Lecture 2 Flashcards
Describe the antigen-specificity of the innate immune system
The innate immune system blocks or attacks microorganisms but responses do not involve highly specific antigens
Describe the antigen-specificity of the adaptive immune system
The adaptive immune system creates immune responses to specific antigens
What are APCs?
Antigen Presenting Cells (APCs) present antigen complexed with MHC class II proteins on cell surface
Where do APCs present antigen? What does it cause?
- Occurs in lymph nodes
- Leads to cytokine signaling and lymphocyte activation (activates T and B lymphocytes)
When activated what do T lymphocytes mature into?
- Mature into Helper T (CD4+) cell
2. Cytotoxic T (CD8+) cell
When activated what do B lymphocytes mature into?
- Memory B cells: 2^0 immune response to the same antigen
2. Plasma B cells: make antibodies – bind to that specific antigen
Examples of APCs?
Dendritic cells and B cells
Why is adaptive immunity said to have “dual nature”?
Dual nature refers the adaptive immune system fighting the infection in 2 diff places. It has both humoral and cell-mediate immunity. T cells and B cells, both components of the adaptive immune system. T cell are responsible for cell mediated immunity, B cell are responsible for humoral immunity; involving Abs
- Humoral immunity fights invaders OUTSIDE cells (coat with Ab and phagocytose)
- Invaders include bacteria and toxins
- Involves B lymphocytes and production of antibodies - Cellular immunity attacks antigens found INSIDE cells
- Viruses; some fungi and parasites
- Involves cytotoxic T cells and Natural Killer cells
Draw a generic Ab molecule
Slide 4
Describe the birth of B cells, its maturation process, to finally its activation and final products.
- B cells (B = “bursa”) PRODUCED and MATURE and undergo CLONAL DELETION in bone MARROW.
- 1st, those that are unable to recognize self (thus recognize YOU as foreign) are killed. Then, those that recognize self with too high affinity are killed (cause —-) - Migrate to LYMPH system (nodes)
ACTIVATION:
3. Antigens that activate B cells directly are called T-independent
4. Most B cells require T-dependent activation with assistance of TH
cell that produces cytokines to activate B cell.
6. Activated B cell undergoes CLONAL
EXPANSION (proliferation)
7. Produces a) plasma cells and b) long-lived memory cells
Describe the pathway of a T-dependent activated B cell from when it encounters its matching Ag to its final pathways
- A B cell is triggered when it encounters its matching Ag.
- The B cell binds Ag with its BCR (Ab) and engulfs (phagocytose) the Ag and digests it
- Then displays Ag fragments bound to its unique MHC class II molecules
- This combo of antigen w/MHC attracts the help of a mature, matching T cell
- Cytokines (IL2/4/5) secreted by the T cell will bind to B-cell IL receptors and help the B cell to multiply and mature in Ab producing cells
- Released into the blood, Abs lock onto matching antigens.
- The Ag-Ab complexes are then cleared by the COMPLEMENT cascade or by the LIVER and SPLEEN
What is an antigen
an antigen is a foreign protein or other molecule that is the target of an immune response
Where do APCs present antigen?
Lymph node
Each B cell carries _____ unique BCRs (immunoglobin ____)
- 10^5
2. IgM/D
Antigens that activate B cells directly are called ______
T-independent
Most B cells require two signals to become active and mature into a plasma cell, what are they?
- Antigen crosslinking with B cell receptor (BCR)
2. T cell receptor (TCR) interaction with antigen presented with MHC class II protein (co-stimulation)
Draw a diagram of T cell-dependant activation of B cell and molecules released
Slide 6
B cells (plasma cells) secrete _____
antibodies
Describe the birth of B cell from its precursor all the way to differentiation into plasma cell
- Stem cells differentiate into mature B cells, each bearing surface Abs against a specific antigen
- B cell encounters its specific antigen and proliferates
- Some B cells proliferate into long-lived memory cells, which at a later date can be stimulated to become Ab-producing plasma cells
- Other B cells proliferate into Ab-producing plasma cells
- Plasma cells secrete Abs into circulation
Draw a flow chart of how a stem cell eventually becomes a plasma B cell
Slide 7
What are the 5 protective mechanisms of binding Abs to antigens
- Agglutination
- Opsonization
- Activation of complement
- Antibody-dependant cell-mediated cytotoxicity
- Neutralization
Draw process of agglutination and describe it
- Process that occurs when Ag mixed with its corresponding Ab, causing clumping
- Reduces # of infectious units to be dealt with
Draw process of opsonization and describe it
Coating Ag with Ab enhances phagocytosis
Draw process of activation of complement and describe it
- Complement is an accessory pathway that helps innate and adaptive immune systems.
- Causes inflammation and cell lysis
Draw process of Ab-dependant cell-mediated cytotoxicity and describe it
- Coat target cell (parasite) in Abs. Cells like T cells, eosinophils, NK cells etc. have Ab receptors and will bind to the Abs on the target cell.
- Causes release of other enzymes to damage invading parasite (thus destruction by macrophages, eosinophils, and NK cells)
Draw process of neutralization and describe it
- Coating the virus/bacteria/toxin to block adhesion of bacteria and viruses to mucosa rendering it unable to get into the cell it would otherwise infect, or or block attachment of toxin; so can’t bind to and harm targets.
Describe the birth of T cells, its maturation process, to finally its activation by APCs
BIRTH:
1. Made in bone marrow (originally a MULTIPOTENT STEM CELL)
MATURATION:
2. Mature and undergo “THYMIC SELECTION” in THYMUS
ACTIVATION
3. Migrate to lymph system (nodes)
- Respond to Ag via T cell Receptors (TCRs; specific for one Ag)
- T cells activated when encounter APCs (e.g. B cell or dendritic cell) that presents Ag complexed with MCH II. Respond to Ag via T cell Receptors (TCRs; specific for one Ag)
- MHC-antigen complex will activate TCR and T cell will released cytokines. Cytokines are released that help T cell mature into either T Helper cells or Cytotoxic T cells
- CD4+ T cells become TH cells (proliferate, secrete cytokines to attract other lymphocytes, recruit immune cells, activate B cells, become memory cells). CD4+ cells interact with MHC II ONLY present on APCs
- CD8+ T cells become TC cells that are cytotoxic and target infected or altered
cells. CD8+ cells interact with MHC I found on ALL nucleated cells
Likely reason why T cells evolved?
T cells likely evolved to combat intracellular pathogens
Difference btwn TH cells and TC cells in terms of fxn and which MHC class it responds to
- CD4+ T cells become TH cells (proliferate, secrete cytokines, recruit immune cells, activate B cells, become memory cells). CD4+ cells interact with MHC II ONLY present on APCs
- CD8+ T cells become TC cells that are cytotoxic and target infected or altered
cells. CD8+ cells interact with MHC I found on ALL nucleated cells of the body
Describe the activation of CD4+ TH lymphocytes by APC in lymph node
- An APC encounters and ingests a microorganism. The Ag is enzymatically processed into short peptides, which combine w/MHC class II molecules and are displayed on surface of APC.
- A receptor (TCR) on the surface of the CD4+ T helper cell (TH cell) binds to the MHC-antigen complex. This includes a Toll-like receptor. The TH cell or APC is stimulated to secrete a costimulatory molecule (required to activate T cells that haven’t previously encountered Ag). These 2 signals activate the TH cell, which produces cytokines.
- The cytokines cause the TH cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated.
- Activated TH cells proliferate
Describe the activation of CD8+ TH lymphocytes by APC in lymph node
- A normal cell will not trigger a response by a cytotoxic T lymphocyte (CTL), but a VIRUS-infected cell or a CANCER cell produces abnormal endogenous Ags.
- The abnormal Ag is presented on the cell surface in association w/MHC class I molecules. Binding of a TH1 cell promotes secretion of cytokines.
- The cytokines activate a precursor CTL, which produces a clone of CTLs.
- The CTL induces destruction of the virus-infected cell by apoptosis
Draw a flowchart showing the cells involved in cell mediated immunity
Slide 12
Multipotent stem cell -> T cell precursor -> Thymus gland -> Cytotoxic T cell OR T Helper cell
Cytotoxic T cell pathway —-kill—> MHC class I APC’s
T Helper cell pathway -> Bind to MHC class II APCs —-secrete—> cytokines that activate other immune cells
From unknown pathway, T cell precursor -> NK cells —kill—> MHC class I antigen-presenting cells OR Ab-coated cells
Complement is part of which immune system?
Component of innate immunity but aids both innate and adaptive system
Describe the classical complement cascade
In the classical pathway:
- Ab bind Ag which activates C1
- C1 will then split into 2, and activates C2 and C4
- C2 will split into C2a and C2b; C4 will split into C4a and C4b
- C2a + C4b will combine to form C3
- C3 splits to form C3a + C3b
- C3a functions in inflammation
- C3b functions in cytolysis and opsonization (coating pathogen) - Complement proteins form a membrane-attack complex which will kill bacteria and cause inflammation
Why is the complement cascade stepwise?
Good for control, don’t want to form MAC unless really need them
What are the 3 outcomes of complement activation?
- Cytolysis
- Opsonization
- Inflammation
Describe cytolysis cause by complement activation
- Activated C3 splits into C3a and C3b
- C3b will activate C5 and cause it to split into C5a and C5b.
- C5b will form a complex of C6. After C5b and C6 join, so will C7. After C7 joins, so will C8. After C8 joins, so will C9. These complement proteins together form a MAC. It is a large protein structure that will insert into PM and crease a non-specific core.
Describe opsonization caused by complement activation
- Activated C3 will split into C3a and C3b.
2. C3b protein will coat microbes to enhance phagocytosis.
Describe inflammation caused by complement activation
- Activated C3 splits into C3a and C3b. Both will eventually lead to histamine release and an inflammatory response.
- Specifically, C3a acts on mast cells which have C3a receptors. Binding of C3a on mast cells (granular cells) leads to histamine release, which mediates localized inflammatory response.
- C3b will activate C5 and cause it to split into C5a and C5b. C5a acts on mast cells which have C5a receptors. Binding of C5a on mast cells (granular cells) leads to histamine release, which mediates localized inflammatory response.
Describe the activation and mechanism of antiviral action of alpha and beta interferons (IFNs)
- Viral RNA from an infecting virus enters the cell
- The virus induces the HOST CELL to produce INTERFERONS mRNA (IFN-mRNA), which is translated into alpha and beta interferons.
- Interferons make contact w/uninfected neighbouring host cells, where they bind either to the PM or to nuclear receptors. Interfeurons induce the cells to synthesize antiviral proteins (AVPs).
- AVPs degrade viral mRNA and inhibit protein synthesis– and thus interfere with viral replication)
Using a graph, show how the number of microorganisms increase or decrease in
1) Normal humans
2) Lacking adaptive immunity only
3) Lacking innate immunity
And describe why each curve looks like so
- Normal: # of microorganisms inc when onset of infection but decrease as innate and adaptive immune systems kick in
- Lacking adaptive immunity only: # of microorganisms increase exponentially and then increase slowly
- Lacking innate immunity: # of microorganisms skyrocket from the beginning.
