Week One, Lecture 1 Flashcards
What are the 8 immune structures?
Lymph nodes Lymph vessels spleen tonsils and adenoids appendix Peyer's patches thymus bone marrow
In gestation, when do the immune stem cells develop?
By the ninth week gestation, in the liver and spleen.
Which lymphocytes dominate in the newborn’s system?
Which lymphocytic system do adults utilize?
Newborns: T H 2
adults: T H 1
Name two factors that impair immune function
stress and depression
What happens to the immune system with age?
It degenerates and the likelihood of cancer and autoimmune disorders increases
What are the two branches of innate defenses?
Physical (surface) barriers and internal barriers
Which are the functional surface barriers of the innate immune system?
skin and mucosa
What are the internal defenses of the innate immune system? (5)
- phagocytes
- fever
- natural killer cells
- antimicrobial proteins
- inflammation
What are the two branches of the adaptive immune system?
Humoral and Cell mediated
Describe each of these cells’ role in the innate immune system:
- macrophage
- B-cell
- T-cell (Helper)
- Natural killer cell
- epithelial cells
- Cleans up debris of viral infections and calls for T-cells
- Clean up viruses and alert other B-cells
- Call for “back up”
- These destroy infected cells with cytotoxins
- Keep things out
What are the two “lines” of innate defense
First line: Physical barriers (skin and mucosa)
Second line: Antimicrobial proteins, phagocytes, other cells (the most important mechanism here is inflammation)
What are some examples of protective chemicals inhibiting or destroying invaders in the first line innate defenses?
- Skin pH
- lipids in sebum/ dermacidin in sweat
- HCl and proteases in stomach
- lysozymes in lacrimal glands and saliva
- mucus as a physical trap
Which cells are involved in inflammatory response?
macrophages, mast cells, WBC’s, NK cells, inflammatory chems
What are two antimicrobial proteins in the innate immune system?
interferon and complement proteins
Describe macrophages
These develop from monocytes to become the main phagocytic cells. They remain as monocytes in the blood.
They can be either free or fixed.
Examples of free macrophages: alveolar, sinus, spleen and lymph macrophages
Examples of fixed macrophages: Kupffer.
When are neutrophils phagocytic
When they encounter infectious materials in the tissues
Explain the process of phagocytosis
- Phagocyte must adhere to pathogen or debris
- Pseudopod formation/this becomes a phagosome
- Phagosome fuses with lysosome forming phagolysosome.
- hydrolytic enzymes from the lysosome destroy pathogen
- exocytosis of vesicle
What is leukocytosis
This is the mobilization of leukocytes from the bone marrow in response to leukocytosis inducing factors from injured cells
What are natural killer cells?
Large granular lymphocytes that target cells that lack self antigen as well as tumor cells and virally infected cells (they induce apoptosis in those self cells)
Which cells have toll like receptors (in the boundary tissues)?
What happens when these receptors are bound and activated?
- Macrophages and epithelial cells
2. Activated TLR’s trigger the release of cytokines
What are three kinds of inflammatory mediators
- histamines (released from mast cells)
- Blood proteins
- kinins, prostaglandins, leukotrienes, complement proteins (released by mast cells, phagocytes, injured tissue, lymphocytes, basophils)
What do inflammatory chemicals do?
Cause dilation of arterioles resulting in hyperemia. Also increase capillary permeability locally inducing edema and release of exudate
What is in exudate?
What is the benefit in the surge of exudate?
Proteins, clotting factors and antibodies
Surge of exudate directs foreign material into lymphatic system and delivers clotting proteins which provide a scaffold for tissue repair and wall of the area
How does IF work?
Virus enters the cell
IF genes are turned on
Cells produce IF molecules and release them
These stimulate neighboring cells to produce antiviral protein.
These proteins block viral reproduction within the cells that produce them.
Additionally, they can activate macrophages and mobilize NK cells and oddly can reduce inflammation.
Which cells produce IF?
Lymphocytes produce gamma (immune) interferon.
Other WBC’s produce alpha interferon.
Fibroblasts produce beta IF.
Why do we genetically engineer IF?
To treat viral hepatitis and genital warts. Also is a treatment for MS
Describe the compliment system in general
It is a system of 20 plus proteins that circulate in inactive form in the blood. The compliment system is a major mechanism for destroying pathogens. Amplifies all aspects of inflammation while killing bacteria and other pathogens by lysis. It enhances both specific and nonspecific defenses.
Name the proteins involved in the complement system and the cells that secrete them
C1-C9, factors B, D, and P and regulatory proteins. Secreted by hepatocytes and monocytes.
What are the two pathways for complement activation?
Classical and alternative.
Each pathway involves activations of proteins in an orderly stepwise fashion. Each step catalyzes the next. Both pathways converge on C3, which cleaves into C3a and C3b.
Describe the classical pathway of complement system
Ab’s bind to the organism, then C1 binds to the Ag-Ab complex (called complement fixation).
Describe the alternative pathway
This one doesn’t require antibodies to start.
Here, C3, D, B and P interact on the surface of MO’s.
Three effects of activated complement system?
- enhanced inflammation
- promotes phagocytosis
- cell lysis
Describe how complement system accomplishes cell lysis.
C3b initiates formation of a MAC. This is a pore and fluid rushes into the organism. C3b also increases opposition, while C3a can increase inflammation.
Which cells can secrete pyrogens?
Leukocytes and macrophages exposed to foreign materials.
What are the benefits of a mild fever?
They cause the liver and spleen to sequester zinc and iron, which are needed by microorganisms. Also speeds up metabolism for faster repair of tissues.
Differentiate between complete and incomplete antigens
Complete: These have immunogenicity (able to stimulate proliferation of specific lymphocytes and antibodies) and reactivity (ability to react with the products of activated lymphocytes and antibodies released).
Examples of complete ag’s: foreign protein, nucleic acids, polysaccharides and lipids.
Incomplete (hapten): Small molecules (hormones, peptides, etc) that are immunogenic when attached to body proteins. They evoke an inappropriate and harmful immune response.
What is an Ag determinant?
The portion of an Ag that is immunogenic. An Ag often has multiple Ag determinants that mobilize different lymphocyte populations.
Where do we find MHC I proteins?
All body cells excluding RBC’s
Where do we find MHC II?
On APC’s
What do MHC proteins do?
They present Ag, usually self Ag. If the cell is infected, it displays foreign material, which mobilizes an immune response.
Mature lymphocytes have which two features?
immunocompetence and self tolerance.
What happens to mature naive lymphocytes?
They get exported to the lymph nodes, spleen, and other lymphoid organs to meet antigen
Explain the T-cell maturation process.
T-cells mature in the thymus under positive and negative selection pressures.
positive: Must be able to bind self MHC protein. These are selected FOR. (aka MHC restriction)
Negative: Must not be able to bind self antigen on the MHC. These are selected AGAINST.
Cells that don’t make the cut at either point of the process must undergo APOPTOSIS
Explain B-cell maturation process
These mature in the bone marrow. Self reactive B-cells undergo apoptosis. Also, some of the receptors can get “edited.” If self reactive B-cells get out of the bone marrow, they typically get inactivated.
What determines what type of pathogens the immune system will be able to recognize and resist?
Genes, because they code for the antigen receptors.
APC’s present Ag to what kind of cells?
T-cells
What are the major types of APC’s?
macrophages
dendritic cells
B-cells
How do macrophages and dendritic cells act differently as APC’s?
While both present Ag to T-cells, macrophages remain mostly fixed in the lymphoid tissues, while dendritic cells internalize the pathogens and then migrate to the lymphatic organs.
What do Tcells do when they are activated by an APC?
They go on to stimulate macrophages to become “insatiable” phagocytes and release bactericidal chemicals.
Which cells are called the professional APC’s and why are they called that?
Dendritic cells:
Only dendritic cells have the ability to produce a primary immune response in a resting naive T-cell. Dendritic cells have the appropriate costimulation molecules. They are also involved in B-cell function and memory. Dendritic cells are important for immune memory.
Where does the first Ag challenge typically occur? What happens if the cell is a B-cell?
Usually in the spleen or a lymph node. If it is a B-cell, then the Ag evokes a humoral immune response and antibodies are produced.
Describe the how B-cells undergo clonal selection.
Antigen binds receptors on the B cell causing the receptors to become cross linked. Only when the receptors get cross linked are they able to undergo receptor mediated endocytosis.
The stimulated cell then grows to form a clone of identical cells bearing the same receptors. (T-cells are also involved but we are ignoring them for now).
What happens to B-cell clones?
Most become plasma cells and secrete antibodies. Some become memory cells.
Where do the Ab’s go?
They circulate in blood and lymph.
What is the difference between a primary and a secondary immune response?
Primary:
occurs on first exposure to Ag, and there is a lag in response, ~3-6 days, and peak plasma Ab levels are seen at 10 days.
Second:
With subsequent exposure to the same Ag, memory cells mount an immediate response, within hours. It only takes 2 days for Ab levels to peak; they can stick around for months. These antibodies also bind with greater affinity.
Why do vaccines sometimes fail to establish full immunological memory?
They only target one kind of helper T cell.
Do we get immunological memory from passive humoral immunity?
No. B-cells don’t get activated, so we don’t get any memory. Protection ends when antibodies degrade.
How many polypeptide chains in an Ab?
Four. Two identical light, and two identical heavy chains.
What does the constant chain do?
Determines Ab class, what it can do, what it can bind to
Describe the IgM
This one is often found as a pentamer. It is first to respond to an infection. High levels may suggest an acute current infection.
Describe the IgA
These are specialized in secretions. They are often found as dimers and prevent pathogens from clinging to epithelial surfaces.
Describe the IgD
Not as much is known about them. They often stick to cell surfaces to act like a receptor.
Describe the IgG
These are most abundant. They are versatile. Good against viruses, bacteria, and toxins.
Describe the IgE
These are associated with allergic reactions and fighting parasites.
What can antibodies do, in general?
They NAP.
That is, neutralization, agglutination, and precipitation
And, of course, complement fixation.
Explain how antigens neutralize?
Ab’s block sites on viruses or bacterial exotoxins to prevent their binding to cell receptors.
Explain agglutination
This happens when Ab’s bind more than one cell bound Ag, causing clumping.
Explain precipitation
This happens when things that were soluble get cross linked and rain out of solution, becoming more susceptible to phagocytosis.
What is the main Ab defense against cellular Ag’s?
Complement fixation.
What does activated complement do?
inflammatory response, opsonization, enlisting more defensive elements
Describe commercially produced immunoglobulins
They are produced by hybridomas ( tumor cell and a B cell fused). They are used in research (cancer) and treatment of disease.
What kind of T cells have CD4?
Helper T cells
Which T cells have CD8?
Cytotoxic T cells
Describe the targets of the activated cytotoxic T cells
Body cells infected by viruses or bacteria
abnormal or cancerous cells
Transplanted or infused foreign tissue
How to T cells get activated?
Simultaneous binding of non self Ag and Self MHC
How do dendritic cells obtain antigen from other cells?
They can either engulf the Ag, or form temporary gap junctions with infected cells.
Describe costimulation of T cell activation
Both T cell receptors AND CD4 or CD8 proteins have to bind the MHC/Ag complex for activation to occur
What is an isograft?
An organ transplant from an identical twin
