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The host immune response is mediated by circulating specialized cell types
- First level of defense: physical barriers
- Second lvel: intrinsic cellular defenses
- Third level: immune response
innate is what
things that we are pre-programmed with they recognize patterns and broad outlines of it
rapid but non-specific
slower but long-lasting and highly specific
take a while to get going but are really powerful once amped up; can learn to recognize and start to fight off these pathogens
Big picture of our immune system
consists largely of a variety of cell types
NK cell: kills cancer and virus-infected cells
- Use molecules made by the adaptive immune system
- acts as a counterbalance to T cells
- Has the same effect as a lot of other cells
Components of innate immunity
phagocytes: fixed macrophages that stay in one place or free wandering macrophages that roam and gather at sites of infection
Components of adaptive immunity
- B lymphocytes
- T lymphocytes
- cytotoxic T lymphocytes
Explain the complement system
serum proteins produced by the liver that assist the IS in destroying microbes. Act in a cascade in a process called complement activation that fits proteins together and catalyzes reactions
It is activated by foreign molecules and acts to destroy those molecules and signal to the rest of the body that something has gone wrong
It's a series of proteins labeled C1 to C9
How were complement molecules discovered?
Originally as a series of molecules that bind to ATs that bind to pathogens and can catalyze a bunch of reactions. Many start off with the letter C and another number
What is the most important complement molecule?
C3: Once activated, it becomes an enzyme that can activate several proteins that can stop an infection by killing off pathogens and also by signaling the rest of the immune system. Discovered as something bound to other parts of our immune system.
There is an alternative pathway with C3. Explain.
it is teh most important
It involves C3 that will bind to almost anything in the bloodstream--our own bodies or that of the invaders--and activate
Explain the first few minutes after an infection?
Complement binds; C3 is activated and a huge chain reaction occurs.
There are three main important things that complement can do that are relevant in fighting off infection
1) Recruit the rest of the molecules from C5 down to C9; and C9 is a pore-forming molecule that will poke holes in the virus envelope and kill it/ ruin the integrity of the virus
2) it can coat cells and label them by targets that need to get phagocytosed (opsonization)
3) Some molecules, once cleaved, can activate and trigger other parts of the immune system--inflammation
Why is the complement system very powerful?
It doesn't need anything to turn on; its default state is to bind to something, activate, and turn on the pathway.
C3 is perfectly capable of doing what; and, what is in place to stop it?
It can bind to human cells and lyse them
We have complement regulators to prevent our own cells from being lysed.
Molecules that have evolved to interact specifically with our own complement and prevent the chain reactions from happing
NK cells in detail
They roam and try to recognize cells that have been altered and might be hiding a viral infection
They induce apoptosis and cause the cell to kill itself
Explain NK cells in detail
NK activity is augmented by interferon-alpha
reduced expression of MHC on target cells causes NK cells to attack by releasing cytotoxic perforin, and granzyme B which activates apoptosis
Normal cells produce __. Explain.
They produce MHC
This MHC is a marker of a regular, normally regulating cell.
If the cell doesn't express it, something is wrong; and, NK cells release signals that kill the cell
The adaptive immune response is based on __. Explain.
B cell receptors are membrane bound antibodies that bind to epitopes on intact proteins
T cell receptors bind to small peptide epitopes produced by intracellular digestion of proteins
The clonal selection theory states that these receptors are created in an antigen-independent manner
- four protein chains form a Y-shape
- - Two identical light and two identical heavy joined by disulfide links
Variable regions at the ends of the arms bind epitopes
A constant (Fc) region is teh stem, which is identical for a particular Ig Class, of which there are five--IgG, IgM, IgA, IgD, IgE
The anatomy of the immune system
- located all over the body
- lymph nodes and ducts, organs like the spleen, etc.
Adaptive immune cells live here
Both B and T are what?
created randomly to recognize different antigens; and, they are selected for. These clones become populous in the body if chosen
Antigens are recognized by our immune system. Explain.
Small pieces of a foreign antigen are recognized. It doesn't ahve to be a whole virus or viral molecule. It can be a few amino acids or few sugars. What each protein and pathogen that evades us is made up of is several antigens since each is so small
Two functions of antibodies
1) Receptor on B cell: that's how its activated
2) Bind to epitopes
Explain the making of antibodies.
- There is a small amount of genetici nfo. We hae 150 genes that the cell uses to make antibodies.
- Every time one binds, it takes a random chunk of genes to form the variable region.
- When we make a B cell, we change the DNA in that cell. In IS cells, not all cells have the same DNA. A piece of DNA is taken out. The rest is lost. The B cell can only make that one combination
They have T cell receptors with an active end and constant regions and signaling models.
What makes T cells different from antibodies?
T cells can't recognize antigens on their own. They need help.
MHC molecules help with this and is how the T cell recognizes the cell
they are antigen presenting molecules that are on just about all of our cells each presenting to different kinds of T cells
We recognize antigens inside of the cell by relying on digestion and then loading onto the MHC molecule--> will be presented to teh T cell--> bind adn recgonize MHC
Explain the division of labor of T cells
cytotoxic T cells: make perforin and kill off cells; recognize MHC Type I molecules (MHC I)
the professional APCs load onto MHC Class II. Only a different type of T cell samples these and sees if there is an infection or not
WHat are the APCs?
- Dendritic cells
engulf and degrade microbes and display them to T cells
FOund in the skin, genital tract, lymph nodes, spleen, thymus, and blood
activated by cytokines or the ingestion of antigenic material
migrate to the lymph tissue, presenting antigen to T cells
cytotoxic T cells (Tc cells)
recognize and kill infected cells
Helper T cells
activate B cells and produce cytokines
CD8 T cell activity
comes along, recognizes MHC Class I, and binds to it. It sends those perforins in the infected cell and allows the cell to undergo apoptosis
CD4 T cells
they are the coordinators; they don't kill directly
- They are presented by professional cells
- They bind to MHC and see if they recognize the antigen. They then turn on the other immune system molecules
Viral strategies they make????
Viruses make proteins that mimic cytokines and cytokine receptors and interfere with host defenses
Virokines and viroceptors combat host immune response
These proteins are also virulence factors as they help the virus to establish and maintain the infection
how do viruses evade innate immune responses?
- Prevention of complement binding to antibody/antigen complexes
- Stealing of complement-regulating proteins
Inhibiting NK and dendritic cells
Interfering with antigen processing and presentation
How do viruses evade adaptive immune responses?
changing epitopes on antigens by antigenic drift
segmented viruses can undergo reassortment of genes during antigenic shift and express new surface antigens
Blocking MHC Class I antigen presentation
How are cytotoxic T cells made?
generated by an encounter between an antigen-presenting cell and a naive CD8 positive T cell
contribute to the maturation of Tc cells via the production of interleukin-2 and interferon-gamma
promotes protective immune responses by its ability to increase the expression of MHC proteins
Macrophages function as __.
key effector cells in innate and adaptive immune responses
Interferons play complex roles in regulating __ since they exert their effects either indirectly, by regulating the development of specific __ or directly at the level of __.
- T-helper cell subsets
- B cells
Several large DNA viruses possess genes coding for viral proteins that mimic __ or __. These proteins are called __ and __, and they combat host immune responses against these viruses.
- cytokine receptors