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Immunity Week1 Basics
UC MED 2015
319
Medical
Graduate
02/29/2012

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Cards

Term
What induces the immune response?
Definition
Antigen
Term
What is formed in response to an antigen?
Definition
Antibody
Term
IF you could define Ag-Ab interactions in two words what would you say?
Definition
Non-covalent and reversible
Term
What are the types of Acquired (adaptive) immunity?
Definition
1) Humoral- Ig (antibody formation) - B cells
2) Cellular- Cellular Responses - T cells
Term
What 3 words would describe Innate Immunity?
Definition
1) Non-specific
2) Constitutive (activity is active always, not inducible)
3) No memory
Term
What 3 words would describe Adaptive Immunity?
Definition
1) Specific for Antigen
2) Inducible
3) Memory
Term
What 5 cells are important for Innate Immunity?
Definition
1) Epithelial barriers
2) Phagocytes
3) Dendritic cells
4) Complement
5) NK cells
Term
What cell type sare important for Adaptive Immunity?
Definition
1) B lymphocytes- antibodies
2) T lymphocytes- Effector T cells
Term
For the primary response in Immunological Memory what is the typical lad phase?
Definition
7 to 10 days
Term
What are 5 keys to the secondary response?
Definition
1) Shorter lag (1-2 days)
2) Higher levels of Abs
3) Longer persistance
4) Affinity maturation
5) Ig Class switching
Term
What are the 4 stages of Clonal Selection?
Definition
1) Lymphocyte clones with diverse receptors arise in generative lymphoid organs
2) Clones of mature lymphocytes specific for many antigens enter lymphoid tissues
3) Antigen-specific clones are activated ("selected") by antigens
4) Antigen-specific immune responses occur (Generation of memory cells happens now)
Term
Where do B cells mature?
Definition
Bone Marrow (remember B's stick together)
Term
Where do T cells mature?
Definition
Thymus (remember T's stick together)
Term
The strength with which one antigen-binding surface of an antibody binds to one epitope of an antigen is called?
Definition
affinity
Term
IN secondary response, the increase in antigen-binding strength is called?
Definition
affinity maturation
Term
The total strength of binding is much greater than the affinity of a single antigen-antibody bond and is called? (Think of IgM esp.)
Definition
avidity
Term
Antibodies produced against one antigen may bind other, structurally similar, antigens. Such binding to similar epitopes is called?
Definition
cross-reaction
Term
What is natural immunity, constitutive defenses?
Definition
Innate immunity
Term
What is specific (adaptive) immunity?
Definition
Acquired immunity
Term
What are examples of first line defenses?
Definition
1) skin
2) mucous membranes
3) enzymes
4) natural microbial flora
5) complement protein
Term
What are examples of second line defenses?
Definition
These are all innate and non-specific...
Phagocytes
–NK cells
–Granulocytes
–Macrophages
Term
What are examples of third line defenses?
Definition
These are all learned and specific immunity...
1) Antibodies
2) Lymphocytes
– T-cells
– B-cells
Term
What are the functions or purposes of Epithelial cells?
Definition
1) External surface of body (e.g. skin, conjunctival surface, digestive, reproductive, respiratory and urinary tracts)
2) First anatomical barrier to penetration by inimical substances.
3) Generate products that initiate inflammation (antimicrobials peptides, chemokines, cytokines)
4) Mucous layer
Term
What things initiate inflammation?
Definition
1) antimicrobial peptides
2) chemokines
3) cytokines
Term
What are the 3 major of Constitutive defenses (not involving specific immunity)?
Definition
1) Mechanical
2) Chemical
3) Biological Factors
Term
What is another word to describe the hosts defenses against entry and adherence?
Definition
Constitutive defenses
Term
What are examples of Mechanical defenses?
Definition
Think of it as the barrier and removal...
1) Armor- skin, mucus (mucociliary blankey)
2) Broom- cilia (mucociliary elevator), peristalsis/ flow
3) Hose down- tears, saliva, urine flow
Term
What are examples of Chemical defenses?
Definition
1) Acid (low pH), fatty acids, lysozyme, bile salts, lactoferrin
2) Anti-bacterial factors (defensins, surfactants, etc.)
Term
What are examples of Biological defenses?
Definition
Normal flora
-Secrete toxic factors
-Compete with pathogens
Term
What are the protective measures of the eyes?
Definition
-Washing tears
-Lysozyme
-blinking
-IgA
-Lactoferrin
Term
What are the protective measures of the Respiratory tract?
Definition
-mucus
-ciliated epithelium
-alveolar macrophages
Term
What are the protective measures of the Genitourinary tract?
Definition
-washing of urine
-acidity of urine
-lysozyme
-vaginal lactic acid
Term
What are the protective measures of the skin?
Definition
-Anatomical barrier
-Antimicrobial secretions
Term
What are the protective measures of the Digestive tract?
Definition
-Mucus
-Stomach acidity
-Normal flora
-Bile
-Peristalsis
Term
Mucin contains...
Definition
-lysozyme
-lactoferrin
-other toxic substances
Term
What can create problems for the eye and respiratory tract defenses?
Definition
-smoking
-alcohol
-pollutants
-infection
-etc. interfere w/ clearance
Term
What problem in the stomach can predispose some to infections?
Definition
decrease in stomach acidity
Term
What can be a biological barrier in the gut?
Definition
normal flora
Term
What is an example of good flora in the vagina?
Definition
Lactobacilli
Term
What are the protective measures of the Nasopharynx?
Definition
-Resident microflora
-Secretions (lysozyme, sIgA, lactoferrin, phagocytes)
Term
What are the protective measures of the Lungs?
Definition
-Macrophages
Term
What are the protective measures of the Mouth?
Definition
-Sloughing cells
-Flow of saliva
-Lysozyme
-IgA
-Resident microflora
-Lactoferrin
Term
What are the protective measures of the stomach?
Definition
-low pH
-Proteolytic enzymes
Term
What are the protective measures of the small intestine?
Definition
-Fast slow
-Peristalsis
-Mucus
-sloughing cells
-bile
Term
What are the protective measures of the colon?
Definition
-slow flow
-mucus
-sloughing cells
-***abundant resident microflora***
Term
What are the protective measures of the bladder?
Definition
-flushing action of urine
-Low pH
-Physical barrier of urethra
Term
What are the protective measures of the vagina?
Definition
-Low pH
-Resident microflora (including lactobacilli)
Term
The inflammatory response is what level of response?
Definition
2nd line defense
Term
What is a local tissue response to injury – physical, chemical or biological - in which body attempts to localize and eliminate the injurious agent – eventually removing and repairing damaged tissue?
Definition
Inflammatory response
Term
What are 3 keys to inflammation?
Definition
1) Occurs rapidly – allowing time for development of specific immune response.
2) Non-specific – same response triggered to a variety of agents.
3) Characterized by edema and recruitment of phagocytic cells.
Term
What are some properties of neutrophils?
Definition
Active types active during acute inflammation
1) (PMNs PNN = polymorphonuclear leukocyte
or neutrophil)= first line of cellular defense
2) Abundant in circulation; transient in tissues
3) More mobile than monocytes
4) Predominant cell to invade infected tissues early in infection
5) Short half-life (1–2 days)
Term
What replaces neutrophils after several days?
Definition
macrophages
Term
What are some properties of macrophages?
Definition
1) Macrophages are major tissue phagocyte; found in lesser numbers in blood than neutrophils
2) Remember macrophages are effector cells in both the innate and the adaptive immune response systems.
3) Both macrophages and neutrophils phagocytose foreign particles and cellular debris
Term
What are the 5 steps of inflammation after tissue injury?
Definition
1) Vasodilation
2) Increased permeability
3) Emigration of leukocytes
4) Chemotaxis
5) Phagocytosis
Term
How is pathogen recognized in INNATE system?
Definition
Role of pathogen associated microbial patterns (PAMPs) and pattern recognition receptors (PRRs; receptors of the innate immune system)
Term
What are some common things recognized on the cell wall or envelope of a gram positive bacteria?
Definition
-Lipoteichoic acid
-PG
Term
What are some common things recognized on the cell wall or envelope of a gram negative bacteria?
Definition
-LPS (lipopolysaccharide)
-PG (peptidoglycan)
Term
What are some keys about PAMPS?
Definition
1) Microbe assoc.
2) Highly conserved
3) not assoc. with intact host cell
Term
What part of a macrophages recognizes a PAMPs?
Definition
PRRs
Term
What are some examples of PAMPs?
Definition
1) LPS (gram-negative bacteria)
2) Lipoteichoic acid (gram-positive bacteria)
3) Peptidoglycan (cell wall gm pos, neg, mycobacteria)
4) Double stranded RNA (RNA viruses)
5) Mannan (yeast cell walls)
6) Flagellin
Term
What are receptors of the innate immune system?
Definition
PRRs (Pattern recognition receptors)
Term
What is the main role of PRRs?
Definition
Help host to “sense” invasion by pathogenic organisms and to respond appropriately to control infection.
Term
Where can PRRs be found on?
Definition
1) dendritic cells
2) macrophages
3) neutrophils
4) epithelial cells
Term
What are the classes of PRRs?
Definition
1) Endocytic PR receptors [lectins (e.g.mannose & glucan receptors), scavenger receptors, CR3, CR4, etc.]
2) Signaling PR receptors – Toll-like receptors
Term
What happens when you activate a Signaling PR receptor?
Definition
Induces the synthesis of inflammatory cytokines to be secreted
Term
What do TLRs do after being activated?
Definition
Start inflammatory response via cytokine release
Term
What is found on host cells are released upon tissue injury and modulate the inflammatory response?
Definition
DAMPs (Damage-associated molecular patterns
Term
What is the role of DAMPs?
Definition
1) Activate pattern recognition receptors
2) May induce the release of proinflammatory cytokines and chemokines
3) Have been shown to initiate or propagate inflammation in non-infectious conditions.
Term
The complex interplay of DAMPs on Dendritic Cells is clinically important, with implications for ...
Definition
-transplantation
-tumor immunity
-rheumatoid arthritis
-autoimmunity
-chronic inflammation
-other conditions of sterile inflammation such as ischemia reperfusion injury.
Term
The complex interplay of DAMPs on Dendritic Cells is clinically important, with implications for ...
Definition
-transplantation
-tumor immunity
-rheumatoid arthritis
-autoimmunity
-chronic inflammation
-other conditions of sterile inflammation such as ischemia reperfusion injury.
Term
Killing of engulfed microorganisms is done by?
Definition
Oxygen dependent and oxygen-independent mech.
- Generation of reactive oxygen intermediates
-Low pH of phagosome
-Fusion with vacuoles that contain antimicrobial proteins, peptides and hydrolases
-Nutrient limitation
Term
What are sparsely distributed, migratory group of cells specialized to sample sites of entry of infectious agents?
Part of innate immune system, but also are the most efficient antigen presenting cells for T cell activation – thus link innate and adaptive immune responses
Definition
Dendritic cells
Term
What is a large multi-protein cytosolic complex that can activate caspase-1? Is responsible for secretion of certain proinflammatory cytokines and induction of cell death
Definition
Inflammasome
Term
What are the three complement pathways?
Definition
1) Alternate
2) Classical
3) Lectin pathway (Mannose-binding lectin)
Term
What are the physiologic activities of complement?
Definition
1) Cellular lysis
2) Opsinization- C3b
3) Release of inflammatory mediators
-Anaphylatoxins (C5a, C3a and C4a-weak)
-Release of chemotactic factors for neutrophils- C5a
Term
What acts on blood vessels to increase vascular permeability?
Definition
Anaphylatoxins
Term
What complements are important in the alternate pathway?
Definition
-C3, C5, (C6, C7, C8, C9)
-Factor B, D
-Properdin
Term
What complements are important in the lectin pathway?
Definition
-C3, C5, (C6, C7, C8, C9)
-MBL, C2, C4
Term
The goal of all three pathways is to make?
Definition
C3 convertase
Term
What does C5 do?
Definition
C5b initiates assembly of the MAC and C5a stimulates inflammation
Term
What are all components of MAC?
Definition
C6, C7, C8, C9
Term
TNF (Tumor Necrosis Factor)
-What are the principal cell sources?
-What are the principal cellular targets and biologic effects?
Definition
Cell Sources:
-Macrophages
-T cells

Targets and effects:
-Endothelial cells- activation(inflammation, coagulation)
-Neutrophils- activation
-Hypothalamus- fever
-Liver- synthesis of acute phase proteins
-Muscle, fat- catabolism (cachexia)
-Many cell types- apoptosis
Term
IL-1 (Interleukin-1)
-What are the principal cell sources?
-What are the principal cellular targets and biologic effects?
Definition
Cell Sources:
-Macrophages
-Endothelial cells
-Some epithelial cells

Targets and effects:
-Endothelial cells- activation(inflammation, coagulation)
-Hypothalamus- fever
-Liver- synthesis of acute phase proteins
-T cells- TH17 dedifferentiation
Term
What two pressures in blood vessels control the inflow or out flow of fluid?
Definition
-Hydrostatic pressure
-Colloid pressure
Term
Macrophages release what to attract lymphocytes?
Definition
-IL-1
-TNF
Term
Lymphocytes release what to recruit Macrophages?
Definition
IFN-gamma
Term
What activates Macrophages?
Definition
-Tissue injury
-Fibrosis
Term
What are the two major vasoactive amines?
Definition
1) Serotinin
2) Histamine
Term
What is the main source of histamine?
Definition
mast cells
Term
What causes a release of histamine?
Definition
(1) physical injury such as trauma, cold, or heat;
(2) binding of antibodies to mast cells, which underlies allergic reactions
(3) fragments of complement called anaphylatoxins (C3a and C5a);
(4) histamine-releasing proteins derived from leukocytes;
(5) neuropeptides (e.g., substance P); and (6) cytokines (IL-1, IL-8).
Term
What causes dilation of arterioles and increases the permeability of venules. It is considered to be the principal mediator of the immediate transient phase of increased vascular permeability, producing interendothelial gaps in venules, as we have seen. Its vasoactive effects are mediated mainly via binding to H1 receptors on microvascular endothelial cells?
Definition
Histamine
Term
What is the action of NO?
Definition
Vasodilation
Term
What is the action of Bradykinin?
Definition
Increased vascular permeability
Term
What factors are responsible for fever?
Definition
-TNF-alpha
-IL-1
-IL-6
Term
What is the function of C-reactive protein?
Definition
opsonization
Term
What is the function of fibrinogen?
Definition
coagulation
Term
What is the function of alpha1-antitrypsin?
Definition
protease inhibitor
Term
What is the function of haptoglobin?
Definition
Binds hemoglobin (if destruction of RBC, prevents damage
Term
What is the function of C3?
Definition
complement
Term
What is the function of ceruloplasmin?
Definition
binds copper
Term
What is the function of alpha2-macroglobulin?
Definition
protease inhibitor
Term
For acute phase proteins, what is present after 6-10 hrs and what is the increase?
Definition
-C-reactive protein
-100-500+
Term
For acute phase proteins, what is present after 24 hrs and what is the increase?
Definition
- fibrinogen (2-5)
- alpha1-antitrypsin (2-3)
-haptogloglobin (2-6)
Term
For acute phase proteins, what is present after 48-72 hrs and what is the increase?
Definition
- C3 (3-5)
- cerulplasmin (3-12)
Term
Neutrophilia is present during what?
Definition
-Bacterial infections
-Burns
-Tissue necrosis
Term
Eosinophilia is present during what?
Definition
-Parasitic infections
-allergic disorders
-Collagen vascular disease
Term
Monocytosis is present during what?
Definition
-Chronic infections (TB)
-Malaria
-IBD
Term
Lymphocytosis is present during what?
Definition
-Viral infections
-Bordetella pertussis
-W/ monocytosis in TB
Term
Plasma from persons recovering from recent pneumococcal infection form ________ when mixed with the capsular (C) polysaccharide of pneumococci
Definition
flocculates
Term
The flocculation is due to a protein, now called
Definition
“C-reactive protein” (CRP)
Term
What do the Toll-like receptors 1-10 recognize?
Definition
-Peptidoglycan
-Lipoproteins
-Lipopolysaccharide
-DNA
-RNA
-Flagellin
Term
What do Toll-like receptors do?
Definition
The outcome of engagement is release of mediators that promote inflammation or type I interferons
Term
What are carbohydrate binding proteins?
Definition
C type lectin receptors
Term
What are some examples of the C type lectins?
Definition
-Dectin 1&2
-Mannose receptor
-Mincle
-CLEC
-Mannose binding protein
Term
What do C type lectin receptors recognize?
Definition
-Mannans
-Beta glucans
-Mannose
Term
What do C type lectins do?
Definition
Actions are numerous and include phagocytosis, complement activation (mannose binding protein), binding of pathogens to cell surfaces of phagocytes, induce signals that promote inflammation
Term
What are examples of Nucleotide binding and oligomerization domain (NOD)-like receptors?
Definition
-NOD 1 and 2 &NLRC
-NOD-like receptors (NLRP) 1-9
Term
What do Nucleotide binding and oligomerization domain (NOD)-like receptors recognize?
Definition
-Bacterial & viral DNA
-Viral RNA
-Bacterial toxins
-Flagellin
-Fragments of peptidoglycan
-Monosodium Urate
-Asbestos
-UV irradiation
Term
What do the Nucleotide binding and oligomerization domain (NOD)-like receptors do?
Definition
-Promote the inflammatory response
-Trigger cell death
-Triggers the formation of an “inflammasome”
Term
What are examples of the Retinoic acid-inducible gene-1 like receptors (RLR)?
Definition
A family comprised of RIG-1, MDA5, LGP2, and IPS-1
Term
What does the Retinoic acid-inducible gene-1 like receptors (RLR) recognize?
Definition
Viral RNA and DNA
-Influenza A &B
-Rabies virus
-Hepatitis C virus
-West Nile
-Respiratory syncytial virus (kids mostly affected)
Term
What to Retinoic acid-inducible gene-1 like receptors (RLR) do?
Definition
This family is important in signaling the generation of type I interferon (a & b). These two molecules are important in controlling viral replication.
Term
What factors affect immunogenicity?
Definition
-foeriegness
-molecular size
-complexity
Term
What factors affect immunization?
Definition
-Doses of Ag
-Route of administration (id, im, iv)
-Adjuvants
Term
What are the two light chain families?
Definition
k(kappa) and l(lambda)
Term
What are the stages of Lymphocyte?
Definition
1) Maturation
2) Ag Reception
3) Cell activation
4) Effector function
Term
Primary adaptive immune response starts with which Ig?
Definition
IgM
Term
Memory response switches to what in the serum?
Definition
IgG
Term
What is the half-life of IgG?
Definition
20 days
Term
What is the secretory Ig?
Definition
IgA
Term
What is the function of CD64?
Definition
-Phagocytosis
-activation of phagocytosis
(high affinity for Ig esp IgG)
Term
What is the distribution of CD64?
Definition
-Macrophages
-neutrophils
-eosinophils
Term
What is the function of CD32? A variety
Definition
-Phagocytosis
-Cell activation (inefficient)
(low affinity for Ig)
Term
What is the distribution of CD32? A variety
Definition
-Macrophages
-neutrophils
-eosinophils
-Platelets
Term
What is the function of CD32? B variety
Definition
Feedback inhibition of B cells
(low Ig affinity)
Term
What is the distribution of CD32? B variety
Definition
B lymphocytes
Term
What is the function of CD16?
Definition
-Antibody-dependent cellular cytotoxicity (ADCC)
(low Ig affinity)
Term
What is the distribution of CD16?
Definition
NK cells
Term
What is the function of FceRI?
Definition
Activation (degranulation) of mast cells and basophils
(High Ig affinity esp IgE)
Term
What is the distribution of FceRI?
Definition
-Mast cells
-basophils
-eosinophils
Term
What Ig's activate complement under the classical pathway?
Definition
IgM and IgG
(GM makes CLASSIC cars)
Term
What Ig plays a role in allergies?
Definition
IgE
Term
Which cells make histamine?
Definition
-mast cells
-basophils
Term
What are some common sources of allergens from inhaled materials?
Definition
1) plant polens
2) dander of domesticated animals
3) mold spores
4) Feces of very small animals (house dust mites)
Term
What are some common sources of allergens from injected materials?
Definition
1) Insect venoms
2) Vaccines
3) Drugs
4) Therapeutic proteins
Term
What are some common sources of allergens from ingested materials?
Definition
1) food
2) orally administered drgus
Term
What are some common sources of allergens from contacted materials?
Definition
1) Plant leaves
2) Industrial products made from plants
3) Synthetic chemicals in industrial products
4) Metals
Term
Immunized individual acquires immunity to
specific antigen.
Definition
Active immunity, active immunization
Term
Transfer of preformed antibodies providing
temporary protection (passive immunity). Individual
does not acquire memory to specific antigen.
e.g. -antitoxins for venoms, toxins
-maternal immunity (IgA through breast feeding,
IgG crossing placental barrier)
Definition
Passive Immunization
Term
What means your prone to developing allergies due to IgE?
Definition
atopy, atopic
Term
What is a small molecule that is not immunogenic?
Definition
hapten
Term
What are the T cell accessory molecules?
Definition
1) CD3 (Signal transduction by the TCR complex)
2) Zeta (ζ) chain (Signal transduction by the TCR complex)
3) CD4 (Signal transduction)
4) CD8 (Signal transduction)
5) CD28 (Signal transduction-co-stimulation)
6) LFA-1 (Adhesion)
Term
What is the function of CD3?
What does it bind to?
And where is the ligand found?
Definition
Signal transduction by the TCR complex
-None
Term
What is the function of ζ?
What does it bind to?
And where is the ligand found?
Definition
Signal transduction by the TCR complex
-None
Term
What is the function of CD4?
What does it bind to?
And where is the ligand found?
Definition
Signal transduction
-MHC class II
-APCs
Term
What is the function of CD8?
What does it bind to?
And where is the ligand found?
Definition
Signal transduction
-MHC class I
-APCs; CTL target cells
Term
What is the function of CD28?
What does it bind to?
And where is the ligand found?
Definition
Signal transduction (co-stimulation)
-B7
-APCs
Term
What is the function of LFA-1?
What does it bind to?
And where is the ligand found?
Definition
Adhesion
-ICAM-1
-APCs; endothelium
Term
What is a non-specific activator of lymphocytes?
Definition
Mitogens
Term
How does MHC class II get its antigen?
Definition
Endocytosis of extracellular protein
Term
How does MHC class I get its antigen?
Definition
It gets it from cytostolic protein which is degraded by PROTEOSOME and then TAP moves the peptode in the cytosol into the Er so it can be added to MHC I
Term
What makes up the binding groove of MHC class I?
Definition
alpha-1 and alpha- 2
Term
What makes up the binding groove of MHC class II?
Definition
alpha-1 and beta-1
Term
What toxins bind to MHC class II molecules and stimulate T cells via the T cell receptor?
-Can have cytokine storm or shock resulting from it
Definition
Superantigen
Term
What are examples of super antigens?
Definition
-Staphylococcal enterotoxins
-Staphylococcal TSST-1 toxin
Term
T cells enter lymph nodes via?
Definition
HEV (High endothelial venules)
Term
T cells do what in the lymph nodes?
Definition
Monitor antigen presentation by macrophages and dendritic cells. Then if they do not encounter a specific antigen, they leave the lymph node. If they do encounter a specific antigen, they proliferate and differentiate into effector cells.
Term
What chromosome is HLA found?
Definition
Chromosome 6- Human Leukocyte Antigens
Term
What means each allele is expressed in the heterozygote, regardless of the identity of the allele on the other chromosome?
Definition
Co-dominant expression
Term
What tissues or cells highly express MHC class I?
And which ones slightly express MHC class I?
Definition
- T cells, B cells, Macrophages, Dendritc cells, Neutrophils

-Thymic epithelium, liver hepatocytes, kidney epithelium, and the Brain
Term
What tissues or cells highly express MHC class II?
And which ones slightly express MHC class II?
Definition
-B cells, Dendritic cell, thymic epithelium (Macrophages not quite as high as these, but not low)
-T cells
Term
What does the Mixed lymphocyte reaction measure?
Definition
1) T cell proliferation
2) T cell cytotoxicity
Term
What are the contents of the granules in neutrophils?
Definition
1) Acid hydrolases
2) Beta glucoronidase
3) Acid proteinase
4) Elastase
5) Myeloperoxidase (only 50% of people have,redundant)
6) Defensins
7) Lysozyme
Term
What is the ideal pH for neutrophils?
Definition
5.5-6.5
Term
What are neutrophils important for?
Definition
Microbial killing
Term
Much of the driving force in attracting neutrophils is through?
Definition
"chemokine" gradients
Term
Neutrophils can migrate in which direction through epithelial cells?
Definition
bidirectionally
Term
The neutrophil contains a complex called the ________that transports electrons.
Definition
NADPH oxidase
Term
What are toxic oxygen intermediates?
Definition
Hypochlorous acid
Superoxide anion
Singlet oxygen
Hydroxyl radical
Term
In parallel with the oxidative burst, neutrophils release granule contents which releases a number of acid compounds that can attack microbes or deprive them of essential nutrients. This is known as?
Definition
Degranulation
Term
Neutrophils have a short life span and therefore one might question how good they are at killing. So what do they do?
Definition
they leave a indelible mark on host defenses when they die by forming NETs (neutrophil extracellular traps). These are composed of DNA and histones and they have the capacity to bind and kill microbes
Term
What are the effector functions of IgG?
Definition
1) Neutralization of microbes and toxins
2) Opsonization of antigens for phagocytosis by macrophages and neutrophils
3) Activation of the classical pathway of complement
4) Anti-body dependent cellular toxicity mediated by NK cells
5) Neonatal immunity: transfer of maternal antibody across placenta
6) Feedback inhibition of B cell activation
Term
What are the effector functions of IgM?
Definition
1) Activation of the classical pathway of complement
Term
What are the effector functions of IgA?
Definition
1) Mucosal immunity: secretion of IgA into lumens of GI and respiratory tracts, neutralization of microbes and toxins
Term
What are the effector functions of IgE?
Definition
1) Defense against helminths
2) Mast cell degranulation (immediate hypersensitivity reactions)
Term
Production of chemotactic factors which attract neutrophils in Type III hypersensitive rxns?
Definition
C3 and C5
Term
What is important in production of anaphylatoxins?
Definition
C3 and C5
Term
What requires T-cell help for antibody response?
Definition
Thymus-dependent antigens
Term
What activates B cells directly w/o T cell help
Definition
Thymus-independent antigens
Term
What is this an example of T-dependent or independent?

Certain antigens containing repeating epitopes that can cross-link the Ig receptors on B-cells. e.g. repeating polysaccharide epitopes found on the capsules of bacteria (pneumococcal vaccine)
Definition
T-independent Ags
Term
What is different about the T-indepenent Ag secondary response?
Definition
Not different from the primary response (still IgM and not bigger or longer)
Term
What is the chemical nature of T-dependent antigens?
Definition
proteins
Term
What is the chemical nature of T-independent antigens?
Definition
Polymeric antigens, eso. polysaccharides and glycolipids, nucleic acids
Term
Is there isotype switching in T-dependent antigens?
Definition
Yes from IgM to IgG, IgE and IgA
Term
Is there isotype switching in T-independent antigens?
Definition
Little or none; maybe some IgG (almost all IgM
Term
Is there affinity maturation in T-dependent antigens?
Definition
yes
Term
Is there affinity maturation in T-independent antigens?
Definition
Little or none
Term
Is there a Secondary response (memory B cells) in T-dependent antigens?
Definition
Yes
Term
Is there a Secondary response (memory B cells) in T-independent antigens?
Definition
Seen only with some antigens
Term
What is this an example of T-dependent or independent?

Antibody response in absence of cognate T cells
Definition
T-independent Ags
Term
What is this an example of T-dependent or independent?

Antibody production in congenital athymic individuals
Definition
T-independent Ags
Term
What is this called...each T cell is specific for peptide epitope and specific MHC allele?
Definition
MHC Restriction
Term
Where does antigen go when it is in the tissue?
Definition
lymph nodes
Term
Where does antigen go when it is in the blood?
Definition
spleen
Term
Where does antigen go when it is in the mucosa?
Definition
MALT (mucosal-associated lymphoid tissue, eg Peyer's patches)
Term
What cells are good at bringing antigen to secondary lymphoid organs?
Definition
Dendritic cells
Term
An activated Th cell will express what to help activate B cells?
Definition
CD40L, also T cell will excrete cytokines to activate B cells
Term
What are the 3 keys to B cell activation?
Definition
-Ag recognition (via Ig)
-CD40L expression by activated T helper cell
-cytokine secretion by T cell
Term
What is created by covalently attaching a poor (polysaccharide organism) antigen to a carrier protein (preferably from the same microorganism), thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides for the prevention of invasive bacterial disease.
Definition
conjugate vaccine
Term
What are 4 general properties of cytokines?
Definition
1) Produced transiently in response to antigen
2) Usually has autocrine and paracrine effects
3) Pleiotropism: each cytokine has multiple biologic actions
4) Redundancy: multiple cytokines may share the same or similar biologic activties
Term
What is the principal action of IL-2?
What is the cellular source?
Definition
-Survival, proliferation, and differentiation of effector and regulatory T cells
-CD4+ and CD8+ T cells
Term
What is the principal action of IL-4?
What is the cellular source?
Definition
-B cell switching to IgE
-CD4+T cells and mast cells
Term
What is the principal action of IL-5?
What is the cellular source?
Definition
-Activation of eosinophils
-CD4+T cells and mast cells
Term
What is the principal action of IFN-γ?
What is the cellular source?
Definition
-Activation of macrophages (suppresses Th2 induction)
-CD4+ and CD8+ T cells and NK cells
Term
What is the principal action of TGF-ß?
What is the cellular source?
Definition
-Inhibition of T cell activation; differentiation of regulatory T cells
-CD4+ regulatory T cells; many other cells
Term
What blocks activation of transcription factor
necessary for activation of IL-2 gene?
Definition
Cyclosporin A
Term
What is the principal cytokine produced by Th1?
Definition
IFN-γ; host defense agaisnt intracellular microbes; inflammation
Term
What is the principal cytokine produced by Th2?
Definition
Il-4,5, 13; host defense against helminths; allergic reactions
Term
What is the principal cytokine produced by Th17?
Definition
IL-17, 22; host defense against some bacteria and fungi; inflammatory disorders
Term
What cytokines promotes Th1 bias?
Definition
IL-12
Term
What does
Definition
Term
What cytokine is made by Th2 cell and suppresses Th1 induction?
Definition
IL-10
Term
What seems to play role in Inflammatory diseases? (Pro-inflammatory cytokine)
Definition
IL-17
Term
Activated T cells need to home back to the original site of infection (inflammation) via changes in?
Definition
expression patterns of selectins/ integrins
Term
Macrophages activated by IFN-γ do what?
Definition
Kill phagocytosed microbes
Term
What cytokine is chemotactic for nuetrophils?
Definition
IL-8
Term
Once the CTL is activated what happens?
Definition
- CTL granules exocytose
-Granzymes enter cell via receptor mediated endocytosis, and enter cytoplasm via perforin-dependent mech
-Apoptosis of target cell
Term
T or F
Preventative suppression is more effective than treating the activated response
Definition
T
Term
T or F
Secondary immune responses are more effectively suppressed than primary responses.
Definition
F
Term
Do modulating agents effect all immune responses?
Definition
No
Term
What are the major drawbacks of Immunosupression?
Definition
-Suppression increases the risks for infections;
-The resurgence of previously controlled infections;
-Cytokine release syndrome (CRS),
-Antibody-injection site lymphomas or related malignancies
Term
What are the major drug classes for Immunosuppression?
Definition
1) Cytotoxic agents
2) Antimetabolites
3) Antibiotics
4) Corticosteroids
5) Immunologic agents
Term
What is most responsible for increasing survival of organ transplant pts?
Definition
Immunosuppressive antibiotics—non-cytotoxic agents
-CsA
-Sirolimus
-Tacrolimus
Term
What type of hypersensitivity is Type I?
Definition
Immediate hypersensitivity
Term
What type of hypersensitivity is Type II?
Definition
Antibodies bound to cells or tissues
Term
What type of hypersensitivity is Type III?
Definition
Immune complex
Term
What type of hypersensitivity is Type IV?
Definition
Delayed type hypersensitivity (DTH)
Term
Which hypersensitivities are Ab-mediated?
Definition
Type I, II, and III
Term
Which hypersensitivities are cell mediated (CMI)?
Definition
Type IV
Term
What is the pathologic immune mechanism in Immediate Hypersensitivity (Type I)?
Definition
-Th2 cells
-IgE antibody
-mast cells
-eosinophils
Term
What is the mechanism of tissue injury and disease in Immediate Hypersensitivity (Type I)?
Definition
-Mast cell-derived mediators (vasoactive amines, lipid mediators, cytokines)
-Cytokine-mediated inflammation (eosinophils, neutrophils)
Term
What is the pathologic immune mechanism in Antibody- Mediated diseases (Type II)?
Definition
IgM, IgG antibodies against cell surface or extracellular matrix antigens
Term
What is the mechanism of tissue injury and disease in Antibody- Mediated diseases (Type II)?
Definition
-Complement and Fc receptor-mediated recruitment and activation of leukocytes (neutrophils, macrophages) and activation of inflammatory cells
-Opsonization and phagocytosis of cells
-Abnormalities in cellular function, e.g. hormone receptor signaling
Term
What is the pathologic immune mechanism in Immune Complex Mediated diseases (Type III)?
Definition
Immune complexes of circulating antigens and IgM or IgG antibodies deposited in vascular basement membrane
Term
What is the mechanism of tissue injury and disease in Immune Complex Mediated diseases (Type III)?
Definition
Complement and Fc receptor-mediated recruitment and activation of leukocytes and activation of inflammatory cells
Term
What is the pathologic immune mechanism in T cell-mediated diseases (Type IV)?
Definition
1. CD4+ T cells (delayed type hypersensitivity)
2. CD8+ CTLs (T cell-mediated cytolysis)
Term
What is the mechanism of tissue injury and disease in T cell-mediated diseases (Type IV)?
Definition
1. Macrophage activation, cytokine-mediated inflammation
2. Direct target cell lysis, cytokine-mediated inflammation
Term
In the second exposure to an allergen what two reactions happen and what is involved?
Definition
1) Immediate hypersensitivity reaction (minutes after repeat exposure to allergen)- vasoactive amines, lipid mediators
2) Late phase reaction (6-24 hours after repeat exposure to allergen)- Cytokines
Term
What means prone to developing allergies due to IgE?
Definition
Atopy, atopic
Term
In the allergy immediate reaction, what comes from granule exocytosis and leads to vascular dilation, smooth muscle contraction and then histamine release?
Definition
Vasoactive amines
Term
In the allergy immediate reaction, what comes from granule exocytosis and leads to tissue damage?
Definition
Proteases
Term
In the allergy late phase reaction what comes from enzymatic modification of arachidonic acids and is a secreted lipid mediator that leads to vascular dilation?
Definition
Prostaglandins
Term
In the allergy late phase reaction what comes from enzymatic modification of arachidonic acids and is a secreted lipid mediator that leads to smooth muscle contraction?
Definition
Leukotrienes
Term
In the allergy late phase reaction what comes from transcriptional activation of cytokine genes and is secreted to cause inflammation (leukocyte recruitment)?
Definition
Cytokines, e.g., TNF
Term
Which Type of Inflammation is TISSUE SPECIFIC?
Definition
Type II
Term
Which Type of Inflammation is Immune complex SYSTEMIC?
Definition
Type III
Term
In sensitized persons, immediate (type I) hypersensitivity responses are primarily the result of liberation of vasoactive substances by the action of which of the following?
Definition
IgE on basophils and mast cells
Term
A healthy 19-year old man receives a tetanus immunization booster prior to induction in the Marines. Six hours later, he has pain and massive swelling at the site of injection. The following day, the skin breaks down, forming an ulcer at the site. Which of the following events plays a critical role in this reaction?
Definition
Local fixation of complement by preformed circulating antibodies. (Arthus rxn)
Term
What are some keys points about Transplantation?
Definition
-rejection can involve multiple effector mechanisms
-strong rejection is mediated by MHC incompatibilities (major)
-weak (chronic) rejection associated with differences in minor histocompatibility antigens
Term
What is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self?
Definition
Central Tolerance
Term
Clonal deletion in developing central tolerance is what type of selection?
Definition
Negative selection
Term
What is immunological tolerance developed after T and B cells mature and enter the periphery. These include the suppression of autoreactive cells by 'regulatory' T cells and the generation of hyporesponsiveness (anergy) in lymphocytes which encounter antigen in the absence of the co-stimulatory signals that accompany inflammation, or in the presence of co-inhibitory signals
Definition
Peripheral Tolerance
Term
In Central tolerance what are the 3 fates of Immature lymphocytes that recognize self antigen?
Definition
1) Apoptosis (deletion)
2) Change in receptors (receptor editing; B cells)
3) Development of regulatory T lymphocytes (CD4+ T cells only)
Term
Can CD8+ cells become T reg cells?
Definition
NO only CD4+ T cells
Term
Where does Central Tolerance occur?
Definition
Generative lymphoid organs (thymus, bone marrow)
Term
Where does Peripheral Tolerance occur?
Definition
Peripheral Tissues
Term
In Peripheral tolerance what are the 3 fates of Mature lymphocytes that recognize self antigen?
Definition
1) Anergy- No rxn
2) Apoptosis (death) of mature lymphocyte
3) Suppression mediated by T reg cells (CD4+ T cells)
Term
T cell development what are the 4 stages ending in a Double Positive?
Definition
1) Stem Cell
2) Double negative (CD4- and CD8-) Pro-T cell
3) Pre-T cell
4) Double positive (CD4+ and CD8+) immature T cell
Term
What are the four possible paths that a Double Positive Immature T cell can undergo?
Definition
Positive Selection
1) Mature CD4+ T cell (weak recognition of class II MHC + peptide)
2) Mature CD8+ T cell (weak recognition of class I MHC + peptide)
Failure of positive selection ("death by neglect")
3) Apoptosis (No recognition of MHC + peptide)
Negative Selection
4) Apoptosis (Strong recognition of either class I or class II MHC + peptide)
Term
Where would you find DOUBLE-NEGATIVE CD3- thymocytes?
Definition
Sub-capsular zone
Term
Where would yoU find DOUBLE-POSITIVE CD3+ thymocytes undergoing POSITIVE SELECTION?
Definition
Thymic cortex (Positive selection occurs here)
Term
Where would yoU find DOUBLE-POSITIVE CD3+ thymocytes undergoing NEGATIVE SELECTION?
Definition
Through the cortex and esp. at the cortico-medullary function
Term
Where do Mature self-restricted, self-tolerant, single-positive CD4 or CD8 T cells leave the thymus?
Definition
Blood venules
Term
What does clonal anergy lack?
Definition
co-stimulatory signal
Term
What is the co-stimulatory signal?
Definition
B7 on APC binding to CD28 on the Naive T cell
Term
Regulatory T cells are called and what cytokine stimulates them?
Definition
-FoxP3
-IL-2
Term
T Reg cells release which inhibitory cytokines?
Definition
-IL-10 (Inhibits Th1)
-TGF-ß(transforming growth factor)
Term
What are the stimulatory cytokines for T reg cells?
Definition
TGF-ß
Term
What are the stimulatory cytokines for Th1 cells?
Definition
IL-12
IFN-gamma
Term
What are the stimulatory cytokines for Th2 cells?
Definition
IL-4
Term
What cytokines do T reg cells secrete?
Definition
TGF-ß
IL-10
Term
What cytokines do Th1 cells secrete?
Definition
IL-2
IFN-gamma
Term
What cytokines do Th2 cells secrete?
Definition
IL-4
IL-5
Term
What happens when an Immature B cell recognizes self antigen?
Definition
1) Negative selection (apoptosis)
2) Receptor editing: expression of new antigen receptor (Light chain rearrangement replacing the original Variable light chain)
Term
What happens if a Mature B cell recognizes self antigen (peripheral tolerance)?
Definition
1) Anergy: block in antigen receptor-induced signals
2) Exclusion of B cells from lymphoid follicles
Term
What is this called when we amount an immune response to antigen but then there is a cross reaction that causes to have an immune response against self?
Definition
molecular mimicry
Term
The adjuvant causes activation of the immune system,
via...
Definition
“innate” mechanisms involving the macrophage/APC.
The activated Macrophages express co-stimulatory
molecules which contribute to the activation of
the autoreactive T cell
Term
The brain is normally what sort of site in immunology?
Definition
immune privileged (pertussis toxin can change this and allow peripheral T cells there
Term
Which Th cells are characteristics of many autoimmune disease?
Definition
Th1 and 17
Term
Amazingly, a “tolerizing” regimen can prevent the
development of MS in these mice, by a “diversion” of the
cytokine response away from Th1
Definition
to Th2
Term
For T cells, there are three major mechanisms for tolerance:
Definition
1) Central (thymic) deletion of autoreactive T cells: TCR repertoire selection
T cells with T Cell Receptors which react too strongly to self proteins are deleted in the thymus. Obviously, central tolerance did not operate in the mice which get MS, since they had autoreactive T cells.

2) “Clonal ignorance”.
T cells could avoid central deletion if their antigen is not expressed in the thymus and sequestered in the periphery such that they never see it. Then, entry of T cells into a “privileged” site would lead to autoimmunity (see above, pertussis)

3) Peripheral tolerance.
CD25+ T “regulatory” cells can control autoreactivity in the periphery

Aberrations in any of these can lead to autoimmunity
Term
What are Immune responses
to foreign (eg bacterial) proteins stimulates the immune system to attack self-proteins which are structurally similar to the pathogen?
Definition
Molecular mimicry
Term
Three mechanisms of loss of tolerance
Definition
1) Molecular mimicry- rheumatic fever
2) Defective MHC mediated negative selection, allowing an autoreactive T cell repertoire
3) Defective T regulatory cells, resulting in excessive, “unopposed” peripheral immune activation
Term
Where is histamine normally stored?
Definition
-mast cells
-basophils
-enterochromaffin-like (ECL) cells
Term
What is insufficient organ perfusion and oxygen delivery?
Definition
Shock
Term
what part of the antigen does the antibody bind to?
Definition
Epitope or antigenic determinant
Term
Can an antigen have multiple epitopes?
Definition
Yes
Term
Can a molecule have more than one antigens?
Definition
Yes, eg virus H1N1(two different antigens)
Term
Superantigens activate which T cells?
Definition
-Ones expressing a certain Vb segment
-Bind to MHC class II molecules
-Cause polyclonal T cell activation
-Function as intact proteins, not as peptide fragments
Term
A deficieincy in dectin-1 causes,
Definition
a deficiency in IL-17
Term
How does normal flora protect us?
Definition
1) Stops other microorganism from reaching the surface
2) Produces toxins
Term
Is a urine a good growth material?
Definition
Yes
Term
Naive CD4 cells express what?
Definition
CD45RA+
Term
Effector and Memory CD4 cells express what?
Definition
CD45RO+
Term
What recognizes C3b?
Definition
macrophages and neutrophils
Term
What induces mast cells to release their mediators in the complement pathway?
Definition
-anaphylatoxins - C5a, C3a, (C4a weak)
Term
What is a chemotactic (attractor) factor for neutrophils?
Definition
C5a
Term
Which two parts of the complement pathway are part of the Innate immunity?
Definition
Alternate and Lectin pathway
Term
The central goal of all of the complement pathways is to?
Definition
put C3 convertase onto the target cell
Term
What does macrophages make?
Definition
TNF
IL-1
Term
What is interesting about TNF?
Definition
fever inducer (IL-1,6) and it has systemic effects
Term
What type of infection will you see type I IFN secreted?
Definition
viral
Term
What does IFN?
Definition
interferes with viral replication
Term
What receptors go about producing the IFN- alpha and beta response?
Definition
TLRs
Term
What is the major histocompatability factor?
Definition
MHC class I
Term
What do virus infected cells do to help with NK cell killing?
Definition
-Expresses more NK activating ligands
-Supressess MHC class I(self complex and inhibitory ligand)
also tumors down regulate MHC I
Term
Macrophages release what to activate NK cells?
Definition
IL-12
Term
NK cells make what to activate macrophages?
Definition
IFN-gamma
Term
What term describes that only one of two parental alleles is expressed by a single B cell?
Definition
allelic exclusion
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