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56 Cards in this Set

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What is the fundamental task of the immune system?
Distinguishing self from non-self
Briefly describe the three layers of immune system defense.
1) Barriers (first line)
2) Innate Immune System (always ready to go if barriers breached; reacts in same way to all intruders)
3) Adaptive Immune System (specific immune response to specific foreign antigen; takes time to develop)
What are the three major classes of barriers to infection? Provide examples for each category.
Physical: Skin, mucous, cilia

Chemical/Environmental: Sweat (salt, pH), acid (stomach, vagina), digestive enzymes, microbicidal substances (skin, mucous)

Biological Barriers: commensal organisms (living in relationship in which one organism derives food or other benefts from another organism without hurting/helping it): skin, GI tract, vagina
What are the three key cell/protein components of the innate immune system?
Phagocytes (macrophages, neutrophils)
Natural Killer (NK) cells--type of lymphocyte
Complement system (proteins)
How do macrophages act as sentinels?
when they encounter a microbe they release cytokines to recruit WBCs (causes inflammation)
How does the innate immune system know what to kill? How does it kill?
Pattern Recognition Receptors (PRRs) Recognize specific patterns of molecules shared by groups of related microbes (not found on human cells). Patterns = PAMPS (pathogen associated molecular patterns)

Macrophages and neutrophils then engulf invader in phagosome and that fuses with a lysosome
Where can PAMPs be found?
bacterial cell wall
What are NK cells and what is their role?
They are lymphocytes (not T or B cells) and are specialized to kill host cells infected with virus or host cells that have become cancerous

Also secrete cytokines
How do NK cells work?
Release small cytoplasmic granules/proteins (perforins and granzymes) into target cells and cause cell to die by apoptosis
How does the complement system work?
Small proteins normally circulating in inactive state in bloodstream. When activated, can kill in several ways:

Direct:
1) attach to invader, triger formation of Membrane Attack Complex (MAC), drill holes into membrane

Indirectly:
2) Complement binding of invader marks it for destruction by macrophages, attract phagocytes (inflammation)
How do vertebrate immune systems differ from invertebrates?
Vertebrate immune systems have adaptive immune system to defend in a custom fashion
What is an antigen?
Molecule recognized by cells of immune system and elicits immune response
What about an antigen elicits an immune response?
Cells of immune system reacts to small molecular domains on antigen known as antigenic determinants or epitopes.

Does not react to whole antigen!
What receptors do B and T cells utilize in the adaptive immune system?
Both use antigen-specific receptors
B cells use B cell receptors (immunoglublins)

T cells use TCRs
When is a B cell considered naive?
When released from BM, B cell circulates in bloodstream and lymphatic tissue in search of COGNATE ANTIGENS (antigen for which it is specific)
Describe the events that occur when a naive B cell binds its cognate antigen. What type of immunity does this comprise?
Once it meets its cognate antigen, it becomes activated by a HELPER T CELL and differentiates into plasma cells.

Plasma cells secrete antibody specific to that antigen, which are recognized by 'eater cells'.

Also produces memory B cells which are long-lived and specific to that antigen. If exposed to this antigen again, these cells will cause a very immediate response.

All apart of HUMORAL immunity.
With regard to vaccinations, how do antibodies concentrations differ in primary and secondary responses?
Primary response = exposure to antigen via vaccine; small increase in antigens; takes about 2 weeks

If exposed again, secondary response is quicker and more intense (higher antibody concentration)
Which types of antigens elicit a humoral response without help from T cells?
Polysaccharides and lipid components of bacterial cell walls
Which types of antigens can only elicit a humoral response with T cell help?
Protein antigens
Describe the general structure of an antibody.
Two heavy chains
Two light chains
Carboxyl end (base of Y) is Fc region--can bind to cell surface)

First 110 aa's near amino-terminal of light/heavy chains is VARIABLE REGION

Antigen Binding Site = variable regions of one heavy and one light chain. Each antibody has two binding sites for same antigen.
How do antibodies employ a modular design?
Mix and match production of antibodies in BM produces B cells that can respond to almost any antigen.
How do antibodies help kill intruders?
1) OPSONIZATION: Mark invader and tag it for destruction

2) NEUTRALIZATION: Block viral entry into cells by binding to virus before they enter a cell.
How is an antibody's class determined?
By its type of heavy chain
What are the five types of antibodies?
IgG: most common; can cross placenta to provide passive immunity

IgA: acts as DIMER, mucosal immunity in gut, respiratory, genital tracts

IgE: hypersensitivity reactions (binds mast cells and basophils)

IgD: not much known

IgM: acts as pentamer; first type of antibody made in response to infection; important in early stages of humoral immunity before there's enough IgG
How is TCR diversity achieved?
Mix and match, modular design
How do T cells follow the principle of clonal selection?
When T cell binds to cognate antigen, T cell proliferates to build up clone of T cells with same antigen specificity. Takes a week to complete, so antibody response is slow and specific.
Can antibodies recognize viruses that are intracellular?
NO
Do T Cells release memory cells upon activation?
Yes
How does BCR differ from TCR?
When B cells differentiate into plasma cells, they secrete antibody (immunoglobulins). BCR is then soluble.

TCR is not soluble or secretory--stays tightly glues to T cell surface.
How do B cells differ from T cells in terms of antigen recognition?
B cells can recognize an antigen by itself.

T cells only recognize an antigen presented by an Antigen Presenting Cell. T cells only recognize protein antigens.
What are the two forms of naive T cells? How do they differ?
CD8 cells: when encounter cognate antigen, become Cytotoxic Lymphocytes (CTLs)

CD4: when activated, become helper T cells (Th1 + Th2 cells)
What is the purpose of CTLs?
Target virally-infected or cancerous cells; make contact and trigger it to apoptose; virus dies inside
How do helper T cells help? How does this differ among Th1 and Th2 cells?
Secrete cytokines

Th1 or Th2 (differentiates into one of these two based on antigen presented) produce different cytokines
What are the three main types of antigen-presenting cells?
Macrophages
Dendritic
B-cells
How do APC's work?
Internalize antigen by phagocytosis or by receptor-mediated endocytosis
Antigen is processed and fragments of antigen are disapleyed on surface (in conjunction with major histocompatibility complex)

T-cells recognize antigen-MHC complex using TCR's
Once an APC has presented an antigen, what must occur for a T cell to recognize it in a timely manner?
APC (along with bacteria and virus) will travel to SECONDARY LYMPHOID TISSUE, i.e., LYMPH NODES

T and B cells circulate form node to node in search of cognate antigen
What are MHC's and what role do they play in transplant surgeries?
MHC = major histocompatibility complex = complex of genes encoding Class I and II MHC molecules
(present on cell surfaces)

One individual expresses only one set of each class, so they're unique on level of individual

Matching MHC molecules (HLA in humans) is basis of transplantation biology
What is an autograft?
Tissue transplanted from one part of body to another in same individual
What's an isograft?
Graft of tissue between genetically identical individuals
What's an allograft?
Graft between two genetically non-identical members of same species
What's a xenograft?
Transfer of tissue from one species to another
Where are class I MHC proteins found?
On surface of ALL nucleated cells
Where are class II MHC proteins found?
only on surfaces of APCs
Compare the structures of Class I and Class II MHC's.
Class I: peptide contained within groove (ends of molec are closed; peptide must be ~9aa long)

Class II: ends of groove are open so larger peptide (~15 aa's) can fit and overflow the groove--like a hot dog in a bun
What type of T cells do Class I MHC proteins associate? Class II?
Class I: CD-8 (8x1=8)
Class II: CD-4 (4x2=8)
Which class of MHC proteins employ an endogenous pathway? What's an endogenous pathway?
Class I MHC:
Intracellular proteins degraded by proteasomes and loaded onto class I MHC molecule, then displayed on cell surface

If cell is infected or cancerous, sample of viral proteins also displayed along side intracell proteins, CTL's (CD-8) recognize
How does the MHC-I/Intracell Protein complex reach the cell surface?
Via TAP--Transporter Associated with Antigen Processing
Where are Class II MHC molecules found?
Macrophages, Dendritic Cells, B cells (all APC's)
Compare the structures of Class I and Class II MHC's.
Class I: peptide contained within groove (ends of molec are closed; peptide must be ~9aa long)

Class II: ends of groove are open so larger peptide (~15 aa's) can fit and overflow the groove--like a hot dog in a bun
What type of T cells do Class I MHC proteins associate? Class II?
Class I: CD-8 (8x1=8)
Class II: CD-4 (4x2=8)
Which class of MHC proteins employ an endogenous pathway? What's an endogenous pathway?
Class I MHC:
Intracellular proteins degraded by proteasomes and loaded onto class I MHC molecule, then displayed on cell surface

If cell is infected or cancerous, sample of viral proteins also displayed along side intracell proteins, CTL's (CD-8) recognize
How does the MHC-I/Intracell Protein complex reach the cell surface?
Via TAP--Transporter Associated with Antigen Processing
Where are Class II MHC molecules found?
Macrophages, Dendritic Cells, B cells (all APC's)
Which class of MHC molecules employ an exogenous pathway? What's an exogenous pathway?
Class II:
"invariant chain" binds Class II MHC after their synthesis (blocks endogenous proteins from binding to it)
Phagosomes containing external proteins enter cell
Binds endosome containing invariant chain with class II
Invariant chain degraded, only peptide-binding groove is left (CLIP)
Antigen peptides loaded
Presented on cell surface
CD4 cells recognize (HELPER T CELLS)
How is activation of B and T cells safe-guarded? Use T cells as example.
Need a second signal.

For helper T Cell, two signals:
1) Recognition of cognate antigen displayed by Class II MHC molecs on surface
2) CD28 receptor on T cells interacts with ligand (B7) on surface of activated B cell or macrophage

Once has both of these signals, proliferates to build clones of many helper T cells that recognize same antigen
How does the adaptive immune system recognize friend from foe?
Innate immune system integrates all information it collects about invader and formulates game plan (delivered to adaptive immune system)