Slide 8 Flashcards
What is the purpose of the immune system?
to protect itself against infectious diseases
What are the three components of the immune system?
lymphoid tissues
various immune cell types
chemical signals that coordinate responses
What does the immune system protect itself aginast?
bacteria viruses parasites foreign molecules dead or damaged cells
What are the pathologies of immune repsonses
- incorrect immune response (autoimmune disease type 1 diabetes)
- overactive immune responses (allergies)
- lack of immune response (immunodeficiency disease AIDS)
What are the two line of defense?
physical and chemical barriers
immune defenses (innate immunity and acquired immunity)
Differenciate the physical and chemical barriers
physical: skin mucous membranes, saliva, epiglottis, lacrimal apparatus (tear drops)
chemical
sebum = low pH inhibits microbial growth
perspiration (flushes out microbes and contains lysozyme)
gastric juice (low pH and presence of enzymes)
urine=flushes out to prevent attachment
What is the reaction time difference between innate and adaptive immunity?
innate: a few hours
adaptive: a few days
What are the four steps in an immune response?
- detect and identify the foreign substance
- communicate with other immune cells
- recruit other immune cells and coordinate response
- destruction or suppression of the invader
What is the purpose of the lymphatic system?
vascular system that collects tissue fluids (screens) and returns it to the blood
What is the lymphatic fluid?
it is called the lymph and is monitored for pathogens by the immune system cells
What are the primary lymphoid tissues?
bone marrow produces blood cells and thymus makes t lymphocytes
What are the encapsulated lymphoid tissues?
lymph nodes and spleen
What are diffuse lymphoid tissues?
less concentrated with lymphoid tissues? also known as lymphoid nodules
Describe the thymus gland
size throughout development and produces?
2 lobed organ in the thorax
reaches optimal size during adolescence and then shrinks and replaced by adipose tissue
during development, cells that are self reactive in the thymus are eliminated
produces: T lymphocytes, peptides (thymosin and thymopoietin, thymulin)
What are the functions of lymphoid nodules?
they are loose connective tissue densely packed with lymphocytes
not surrounded by fibrous capsule
germinal center contains dividing lymphocytes
size can increase or decrease depending on number of lymphocytes present (when you sick you might have inflamed throat??)
Where are lymphoid nodules located?
beneath the epithelial lining of organs that have direct contact to the outside world
(digestive, respiratory (tonsils) and urinary)
How does the lymph filtrate or reabsorb?
filtration into the lymph: if capillary hydrostatic pressure is GREATER than blood osmotic pressure (fluid pushed out)
=> in arteriole
Reabsopriton out of the lymph: if blood osmotic pressure is GREATER than capillary hydrostatic pressure => venule
between arteriole and venule: no net movement of fluid because capillary hydrostatic pressure = blood osmotic pressure
How do bacteria and viruses differ? structure, living conditions and vulnerability to drugs
structure:
bacteria- surrounded by cell wall
viruses - NOT CELLS, nucleic acid core+ protein coat
living conditions
bacteria- most can survive and reproduce outside the host
virus - PARASITIC, NEEDS host to reproduce
drugs:
bacteria-can be killed or inhibited by antibiotics
virus: cannot be killed by antiobiotics, need anti viral drugs (some)
What is the viral structure and replication?
- virus invades the host cell
- synthesized new viral nucleic acids and proteins (uses host machinery)
- self assembly of new viral macromolecules into new virus particles
- virus particles released from host cell
What are interferons and how do they work?
if a host cell is infected,
1. the viral replication triggers the expression of alpha or beta interferon (depending on host cell type)
- the IFN is released and attached to uninfected neighboring receptors
and the infected cell dies and releases virus
- the receptor binding triggers an expression of AVP genes (that is inactive)
- now if a viral particle enters this cell to replicate, it activates the AVP by contact of the double stranded RNA
- the active AVP degrade the viral mRNA to stop the viral replication and inhibit the protein synthesis of the virus
What is the structure of a lymph node?
at the lymph node:
there is an artery and vein
efferent and afferent lymph vessel
Describe the lymphatic system part of the kidney.
membrane: afferent lymphatic vessel
cortex: primary lymphoid follicle (mostly B cells)
paracortical area:then T cells (mostly)
medullary cords: macrophages and plasma cells
medullary sinus (inner most part): … efferent lymphatic vessel
Describe the regions of the spleen
red pulp: extensive blood vessels and open venous sinuses (darker like RBCs)
white pulp: resemble interior of lymph nodes and composed mainly of lymphocytes
have vein, artery and capillaries
What is the composition of whole blood?
plasma vs. formed elements
plasma: H20, plasma proteins (albumin regulatory proteins fibrinogen globulins), other solutes
formed elements: RBCs, WBCs (granulocytes vs. agranulocytes)*, platelets
- granulocytes: neutrophils, basophils, eosinophils
agranulocytes: monocytes and lymphocytes
What are the granulocytes and agranulocytes?
granulocytes:
eosinophils, destroy esp. antibody coated parasites
basophils & mast cells,release chemicals that mediate inflammation and allergic response
neutrophils, ingest and destroy invaders
agranulocytes: monocytes & macrophages, ingests and destroy invaders = antigen presenting MHC2
lymphocytes (T and B) & plasma cells, specific response to invaders and produce antibodies
dendritic cells, aka Langerhans cells = recognize pathogens and activate other immune cells by antigen presentation
What are some types of macrophages and where do we have them?
microglial = brain alveolar = lungs kupffer cells = liver endothelial spleen kidneys dendritic joints
What do macrophages do?
phagocytose and activate bactericidal mechanism
antigen presenting
What are dendritic cells?
antigen uptake in peripheral sites
antigen presenting
What do neutrophils do?
phagocytose and activate bactericidal mechanism
What do mast cells do?
release granules containing histamine and active agents (make hole in the cells)
What do eosinophils do?
kill antibody coated parasties
What basophils do?
unknown
What is the purpose of the first line of defense?
most pathogens do not enter the body (kept out of surface tissues )
they secrete:
on physical barrier = mucous and skin
chemical barriers = stomach acid ad lysozyme
What types of phagocytosis are there and how do they differ?
without capsules: engulf and phagocytose pathogen
with capsule: antibody molecules attach to the capsule and attached antibodies bind to the membrane receptor of phagocytes and then gets engulfed within cell
What happens after pathogens are phagocytosed? (within cell)
they are ingested and killed by lysosomal enzymes
phagosomes (after phagocytosing something)
- lysozomes that contain enzymes and oxidants
fuse with
- ingested pathogen
become digested into pieces
What is the difference between immature dendritic cells and mature dendritic cells?
immature: reside in peripheral tissues
mature: after migration via lymphatic vessel to lymph nodes
they activate naïve T cells in lymphoid organs
What is the special feature of antigen presenting cells?
they ingest the pathogen and then digest in lysosome and then display the antigen fragements on the receptors
What do NK cells do? How do they do it?
kill infected and tumor cells by: -inducing apoptosis in infected cells -attack tumor cells -secrete chemical signals = interferons (alpha+beta = prevent viral replication & gamma=activate macrophages and other immune cells)
What is the purpose of inflammation?
attract immune cells and chemical mediators in infection sites
create physical barrier to prevent infection to spread
promote tissue repair
What are the steps in inflammatory response? list chemical releases
- damage/infection: cytokines and acute-phase proteins are released
- acute phase proteins: help prevent tissue damage
- cytokines: stimulate histamine release from mast cells
- histamine: causes local vascular changes
- vasodilation -> leads to heat and redness
- nearby capillaries become more permeable -> WBCs and plasma proteins move into tissue + edema or swelling results from osmotic effect of plasma protein
Other chemicals:
interleukins: subset of cytokines that cause fever and blood vessels become more permeable to WBCs and proteins and acute phase proteins
Bradykinin: pain and swelling
complement proteins: inactive as plasma proteins but the cascade produces MAC membrane attack complex and inserts into foreign cell membranes to result in lysis
What are cytokines and acute phase proteins?
acute phase proteins: help prevent tissue damage
cytokines: proteins that stimulate or inhibit many normal cell functions like growth and differentiation
released by macrophages to stimulate inflammation and attract other immune cells to increase tissue permeability and cause fever
How does the MAC complex work?
the complement proteins insert themselves into the membrane of the pathogen
the proteins create pores in the membrane
now the membrane cannot keep homeostasis, ion balance etc.
cell dies
What are acute phase proteins?
liver proteins act as opsonins that enhance inflammatory response
What are opsonins?
proteins that coat pathogesn so phagoytes can recognize and ingest easily
What are chemotaxins?
attract phagocytes to a site of infection
What are cytokines?
proteins released by one cell to affect growth or activity of another
What are pyrogens?
fever inducing substances
What are antibodies?
immunoglobulins secreted by b cells to fight specific invaders
What do C reactive proteins do?
activate complement cascade
How T cell receptors work?
recognize and bind antigen presented by MHC receptors
What are TNF?
tumor necrosis factors that promote inflammation and cause cells to self destruct via apoptosis
Describe the acquired immunity. What helps regulate innate and acquired immune responses?
reacts and targets specific foreign molecules => antigen
presence of antigen activates:
active (lymphocytes exposed to foreign antigen) and passive (when we receive antibodies elsewhere) immunity
cytokines regulate both innate and acquired immune responses
memory cells are produced in case of future re-exposure
What is the course of adaptive response?
- extracellular antigen fragments presented to Th (helper cell) on B cell receptor [once B cell finds the antigen to the antibody] or antigen presenting cell (ie macrophage)
- Th gives permission to B cell to differenciate into a plasma cell (that can have anitbodies to shoot out)
Th also activated macrophages so they are really efficient in phagocytosing
Th also activates naïve cytotoxic T cell
- activated cytotoxic T cell kill target cells
- B cells and cytotoxic T cells also makes memory cells so there is a more rapid response on secondary encounter
What are the subdivision of lymphocytes?
- T cells (cytotoxic directly attack infect cells and helper secrete cytokines)
- B cells (differenciate into plasma cells and then secrete antibodies)
- NK cells (natural killer cells)
What are the 4 main types of T cells? they are most abundant in the circulating lymphocytes 80%
cytotoxic T cells
Helper T cells
suppressor T cells
memory T cells
What is the role of B cells?
make 10-15%
differenciate into plasma cells once activated by Th cells
plasma cells: produce and secrete antibodies [immunoglobulin proteins]
antibody mediated immunity: destroys and target compounds or organism
What are the natural killer cells?
they are large and granular lymphocytes
responsible for immunological surveillance
attack foreign cells, virus infected and cancer cells
Which lymphocytes are part of specific and non specific immunity?
specific: B cells and T cells
non-specific: NK cells
How are T cells produced?
From the red bone marrow, hemocytoblasts become lymphoid stem cells
migrate to thymus
and thymic hormones will have the production and differentiation of Tcells into mature T cells
they are then transported in the bloodstream to the peripheral tissues and red bone marrow
How are B cells and natural killer cells produced?
In the red bone marrow, differenciating in the lymphoid stem cells to B cells and Natural killer cells
B cells: travel to peripheral tissues to antibody mediated immunity
Natural Killer cells: travel to peripheral tissues for immunological surveillance
What are lymphocyte clones?
lymphocytes have proteins on their cell surface that can bind a specific antigen
lymphocytes that can bind the same particular antigen are called clones
What are the steps in an immune response?
Naïve lymphocytes: not stimulated BUT
- once antigen stimulates a specific lymphocyte clone that have the receptors for this antigen
- there is clonal expansion = cells multiply rapidly in response to antigenic stimulation
- new cells differentiate into three effector cells: plasma cells, Th cells, cytotoxic T cell)
- others become memory cells for net time (memory T helper, cytotoxic and B cells for each effector cell)
What is the primary and secondary immune response?
Primary immune response: antigen first exposed to naïve lymphocyte = activates B cell and reproduces via clonal expansion
- effectors are short lived and carry immediate response
- memory cells are long lived and continue to reproduce
secondary immune response:
once antigen is introduced again, the clone expands more rapidly this time creating even more effector and memory cells
What is humoral immunity?
B lymphocytes/ B cells (response) are responsible for this
clonal expansion gives rise to production of plasma cells
each clone of plasma produces specific antigen binding protein called antibody
and memory cells are also produces for rapid and stronger secondary antibody response if antigen is encountered again
What is the memory effect in a humoral response?
primary: chi square/normal distribution = takes many week, and peaks at 2 wekks
secondary: greater response and much faster = exponential growth
What is the antibody structure? Which are the five types?
Y shaped, Fc region varies
2 binding sites
known as gamma globulins (5 types) - IgG most common, secondary response - IgA secretory form like saliva, tears, breast milk - IgE allergic rx - IgM antibodies in primary response - IgD found on B cell surface
What are the functions of antibodies?
- activate B cells to plasma cells and memory cells
- acts as opsonins: coat antigens for phagocytosis
- cause antigen to clump and inactive bacterial toxins by binding to them
- activates antibody dependent cellular activity (NK cells or eosinophils)
- triggers mast cells to degranulate = create pores in cells
- active complement = MAC complex to makepores in membranes
What is the specialization of T cells?
defend against intracellular pathogens
contact dependent signaling
recognize foreign antigents via MHC (major histocompatibility complex)
How are T cells activated?
MHC antigen complex presents foreign antigen fragments and binds to T cell
signal transduction activates T cell
How do T cells develop into an effector cell?
T cell precursor migrates to thymus to become Cytotoxic or helper t cell
NK formed from precursors and kill antibody coated cells or MHC 1 target
Cytotoxic T cells: kill MHC1 (on all cells so recognize foreign things in self cells = meaning they are infected)
Helper T cells bind to MHC2 and secrete cytokines
What are the two division of MHC?
antigen presenting marker of self = tissue rejection issues
MHC1: found on all cells in body
regonized by NK cells and cytotozic T cells via CD8
MHC2: found on antigen presenting cells only (dendritic, macrophages and B cells)recognized by Helper T cell via CD4
Describe the process of antigen presentation with B and T cells involved.
B cells recognize the antigen and bind to it in the lymph, interstitial fluid or blood plasma
T cells only recognize the fragments proteins of the antigen when they are displayed on MHC
The MHC then inserts itself on cell membrane of the cell
How to cytotoxic T cells and Helper T cells differ in their roles?
Cytotoxic T cell: display CD8 for MHC1 attack and destroy infected cell: - release perforin to create holes in the infected cells -stimulate apoptosis in the cell
Helper T cell:
secrete cytokines that influence other immune cells
bind to B cells to promote differentiation into plasma cells
display CD4 (for MHC2)
What is the general pattern in an immune response pathway?
- innate response acts quick (general)
- acquired response takes longer but stronger
- cytokines from both innate and acquired coordinate reinforcement of the two responses
Describe the immune response to extracellular bacteria
- activate complement system by bacterial cell wall components
- act as opsonins, activate MAC, mast cells and chemotaxins.. refer to diagram - phagocytes are activated: uncapsulated - immediate ingestion, if capsulate: discuise until antibody comes and binds to it so it can bind to macrophage receptor
- role of acquire immune response (lymphocyte action)
- initiation of repair, recruitment of platelets and protein coagulation cascade
when bacteria removed, growth factors and cytokines come
What is the immune response to viruses?
- antibodies act as opsonins to coat viral particles and make them better targets for antigen presenting cells like macrophages
- macrophages ingest viruses insert fragments of viral antigen into MHC 2 molecules on membrane
macrophages secrete cytokins and interferons - Th cells bind to viral antigents on MHC2 and become activated, secrete cytokines to stimulate B cells and cytotoxic T cells
- last exposure to virus can make memory B cells with viral antibody on their surface = more memory cells are activated and promotes palsma cells differenciation
perforing molecules insert pores into host cell membrane to allow granzyme to enter cell for apoptosis
What is hypersensitivities and what are the types?
any immune response against a foreign antigen exaggerated beyond the norm
Type 1 immediate
Type 2 cytotoxic
Type 3 immune complex mediated
Type 4 delayed or cell mediated
What is a type 1 hypersensitivity?
can be localised or systemic resulting from release of inflammatory molecules in response to antigen
seconds or minutes to exposure to antigen
called allergies
antigens called allergens
What is the reaction that occurs? 2 step process
sensitization upon exposure:
allergen ingested by APC, present on MHC2 and activates Th cell which self activates and activates B cell to become plasma cells that secrete antibodies and make memory B and T cells
degranulation of sensitized cells: (reexposure)
when allergen is introduced again,
binds to IgG = activates complement proteins and inflammation,
binds to IgE = activates mast cell and degranulation and release of cytokines, histamines for vasodilation, bronchoconstriction and increased vascular permeability = inflammation
activates T cell to release cytokines
What is the role of mast cells for type 1 hypersensitivity?
degranulation
distributed throughout CT
have granules that contain inflammatory chemicals (degranulation relseases histamine, kinins, proteases, leukotrienes and prostaglandins (mostly smooth muscle contraction and inflammation)
What is the role of basophils and eosinophils during Type 1 hypersensitivity?
basophils: least numebrous
have granules that have inflammatory chemicals
degranulate like mast cells when allergens are there
eosinophils: accumulate in the blood
mast cell degranulation trigger release of eosinophils from bone marrow
releases lots of leukotriens and hypersensitive response
What are some clinical signs of type 1 immediate hypersensitivity?
mild or localised
site of reaction is at portal entry
inhaled = hay fever
small inhaled amount= asthma
inflammation of skin = hives or urticarial
acute anaphylaziz or anaphylactic shock must be treated with epinephrine to relax the smooth muscles?
What is diagnosis if type 1 hypersensitivity?
high IgE (immunoglobulin E) skin tests
What are some treatments of type 1 hypersensitivity and some prevention technique?
prevent: identify and void allergens, use eliminiatino diet and allergy shots [not effective for asthma]
treatment: antihistamine neutralize histamine, asthma= glucoritcoid and bronchodilator, epinephrine neutralized anaphylazis by relaxing smooth muscle
What is an example of type 2 hypersensitivity? (cytotozic)
Rh system and hemolytic diseas of the newborn
Rh antigen common to RBCs
85% Rh+
this disease is is mom: Rh- and fetus Rh+ then first exposure = Rh antibodies to created in mom so no effect on fetus
second exposure: antibodies can harm fetus (because placenta shares blood and does not block out Rh antibodies = destroy fetus blood
treatment: anti Rh immunoglobulin (RhoGAM)
What is a type 3 hypersensitivity?
caused by immune complexes = triggers inflammatory chemicals
causes localized reactions
causes systemic reactions (rheumatoid arthritis
basically:
antigens coming with antibodies IgG = complex formed
phagocytes remove the complex by ingesting but some stay in blood vessel walls
they stay there and activate the MAC
attract neutrophils and complements to release enzymes
enzymes and inflammatory chemicals damage tissues surrounding it
What is an exmaples of type 3 hypersensitivity?
rheumatoid arhtirtis
when immune complexes in the joints so breakdown of joints and becomes more and more severe
treated with anti inflammatory drugs
