Overview of Fundamentals of Immunology Flashcards
Describe 4 levels of protection from disease-causing pathogens
1) Anatomic Barriers (e.g. skin)
2) Complement/Antimicrobial proteins (e.g. C3, defensins, RegIII-y)
3) Innate immune cells (e.g. macrophages, granulocytes, NK)
4) Adaptive immunity (e.g. T cells, B cells/antibodies)
Compare general differences between innate and adaptive immunity
Innate:
- always available
- first line of defense
- specific for general types of pathogens but not individual pathogens
- no lasting immunity
Adaptive
- develops during lifetime as adaptation to infections with pathogens
- antigen specific
- confers long-lasting immunity
List general categories of immune response
Immune recognition
Immune effector function
Immune regulation
Immunologic memory
Pluripotent hematopoietic stem cell gives rise to 2 progenitor cells = ?
1) Common lymphoid progenitor
2) Common myeloid progenitor
Common myeloid progenitor gives rise to which types of cells (terminal line)?
- eosinophils, basophils, mast cells
- neutrophils, dendritic cells, and macrophages
- platelets
- erythrocytes
List granulocytes & their function
Neutrophil: phagocytosis and activation of bactericidal mechanisms
Mast cell: release of granules containing histamine and active agents
Eosinophil: killing of antibody coated parasites
Basophil: promoting of allergic responses and augmentation of parasitic immunity
List phagocytes
- Neutrophils
- Monocyte (circulation in blood) –> macrophage (differentiation in tissue): reside in tissues and act as scavengers; poor APC
- Dendritic cell: antigen uptake in peripheral sites –> good APC and phagocytose small particles
Common lymphoid progenitor cell gives rise to?
Adaptive lymphocytes (unique receptor for Ag):
- B-cells
- T-cells
Innate-like lymphocytes (lack Ag receptors; produce cytokines)
- NK cells
- Innate Lymphocyte cells (ILCs)
Overlapping functions of innate and adaptive cells - Effector modules:
1) Cytotoxicity
2) Intracellular immunity (Type 1)
3) Mucosal and barrier immunity (Type 2)
3) Extracellular immunity (Type 3)
1) Cytotoxcity
NK cells and CD8 T cells
-elimination of virally infected and metabolically stressed cells
2) Intracellular immunity
ILC1 and Th1 cells
-elimination of intracellular pathogens; activation of macrophages
3) Mucosal and barrier immunity
ILC2 and Th2 cells
-elimination and expulsion of parasites; recruitment of eosinophils, basophils, and mast cells
4) Extracellular immunity
ILC3 and Th17 cells
-elimination of extracellular bacteria and fungi; recruitment and activation of neutrophils
Describe primary and secondary lymphoid organs
Primary lymphoid organs
- thymus: site of T-cell development
- bone marrow: site of myeloid and B-cell development
Secondary lymphoid organs
- Lymph nodes: collect lymph and antigen from peripheral sites through lymphatic vessels
- spleen: collect antigens from circulating blood
Describe areas in LNs where immune cells reside
Primary lymphoid follicle: mostly B-cells
paracortical area: mostly T-cells
medullary cords: macrophages and plasma cells
germinal centers: mature activated B-cells
[see fundamental of immunology lecture 1 diagram: slide 17]
What are Peyer’s patches?
- LNs on the surface of the intestinal lumen
- covered by an epithelial layer containing specialized cells called M cells
Give examples of diffuse aggregates of lymphocytes/follicles
- Peyer’s patches
- NALT (nasal associated lymphoid tissue)
- BALT (bronchus associated lymphoid tissue)
- GALT (gut associated lymphoid tissue)
Spleen
1) function
2) architecture
1) collects Ag from circulating blood and eliminate old RBCs; important for blood-borne pathogens
2) Red pulp = RBC disposal. White pulp = leukocytes with B-cells, T-cells, macrophages
[see lecture 1 diagram - slide 20]
List 4 classes of pathogens that the immune system defends against
1) viruses
2) intracellular bacteria, protozoa, & parasites
3) extraceullar bacteria, fungi, & parasites
4) Parasitic worms (extracellular)
Pathogens with different lifestyles require different response for immune system recognition and destruction
How are innate immune system responses initiated?
Initiated upon recognition of “danger signals” by pattern recognition receptors
Give examples of danger signals & pattern recognition receptors
Danger signals
- pathogen-associated molecular patterns (PAMPs)
e. g. bacterial proteins, viral DNA/RNA - damage-associated molecular patterns (DAMPs)
e. g. products of dying cells
Types of PRRs (can be on cell surface or intraceullar)
- toll-like receptors (TLR)
- c type leptin receptors
- NOD-like receptors (NLRs)
- RIG-I like receptors
How do infectious agents cause an inflammatory response?
1) Bacteria trigger macrophages to release cytokines and chemokines
2) vasodilation and increased vasc. permeability –> redness, heat, and swelling
3) inflammatory cells migrate to tissue, releasing inflammatory mediators that cause pain
(adaptive cells come later)
What are some functional differences between immature and mature DCs?
Immature DCs = very efficient at Ag processing
Mature DCs = very efficient at Ag presentation
How are Ag processed on MHC Class I after being infected by virus?
Virus infected cell –> viral proteins synthesized in cytosol –> Peptide fragments of viral proteins bound by MHC class I in ER –> bound peptides transported by MHC Class I to the cell surface
[see slide 26]
MHC Class I is expressed by ______ cells and presents peptides from the ________.
nucleated; cytosol
MHC Class I/peptides recognized by ______
MHC Class I proteins recognized by ______
CD8+ T cells; NK cells
How do macrophages process Ag?
Bacterium infects macrophage and enters vesicle, producing peptide fragments –> bacterial fragments bound by MHC class II in vesicles –> bound peptides transported by MHC Class II to the cell surface.
[see slide 27]
How do B-cells process Ag?
Ag bound by B-cell receptor –> Ag internalized and degraded to peptide fragments –> fragments bind to MHC class II and are transported to the cell surface
[see slide 27]
MHC Class II typically expressed by ______ and presents peptides derived from ________ proteins. MHC Class II/peptides are recognized by ____.
professional APCs; exogenous; CD4 T cells
What’s an important bridge between innate and adaptive responses?
DC = important for initiating adaptive immune responses.
immature DC reside in peripheral tissues –> DC migrate via lymphatic vessels to regional LNs –> mature DC activate naive T cells in lymphoid organs such as LNs
_____ are responsible for the effectiveness of adjuvants
PAMPs
Describe the structure of antigen receptors
Antibody
- variable region = antigen binding site
- constant region for effector function
- Ab can be on cell surface and be secreted
T-cell receptor
- variable region = antigen binding site
- constant region
Constant region = shared among many cell types
variable region = unique
How is Ag receptor diversity generated?
Gene rearrangement
- inherited gene segments –> unique combo of segments becomes joined by somatic gene rearrangement –> chain pair to give unique receptor for each lymphocytes
- Recombination [used for Ig & TCR; irreversible; different in each cell; generates vast combinations of receptors within organisms]
- Occurs in development before cell sees antigen
What is an epitope?
How are TCR epitopes different from Ab epitopes?
Region on Ag recognized by Ab.
-Ab recognizes portions of proteins
Epitopes recognized by TCR is usually buried in the protein structure and thus need to be processed and presented on MHC class molecules
What’s the central principle of adaptive immunity?
1) single progenitor cell –> large #lymphocytes with unique Ag receptors
- vast pool of immature cells (non-functional)
2) Removal of potentially self-reactive immature lymphocytes by clonal deletion
- shapes repertoire of Ag responsive cells
3) Pool of mature naive lymphocytes
- cells that recognized specific Ag = very rare
- this explains why adaptive response takes more time
[Ag recognition –> activation]
4) Proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells following recognition of Ag (activation)
- effectors are all derived from same parent cell
- all have same Ag receptor/specificity
What’s the mechanism of central tolerance?
Elimination of cells that can recognized self Ags
How long does lymphocyte activation take? What occurs during this time?
- Process takes 4-5 days
- Expansion and acquisition of effector functions
Where does lymphocyte development and activation occur?
- Development in primary lymphoid tissues
- Activation in secondary lymphoid tissues
Activation of T & B cells occurs through?
Signal 1 = antigen receptor
Signal 2 = costimulatory molecule
Absence of costimulation—> peripheral tolerance = backup for central tolerance
T-cells activated by mature DC
B-cells activated by T-cells
Describe subtypes of T-cells
CD8+ T-cell = cytotoxic T-cell
-recognized MHC Class I/peptide and kills cell
CD4+ T-cell = helper T-cell
-recognizes MHC Class II and helps activate B cells
Other subtypes = Th1, Th2, Th17, and Tregs
What are Ab functions that are produced by B-cells?
- Neutralize
- Block protein functions
- Promote engulfment
- induce complement mediated lysis
Different types of Ab Classes = IgM, IgG, IgE, IgA
What is opsonization?
coating of a particle with proteins that facilitate phagocytosis of the particle by tissue macrophages and activated follicular dendritic cells (FDCs) as well as binding by receptors on peripheral blood cells
What is different in the secondary immune response compared to the primary immune response?
Larger, faster, and more effective response.
Memory can lasts for decades
Describe the dominant response for the types of pathogens
1) extracellular bacteria, parasites, fungi
2) intracellular bacteria, parasites
3) viruses (intracellular)
4) parasitic worms (extracellular)
Dominant response
1) Macrophages, Bcells - IgG
2) CD8 T cells, CD4 T cells
3) CD8 T cells, IgG
4) CD4 T cells, IgE
What are MDSCs?
- heterogeneous, immature myeloid phenotype
- produce immunosuppressive cytokines, IL-10, TGF-B
- Expand during inflammation, infection, and cancer
- enriched in the TME
What are T-regulatory cells?
- inhibit or suppress other adaptive immune responses
- recognize self Ag
- Produce TGF-B and IL-10
- Different subsets: 1) generated during development or 2) induced from naive T cells in the periphery
- enriched in the TME
Compare the receptors in innate vs adaptive immunity
Receptors in Innate immunity
- specificity inhered in the genome
- expressed by all cells of a particular type (e.g. macrophages)
- triggers immediate response
- recognizes broad classes of pathogens
- interacts with a range of molecular structures of a given type
Receptors in Adaptive immunity
- encoded in multiple gene segments
- requires gene rearrangement
- clonal distribution
- able to discriminate between even closely related molecular structures
