Immunology Flashcards
Cells involved in innate immunity
Granulocytes, macrophages, dendritic cells, NK cells
Where are immune cells created and differentiated?
Bone marrow
Adaptive immunity cells
T-cells, B-cells, macrophages, dendritic cells
Rate of response for innate immunity and specificity
Fast; unspecific
Rate of response for adaptive immunity and specificity
Delayed response and specific
Lymphocytes
B-cell, T-cells, monocytic cells, NK cells
B-cell: location of maturation and characteristics
Bone marrow; Produces antibodies, B cell receptor pathogen recognition, MHC class 1 and 2 APC
Plasma cells
B-cells that are short lived and actively produce antibodies
Memory cells
B-cells that are long living and protect against reinfection
T-cells: location of maturation
thymous
Tc cell
Cytotoxic T cell that induces death via direct cell-cell contact
T-h cell
Helper T cells that release cytokines for immune modulation
Cytokines
Chemical messengers that direct the immune response
Regulatory chemical messengers that cells with surface receptors for specific cytokine types respond to
T-reg
Regulatory T cells that suppress immune response when an infection is under control
Activated T-cells
Effector and memory cells
NK Cell characteristics
Leukocyte that is part of the innate response; non-adaptive; effective in early viral infections; cytotoxic to healthy cells
Perforin
The substance secreted by a NK cell to bore holes into another cell’s plasmalemma
Granzymes
Cytotoxic chemicals that enter perforins and trigger apoptosis (NK cells)
Phagocytic cells
Neutrophils and monocytic cells; eosinophils can also, but only secondary
Cytokine producers (major)
T-helper cells (adaptive) and macrophages (innate)
Degranulation
Mast cells and basophils- chemical mediators
Eosinophils and neutrophilsp- cytotoxic substances
Granules released from the surface of granulocytes that trigger a response (innate)
Pattern Recognition Receptors
Receptors used by phagocytic cells to determine what cells they will eat
Length of time a monocytic cell circulates before differentiation
One day
Shape of monocytic nucleus
C/horseshoe shaped
M1 vs M2 Macrophagic functions
M1- cytotoxic (also to human tissue)
M2- immunosuppressant and tissue repair
Phagocytosis, antigen presentation, inflammation, and cytokine production
Plasmacytoid Dendritic Cells produce…
…interferons (anti-viral cytokines), and have innate functions
Where are conventional DCs located?
Peripheral tissues
What cell serves as the link for innate and adaptive immune response?
Dendritic Cells (DCs)
Also known as polymorphonuclear leukocyte, this cell is the first responder in cell-mediated immunity and can use phagocytosis, degranulation, and NETs
Neutrophils
Horseshoe shaped nucleus with segmentation. Segmentation alterations can be indicative of deficiency of this vitamin
Neutrophil; Vit B12
Primary effector is degranulation, but can phagocytosis something. Parasites are usually targeted by this cell. IgE opsonizes parasites
Eosinophils
Involved in allergic response via IgE surface receptors, granules contain histamine and herapin, and circulate in blood
Basophils
Histamine and herapin granules, found in tissues, IgE surface receptors (high affinity), main participator in allergic response
Mast Cells
Low WBC count can be caused by..
Chemotherapy, radiation therapy, lupus and lyme, HIV, steroid use
These include Monocyetes, lymphocytes, granulocytes
High WBC count can be caused by..
Infection/chronic inflammation, and some canacers
Low lymphocyte count can be caused by..
(B,T,NK cells) Medications (corticosteroids), stress, intense exercise, chemo and radiation
High lymphocyte count can be caused by..
Lymphocytosis- infections, leukemias and lymphomas
High monocyte count…
Chronic inflammation
Low monocyte count…
Steroids, stress, acute infection
Neutrophilia/penia
Infection, inflammation, injury /or/ increased risk of infection
What are the primary lymphoid organs?
Bone marrow, thymus, and fetal liver (not applicable for most cases)
What are the secondary lymphoid organs?
Lymph nodes, spleen, mucosal-associated lymphoid tissue (MALT)
What do the primary lymphoid organs do?
Site of lymphocyte production and maturation
What do secondary lymphoid organs do?
Site of lymphocyte activation
What do lymphatic vessels do?
Transport lymph and luekocytes
Where are lymphocytes all produced?
Bone Marrow
Where do B-cells, NK cells, and T-cells mature?
Bone marrow and thymus, respectively
How does the thymus respond to aging?
Replacement of active tissue with fat; basically, it shrinks
How can the thymus cortex be identified histologically? What does it predominantly contain?
Darker staining compared to medulla; T-cell rich
How can the Thymus medulla be visualized via staining? What leukocytes is this component rich in?
Lighter staining; antigen presenting cells and macrophages
What is the function of the hassall’s corpuscules?
Nobody really knows
What is the progenator of T-cells?
thymocytes
About how many lymph nodes are in the body?q
500-700
What lymphocytes are primarily contained in the primary lymphoid follicle of a lymph node?
B-cells
What lymphocyte(s) is most abundant in the parafollicular cortex of a lymph node?
T-cells
How is lymph circulated in the body?
Muscular contractions and one-way valves
What are swollen lymph nodes indicative of?
Active viral or bacterial infection; OR blockage following an infection that is benign in nature
Secondary swelling concerns: cancer, arthritis, and allergic reactions
What is the primary function of the spleen? What is the secondary function of the spleen?
1*: filter and discard/recycle red blood cells
2*: Halting circulatory pathogens while filtering blood
The red pulp of the spleen acts to…
…phagocytose worn out RBCs and components and antigens/microbes in the blood stream
The white pulp of the spleen is…
..areas of lymphocytes around arterioles. (There is some separation of B and T cell areas)
What does PALS stand for? What does it do?(Spleen)
PeriArteriolar Lymphoid Sheath; contains WBC to filter blood and stop circulatory pathogens
What secondary lymphoid organs and tissues encounter more pathogens and thus require mucosa to deter infection?
GI tract, respiratory system, urogenital system, and salivary
What are the organized uncapsulated lymph nodes in the gut?
Peyer’s patches
What areas are lymph nodes NOT found?
Cartilege, CNS, cornea, epidermis
T or F: Lymphatic vessels and the blood stream are independent of one another
FALSE
Where do lymph vessels enter the blood stream?
Thoracic duct and cisterna chyli
What are the weak cell adhesion molecules present on lymphocytes?
Selectins
What are the strong cell adhesion molecules on lymphocytes?
Integrins
What is the movement of blood cells trough an unruptured vessel wall into the surrounding tissue?
Extravasation
What upregulates the production of integrins on a WBC?
Inflammatory mediators
Where do lymphocytes enter the blood stream?
thoracic duct and lymphatics
Where do lymphocytes re-enter lymph nodes?
High endothelial venules
Where do lymphocytes enter and exit the spleen?
Blood vessels
OG Definition: Any substance that could induce the generation of antibodies
Current Def: Any molecule that can bind specifically to an antibody or to antigen receptors on the cells of the immune system
Antigens (or self antigens in case of autoimmunity
Antigens can be composed of…
Proteins, carbs, lipids, nucleic acids, or any combo of these
What are epitopes?
The smallest unit of an antigen that is recognized by antibodies/antigen receptors
What molecules are commonly have multivalent epitomes?
Carbohydrates with repeating monosaccharide unites
What molecules are commonly polyvalent epitopes?
Proteins
What are conformational epitopes? Where are they found?
3-D structure of epitopes usually found in the native structure of the epitope (no alteration)
What are linear epitopes? Why/How do they exist?
Denatured structure of conformational epitopes
What immune structures recognize conformational epitopes?
Antibodies, B-cell receptors, Innate receptors
What immune structures present and recognize linear epitopes?
Presented by: MHC and recognized by T-cell receptors
Subscript: can also be recognized by B cell/antibody/innate receptors
How many antibody types can one B-cell produce?
ONE
What antibody types are typically stimulatory of immune generation when they bind to an antigen?
Immunogens
What antibody type cannot induce immune response without being bound to a carrier molecule first?
Haptens
What antibody type can bind and induce an immune response, but this response decreases with subsequent exposure?
Tolerogens
What antibody type can induce non-specific division and differentiation of leukocytes?
Mitogens (think MITosis)
What is mixed with antigens to increase the immunogenicity of the bound antigen? What is this commonly used for?
Adjuvants; vaccine boost of immune response and memory cell increase
What type of antigen receptors do the innate immune system use?
Pattern Recognition Receptors (PRRs)
What type of antigen receptors are used primarily by the adaptive immune system?
Antigen specific receptors (BCR and TCR for B and T cells respectively)
What antigen presentation can the TCR ONLY see?
MHC-presented antigens
What word best describes the adaptive immune response?
Discriminatory
What word best describes the innate immune response?
General/ Unspecific
What do PRRs recognize on antigen cells?
PAMPs (pathogen-Associated Molecular Patterns)
Unprocessed antigens are recognized by which antigen receptor and immune cell? What of the two types can this receptor recognize?
BCR/B-cells; Linear and conformational epitopes
What cell and receptor recognizes processed peptides presented by MHC? What classifications is this epitope?
T-cell/TCR; linear epitopes
Are cytokines stored in the cell or synthesized directly prior to release?
Synthesized prior to release
Where on a cytokine response able cell is the receptor located?
Surface of cell
Is a cytokine surface receptor specific to a type of cytokine or general to all cytokines?
General
What are the five classes of cytokines?
Interferon, interleukin, chemokine, TNF-alpha, and Growth Factors
What two immune cells excel at cytokine production
Macrophages and CD4+ T cells
What immune responses are regulated by cytokines, innate or adaptive?
Both
Can one cytokine produce different immune results depending on the immune cell it acts on?
Yes. IE: B-cells can be stimulated to produce IgE, CD4+ cells can be stimulated to enact Tm2 production, and Macrophages can be inhibited all by the same cytokine type.
Can multiple different cytokines illicit the same response on certain immune cells?
Yes. IE: IL-2,4,5 can cause a B-cell to proliferate
Can different cytokines be synergistic, both binding to one cell to increase the response strength?
Yes
Can different cytokines be antagonistic?
Yes
What are the most important cytokines in the acute inflammation response?
IL-1, IL-6, and TNF-alpha
What is the type 1 interferon (INF) mechanism?
1) binds to cell surface
2) triggers RNAse
3) RNAse lyses viral RNA prior to translation
4) viral replication stopped
What cells secrete INF-gamma?
T-cells and NK cells
What does INF-gamma do?
1) increase microbicidal activity of macrophages
2) Increase cytotoxic activity of NK cells
3) stimulates antibody production from B-cells
What two complementary pathways are identical after the initial step?
Lectin and Classical
What complement proteins trigger inflammatory response?
C3a and C5a (also C4a)
What triggers the alternate complement pathway?
Random encountering of C3b to microbes
What triggers the classical complement pathway?
Attachment of IgG to a microbe, then binding of C1 to Fc on IgG
What initiates the lectin complement pathway?
Binding of mannose-binding lectin to a microbe
What does Factor D do in the complement pathway?
Cleaves Factor B to Ba and Bb
What activates C4 and C2 in the classical/lectin pathways?
C1r/s
What are the components of the MAC?
C5b, C6-9
What microbes are susceptible to MAC?
Those with thinner cellular membranes or no glycocalyx
What molecule of the complement pathway is an opsonin? What does this do?
C3b; CR-1 expressed on phagocytes recognizes this and induces phagocytosis
What complement proteins are chemotaxic for neutrophils? What else do they do?
C3a and C5a; also induces inflammation; also stimulates movement of plasma proteins and leukocytes into the tissue
What does a C3 deficiency lead to?
Increased susceptibility to bacterial infections, lower complement action
What does C2&4 deficiency result in?
No consequence, increased infection susceptibility, or induce lupus incidence (unsure)
What inhibitors regulate the complement pathway?
C1 INH, DAF (Decay Accelerating Factor), Cofactors Factor H and I
What does a deficiency of C1INH cause?
Buildup of inflammation, increased complement activity, fluid leakage into ISF (edema)
What does a deficiency of DAF induce?
Unchecked complement activity and RBC lysis
What does a deficiency of Factor I and H do?
Increased complement activity, but lower C3 levels due to less C3b
What cells produce immunoglobulins?
B-cell
What are the two major functions of antibodies?
1) Specifically bind to a pathogen
2) Recruitment of cells and molecules to destroy pathogen
What are the two basic structural components of antibodies?
Heavy and Light chain (both contribute to binding site)
What is Fab and Fc on an antibody?
Fab= fragment antigen binding Fc= Fragment crystallizable (Fc effector binds to various cell receptors and complement)
What kind of bond do antibodies form to conformational epitopes?
Non-covalent
What is an epitope?
The part of an antigen that is recognized by the immune system
What types of antigens can be bound to by antibodies and illicit an immune response?
Immunogen, Haspten, and Autoantigen
What is combinatorial diversity of antibodies?
Generating a large number of combinations of the VDJ segments to create antibodies that can bind to pathogens without encountering first
What is the valence of a monomer immunoglobulin?
2
What creates junctional diversity in antibodies?
Addns, deletions at nucleotide junctions during recombination
What is the antibody affinity and avidity?
Affinity=binding strength at a single site
Avidity= summative binding str of all sites
What is Omenn Syndrome? What cells are affected?
It is Auto Recess mutation of RAG enzymes; B/Tcells low counts
Characterized by failure to thrive, erythroderma, diarrhea, immunodefic.
What is SCID? How is this different than Omenn Syndrome?
NO RAG activity or B/T cells; auto-recessive null mutations in RAG gene
Signs: Interstitial lung disease, diarrhea, severe infections, fail to thrive
What determines the antibody class (isotope) and antibody function (broad scale)?
Heavy chains: mu, gamma, sigma, alpha, and epsilon
Do changes in light chains result in different functions? What is the normal kappa:lambda ratio of light chains? What can variations of this ratio indicate?
No; 60:40; B-cell cancer
What are expressed as BCR? What do naive, mature B cells express? Memory B-cell expression?
Immunoglobulins; IgD and IgM; any isotype as BCR
What triggers B-cell activation? Clonal expansion? Antibody production?
BCR binding to an antigen; all create variable antibodies; plasma cells create antigen-specific antibodies based on what the BCR is bound to
What structural component in Ig determines free form or membrane bound?
Transmembrane anchor on the heavy chain
What are the five functions of antibodies?
Neutralization, complement activation, opsonization, antibody-dependent cell-mediated cytotoxicity (ADCC), mast cell degranulation
What function does secreted IgG (subtypes in blood/tissues) and dimeric IgA perform?
Neutralization
What Ig can trigger the complement pathway?
IgM (pentamer) or 2 IgG
Fc receptors on what molecules recognize antibodies on pathogens to induce phagocytosis? What antibody is recognized? What is this antibody function called?
Phagocytes; IgG; opsonization
What immune cell is activated via ADCC? How do antibodies recognize virally infected cells? What receptors on the effector cell (first Q) recognize these antibodies?
NK cells; they bind to viral proteins on the surface of virally infected cells; Fc receptors (specifically CDD16 or Fc-gamma-RIIIA)
What antibody is recognized by mast cells via the Fc-epsilon-R receptor to induce allergic response?>
IgE
What antibody opsonizes parasites? What does an IgE-coated parasite stimulate eosinophils to do?
IgE; degranulate then phagocyte the resulting parasitic debris
What granules are released from eosinophils?
Major basic protein (MBP); Eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO)
What isoform is IgM secreted as? Membrane-bound as? What can this antibody do?
Pentamer; monomer; activate complement pathway (classical)
What is the general valence of IgM? What causes the IgM to be transported across epithelium?
Valence=10; J-chain
What syndrome is associated with elevated IgM levels, decreased presence of other isotypes, and presents in children via recurrent resp infections?
X-linked Hyper IgM syndrome
What is the function of IgD? Where can they be mostly found?
Unknown; upper respiratory tract
What antibody is 80% of the serum’s antibody?
IgG
What antibody notably crosses the placenta?
IgG
What are the four main functions of IgG?
Neutralization, Opsonization, Complement activation, and ADCC
What immunoglobulin is secreted as a monomer, less than 1% of serum Ab, and has a major role in allergic and parasitic response?
IgE
What is the antibiotic that has a common allergy response? What Ig is responsible? What is the biochemical structure that reacts with the antibody?
Penicillin; IgE; beta-lactim rings (PCN, cephalosporins, carbapenems)
What Ig is a monomer in blood and a dimer in secretions/mucous?
IgA
What antibody is the primary class in secretory/mucosal?
IgA (breast milk, tears, saliva)
IgA binds to polymeric-Ig receptor to pass through what?
Epithelial cells
Antibody deficiencies result in which characteristic infections?
Recurrent pyogenic infections, encapsulated bact infections, repiratory infections, and enteritis
What are some ways pathogens can bypass antibodies?
Antigenic variation (modification of surface antigens/epitopes to prevent binding)
Encapsulation (hyaluronic acid capsules act as “slippery” to antibodies, difficulty binding)
What are the three main antigen presenting cells (APC)? What do they do?
Dendritic cells, macrophages, B-cells; present antigens to T-cells
