.
True
False
True
Match the entity that is tested for with the correct type of testing.
Presence of specific antigen in patient sample (serum, sputum,…)
Presence of specific antibody in serum sample
Direct
Indirect
Presence of specific antigen in patient sample (serum, sputum,…) = direct
Presence of specific antibody in serum sample = indirect
Which of the following uses labeled antibodies?
Agglutination
Neutralization
Precipitation
ELISA
ELISA
A population has ______________ immunity, when a significant portion of the population is immune and provides immunity to those who are not immune.
naturally acquired
adaptive
innate
herd
Herd
Live attenuated vaccines consist of what?
—>Weakened strain of a pathogen
– > subclinical infection that activates adaptive immune response
– ‘Attenuation’ = processes that decrease pathogen’s virulence
– Genetic modification – Cultivating (‘breeding’) strains with lower virulence
—> Live organisms lead to stronger and more comprehensive immune
response
(cell-mediated and humoral for viruses)
– Typically, fewer booster shots required compared to other vaccines
– Can be developed to be administered via mucous membrane uptake
(influenza mist, oral polio vaccine)
– Can even lead to transmission and indirect immunization of others
What are the disadvantages of live attenuated vaccines?
Disadvantages:
– Challenges with long-term storage and transportation (especially to remote areas in
the developing world) – Chance of developing signs and symptoms of disease that can become dangerous
in immunocompromised individuals not administered to
– Cancer patients – Transplant recipients on immunosuppressive drugs – In first few months of life and to elderly
– Risk of reversion of genetic modification (known for the live attenuated polio
vaccine)
– Salk (IPV) vs Sabin (OPV)
Explain inactivated vaccines. What are the disadvantages?
—> Whole pathogen, killed or inactivated (heat, chemicals, radiation)
– Method of killing cannot destroy key antigens that trigger the development of immunologic
memory
– No active infection —> No risk of developing active disease – Typically, very stable and easy to transport –
Disadvantages:
– Weaker immune response, less comprehensive (humoral only)
– Typically, higher doses and more boosters required potential for inflammation at site of infection
Explain Subunit Vaccines (similar to inactivated vaccines) What are the disadvantages?
- Key antigens of a pathogen – Produced through
– Processes that degrade pathogen or
– Genetic engineering of antigens – Low risk of side effects –
Disadvantages
– Weaker immune response (humoral only); requires multiple boosters
– No protection from antigenic variation
– Not very stable
Explain conjugate vaccines (subtype of subunit vaccines). What are the disadvantages?
Special type of subunit vaccine
NORTHWESTERN HEALTH SCIENCES UNIVERSITY | nwhealth.edu 13
– Antigen (capsule polysaccharide) covalently bound to a protein – Creates a T-dependent response to antigen (memory B cells and T cells) –
Disadvantages
– Costly to produce
– No protection against antigenic variation
– May interfere with other vaccines
Explain toxoid vaccines. What are the disadvantages?
Inactivated bacterial toxins
Openstax Microbiology: Table 18.3 is a nice compilation of these vaccines with examples of vaccines that are currently in use
– Activate humoral immunity that neutralizes toxin in case of real infection
Disadvantage:
– Weak response (humoral only)
– Does not prevent infection
Explain nucleic acid vaccines. What are the disadvantages?
- Injection of DNA or RNA that codes for specific antigen
*DNA —> mRNA —> protein
*RNA —> protein – - Studied and under development since the 1990ies
– First DNA vaccine approved: West Nile virus in horses (2005) – Can be developed very quickly through genetic engineering and upscaled in
production using PCR
Disadvantages:
– RNA-based vaccines are not very stable (must be stored below freezing; difficult to transport
to remote areas)
NORTHWESTERN HEALTH SCIENCES UNIVERSITY | nwhealth.edu 15
What does passive immunotherapy involve?
– Administration of antiserum containing preformed antibodies
– Immediate protection against recent infection or ongoing disease
– Limitations of antisera:
– Contain antibodies against many antigens
– Can trigger an allergic reaction called serum sickness
– Viral pathogens may contaminate antisera
– Antibodies of antisera are degraded relatively quickly
– Limitations: are overcome through development of monoclonal
antibodies
What is the definition of serologic? What are the two categories?
Study and diagnostic use of antibody-antigen interactions in blood serum.
Two categories:
- Direct testing - looking for presence of antigen interactions serum
- Indirect testing - looking for the presence of antibodies in serum
What are the 5 serologic tests?
- Precipitation test
– Agglutination tests
– Neutralization tests
– Complement fixation tests
– Tagged antibody tests
Overview of precipitation test (type of serologic test).
- One of the easiest of available serological tests – A soluble antigen and antibodies are mixed in the proper
proportion and form large complexes called ‘precipitates’ (or
precipitin’): visible cloudy –
Immunodiffusion: Determines optimal antibody and antigen concentrations
What is agglutination?
What is hemagglutination?
What does the term ‘titer’ mean in the context of aggulatination tests?
Agglutination: refers to the process by which particles, such as cells, clump together. It typically occurs in biological contexts, like when red blood cells clump due to the reaction between antibodies and antigens. Agglutination is commonly used in laboratory tests, like blood typing, where specific antibodies cause clumping when they encounter corresponding antigens.
Hemagglutination: Agglutination of red blood cells
– Can be used to determine blood type
– Coomb’s test: Used to check for compatibility between transfusion recipient and donor
blood
Titer: is the highest dilution where aggulation is still visible. This can be helpful in diagnosing.
Explain neutralization test (type of serologic test).
*Can only be used for indirect testing (checking for presence of
antibodies)
*For certain viral diseases: these viruses must have a cytopathic effect,
which means lyse cells (typical for non-enveloped viruses):
– If antibodies are present, they will neutralize the virus that is mixed with the patient’s serum, and the cells will not lyse: the solution stays cloudy
– If antibodies are not present, there is no neutralization of the virus and the
cells in the solution will lyse: the solution becomes clear
T or F
Typical viruses that have cytoplasmic effects that leads to lysis of cells quickly are non-enveloped
T
Because the only way that they can be released from the infected cells is through lysis of the host
During a neutralization test when cells are added to a serum that already has antibodies there will be?
A. Lysis
B. Neutralization of cells
C. No lysis
D. Solution will become darker
C
So if the solution stays cloudy and bothering happens, then that is a positive result for the presence of antibodies.
If no antibodies are present, there is no neutralization of the virus. In infects the cells, the cells will lysis and solution will become clear.
Explain complement fixation test (type of serologic test).
– Based on formation of membrane attack complexes during complement
activation if there are antibody-antigen complexes formed (upregulation
through classical pathway)
– Indirect testing only (presence of specific antibodies in an individual’s
serum)
– More sensitive than agglutination
– Nowadays less commonly used
T or F
The upregulation of complement happens through antibody antigen complex formation in the classical pathway
T
This is only usable for indirect testing. To test for the presence of antibodies interactions an individuals serum.
What is a labeled antibody test?
– Uses antibody molecules linked to some
“label” that enables them to be easily
detected
– Used to detect either antigens or
antibodies (direct or indirect)
– Label attached to F c region
Types of tests:
- Fluorescent antibody test: involves antibodies that have a fluorescent dye attached
- ELISA: (enzyme linked immuno sorbent assate)- transfers substrate into product. Substrate is added; if present, enzyme converts substrate to colored product. Positive sample is bound means antibody is bound to antigen. Unbound sample is washed away.
- Western Blot (uses ELISA principle)
Explain direct vs indirect labeled antibody tests.
A direct labeled antibody test, the primary (or “direct”) antibody is labeled with a detectable marker (such as a fluorescent dye, enzyme, or radioisotope) that allows it to be visualized when it binds to the antigen.
In an indirect labeled antibody test, the primary antibody (which binds to the antigen) is not labeled. Instead, a secondary antibody, which is labeled with a detectable marker, binds to the primary antibody. This indirect method amplifies the signal because multiple secondary antibodies can bind to a single primary antibody.
- look up more differentiation later
– Indirect labeled antibody tests more common; labeled
antibody is binding to Fc of antibodies and is universally
usable as it is an anti-antibody – Direct testing requires unique monoclonal antibodies against
each specific antigen: ‘Sandwich ELISA’ (the antigen sits
between two antibodies)
What is immunochromatography?
Immunochromatography is a technique used to rapidly detect the presence of specific substances, such as antigens or antibodies, in a sample. It’s commonly used in diagnostic testing, particularly for point-of-care testing, due to its simplicity, speed, and ease of use.
T or F
Come cytotoxic T cells differentiate into long live memory T cells, but most mature to attack and destroy infected cells
T
What is the site of antigen-presentation that leads to adaptive immunity?
Lymph nodes
Bone marrow
Thymus
Serum
Lymph Nodes
