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what are two defense mechanisms
1. innate community (nonspecific)
2. Adaptive immunity (specific)
Innate immunity includes what kind of defenses, and what to these defenses represent?
- includes both external and internal defenses
these defenses are always present in the body and represent the first line of defense against invasion by potential pathogens.
what are three major groups of phagocytic cells?
1. neutrophils
2. the cells of the mononuclear phagocyte system, includes monocyte and macrophages.
3. organ-specific phagocytes in the liver, spleen, lymph nodes, lungs, bran (microglia)
Macrophages derived from ____ in the connective tissues. *Monocytes in the blood
monocytes
Why phagocytes remove foreign particles form the blood?
So that blood is usually sterile after a few passes through the liver and spleen.
The spleen contains what kind of cells?
Kupffer cells
_______ have a resident population of all leukocyte type.
Connective tissues
Link between chemotaxis and Leukocytes
Leukocytes act on the site of an infection by chemotaxis.
What is chemotaxis?
movement toward chemical attractants which are a subclass of cytokines known as chemokines.
During chemotaxis what kind of cells are the fist to arrive at the site of infection?
Neutrophils
What kind of cells arrive later?
Monocytes which can be transformed into macrophages.
What area of the brain regulated temperature?
hypothalamus in response to PGE2
Temperature mechanism
the release of PGE2 occurs from a pyrogen which acts as a trigger.
The _____ generates a response a response back to the rest of the body, making it _______ the ____.
hypothalamus
increase
temperature set-point
Substance that induces fever?
Pyrogen
Pyrogens can be either?
internal
or external
internal pyrogens are called?
external pyrogens are called?
endogenous
exogenous
Cytokines such as (interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and can cause? _____
increase in the thermoregulatory set-point in the hypothalamus.
examples of endogenous pyrogens
interleukin 6 (IL-6) and the the tumor necrosis factor-alpha
Cytokine factors are released into general circulation, and they migrate to and produce what effect in the brain?
migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced.
cytokine factors bind with _____ on vessel walls
or
interact with local ___ cells
endothelial receptors
microglial
What happens when cytokine factors bind?
they activate the arachidonic acid pathway
PGE2 release comes from what kind of pathway?
arachidonic acid pathway
arachidonic acid pathway as it relates to fever is mediates by ?
enzymes phospolipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase
What do the previous enzymes to?
mediate the synthesis and release of PGE2.
What is the ultimate mediator of the febrile response?
PGE2
What is an antigen or immunogen
a molecule that stimulates an immune response
Antigens are usually?
protein or polysaccharides
(includes parts such as coats, capsules, cell walls, flagella, fimbrae, and toxins of bacteria, viruses, and other microorganisms
when combined with proteins and polysaccharides, lipids and nucleic acids are?
antigenic
what stimulates the production of specific antibodies?
antigen
What are haptens?
low molecular weight molecules
hapten contain?
an antigenic determinant but which are not itself antigenic unless complexes with an immunogenic carrier
if hapten binds to protein it thus becomes?
an antigenic determinant on the proteins
what are the 3 major types of lymphocytes?
T cells,
B cells,
and natural killer (Nk cells)
Nk cells are part of an innate immune system and ______?
play a major role in defending the hosts from tumors and virally infected cells
how are NK cells activated?
in response to a family of cytokines called interferons
What do activated NK cells release?
cytotoxis (Cell-killing) granules which then destroy the altered cells
the response of the organism to the pathogen?
inflammation
______ secrete antobodies that can bind to antigens in a specific fashion?
B lymphocytes
Also known as immunoglobulins?
antibody proteins
where are antibody proteins found?
gamma globulin class of plasma proteins
what are the 5 distinct bands of protein that apear?
albumin
alpha-1 globulin
alpha-2 globulin
beta globulin
gamma globulin
how were the 5 distinct bands of protein that are identified by what technique?
electrophoresis
what are the five immunoglobulin subclasses
IgG
IgA
IgM
IdD
IgE
Most antibodies in serum are in which subclass?
IgG
Antibodies in external secretion (saliva and milk)
IgA
Antibodies in the ______ are involved in _______?
IgE
Allergic reaction
how many polypeptide chains are antibodies composed of?
four polypeptide chains
describe the four polypeptide chains of antibodies?
two are heavy (H) and two are light (L)
T/F the combination of antibodies with antigens does not itself cause destruction of the antigens or the pathogenic organisms that contain these antigens
TRUEEEE
what do antibodies do?
serve to identify the targets for immunological attack and to activate nonspecific immune processes that destroy the invader
Example of bacteria thats buttered with antibodies
better targets for phagocytosis by neutrophils and macrophages
What is the ability of antibodies to stimulate phagocytsis?
opnosizantion
immune destruction of bacteria is also promoted by?
antibody-induced activation of a system of serum proteins known as a complement
Complement protein
C1 - C9
Where are C1-C9 proteins present and in what state?
present in an inactive state within plasma and other body fluids and become activated by the attachment of antibodies to antigens
Complement proteins can be subdivided into three components?
1. recognition - C1
2. Activation - C4, C2, and C3. in that order
3. Attack - C5 through C9
Recognition
C1
Activation
C4, C2, and C3
Attack
C5 through C9
Attack phase consists of complement fixation which is ?
when complement proteins attach to the cell membrane and destroy the victim cell
IgG and IgM antibodies activate?
C1
what does C1 catalyle?
the hydrolysis of C4 into two fragments = C4a and C4b
T/F The C4b fragment binds to the cell membrane and become an active enzyme?
TRU
How is C3 cleaved into C3a and C3b ?
the splitting of C2
C3b converts C5 into C5a and C5B
TRUE
what do C3a and C5a stimulate?
mast cells to release histamine;
What else does C5a do?
serves as a chemokine to attract neutrophils and monocytes to the site of infection
What do C5 and C9 do?
they are inserted into the bacterial cell membrane to form a membrane attack complex
Describe an attack complex
a large pore that can kill the bacterial cell through the osmotic influx of water
T/F antibodies directly kill the cell?
F completement proteins do
What do antibodies do then?
serve only as activators of this process in the classic pathway
CD8+T (a T Cell subset) associates with ?
MHC class 1
CD4+T (a T cell subset) associates with?
MHC class 2
The middlemen of the adaptive immune system
Helper T Cells
Once activated ______ divide rapidly and secrete small proteins called ______?
Helper T cells
cytokines
What do cytokines do?
regulate or "help" the immune response
What do helper Tcells differentiate into from the cytokine signals recieved?
Th1, Th2, Th17 or other subsets
*** secret different cytokines
Cytotoxic T cells destroy?
virally infected cells and tumor cells, and are also implicated in transplant rejection
Cytotoxic cells are also known as ?
CD8+ T cells because they express the CD8 glycoprotein at their surface
How can cells be transformed into suppressor T cells?
CD8+T cells interacting with helper T cells
Suprressor T cells prevent?
autoimmune diseases such as experimental autoimmune encephalomyelitis (MHC 1)
Subset of antigen-specific T cells
memory T cells
What do memory T cells do?
Persist long-term after an infection has resolved
How do Memory T cells provide the immune system with "memory" against past infection.
they quickly expand to large numbers of effector T cells upon re-exposure to thier cognate antigen
subtypes of Memory T cells?
-TCM cells (central memory T cells)
-TEM cells (effector memory T cells)
Memory cells may be either?
CD4+ and CD8+
Regulatory T cells (Treg cells) are formerly known as ?
suppressor T cells
What are regulatory T cells crucial for?
the maintenance of immunological tolerance
What are regulatory T cells major role?
Shur down T cell mediated immunity towards the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus
Two major classes of CD4+ regulatory T cells?
1. naturally occuring Tref cells ( also known as Cd4+cd25+foxp3+treg cells)
2. adaptive treg cells (Tr1 and Th3)
naturally occuring treg cells arise in the?
thymus
Adaptive treg cells may originate during?
a normal immune response
A special kind of lymphocyte that bridges the adaptive immune system with the innate immune system
Natural Killer T cells
conventional T cells recognize peptide antigen presented by major histocompatability complex (MHC) molecules
vs. NKT cells which recognize?
glycolipid antigen presented by a molecule called CD1d
Autoimmunity disease
Diabetes type I
failure of an organism to recognize its own constituent parts (down to the submolecular levels) as "self"
autoimmunity
results in an immune response agaisnt its own cells and tissues?
autoimmunity
immune disease include?
autoimmune diseases
complex diseases
allergies
Allergies can be broken down due to their sensitivity can be?
immediate hypersensitivity
delayed hypersensitivity