Module 9 - Notes Flashcards
What is immunology?
The study of the immune system and immunity
What is Immunity?
The ability of an organism to resist infections
What are the 2 main branches of immunity?
Innate immunity
and
Adaptive immunity
What is innate immunity?
a multifaceted system of defenses targeting invading pathogens in a non-specific manner.
What is adaptive immunity?
a multifaceted system of defenses that specifically targets invading pathogen and that develop memory to the invading pathogens.
What are the main features of the innate immunity system?
non-specific
quick response (within hours)
No previous exposure is required
Physical & chemical barriers
Phagocytes (neutrophils, macrophages, dendritic cells and eosinophiles)
Inflammation (mast cells & basophils)
What are the main features of the adaptive immunity system?
activated when the innate system fails
has specific recognition of pathogens
Slow process (multi steps to process antigens/epitopes)
Develops memory
T-Cell
B-cells and antibodies
The innate system is composed of:
A) Barrier defense, phagocytes, and the complement system
B) Both barrier defense and phagocytes
C) Several non-specific mechanisms that include barrier defenses, phagocytes, the complement system, inflammation, and fever.
D) Only phagocytes
E) Only barrier defenses
C) Several non-specific mechanisms that include barrier defenses, phagocytes, the complement system, inflammation, and fever.
What are the physical barriers in innate immunity?
Cellular barriers that deny entry
- skin
- mucous membrane
- endothelial cells
Mechanical defenses that remove potential threats
- shedding of skin cell
- mucociliary sweeping
- peristalsis
- flushing action of urine & tears
Microbiome
- complete with pathogens
What are the chemical barriers in innate immunity?
Body fluids
- chemicals that regulate pH & inhibit microbial growth
- enzymes (lysosymes)
Antimicrobial components
- antimicrobial peptides (AMPs)
- bile acids
Complement systems
Cytokines
Mediators of inflammation
Why would a fishmonger develop fish tank granuloma (ie. Skin infection caused by mycobacterium marinum)?
A) The bacteria used their flagellum to dig a hole in the skin
B) Cuts on the skin remove a layer of the innate protection and allow entry of bacterial pathogens
C) The slime layer of the skin was dissolved by salt water
D) Macrophages accumulated under the skin in response to traumatic shock from a fish bite
B) Cuts on the skin remove a layer of the innate protection and allow entry of bacterial pathogens.
What is the complement system of innate immunity?
Plasma proteins
- Sequential interaction (cascade)
- Enzymes
- Membrane attack complex (MAC)
C1, C2, C3…..C9
What is a membrane attack complex?
Plasma Proteins that creates a hole inside the membrane causing the cytoplasm content to leak out
C6/C7/C8/C9
How is the complement system activated
3 different triggers - all result in the activation of the C3 complement protein
Classial Pathway - C1
Lectin Pathway - Mannose-binding lectin
Alternate pathway
Ultimately the all cleave and result in C5b which activates the Membrane Attack Complex = C6/C7/C8/C9
How are the proteins of the complement system designated?
C = complement
# = order of discovery
a = anaphylatoxin = inflammation
b = opsonization
What happens with opsonization?
The bacteria is coated with proteins that signal a macrophage to eat it.
What is the role of Cytokines & Chemokines in innate immunity?
They act as molecular messengers of the immune system.
Cytokines bind to receptors
-signal a cascade leading to transcription activator
Chemokines are a subclass of cytokines
-recruit circulation immune cells to site of injury
What is an autocrine function?
The same cell that releases the cytokine is the recipient of the signal
self-stimulation
What is a paracrine function?
involves the release of cytokines from one cell to other nearby cells, stimulating some response from the recipient cells.
activates a community response
What is an endocrine function?
occurs when cells release cytokines into the bloodstream to be carried to target cells much farther away
What are interferons?
sub-class of cytokines
there to stimulate the immune system to mount a proper defense against viruses
activate anti-viral response of nearby cells
Which organs of the body are involved with the innate immune system?
Blood & lymphatic systems
- allow circulation and distribution of immune cells
-lymph dumps antibodies and immune cells in the blood
Secondary lymphoid organs
- lymph nodes - leukocytes to detect antigens or pathogens circulation in the lymphatic system
- mucosa-associated lymphoid tissue (MALT)
- spleen
What are the key cellular players in innate immunity?
Derived from pluripotent hematopoietic stem cells
- Erythrocytes (red blood cells)
- Leukocytes (white blood cells)
- Platelets
Monocytes - immature
- mature/differentiate
Granulocytes
- granules that can be stained
- toxins and enzymes
- destroys their targets
What is the role of Dendric Cells?
antigenic-presenting cells (APCs) residing in the skin and mucous membranes
Process and ID antigens then present those antigens to other cells
What is the role of Macrophages?
APCs residing in the tissues and organs (Spleen, lymph nodes, MALT)
Process and ID antigens then present those antigens to other cells
What is the role of Neutrophiles?
elimination and destruction of extracellular bacteria
What is the role of Eosinophiles?
Protection against protozoa and helminths (parasites) and they play a role in allergies
What is the role of Basophiles?
role in inflammation and allergic reactions, found in the blood.
What is the role of Mast Cells?
role in inflammation and allergic reactions; found in the tissues
What is the role of Natural Killer Cells?
Kill virus-infected cells and cancerous cells
(lymphocyte)
What kind of lymphocytes would you expect to be over-represented at the site of a viral infection?
A) Basophils
B) Macrophages
C) Neutrophiles
D) Natural Killer Cells
E) Eosinophiles
D) Natural Killer Cells
They are the only one on the list that are lymphocytes
what is MHC1?
a molecule on the surface of cells that IDs them as part of the natural host
They are the secret handshakes
Major Histocompatibility Cell
How does a natural killer cell act on intracellular pathogens?
If it does not recognize the MHC1 on the cell then it will kill it.
What happens when your body is subjected to a microbial invasion at a cut?
Tissue damage will activate phagocytes (macrophages)
Release of cytokines and chemokines
recruits neutrophil and T-Cells
Neutrophils enter tissue by sticking to capillary wall (Margination), rolling and squeezing in the cellular junctions (diapedesis)
How does your body recognize pathogens?
Pathogen-Associated Molecular Pattern (PAMS)
-unique microbe structures
Pattern Recognition Receptors (PRRs)
- toll-like receptors (TLRs) External
- NOD-like receptors (NDRs) Internal
Signal transduction
Phagocytosis
-engulfment of pathogen
How can the immune response recognize pathogens during their first encounter?
Pathogen-associated molecular patterns - recognized by pattern recognition receptors.
What is phagocytoisis?
The uptake of extracellular pathogens (phagosome) by a macrophage.
The purpose is to destroy the pathogen
Macrophage has membrane-bound inclusions (Lysosomes) which have bactericidal substances & enzymes
The lysosome fuses with the phagosome to become a phagolysosome
Why would a fishmonger develop granuloma in response to mycobacterium marinum infection?
Aggregation of macrophages and other immune cells formed in response to chronic inflammation
What is acute inflammation?
Normal biological response
-promotes healing
Characterized by redness, swelling, pain, and heat
Production of activators
- Pro-inflammatory molecules (histamine)
- Phagocytes & Lymphocytes
- Induce vasodilationn
- Increase vascular permeability
Influx of phagocytes
- increase inflammation
What happens when you get a fever?
Fever is not an inflammatory response
(not localized) if you increase the temperature, bacteria will start to die. Same with viruses
Cytokines will induce fever
- endogenous pyrogens
LPS will induce fever
- exogenous pyrogen
Act on prostaglandins
- act on hypothalamus
Limit growth of pathogen
Uncontrolled inflammation
- toxic/septic shock
Why would treating a fever with antibiotics be contradicted?
A fever is a non-specific symptom that could be triggered by an array of microbial pathogens
What are the 2 components of adaptive immunity?
Humoral immunity
Cell-Mediated Immunity
What is adaptive immunity?
adaptive & specific response
Discriminate - distinguish between specific foreign molecules
Diversify - recognize many possible foreign molecules
Memorize - remember foreign molecules after the first exposure
What is humoral immunity?
antibodies produced by B-cells (Bone marrow lymphocytes) in response to antigens
What is cell-mediated immunity?
Activation of T-Cells (thymus lymphocytes) to control intracellular microbes (virus, bacteria, parasites)
What is the difference between the antibody production in an immune response vs an adaptive response?
This graph illustrates the primary and secondary immune responses related to antibody production after an initial and secondary exposure to an antigen. Notice that the secondary response is faster and provides a much higher concentration of antibody.
What is an antigen?
a molecule/substance that interacts with antibodies or a T cell receptor (TCR)
- Not all antigens induce an immune response
What is an Immunogen?
It activates an immune response
What is a hapten?
a small molecule that binds to an antibody
-does not induce an immune response
- needs a carrier to be an immunogen
What is immunogenicity dependent on?
- Complexity
- Physical form and structural form
- Dose
What are epitopes?
Sections of specific regions of an antigen that are recognized by an antibody
What is the relationship between antibody/antigen recognition?
1 epitope is recognized by 1 antibody
an antigen can be recognized by multiple antibodies because 1 antigen can have multiple different epitopes.
What are antibodies?
Immunoglobulin
- glycoproteins
Monomer
- 4 protein chains held by disulfide bond
Y-Shaped
- 2 heavy chains + 2 light chains
Fragment of antigen binding - FAB region
- variable: diversity & specificity
- Provide function (binds to the antigen)
Fragment crystallization - FC region
- binds to complement and phagocytes
What are the 5 different functions of antibodies?
- Opsonins (opsonization)
- Neutralization
- Agglutination
- Immune Activation
- Cell-Mediated Cytotoxicity
How does opsonization work?
It coats the bacteria with antibodies
The FC region will recognized by the macrophage
How does neutralization work?
neutralizes the function
prevents the spike protein from attaching to target cells
How does agglutination work?
Binds epitopes simultaneously forming little balls
How does cell-mediated cytotoxicity work?
antibodies bind to a large pathogenic cell that is too big for phagocytosis and then bind to Fc receptors on the membrane of a natural killer cell. This interaction brings the NK cell into close proximity, where it can kill the pathogen through release of lethal extracellular cytotoxins.
What are the immunoglobulin classes?
IgA
IgD
IgE
IgG
IgM
What is IgA?
Major secretory antibody
Function using Neutralization
The dimer is found in secretions
The Monomer is found in blood
What is IgD?
Acitvate B-Cells
functions as a B-Cell Receptor
found in B-cells
What is IgE?
Parasite Immunity
FC binds and activates mast cells and basophils (play a role in allergies)
Found in blood and lymph
What is IgG?
Major circulating antibody
Fc binds phagocytes
Crosses placenta
Function using neutralization, agglutination, complement activation, opsonization, cell-mediated cytotoxicity
Found in blood, lymph and extracellular fluid
What is IgM?
First antibody to appear
Functions using Neutralization, agglutination, complement activation.
Found in blood and lymph
What is the role of antibodies against the spike proteins of SARS-C0V-2 if the antibodies block viral attachment?
- Opsonization
- Neutralization
- Agglutination
- Immune Activation
- Cell-Mediated Toxicity
Neutralization
What is the difference between MHCI and MHCII?
MHCI
- found on all nucleated cells
- present self antigens
- present non-self antigens
(secret handshake)
MHCII
- found on macrophages, dendritic cells, and b cells
- Present non-self antigens
What are Antigen presenting cells (APCs)?
Antigen-presenting cells
- cells that process and present antigen
- macrophages, dendritic cells, and b cells
- recognize and progress antigens differently
MHCII Processing and Presentation
-B cells vs Phagocytes
-Antigen processing occurs in the phagolysosome
- not all antigen presented
- immunogenic and/or dominant
Explain T cell selection
Differentiate between host antigens self and danger anitgens non-self
Each T cell receptor (TCR) binds a different antigen
Selection occurs in the thymus
Positive Selection TCR with weak interaction = does not lead to an immune response. The T cell continues to interact and grow
Negative Selection TCR with strong interaction = cell death
What are the classes of T cells?
Helper T Cells
Regulatory T Cells
Cytotoxic T Cells
Helper T cells are divided into which subclasses?
Th1
Th2
Th17
Memory
What is the function of Th1?
Activation of cytotoxic T-Cells, neutrophile, NK and macrophage
activated by APC with antigens + MHCII
Surface CD Molecules = CD4
The outcome is cell-mediated immunity
What is the function of Th2?
Activation of B cells
Activated by APC with antigens + MHCII
Surface CD Molecules = CD4
The outcome is antibody-mediated immunity
What is the function of memory T cells?
Remember specific pathogens
Activated by APC with antigens + MHCII
Surface CD Molecules = CD4
The outcome is a strong secondary response.
What is the function of Regulatory T Cells?
Tolerance and prevention of an autoimmune response
Activated by APC with antigens + MHCII
Surface CD Molecules = CD4
What is the function of Cytotoxic T Cells?
Destroy cells with intracellular pathogen
Activated by APC or infected cells with antigen + MHCI
Surface CD Molecules = CD8
The outcome is cell-mediated immunity
Leads to memory cytotoxic t cells
Explain T Cell Receptors.
Bind Antigens
Initiate activation
T-Cell co-receptors
-strenghten the interaction between TCR & MHC
CD4 binds MHCII
CD8 bind MHCI
What are CD molecules?
Cell differentiation molecules
cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells
If you are designing a vaccine and want a strong antibody response, what type of T cells would you target to ensure strong B Cell activation?
Th1 Cells
Th2 Cells
Th17 Cells
Treg cells
Cytotoxic T Cells
Th2 Cells
What are the different vaccine classes?
Live Attenuated
Whole Inactivated
Toxoid
Conjugated
Viral-Like Particle
Viral Vector
RNA
DNA
what are live attenuated vaccines?
non-pathogenic viable microbe
mimics a “real” infection and provides balanced immunity
Not safe for immunocompromised people & there is a risk of reversion
What are Whole inactivated Vaccines?
Pathogen is dead
You are injected with the entire microbe without risk of infection
Provides a weaker immunity and you often need a stronger dose plus boosters
What are toxoid vaccines?
Immunogenic pieces of the microbe with inactivated toxins.
Produce limited side effects
Booster shots are required and they don’t last long
examples = tetanus, diphtheria, pertussis
What are conjugated vaccines?
low immunogenic antigen attached to an immunogen
Effective in younger kids
Costly to produce and they may interfere with other vaccines
What are viral-like particle vaccines?
Proteins that assemble as a capsid
Mimic the virus
They have low immunogenicity and they are complicated to manufacture
What are viral vector vaccines?
a virus expressing an antigen
They mimic a natural infection
Risk of genomic integration and there could be a natural immunity to the vector
Example is the HPV Vaccine
What are RNA vaccines?
RNA Strand that can be translated
Highly adaptable and provide strong cell-mediated immunity
Costly to store and they provide weak humoral immunity
What are DNA vaccines?
DNA strand that can be transcribed
Highly adaptable vaccines
But there is a risk of genomic integration
