Viral Immunity II

• First level of defense: physical barriers
• Second lvel: intrinsic cellular defenses
• Third level: immune response

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

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

Complement system

polymorphonuclear leukocytes

NK cells

monocytes

macrophages

monocytes

macrophages

phagocytes: fixed macrophages that stay in one place or free wandering macrophages that roam and gather at sites of infection

• B lymphocytes
• antibodies
• T lymphocytes
• cytotoxic T lymphocytes

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

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

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.

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

Complement binds; C3 is activated and a huge chain reaction occurs.

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

It doesn't need anything to turn on; its default state is to bind to something, activate, and turn on the pathway.

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

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

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

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

antigens

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

• located all over the body
• lymph nodes and ducts, organs like the spleen, etc. 

Adaptive immune cells live here

created randomly to recognize different antigens; and, they are selected for. These clones become populous in the body if chosen

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

1) Receptor on B cell: that's how its activated

2) Bind to epitopes

• 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.

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

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

• Dendritic cells
• macrophages

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

recognize and kill infected cells

activate B cells and produce cytokines

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

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

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

• Prevention of complement binding to antibody/antigen complexes
• Stealing of complement-regulating proteins

Inhibiting NK and dendritic cells

Interfering with antigen processing and presentation

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

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

key effector cells in innate and adaptive immune responses

• T-helper cell subsets
• B cells

• cytokines
• cytokine receptors
• virokines
• viroceptors