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3/28/12
Host Immunity
Humans are difficult environments for newly introduced microorganism
Kind of like old pioneer movie
Many kinds of obstacles and barriers
Physical barriers:
Skin-covers most of exposed areas
Skin cells die and slough off
Mucus-covers majority of respiratory and GI tracts
Helps prevent bacterial interaction with host cells
Mechanical defenses:
Ciliary escalator: Moves microorganisms out of area
Most important in respiratory tract
Can be damaged by smoking, disease or trauma
Urine flow
Makes pathogens fight against flow of liquid
Coughing, sneezing and peristalsis
Muscles work to move irritants out
Chemical defenses:
Lysozyme
Enzyme in tears and mucus that degrades bacterial cell walls
Very important for protection of eyes
Stomach acid
Low pH conditions prevent most bacteria from persisting in
stomach
Most GI pathogens have temporary means to survive low pH
Immune responses:
Broken down to two types of response
Humoral response
Involves B-cells, antibodies and complement
Cellular immune response
T-cells are main player
Definitions:
Cytokine-soluble molecule that helps regulate immune functions.
TNF, IL-I, IL-6, IL-10 etc.
Inflammation-host immune response that is includes increased localized
temperature, increased permeability of the capillaries, increased blood flow.
Leukocyte-any "white blood cell"
Lymphocytes-T-cells and B-cells
PMN's=polymorphonuclear luekocytes-includes neutrophils, eosinophils
and basophils
Mononuclear cells-includes lymphocytes, monocytes and macrophages
Immune response and disease:
Many of the symptoms associated with microbial infection are caused
by host immune response
Fever, inflammation, change in blood pressure
We are now beginning to examine if it is best to treat symptoms or not
Fever plays an important role in host defense
Many NSAI drugs block fever and inflammation
Many new treatments allow body to do its part
Antigen-a molecule or portion of a molecule capable of eliciting an immune
response
Immunoglobulin-a family of molecules that bind to antigens. Includes
antibodies and T-cell and B-cell receptors
MHC-Major Histocompatability Complex
The role of antigens in host immunity
Host needs to determine what is self and what is foreign
This is accomplished by sampling antigens
Reacts with foreign antigens but normally will not react with
self antigens.
Presence of foreign antigens suggests presence of infectious agent
Types of antigen presentation:
Soluble antigen will occasionally bump into a soluble antibody.
Simple but very rare
MHC I molecules present endogenous antigens
All nucleate cells produce MHC I
Used for self/not self
Useful for detecting viral or intracellular bacterial presence
MHC II cell are present on "antigen presenting cells"
Includes macrophages and "APCs"
Usually begin with an infectious agent being phagocytized
Organism is degraded and protein fragments are presented on
MHC II molecules
This signals the presence of extracellular infecting agents.
Antibody structure
Several kinds of antibodies but they have basic structures
Y shaped with two heavy and two light chains
Fab fragment binds antigen
Fc fragment interacts with host cell
Fab regions vary greatly and allows for a huge number of unique
antigen recognition sites within a single host
Each B-cell produces antibodies with only a single antigent
recognition site
Antibody production
Facilitated by B cells
B cells possess receptors on their surface that interact with antigens
presented on MHC II molecules
This B-cell receptor is very similar to an antibody molecule
Once a B-cell receptor interacts with an antigen/MHC II complex, this
causes the cell to undergo rapid reproduction
During proliferation two new cell types arise:
Memory cell: persist in case antigen is ever seen again
Plasma cell: antibody factories.
Antibodies bind to antigens and coat infecting organisms
This process is called opsonization
Opsonization increases the likelihood of phagocytosis
Cellular Immune response
Largely dependent on T cells
T cells come in two main types
Cytotoxic T cells (killer T cells)
Possess CD8 marker
Helper T cells
Possess CD4 marker
Cytotoxic T cells
T cell receptor recognizes antigens presented by MHC I molecules
CD8 molecule interacts with MHCI as well
Identifies cells with intracellular infections and kills them
Direct killing
Perforin-punches holes in infected cell
Granzymes enters through holes and kills cell
Indirect killing-signals host cell to kill itself (apoptosis)
While TCR and CD8 interact with MHCI/antigen
complex, FasL (T cell) and Fas (infected cell) proteins
interact
This interaction causes host cell to self-destruct
Helper T cells
TCR recognizes antigens presented by MHCII molecules
CD4 molecule interacts with MHCII
Identifies presence of extracellular pathogens
Two types of Helper T cells TH1 and TH2
TH1 triggers inflammation and cellular response
TH2 triggers B cell proliferation and humoral response
Also responsible for production of Memory cells
Large amounts of antigen presentation will signal TH1 response
After duration of cellular response, the amount of antigen
presentation begins to drop and TH2 response kicks in
Helper T cells direct immune response and gives orders to other cells
via cytokines
Other cells
Natural Killer Cells (NK) bind to host cells and will kill them unless
they receive the correct signal
Do not rely on antigen presentation
Presence of MHC I molecules is the signal
Prevents intracellular pathogen from shutting off MHCI
Often important in early stages of viral infections
Neutrophils: important cells
Recruited during inflammation
Phagocytize foreign cells
Granules burst inside of neutrophil
Releases chemicals that kill invader
Eosinophils-Important in multicellular parasite infection
Parasites are too large to phagocytize
Antibodies against parasite accomplish opsonization
Eosinophils interact with antibodies
Eosinophils contain granules like neutrophil
Deliver granule contents to outside when bound to
parasite