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Host Defenses
Test 1
114
Immunology
Professional
01/21/2011

Additional Immunology Flashcards

 


 

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Term
Name infectious agents
Definition
Viruses
Bacteria
Fungi
Parasites
Term
Neoplasia
Definition
Distinguishing self from altered self
Term
Describe innate immunity
Definition
Born with it
Non-specific
Starts immediately (near entry points)
Sees whole pathogen
Non-clonal
Monocytes, NK Cells, granulocytes
Complement, cytokines, antimicrobial peptides
Term
Describe adaptive immunity
Definition
Acquired
Specific
Takes a while to start up (most effective)
Induced
Clonal
B Cells and T Cells (memory)
Antibodies
Have surface receptors for antigens
Term
Edward Jenner
Definition
1798 - Smallpox vaccine
"Founder of immunology"
Term
Louis Pasteur
Definition
1879: Attenuated vaccine for chicken cholera
Term
Karl Landsteiner
Definition
1901: A, B, O blood groups
Term
Rodney Porter
Definition
1959-1962: Antibody structure
Term
Rolf Zinkernagel and Peter Doherty
Definition
1974: MHC restriction discovery
Term
Tsutsumu Tonegawa and Leroy Hood
Definition
1985: Immunoglobulin gene discovery
Term
Leroy Hood
Definition
1987: T cell receptor genes identified
Term
Steinman
Definition
1989: Dendritic cells present antigen to T cells
Term
Nomura and Charles Janeway
Definition
1994 - 1998: Toll-like receptor discovery
Term
3 components of the immune system
Definition
Soluble: released by cells, affect differentiation and activities of immune cells.
Cellular: Innate and adaptive responses
Tissues: Primary and secondary organs
Term
Life cycle of immune cells
Definition
Originate in bone marrow
Migrate through blood and lymph
Mature and function in peripheral tissues
Term
What cells drive differentiation of immune cells?
Definition
Cytokines
Term
Paths of hematopoietic stem cells
Definition
1: lymphoid progenitor --> B-Cells, T-Cells, NK-Cells

2: Myeloid progenitor --> Granulocytes (neutrophil, eosinophil, basophil, mast cell, monocyte) or erythrocytes --> megakaryocytes

Monocytes / mast cells --> macrophage / mast cells

3: Erythroblast --> erythrocytes
Term
Most concentrated leukocyte in the blood?
Definition
Neutrophils (4400/ml). Can be quickly distributed in response to an inflammatory stimulus
Term
Leukocytes
Definition
AKA: White blood cells
Originate in bone marrow from hematopoietic stem cells
First produced in liver/yolk sac in young fetus
Term
Neutrophils (PMNs)
Definition
Most numerous leukocyte
Phagocytosis/digestion of bacteria/particles
Multi-lobed nuclei
Short life span
Travel to site of inflammation
Term
Granulocytes
Definition
Eosinophils: Parasites
Basophils: Cytokines
Mast cells: Release histamine
Term
Macrophages
Definition
MOST IMPORTANT phagocytic cell
Role in killing bacteria
Secrete pro-inflammatory cytokines
Long-lived

(can present processed antigens to T cells, and regulate wound healing/homeostasis)
Term
Dendritic cells
Definition
MOST IMPORTANT antigen presenting cells
Link between innate and adaptive immunity
Take the epitope to the lymph
Found in low numbers in tissues
Term
Lymphocytes
Definition
Leave bone marrow only partially mature
B Cells differentiate in bone (mature in lymph nodes)
T Cells differentiate in thymus
Cannot be differentiated visually
Mediate adaptive immunity
Term
Natural Killer (NK) Cells
Definition
Lymphocytic lineage (NOT T-CELLS)
Kill tumor cells and virally-infected cells
Possess Fc receptor
Secrete interferons
Term
Consequences of immunity
Definition
Autoimmunity
Graft rejection
Hypersensitivity
(can't distinguish self form non-self)
Term
Primary organ
Definition
Where leukocytes are differentiated and produced
(not yet committed)
Bone marrow
Thymus
Bursa of Fabricius
Peyer's patches
Term
Secondary organ
Definition
Site where B and T cells are induced to function. (develop and respond)
Lymph nodes
Spleen
Bone marrow
Peyer's patches
Term
Eosinophils
Definition
Mature in the spleen, then go to tissues
Phagocytosis and killing of parasites
Fc receptors on surface
Bi-lobed nuclei
Promotes inflammation
Mostly deal with large pathogens
Term
Basophils
Definition
Low numbers
Multi-lobed nucleus
Contain inflammatory molecules
Small role in killing parasites
Fc receptors
Term
Mast Cells
Definition
Multi-lobed nuclei
Different morphologies in different tissue
Fc receptors (for parasites)
Secretes histamine & serotonin
Vasodilator
Term
Bone Marrow / Bursa of Fabricius
Definition
Bursa of Fabricius is in birds
B-Cell receptor rearrangement occurs here
If excessive blood cell production is demanded, liver and spleen produce lymphocytes.
Fewer B-Cells toward center of marrow
Site of hematopoiesis
Adipose provides energy
Term
Thymus
Definition
T-cell maturation (move toward medulla)
Variation in size shape in animals
Presentation of self antigens ONLY
Involutes after sexual maturity
Term
Hassall's corpuscle
Definition
Epithelial cells that "tolerize" T-cells
Ability to generate immune response
Cortex: Dense, immature
Medulla: Less dense, mature
Term
Peyer's Patches
Definition
Structures along GI tract in lamina propria
Contain mostly B-cells
B-cells central; T-cells surrounding
Immune response for ingested antigens
M-cells: Site for antigen entry!
Take up antigen via immune cells and transport them to lymph nodes
Term
Germinal center
Definition
Site where B-cells are rapidly dividing
Term
Spleen
Definition
Secondary lymphoid organ (largest)
Encased in a thick capsule
Red pulp: Phagocytes
White pulp: Lymphocytes (mostly B-cells)
Filters out effected RBC's
RBC storage, and backup proliferation
Major site of adaptive response to blood-borne pathogens
Term
Two components of the White pulp of the spleen
Definition
Splenic nodules: B-cells
Periarterial Lymphatic Sheaths (PALS): T-cells that line the arteries
Term
Lymph Node function
Definition
Points of convergence for blood and lymph
Collects lymph for return to blood
B-cells: primary lymphoid follicle
T-cells: cortical area
Term
Lymph node structure
Definition
Bean-shaped
Cortex around medulla surrounded by capsule
Dendrites and lymphocytes can enter from afferent lymph or from the blood
Have germinal centers
Term
Lymph System
Definition
Distributed throughout body
Collect and sample antigens
Only lymphocytes can use HEV's!
Term
Flow of lymph through a lymph node
Definition
Afferent lymph vessel -->
Subcapsular sinus -->
Cortical sinus -->
Medullary sinus -->
Efferent vessel
Term
High Endothelial Venules (HEV's)
Definition
Found in the lymph nodes
Specialized capillaries where lympocytes exchange from blood.
Cells LACK tight juncitons!
Used a lot by T-cells
Term
Cytokines
Definition
Small soluble proteins and glycoproteins
Regulate and mediate immune responses
Large number and variety
Homeostatic roles
Activate or suppress immune activities
NOT antigen-specific!
pleiotripic (diff. activities)
Highly regulated expression
Redundant actions
Influence synthesis/action of others
Many non-immune functions (wound repair)
Term
4 families of cytokines
Definition
Growth factors
Interleukins
Interferons
Chemokines
Term
Growth Factors
Definition
Family of cytokine
Simulate hematopoiesis
Regulate leukocyte growth/differentiation
Term
Interleukins (IL)
Definition
Mediators and regulators of mature lymphocytes and leukocytes
(Innate and adaptive immunity)
Very diverse group
Term
Interferons (IFN)
Definition
Mediate and regulate antiviral and innate immunity.
Inhibit viral replication (block receptors)
Regulate developing fetus
Accelerate B-cell diferentiation
Mostly from: T-cells, macrophages, fibroblasts
Term
Chemokines
Definition
"Chemoattractants." Regulate directed movement of immune cells
Induced by a variety of stimuli
Divided into 4 classes
Term
Cytokine Receptors
Definition
HIGHLY specific!
Single or multimeric
Some share common subunits
Receptors can be grouped into families
A cell can have receptors for many cytokines
Term
Jobs of type I interferons a/B
Definition
Induction of "antiviral state"
Increase expression of MHC1 on host cells
Activate NK cells to kill viral cells
Term
IFN y (type II)
Definition
produced by helper T-cells and NK cells
ACTIVATES macrophage immune function!
Isotype switching to opsonize antibodies
Increases MHC expression
Term
Colony Stimulating Factors
Definition
Promote differentiation of progenitor cells. Different kinds:
Granulocyte (GSF): Neutrophils, eosinophils
Macrophage (GSF): Monocytes, macrophages
GM-CSF: Granulocytes or Macrophages
IL-3: Macrophages or granulocytes
IL-7: Produced by stromal cells in bone/spleen
Term
IL-1
Definition
Regulates host inflammatory response
Produced mostly by macrophages and epithelial cells
2 forms: 1a and 1B (overlapping activities)
CNS: fever, sleepiness
Vascular: adhesion molecules, IFN-y
Liver: Acute phase protein production
Term
IL-2
Definition
Produced by: Th1
Causes autocrine proliferation of T-cells
Augments Ig synthesis
PRIMARY growth factor for T-cells!
Term
IL-6
Definition
Produced by: macrophages and T-cells
Liver: Acute phase protein expression
Hypothalamus: fever by pyrogen
Adipose: Decreased fat storage
Term
IL-12
Definition
CRITICAL cytokine
Differentiation of T-cells toward Th1
Produced by: Dendrites and macrophages
Activate NK cells for IFN-y
Term
Tumor Necrosis Factor (TNF-a)
Definition
MEDIATOR of ENDOTOXIC SHOCK (gram- sepsis)
Produced by: Macrophages, NK cells
Activities:
Cell killing
Immunocyte activation
Liver: acute phase protein expression
Fever
Regulates hematopoiesis
2 different receptors (shed during response)
Term
Cells affected by TNF-a
Definition
Monocyte
Endothelium
Brain (hypothalamus)
Liver (acute phase...)
Term
How does TNF-a work on vascular endothelium?
Definition
Macrophages make TNF-a which signals the endothelium to make adhesion molecules which grab the neutrophils in the blood and bring them through the epithelium and into the tissue to act on bacteria
Term
Local effects of TNF
Definition
Macrophages make TNF to bring phagocytes and lymphocytes into tissues. Increased platelet adhesion. Phagocytosis of bacteria. Plasma and cells drain into lymph nodes. Removes infection via adaptive immunity.
Term
Systemic effects of TNF
Definition
Liver and spleen make macrophages to make TNF for blood. Causes systemic edema, decreased blood volume, neutropenia. Leads to intravascular coagulation and organ failure. DEATH
Term
Cytokine storms
Definition
Since cytokines work together to impact peripheral immune events, "storms" can lead to tissue injury, shock, death.
Term
Endotoxic/spetic shock
Definition
Overexpression of cytokines
Caused by Gram- cell walls (LPS)
TNF-a is major cytokine responsible
Species vary in sensitivity to LPS-induced shock
cat, horse, pig>dogs>mice>>birds
Term
IL-4 and IL-10
Definition
Regulate humoral immune response!
"anti-inflammatory"
Inhibits macrophage activation
IL-4 acts on T-cells:
Promotes Th2
Enhanced proliferation
Produce Th2 cytokines
Inhibit Th2 differentiation
Term
IL-8 Chemokine
Definition
Chemotactic for neutrophils
Term
MIP-1 Chemokine
Definition
Chemoattractand for CD8+ T cells and neutrophils
Term
Rantes (CCL5) Chemokine
Definition
Chemoattractant for memory CD4+ T cells, eosinophils, and monocytes
Term
MCP-1 Chemokine
Definition
Chemoattractant for monocytes
Term
IP-10 (CXCL10) Chemokine
Definition
Chemoattractant for NK cells and resting T cells
Term
Cytokines for communication
Definition
B and T cells communicate using cytokines
Used for activation of B cells, B cell differentiation into plasma cells, and Ig class switching (isotypes)
Term
SNP's
Definition
Single nucleotide polymorphisms in cytokines that are linked to changes in gene expression.

Can change the nature of the inflammatory response
Term
Manipulating immune response
Definition
Cyclosporin A: inhibits transplant rejection
Corticosteroids: inhibits inflammation
Anti-TNF-a therapy: for rheumatoid arthritis
Term
Pro-inflammatory cytokines
Definition
TNF
IL-1
IL-6
Chemokines
Term
Anti-inflammatory cytokines
Definition
IL-10
IL-1ra
TGF-B
Term
Cytokines that inhibit virus replication
Definition
IFN a/B
Term
Macrophage activating cytokines
Definition
IFN-y
Term
B-cell activating cytokines
Definition
IL-4
IL-5
IL-6
IL-21
Term
T cell stimulating cytokines
Definition
IL-2
IL-4
IL-12
IFN-y
Term
Eosinophil/Mast cell activating cytokines
Definition
IL-3
IL-4
IL-5
IL-13
Term
Antigen
Definition
Substance that induces antibody generation
Induces a specific immune response
AKA: Immunogens
B cells recognize large molecules
T cells only recognize epitopes
Allergen: antigen causes allergic reaction
Term
Epitope
Definition
Part of large molecule bound by antibody
Multivalency: Sometimes repeated many times on a macromolecule
Spatial arrangement affects Ab binding
Term
Haptens
Definition
Small molecules, not normally immunogenic, but are antigens when linked to a carrier.
Linkage forms a new epitope
Ex: Penicillin to albumin
Term
3 types of antibodies generated by haptens
Definition
1. Against the carrier
2. Against the hapten
3. Against the new epitope by hapten-carrier linkage
Term
What makes a good antigen?
Definition
1. Foreignness
2. Complexity
3. Size
4. Stability
5. Speed of release

Proteins are best, lipids are worst
Host factors affect potential immunogenicity
Term
Cross-reactivity
Definition
One epitope is similar enough to trigger response against a different epitope, even on different molecules.

Results in immunity against unrelated antigens
Term
Response toward antigens in tissues
Definition
Taken up by dendrites and macrophages
Moved to lymph nodes
Elicit IgG isotype
Term
Response toward antigens in mucosal surfaces
Definition
Taken up by M-cells or dendrites
Extend through epithelial lining
Elicit IgA and IgE isotypes
Term
Antigen processing
Definition
Degradation of proteins into epitopes to bind MHC for presentation
Term
Antigen presentation
Definition
Displaying antigens as peptide fragments
Exogenous (ouside cell): MHC II
Endogenous (inside cytosol): MHC I
Term
Autoantigens
Definition
Normally, immune system cannot recognize self proteins.

Errors cause antibodies and T-cells to be made against self-antigens. "Auto-antigens"

4 Classes
Ex: Sperm, mitochondria, insulin...
Term
Molecular Mimicry
Definition
Some pathogens express proteins that resemble host molecules. T-cells will then also recognize host cells presented by MHC I
Term
2 ways to induce autoimmunity
Definition
Disruption of cell/tissue barrier
Molecular mimicry
Term
Tumor antigens
Definition
Presented on surface of tumor cells
MHC I and MHC II
Not found on normal cells
Term
Super antigens
Definition
Exotoxins that highly stimulate T-cells
Do not require prior processing
Cross-link MHC and T-Cell receptor
Over-stimulates T-cells (overproduce cytokines)
Drive hyperinflammation
Term
3 Functions of antibodies
Definition
Opsonization
Complement Activation
Neutralization
Term
How does complement action work?
Definition
Lyses bacteria
Term
What is opsonization?
Definition
Coating foreign particle with antibodies
Helps neutrophils/macrophages become phagocytic
Term
Adaptive immunity from antibodies
Definition
Antibody production begins 4-7 days after exposure
Antibodies are antigen-specific, principle mediators of adaptive immunity
Ab's are found in plasma and on mucosal surfaces
Term
Antibody structure
Definition
Heterodimeric, produced by B-cells
Antigen specific
Function in many environments
Interact w/ Ag's non-covalently!
Different constants make diff. isotypes
SUBunits are covalently linked
Heavy subunit determines isotype
Fab contains Ag binding site
Digested via Papain
Term
Constant region confers functional specificity by:
Definition
IgG and IgM activate classical pathway
IgE binds to mast cells and basophils
IgG binds to receptors on macrophages, neutrophils, NK cells
Term
Expression of isotypes in blood vs. mucosal surfaces
Definition
IgG>IgM>IgA in blood
IgA>>IgM>IgG on mucosal surfaces
Term
Function of IgD
Definition
Does NOTHING special
Antigen receptor on naive follicular B cells
Term
Function of IgE
Definition
Mast Cell Activation (and basophils)

Induced by IL-4
Term
Functions of IgA
Definition
Cross epithelium
Neutralization
Vascular diffusion

Induced by TGF-B
Term
Function of IgM
Definition
Complement activity

Inhibited by IL-4, IFN-y, TGF-B
Term
Functions of IgG1
Definition
Opsonization
Cross placenta
Vascular diffusion
Complement activity
NK Cell activation
Neutralization

Induced by IL-4
Term
Functions of IgG2
Definition
Vascular diffusion
Cross placenta
Neutralization
Complement activity

Induced by IFN-y and TGF-B
Term
Allelic exclusion
Definition
Rearrangement of DNA only occurs on one chromosome for each light or heavy chain genes.
"Chromosomal silencing"
Term
Allelic exclusion
Definition
Rearrangement of DNA only occurs on one chromosome for each light or heavy chain genes.
"Chromosomal silencing"
Term
4 ways to contribute to antibody diversity in bone marrow
Definition
Multiple germline genes
H and L chain recombinations
Imprecise joining of segments
Random insertion of bases

Somatic hypermutation: only after encounters an antigen
Term
RAG proteins
Definition
Recognize conserved sequences flanking each gene segment
Cleave out intervening DNA
Deficiency in RAG = immunocompromised
High rate of mistakes
Term
Somatic Hypermutation
Definition
When a B cell is active and proliferating, an enzyme chemically changes bases to a different base for a new codon.

AID enzyme converts cytidine to thymididine

Impacts the V region segment
Term
Affinity maturation
Definition
If a mutation provides better binding, these B-cells are selected.
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