Immunology Flashcards
The function of the immune system is to…..
Prevent and control infections, eliminate pathogens and their harmful products.
The immune system is characterized by layering and redundancy. WTF does that mean?
Layering- Multiple layers of protection.
Redundancy- A single pathogen can be fought by the immune system in multiple ways.
What are the two major types of immunity?
Innate, Adaptive/acquired
Pathogen motif receptors and Antigen-specific receptors are used to tell the difference between….
Self and Non Self
Blood is an important component of the immune system, it contains….
Leukocytes, Lymphocytes, Clotting Factors, Complement, Antibodies
The immune response consists of two parts, ____ and recruitment of effector mechanisms.
Recognition of pathogens
What do Lymph Nodes do?
Filter interstitial fluids, removes antigens and makes them available to B/T cells, place for B cells to make antibodies.
Which immune system is present at birth, and is always present at basal levels?
Innate immunity
T or F. The innate immunity provides immunological memory.
False. Adaptive/acquired immunity
T Lymphocytes have _____ that recognize the pathogen participate in the adaptive response.
Receptors
What are the two categories of adaptive immunity?
Humoral, Cell Mediated
What cellular/noncellular components make up innate immunity?
Leukocyte, Biochemical constituents (enzymes), anatomical/physical barriers, proteins (complement, cytokines, chemokines), inflammation
What are the 3 properties that make Adaptive Immunity so effective and protective?
Diversity, Specificity, and Memory
_____ respond to a single foreign antigen and become activated only when that antigen is encountered.
Lymphocytes
Name the 3 states of a mature Lymphocyte.
Naive, Effector, Memory
Name 3 different Leukocytes/Granulocytes.
Basophils, Eosinophils, Mast Cells
Antigen Presenting Cells engulf pathogens and present them to T Cells. Name 3 types of APCs.
Dendritic cells, macrophages, B cells
_____are produced by activated B-Cells.
Antibodies
_____are mainly produced by activated immune cells like T-cells, Macrophages, and NK cells.
Cytokines
This subset of the adaptive immunity protects against EXTRAcellular pathogens.
Humoral Immunity
T or F? CD4 TH1 is found in the Humoral Immunity.
False. CD4 TH2
This subset of the adaptive immunity protects against INTRAcellular pathogens.
Cell Mediated Immunity
Phagocytes process and present enulfed antigens to T Helper cells to activate what?
Adaptive Immunity
The production and secretion of what results in the upregulation of MHC class I molecules for more productive antigen presentation to cytotoxic T cells?
Interferon (IFN)
_____on the surface of an antigen can enhance B cell activities.
Complement Proteins
Cytokines upregulate ______ molecules on phagocytes for better antigen presentation to T Helper cells.
MHC class II
What recognizes LPS and sends a signal to activate NF-kappaB which leads to production of cytokines and the upregulation of molecules important for B/T cell activation?
TLR 4
Name 3 ways the adaptive immunity activates/regulates the innate immunity?
T cells produce cytokines that enhance phagocytosis and oxidative burst.
Antibodies bound to the surface of an antigen increase their uptake by phagocytes (opsonization)
Cytokines produced by activated CD4 T cells (T 1 Helper cells) activate macrophages and upregulate expression of Fc receptors on macrophages, NK cells, and neutrophils.
The ____branch of the adaptive immunity has both T helper 1 and T helper 2 cells.
Humoral
What is the single effector function of B cells?
To produce antibodies
What is a membrane form of an antibody that plays an important role in B cell activation?
B Cell Receptor (BCR)
What is the role of soluble (secreted antibodies)?
Recognize and bind extracellular pathogens and their products and deliver them to phagocytes for removal
(edited by KH)
What allows antibodies to share common effector functions?
Conserved sequences.
T or F? Antibodies can kill and remove pathogens by themselves.
False.
The specificity of an antibody is attributed to to the _____ region.
Variable.
The biological activity of an antibody is determined by the _____ region.
Constant.
Do constant regions of antibodies differ between different isotypes?
Yes.
How many light and heavy chains does an antibody molecule have?
2 Heavy, 2 Light.
The two L chains do NOT interact with each other.
……
What type of bond connects each L chain to an H chain?
Interchain disulfide bonds.
What type of bond connects the two H chains to one another?
Interchain disulfide bonds.
How heavy are heavy chains?
50,000 Da
How heavy are light chains?
25,000 Da
The variable region of the L and H chains determine specificity. Where is the variable region?
The N-Terminal.
Why do different antibody isotypes have different functions?
The constant regions.
The constant region of the heavy chain is subdivided into __domains.
Three
The constant region of the light chain is subdivided into __ domains.
One
Which Immunoglobulins have 4 CH domains?
IgM, IgE
The antibody molecule can be divided into functional regions, they are……
Fab- Fraction antigen binding
Fc- Fraction crystallizable
Hinge- Present in IgG, IgA, and IgD (all have 3 CH domains)
What enzyme is capable of breaking an antibody into 2 Fab and 1 Fc?
Papain
This region of an antibody retains the ability to bind antigen, consists of the VH, VL, CL, and CH1 domains. Each full antibody also contains TWO of these fragments.
Fab
What two distinct functions are served by the Fc region?
Delivers the antibody to specific anatomical sites (she spells it sights in her notes….?)
Assists in Opsonization by binding to Fc receptors on immune cells that phagocytose the attached antigen.
This portion of the antibody molecule contains CH2, CH3, and CH4 (if it exists), and most of the hinge.
Fc
How many fragments of Fc per antibody?
One
If Pepsin is used to generate an F(ab)2, which portion was NOT generated?
Fc. It is cleaved BELOW the hinge.
What AA residues primarily make up the hinge region?
Pro, Ser, Thr
What allows the 2 Fab arms to open/close to accommodate binding to 2 epitopes?
The Hinge region
The hinge region is found between what two domains?
CH1 and CH2
T or F? IgG, IgA, and IgD all have 3 CH regions, which means they DO NOT have a hinge region.
False, they do! Seriously. They do.
What two fragments retain the ability to bind antigen?
Fab and F(ab)2
What is the small glycoprotein associated with POLYMERIC IgA and IgM (Not hexameric IgM)?
J chain
How many J chains per antibody?
One
What is the function of the J chain?
Polymerization and interaction with the poly-Ig receptor (transports antibodies from the basal side of the epithelium onto the luminal side of the mucosal surface)
What type of bonds give antibody molecules their globular shape and separate the domains of each chain?
Intra chain S-S Bonds
Which portions of the L chain interact with what portions of the H chain in the Fab portion?
VL with VH
CL with CH1.
Within the Fc portion, the CH3 domains interact, but the two _____ domains do not.
CH2
The V region is subdivided into what two regions?
Hypervariable and framework regions.
What region of the Variable region actually makes contact with the epitope?
Hypervariable
The hypervariable region is present in both the VL and VH regions. True or false: There are 3 different stretches of 8-11 AAs in both regions.
True
Hypervariable regions are also known as……
Complementarity-Determining Regions.
How many CDRs per monomeric antibody molecule?
12 (3 from each L chain and 3 from each H chain)
The remaining 80ish AAs of the V region between CDRs are called…..
Framework Regions
How many Framework regions in each V region?
Four
What are the two types of light chains?
Kappa and Lamdba
T or F? Both L chains in a given antibody molecule are NOT the same.
False. They are identical (both Kappa or Lambda)
T or F? There is no known effector function associated with the L chain.
True.
What chain determines the class/isotype and the effector function of the antibody?
H-Chain
What are the 5 major H chain isotypes?
IgA, IgD, IgE, IgG, IgM
IgG is subdivided into how many classes in humans?
Four. IgG1, IgG2….
IgA is subdivided into how many classes in humans?
Two. IgA1, IgA2
T or F. Since Isotype is determined by the C region, it has nothing to do with antigen specificity.
True. Specificity is controlled by the V region.
What is the first isotype secreted when B cells are activated by T cells?
IgM
IgM is made almost exclusively as a _____, but has been found as a hexamer.
Pentamer.
What is the most efficient isotype for activating the classical complement pathway?
IgM
What is the only isotype made by a fetus?
IgM
What is the half life of IgM?
5 days
If you have an IgA deficiency, how does that affect IgM secretion?
IgM secretion increases.
What is the major source of IgM in saliva?
Gengival cervicular fluid
What is the half life of IgG?
23 days. Except for IgG3, which is 7 days.
What isotype is the most abundant in tissues and serum?
IgG
What is the only isotype that crosses the placenta?
IgG (IgG1>IgG3>IgG2>IgG4)
Which isotype is bound Fc receptors and can participate in ADCC?
IgG
When does IgG production start in infants?
4-6 months
The small size of IgG allows it to do what?
Cross the vasculature and endothelium.
Which subtype of IgG is found in about 50% of the Caucasian population?
IgG2
How many subclasses of IgA are in humans?
Two
WHat is the half life of IgA?
Five days
What is special about dimeric IgA + Lysozyme?
It can kill a pathogen (Protective for breast fed infants).
_____is usually directed against protein epitopes.
IgA1
_____is usually directed against polysaccharide epitopes.
IgA2
The most abundant of all the antibodies.
IgA
What is the most predominant isotype found in secretions and mucosal surfaces?
IgA (specifically Dimeric SIgA)
Where is most monomeric IgA found?
The serum
IgA is second to ____ in regards to being found in serum.
IgG
SIgA is secreted by salivary glands into the…..
Oral cavity
Most IgE is bound to ____receptors on the surface of mast cells, basophils, and eosinophils.
Fc-epsilon
What is the half life of IgE?
Two days
This isotype mediates immediate hypersensitivity reactions.
IgE
Most IgE secreting plasma cells are thought to be located primarily in the ______
Pharyngeal tonsils
IgE binds to _____, casusing degranulation of attached granulocytes.
Parasites
Which isotype is found primarily on the surface of naive, mature B cells after they leave the bone marrow?
IgD
What role does IgD hold as a BCR?
B cell activation
What is the least common Ig made?
IgD
If IgD is missing from the B cell surface, what can happen?
Self reactive B cells can enter lymphoid organs and proliferate.
What isotypes contain a J chain?
IgA + IgM
What isotype contains an S component?
IgA
What study partners do you stay up for until 2am working on cards so you won’t let them down?
Karin Hwang
Sarah Stamper
What is hematopoiesis?
the production of immune cells
What cells develop into cells of all different lineage and function?
Pluripotent stem cells
What can hematopoetic stem cells develop into?
Self- renewing stem cell Myeloid cell (and later into RBC, erythroid cells, monocytes/macrophages and granulocytes) Lymphoid cell (T cell, B cell, NK cell)
Where do hematopoiesis occur in children and adults?
Bone marrow and Thymus
How long do monocytes circulate in the blood?
1-3 days
How do macrophages relate to monocytes?
Macrophages are monocytes that have exited the blood and become fixed in tissues
What is another name for macrophages that have exited the blood and become fixed in tissues?
Tissue Fixed Macrophage
What are common surface receptors for macrophages?
CR3 (complement receptor 3) and Fc (the Fc portion of IgG and IgE antibodies)
What is the role of the CR3 surface receptor on macrophages?
allows for complement protein C3B to bind (aids in opsonization)
What is the role of Fc surface receptor on macrophages?
Aids in opsonization or ADCC (Antibody-dependent cell-mediated cytotoxicity)
How can macrophages be activated from their resting state?
1) Interferon-gamma
2) Pathogen-Associated Molecular Patterns (PAMPs)
3) Opsonization
Opsonization is ______________ of antibody-coated or complement coated antigen that occurs via Fc or CR3 receptors
enhanced phagocytosis
What are the main functions of macrophages?
- Phagocytosis
- Antigen Processing & Presentation
- Production of soluble mediators
- Antibody-dependent Cell-mediated Cytotoxicity (ADCC)
What are the 3 states for macrophages?
1) Resting
2) Activated
3) Hyperactivated
Resting macrophages are also known as ______________, because they take up debris and dead cells.
“garbage collectors”
How is phagocytosis in activated macrophages different than resting macrophages?
Activated macrophages actively take up foreign invaders by recognition of a PAMP or opsonization.
How do hyperactivated macrophages kill pathogens?
Hyperactivated macrophages secrete cytokines and complement proteins and kill pathogens via OXIDATIVE BURST.
What is oxidative burst?
The release of toxic oxygen and nitrogen radicals (NO, NO2, HNO2, HCLO-, H2O2, O2-)
How does antigen processing and presentation work with macrophages?
Macrophages break down (“processes”) antigens into small peptide fragments and “presents” the antigen on its surface to T cells via MHC class I or II molecules.
Name an example of a PAMP (pattern associated molecular pattern).
PRR (pattern recognition receptor)
When the first phagocytic cell (like a macrophage) senses an invading microbe, what does it do?
It phagocytoses it and begins secreting cytokines
What cytokines does the first phagocytotic cell that senses an invading microbe release?
IL-1, IL-6, TNF-alpha
IL = Interleukin
What soluble mediators do macrophages release?
cytokines and complement proteins
For macrophages, what is Antibody-dependent cell-mediated cytotoxicity?
When the macrophage detects a target coated with a ton of a specific antibody, it releases radicals and enzymes at the surface to kill the target cell WITHOUT phagocytosis.
ADCC via macrophages occurs when the target is coated with what specific antibodies?
IgG
Which cell in the immune system is the best for phagocytosis?
Neutrophils
What are neutrophils?
Short lived dedicated killers that circulate in the blood until recruited.
What is the most predominant granulocyte, making up >90% of circulating granulocytes and 50-70% of all circulating WBC?
neutrophils
What is another name for neutrophil?
Polymorphonuclear cells (PMNs) because of their multilobed nucleus
What is immunopathology?
The release of enzymes that result in collateral damage to innocent cells during an infection
How long do Neutrophils live?
less than or equal to 2 days
What are the main functions of neutrophils?
Phagocytosis and cytokin production.
What do neutrophils release during phagocytosis?
Lytic enzymes and Defensins
What are defensins?
Small peptides that poke holes in membranes to kill phagocytosed pathogens
True or false: Neutrophils also have oxidative burst, like macrophages.
True
What pro inflammatory cytokines do Neutrophils produce?
IL-1, IL-6, IL-8, TNF-alpha
Which granulocytes have high affinity surface receptors for IgE antibodies?
Eosinophils, Basophils and Mast cells
Which granulocyte has low affinity surface receptors for IgG antibodies?
Eosinophils
What is a key role of eosinophils?
Fighting parasitic infections
True or False: Eosinophils are not phagocytic.
False; eosinophils are phagocytic.
Which granulocytes have a role in allergic reactions?
Eosinophils (major role), Mast cells (major role), and Basophils (minor role)
Which granulocyte has an important role in the pathogenesis of asthma and other chronic inflammatory diseases?
Eosinophils
What is degranulation?
The release of contents from granules
Which granules do basophils and mast cells release during degranulation?
histamine and vasodilators
Where are mast cells normally found?
Along connective tissue and skin
What is the main function of platelets?
Involved in blood clotting & inflammation
What amount of platelets are in circulation vs. in the spleen?
2/3 in circulation; 1/3 in spleen
Platelets have surface receptors for what?
1) Fibrinogen (clotting)
2) Complement protein C3b (inflammation)
3) Cytokines (CXCR4)
How do you ID dendritic cells (DCs)?
They have cytoplasmic extensions called dendrites.
Where are dendritic cells (DCs) found?
Mostly in the skin and 0.1% in the blood (i.e. rarely found in circulation)
What is main role of dendritic cells (DCs)?
Migrate to the hearest lymphoid organ to present to T cells
Name the four major functions of DCs.
1) Phagocytosis
2) Antigen presentation
3) Negative selection
4) Cytokine production
True or False: Immature and mature DCs are phagocytic.
False! Only immature DCs are phagocytic. Mature DCs are NOT phagocytic.
Which cell is the most are the most effective antigen presenting cells (APCs)?
dendritic cells (DCs)
Immature DC phagocytoses antigen and then ______ to a secondary lymphoid organ where they mature to interdigitating cells to ___________________ to T cells.
migrates; present processed antigens
DCs cell present antigens via _____________ to CD4+ cells.
MHC class II molecules
DCs cell present antigens via _____________ or _______ to CD8+ cells.
MHC class I molecules or CD1
In the thymus, DCs present self-antigens to developing T cells to determine if the developing cell is self-reactive and needs to be destroyed. What is this process called?
Negative selection
What is a thymocyte?
a developing T cell
What cytokines do DCs cells produce?
IL-1beta, TNF-alpha, IL-12
IL = interleukin
T or F: Follicular Dendritic Cells have nothing to do with Dendritic Cells.
True.
T or F: Follicular dendritic cells (FDCs) are phagocytic.
False. Follicular cells are NOT phagocytic. Antigen binds to FDC surface, but is not internalized.
Where are Follicular Dendritic cells (FDCs) found?
In germinal centers & follicles of lymphoid tissues
Follicular dendritic cells (FDCs) are involved in Antigen presentation to ________.
B cells. Note: They present whole, unprocessed antigen to B-cells to keep them activated during affinity maturation.
Follicular dendritic cells (FDCs) are related to the humoral or adaptive immune system?
Adaptive Immune System, since the B cells improve their antibodies.
FDCs do not express MHC molecules. What does this mean?
They cannot present processed antigens to T cells!
FDCs have extensive surface processes that bind ___________ via the Fc portion of the antibodies.
antigen-antibody complexes
The dendrites of FDC cells are covered with Fc receptors that allows them to do what?
Present whole, unprocessed antigens to B-cells in lymphoid germinal centers.
How does FDC’s present antigens to B cells affect B cells?
Results in affinity maturation of B cells and maintenance of immunologic memory of B cells.
All T cells have a surface receptor called …?
T cell receptor (TCR)
What is the role of TCR?
TCRs recognize a specific particular antigen.
T cells are categorized into sub populations based on what?
Function and surface proteins
What are the two subcategories for T cells?
CD4+ and CD8+
What is the effector function for CD4+ T cells?
the production of cytokines
What is the effector function for CD8+ T cells?
kill infected host cells or tumor cells
True or False: CD4 and CD8 are antigen co-receptors.
True
True or False: CD4 and CD8 are expressed in a mutually exclusive fashion.
True
CD4 recognizes which MHC Class molecules?
MHC Class II
CD8 recognizes which MHC Class molecules?
MHC Class I
CD4 T-Helper cells can be subdivided based on _______________________.
cytokine production
What molecules play an important role in the development of T-helper 0 cells into TH1 and TH2 cells?
Cytokines
What cells produced by TH1 cells inhibit TH2 differentiation?
Interferon-gamma (INF-gamma)
Which cytokines inhibit TH1 differentiation?
IL-4 and IL-10 produced by TH2 cells
Which cytokines favor TH1 differentiation?
IL-12 (produced by DCs, Macrophages, and neutrophils)
What are the main functions of T-helper 1 cells?
Produce cytokines
Stimulate CD8+ T Cells (cell-mediated response)
Stimulate isotype switching in B cells
Which T cells stimulate CD8+ T cells?
CD4+ T-helper 1 cells
Which T cells stimulate B cells to produce antibodies?
CD4+ T-helper 2 cells
What are the main functions of T-helper 2 cells?
Produce cytokines
Stimulate B cells to produce antibodies (humoral response)
Stimulate isotype switching in B cells
T-helper 1 cells stimulate isotype switching in B cells to produce what?
IgG2, IgG3, and IgA
T-helper 2 cells stimulate isotype switching in B cells to produce what?
IgG1, IgE, and IgA
TH1 and TH2 phenotype can affect clinical presentation and severity the disease. Dominance of which one results in horrible allergies?
T-helper 2 cells (TH2)
If leprosy is an intracellular pathogen, which type of CD4+ cells do you need to battle it?
T-helper 1 cells (TH1). They work to stimulate CD8+ T cells, which is a cell mediated response (which affect intracellular).
T or F: Most adaptive immune responses involve both TH1 and TH2 cells, with a bias toward one or the other.
True
What are other names of CD8+ T cells?
Cytotoxic T cells, Tc, or CTL
What is the role of CD8+ T cells or Cytotoxic T cells?
Kill target cells through the release of cytotoxic enzymes and receptor mediated apoptosis.
Which T cells result in the direct killing of an infected target cell?
CD8+ T-cell
B lymphocytes have a surface receptor for antigen called what?
B cell receptor (BCR)
Naive B cells have what antibodies on their surface.
IgM and IgD
Activated B cells have only 1 type of BCR on their surface. Which antibodies/BCR can they have?
IgM, IgG, IgE, or IgA (essentially all of them except for IgM)
B lymphocytes can express what type of MHC molecules?
I and II
What surface receptors are on B lymphocytes?
Fc-gamma (for IgG) and epsilon (for IgE)
CD40
CD80/CD86
CD40 on B-lymphocytes interact with what on T cells?
CD40L
When CD40 on B-cells interact with CD40L on T cells, what happens?
This second activating signal for B cells signals the B cell to undergo isotype switching.
When CD80.CD86 (B7) on B-cells interact with CD28L on T cells, what happens?
it provides the second activation signal for the T cell and initiates isotype switching for T cells.
Terminally differentiated B cells that become antibody factories are?
Plasma cells.
T or F? Plasma cells produce antibodies with specificity for multiple antigens.
False. Single Antigen
____ develop from Naive B Cells activated by antigen. They return to a resting state waiting to be activated again.
Memory B Cells
B cells take up antigen through the membrane bound antibody (BCR) or through what?
PRRs on their surface (TLR)
____cells have no TCR or BCR and are part of the innate and adaptive immune systems.
NK (Natural Killer) cells.
NK cells kill via ADCC when ____receptors on cell surface bind IgG coated antigen.
Fcy
NK cells recognize ____on the surface of tumor cells.
MICA
NK cells stimulate cytotoxic activity of ___cells and activate macrophages.
Tc
Name the primary lymphoid organs.
Bone Marrow, Thymus.
Cells that eventually become B cells remain in the _____
Bone Marrow
Cells that become ____ cells leave the bone marrow and enter the thymus.
T Cells
The process in which self reactive T cells are eliminated, while those that do not recognize self antigens enter the bloodstream is called?
Thymic Selection
What happens (in general) in the secondary lymphoid organs?
Mature B/T cells interact with antigen, allowing them to undergo further differentiation and proliferation.
Red pulp acts as a filter to remove…..
Pathogens and damaged RBCs
25% of the body’s mature lymphocytes are contained in the….
White pulp of the Spleen
After pathogens exit the blood of the red pulp, they encounter immune cells in the……
White Pulp
Where are blood borne antigens processed and presented?
White Pulp
Where are antigens from the tissues processed and presented?
Lymph Nodes
How do pathogens arrive in MALT?
Direct delivery across the mucosa by specialized mucosal epithelial cells.
MALT consists of…..
D-MALT, O-MALT, GALT, BALT
For antibodies to be made, ____and ____ cells specific for the antigen must interact.
T and B
T or F. The majority of lymphocytes are in the blood.
False. Lymphoid tissues.
Naive T cells have ______ surface receptors that allow them to enter lymph nodes.
L selectin
Where do Naive T cells migrate to? (Hint, this is where antigens are on display by professional APCs)
T Cell Zone
Why do Effector T cells not reenter other lymph nodes to search for antigen?
They lose their L-Selectin receptors
Where do Effector T Cells preferentially migrate to?
Tissues
Some mature cells reenter lymph nodes where they can mount a secondary immune response. These are called…..
Memory T cells
_____and______ are next to one another and adjacent to sites where antigens enter the lymphoid tissue.
B cell zones and T cell zones.
What is Psoriasin?
Small fatty acid with antibacterial and chemotactic properties.
Sebum is sometimes used by bacteria as a nutrient. It also lowers skin pH to about….
4
Keratinocytes stimulate inflammation and attract monocytes to the injury through the production of what?
Cytokines and Chemokines
Langerhans cells are located…..
Between and among epithelial cells.
_____consists of 90% of our surfaces exposed to antigens, and are 80% as effective as skin despite being only one cell layer thick.
Mucosal Surfaces
Mucus generally contains…..
Glycoproteins, proteoglycans, and enzymes.
______move mucus trapped particles to the pharynx, where they are swallowed and expelled.
Cilia
Tears contain _____.
Lysozyme
What is the immunological function of fevers?
Retard and prevent growth of pathogens.
Lysozyme and Lactoperoxidase are found in…..
Tears, Mucus, and Saliva
______cleave and destroy extracellular proteins on pathogen surface.
Proteases
How do Antimicrobial peptides destroy membrane integrity?
Insert into membrane.
Antimicrobial Peptides (Defensins) are most effective against what kinds of bacteria and viruses?
Gram negative bacteria and enveloped viruses.
Where are Antimicrobial peptides (Defensins) found?
Mucosal secretions and cytoplasmic granules of phagocytes.
