immunity
what is the purpose of the immune system?
to keep infectious microorganisms such as bacteria, viruses and fungi out of the body and destroy them if they invade the body
what is immunocompetence
is the ability of individual cells to recognize a specific antigen by binding to it
phagocytes are
cells that eat
what are immunocompetent cells
distinguish self from nonself
what are the parts of immune system
1 nonspecific (innate)
2 specific (adaptive)
what is non specific or innate
routine protection, regardless of pathogens, always present. (from birth)
what are specific or adaptive
protection against particular pathogen. (develops throughout life)
what are antigen
foreign substance that causes an immune response to produce antibodies
what are antiboies
Y shape protein that bind to antigen for destruction
they are
glyoproteins also known as immunogobulins
where is the immune system located
origin is bone marrow (hemapoietic stem cells) and transported
throughtout body by blood.
lymphatic system controls it
parts of nonspecific (innate)
1st line and second line defense
what are 1st line defense
physical and chemical barriers ex: skin, mucous membrane and secretions
what are 2nd line defense
it is reactive ex: inflammation and fever
Involves :
phagocytosis, complement activation, interferons and NK cells
explain more about 1st line defense
physical barriers which is the skin that covers majority of surface. Also mucous membrane barriers that line digestive tract, respiratory tract and GI tract. Mucous protects these surfaces from infections
How do skin protect the body?
1. it has epiermal layer with waterproofing protein keratin.
2.
shedding (takes off anything that adheres to it)
3. dry
-slougged off with flakes of dead skin
4. acidic fatty acids in
sebum(sebaceous/oil gland)
and lysozyme(sweat gland)
How does mucous membrane protect our body?
1. Barrier is epithelial layer with moist sticky flowing mucous
covering
2. cleaning/washing action removes microbes ex: tears,
urination
3. mucociliary escalator in lower respiratory tract
4. chemicals control microbes.
Skin and mucous membranes are protected by variety of antimicrobial substances. Name them
1 .lysosome
2. peroxide
3. lactoferin
4. defensins
Lysosome
enzyme that degrades peptidoglycan(destroys cell walls of bacteria)
found in tears, saliva, blood and phagocytes
Peroxidase enzyme
breaks downs hydrogen perioxide to produce reactive oxygen.
found in saliva, body tissue and phagocytes
Lactoferin
iron building protein that witholds iron preventing microbial growth
found in saliva and some phagocytes
transferin- found in
blood and tissue fluid
Denfensins
antimicrobial peptides inserted into microbial membrane forming pores
that damage cells
found in mucous membraes and phagocytes
Secretions
stomach ---- gastric juice
skin ------ sebum (fatty acid)
conditions that foster entry of pathogens
1. In skin -- wounds, excess moisture
2. In mucous membranes --
reduced movement of cilia that can be caused by smoking, narcotics,
viral infection, allergies, chilling
3. In GI -- by reduced
stomach acid, ingestion of antacid
4. distruction of normal
flora with antibiotics, hormonal change
hemotopoietic stem cells
blood cells that give rise to all other blood cells that are located in bone marrow
Hematopoiesis
production, formation and development of blood cells
What process are involved in the 2nd line of defense of the body?
Phagocytosis, complement, interferon and inflammation
process of phagocytosis
chemotaxis, adherence, ingestion, digestion, killing
what are Granuloccytes? give examples of granules
category of WBC that contains cytoplasmic granules
ex:
neutrophil, basophil and eosinophil
What are monocytes? give example
WBC that doesnt contain granules
they differentiate into
either macrophages or dendritic cells when they migarte into tissue
Role of Monocytes
1. replenish resident microphages and dendritic cells under normal
state
2. can move quickly to site of infection in the tissue and
divide the macrophages to elicit an immune response
Role of Granulocytes
they are phagocytes that ingest foreign cells such as bacteria, viruses and other parasites
Role of Neutrophils
they are most common type
they phagocytize and digest engulfed materials
Role of Eosinophils
they are involved in allergic reactions and attack multicellular parasites like worms. Also participates in INFLAMMATORY reactions and immunity to some parasites
Role of Basophils
they mature in mast cells, they release histamine which helps trigger inflammation and heparin which prevents blood from clotting.
What are lymphocytes
they are small wbc that help regulate the bodys immune system (agranules)
what are mononuclear phagocytes
monnocytes, macrophages, dendritic cells
they are either
stationary or wandering macrophages.
types of lymphocytes
B cells, T cells, NK cells
location of lymphocytes
in lymph organs, lymph nodes, spleen, thymus, appendix, tonsils
What do B cells do
they release antibodies Y-shaped that bind to infected microbes to mark them for attack by T cells
What are dendritic cells
they are initialy in tissues but migrate to secondary lymphoid organs
such as lymph nodes, spleen, tonsils
Role- collect antigen from
the tissues and then bring it to lymphocytes that gather in the lymph organs
Mononuclear phogcytic system
wandering and stationary macrophages
difference between monocyte and macrophage
monocyte--circulate in blood
macrophages-- when monocyte leaves
bloodstream and migrate to tissues it becomes macrophages.
How do macrophages protect us against invasion of microbes?
they engulf microbes, then mark them as antigen so antibodies can be produced and also help stop inflammation process by removing dead cells from tissues and repairing wounds
Steps of phagocytosis
1. chemotaxis (movement)
2. Adherence (stick-macrophages stick
to microbes)
3. Ingestion (surround by cell membrane/take in
microbe)
4. Digestion (break down/kills-involves
lysosomes/peroxide
5. Absorption
What is chemotaxis
movement towards chemical signals
ex; lymphokines and complements
what is adherence
attachment of macrophage to microbe
what is ingestion/endocytosis
surround microbe with cell membrane forming phagosome
what is digestion
by fusion w/ lysosome
digestion is carried out by lysosomal
enzymes, killing from acids and toxic compounds such as hydrogen
perioxide, nitric acid and hypocloride
which step of phagocytosis is affected by the presence of a capsule in bacteria
Aherence -- microbes adheres to capsule or else will escape
what are complement system
they are like "bombs" they aim in destroying pathogens
steps of inflammation
injury--mast cells release histamines---causes vasodialation and increase permeability---phagocyte migration/wall off---phaygocytosis--tissue repair
where is the complement system
they are proteins that circulate in blood and fluid that bathes the tissues
complement is composed of
1. family of proteins in blood
2. has enzymatic activity
3. activates in cascade fashion
4. kill foreign microbes
5. act as signal to the immune system
what triggers complement
antibodies and other carbohydrates
what are 3 pathways of complement for activation
alterative pathway, classical pathway and lectin pathway
alternative pathway of complement
- quickly and easily initiated
- is triggered when C3b binds to
foreign cell surface
- initiates activation of other compliment
proteins
- allows formation of complement complex
(c3b
always circulates in blood)
Lectin pathway
- activation requires MBL (mannose binding lectin)
- pattern
recognition molecules that detect mannose
- MBL attachs to
surface
- activates complement proteins
Classical pathways
- activation requires antibodies
- antibodies interact
complement C1
- activates protein
- leads to activation of
all complex proteins
What is the job of complement
1. kills bacteria directly
2. Opsonization - enhance
phagocytosis
3. Provide signals to recruit microphages to the area.
what is opsonization
a process where a pathogen coats with opsonins which enhances phagocytosis
what are NK cells
they are in blood and lymph cells that can lyse and kill cancer cells and viruses infected body cells before adaptive immune system is activated
What are the outcomes of Complement activation
1. Opsonization
2. Inflammation
3. Lysis of foreign cells
what is inflammation
complement components C3a and C5a induce changes to endothelial cells
it effect vascular permeabilty associated with inflammation
a localized physical condition in which part of the body becomes
reddened, swollen, hot, and often painful, especially as a reaction to
injury or infection.
how does opsonization work
C3b binds foreign material, allowing phagocytes to easily grab particles
Lysis of foreign cell through complement activation
- c5b combine with ,C6,C7,C8,C9 to form Mac
- spontaneously
assemble
- forms donut shaped structure called MAC
-
creates pores in membranes
- most effective on G-
What is alternative pathway (antibody independent)
-activated by bacteria and some fungi
- binding to certain
proteins or carbohydrates on microbe by factors activate cascade sequences
How is the complement system activated?
The complement system can be activated in two main ways. The first
means of activation is part of the innate (natural) immune response.
(i.e.; neither antibodies nor T cell receptors are involved.) For
example, certain polysaccharides found on the surface of bacteria can
activate the system. This can occur immediately and does not require
prior exposure to the molecules.
The second and most potent means occurs in a adaptive immune
response when antibodies (IgG or IgM) binds to antigen at the surface
of a cell. This exposes the Fc region of the antibody in a way that
allows the first complement protein (C1) to bind.
What happens as a result of the activation
Name a molecule that activates the complement system as part of a specific immune response.
antibody
Name a component of the activated complement system that serves as a good opsonin.
C3b
how complement deals with inflammation
opsonization
chemotaxis
inflammation
lysis, apoptosis
Which type of immunity triggers the complement system via polysaccharides without any prior exposure
innate
which complement components is formed that results in killing of target cells
membrane attack complex (MAC) c56789
how are target cells killed by complement activation
by lysis
what is opsonization? what does it achieve?
it coats the outer surface of pathogen, achieves enhanced phagocytosis
function of compliment
1. cell lysis with MAC (kills tagged cells)
2. Opsonization of
pathogesns (enhance phagocytosi)
3. recruitment of inflammatory
cells (chemotaxis factor, activation of mast cells signaling phagocytes)
function of the inflammatory response?
- prevents the spread of the injurious agent to nearby tissue
- disposes of cellular debris and pathogens
- sets the
stage for repair processes
7) The antibody molecule is held together by ________ bonds.
disulfide bond
what is the purpose of inflammation
1. destroy injurious agents
2. confine or wall off infectious
agents and its by products
3. repair or replace damaged tissues
symptoms of inflammation
1. redness - increase blood flow to area
2. pain - tissue
damage
3. heat- accumulation of blood
4 swelling -
accumulation of fluid and mast cells
how is inflammation achieved
though vasodilation-- widening of blood vessels
When more blood
comes to area, more pressure is build, that widens the blood vessels.
When vessels vasodialate, pores get wider and bacteria leak out and
are surrounded by phagocytes
what helps reduce inflammation
aspirin and epinepherine
sequence of events in inflammation
1. damage/tissue injury
2. mast cells signal-- release
histamins
3. vasodialation
4 phagocyte migration and wall
off (neutrophils /monocyte migrate to tissues)
5. phagocyte
migration and phagocytosis (microbes englulfed and destroyed by wbc)
6 tissue repair
what is a pus
abscess from collection of dead tissues/cells , fluids, microbes in a cavity
why should you remove pus
to heel quicker and improve circulation
In clonal selection of B cells, which substance is responsible for determining which cells will eventually become cloned?
antigen
the redness and heat of an inflamed area are due to a local hyperemia caused by ________.
vasodialation
why does your skin turn red and swell when it becomes infammed
red-blood flow on surface
swell - more mast cells
can inflammation be harmful
yes if there is swelling of airways, swelling of tissues, internal swelling because it can cut off circulation
what types of inflammation are harmful
over inflammation and systemic inflammation (anaphalyxsis)
how is inflammation beneficial
1 prevents the spread of damaging agents to nearby tissues
2.
disposes of cell debris and pathogens
3. alerts the adaptive
immune system
4. set the stage for repair
what is systemic inflammation/anaphylaxis
1. bronchioles constrict
2. vasodialation
3. fluid loss
4. BP drops
5. death
how is fever triggered
---in response to foreign invasion such as endotoxin production of
interleuking by macrogphages (systemic response to invading
microphages)
-- stimulation of hypothalamus
--- higher
metabolic activity
can fever be beneficial
if it is within limits, can enhance reaction
increase rate of
chemical reactions , more rapid repair
-inhibits growth of some microbes
what are interferons
(natural substance produced by all)
1. calls of antiviral
protein
2. produced by different viral infected animal cells
3. binds to uninfected cells to make them resistant to infection
by virus "anti-viral state"
4. stimulation of other
cells of immune system
Interferons are named for their ability
to "interfere" with viral replication by protecting cells
from virus infection.
IFNs also have other functions: they
activate immune cells, such as natural killer cells and macrophages;
they increase host defenses by up-regulating antigen presentation by
virtue of increasing the expression of major histocompatibility
complex (MHC) antigens.
what are te main types of interferon
1. alpha interferon - produced by microphages and monocytes
2.
Beta interferon - produced by fibroblasts and other cells
3.
gamma interferon- macrophage activation, promotes certain adatptive
immune response like inflamatory response.
Alpha Interferon does what
induces fever , contributes to inflammation
what is the role of NK cells
1 kills cell with reduction or absense of selfmarker (MHC)
2.
kills infected/tumor cells triggered wit antibodies (ADCC)
They
directly attach cancer or virus cells without having to activate by
attaching to antibodies and secreting perforin that causes apoptosis.
Also produce cytokines that regulate n direct immune responses.
how does compliment and antibodies work together
compliment bind wit antibodies to kill microorganism
antibody
when bind to antigen changes shape
membrane attack complex MAC
the complex of terminal complement components that forms a pore in the membrane of the target cell, damaging the membrane and leading to cell lysis
how does complement system ddestroy cells
lysis
types of antimicrobial proteins
interferon and complement
what do antimicrobial proteins do
they attack microbes directly or limit their ability to reproduce
form of complement protein
group of plasma protein that circulate through blood in an inactive state and are activated by immune system signal of presence of microbes
why is high fever dangerous
becoz it denatures enzymes
types of specific immune responses
humoral and cellular
humoral repsonse is
cells derived from B cells secrete antibodies that bind to microbes to target them for distruction
cellular reponse
cytotoxic lymphocytes directly destroy infected body cells, cancer cells, and foreign tissues
advantage and disadvantage of specific immune repsonse
adv: more vigorous and effectivve against particular foreign invader
disadv: takes time
what is adv of nonspecific response
always present and defesne is immediate
hallmark of specific response
recognition, memory and regulation
what is recognnitized by specific response
speicific shapes and antibody generator
what are antibodies
glycoproteins known as immunoglobulins
what is antigen
substance that can trigger an immune response and sepcifically directed against it
what are antigens made of
proteins n carbohydrates , molecules weigh less then 10,000 molecular weight
what are haptens
small molecule that become antigenic only when combining wiht larger
molecule
antibody once generated will bind hapten
what is recognized by antibody
specific part of antigen called antigenic determinant epitopes
what produces antibodies
plasma cells (b cells)
structure of antibody
2 identical heavy chains and 2 light chains
heavy chains
identify antibody class (GAMED)
Each chain has a constant region
(C) and a variable region (V)
variable region
can change in response to antigen
antigens react to variable
regio
marcropages introduce antigens to variable region
which antibodies are always on B cell receptors
IgD and IgM
IgM
primary antibody response. first to appear ater exposure to antigen
short lived
IgG
secondary response
main class/most common
IgA
found in body secretions like saliva, milk, tear
monomer in serum
IgD
part of antigen receptor on Bcells
unknown functio
IgE
bind to receptors on mast cells n basophils in allergic response and parasitic infection
outcomes of antibody
opsonization, complement activation (antibody binding triggers
classical pathway)
, antibody dependet cellular cytotoxicity
opsonization
caoating of bacteria with antibody to enhance phagocytosis
do we have enough Dna to encode all the antigen receptors
antigen receptor genes
and mutations
are all B cells genetically identical?
No
after DNA rearangement each B cell is different
B
cells cloned after antigen exposure is identical
what is MHC
major histocompatibility complex
on the surface of all cells
how does antibody kills microbes
attaching to complement, enhanced phagocytosis, killer cells
parts of cellular response
T cells
virus infected cells
tumor cells
antigen presentation by APC by macrophage
1 macrophage digest microbes
2. associates with MHC
3
.antigens present on surface of APC
4. bind wit t cell
5.
bind releases cytokines turn on t effector cells to activate t helper cell
how are helperT cells activated
when they are presented with antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response
how do cytotoxic (killer t) cell kill microbes
once they bind with the specific antigen, killer cells release cytokines and perforin .Perforin first makes a pore, or hole, in membrane of the infected cell. Cytotoxins go directly inside the cell through this pore, destroying it and any viruses inside.
difference between NK cells and killer cells (cytotoxic)
NK are part of innate that kills viurs and tumor cells
cytotoxic cells are released by t cells to directly kill the microbes
which type of T cell lyses cells that have been infected with viruses?
cytotoxic t cells
Your body has millions of different antibodies for detecting millions of different antigens because
antibody genes undergo somatic rearrangement and somatic mutation
Which type of surface marker is present on every nucleated cell in your body?
MHC1
Activated helper T cells release regulatory molecules called
lymphokines
what do memory B cells do
provide an accelerated immune response upon second exposure to a particular antigen
Complement and antibody are similar in that both
may make bacteria more attractive to phagocytes
How do macrophages kill bacteria cells
by engulfing the one presenting appropriate antigen
how does the complement system work
the complement system is composed of a series of about 20 freely-circulating proteins in the blood. When they encounter an infected cell, they assemble an "attack complex" that creates a pore in the membrane of the infected cell. Water can then enter the cell, ultimately causing it to burst
MHC1 MHC2
MHC I proteins are found on all nucleated cells in the body, identifying it to the body as "self," so that when an immunological attack is in progress, the body does not destroy its own cells along with the pathological invaders. MHC II proteins are found only on macrophages, B-cells, and CD4+ T cells; they function in identifying each other.
How do macrophages activate helper T cells?
Macrophages activate helper T cells by engulfing the invading pathogen and presenting the pathogen's antigens on its surface for the helper T cells to recognize. Macrophages also secrete interleukin-1 that stimulates the helper T cells. Once activated, helper T cells secrete lymphokines that mobilize cytotoxic T cells to fight off the pathogen
how do B cells mature?
When a B lymphocyte responds to an antigen, it is stimulated to replicate, producing a clone of cells that provides an initial, weak immune response. Some of the cells become memory B cells. The next time the body is invaded by the same pathogen, it is ready to provide a rapid, strong secondary immune response.
complement protein works by
forming pores in the membrane of the target cells
how is complement triggered
1 classical pathway - involves antibodies
2. alternate pathway
- involves bacterial chemicals
what is antegenic determinant
3D shape of a region of an antigen that is recognized by the immune system.