Lecture 3 Flashcards
Why should PTs care about the immune system?
immune system can be impacted by healthy exercise
Changes with adults & immune ssystem
increased susceptibility
more frequent reactivation of diseases
decreased vaccine efficacy
increased incidence of chronic/autoimmune/cancer
Immunosenescence
the decline in normal functioning of the immune system with aging
Inflammaging
chronic, mostly asymptomatic low grade inflammatory state that can eventually lead to chronic illnesses
examples include CVD, type 2 diabetes, some cancers, alzheimers
Can exercise cause changes in the immune system?
YES
intensity and direction of these changes depends on regularity, type, duration, and intensity
Antigens
any foreign molecules that do not have self-characteristic surface markers
Major histocompatability complexes (MHCs)
membrane surface proteins that mark each of our body’s cells
present antigenic peptides for recognition by T cells
have 2 classes; Class 1 and Class 2
Class 1 MHC
expressed on surface of almost all nucleated cells
we INHERIT these
Class 2 MHC
expressed on surface of antigen-presenting cells. Macrophages, dendritic cells, B-cells.
on cells that fight infections, not on infection themselves
Immune system
all the structures and processes that provide defense against potential pathogens
has innate and acquired
Innate immunity
nonspecific, we are born with it
inhereited defense mechanisms that are present at exposure to a threat. have external and internal defenses
Acquired immunity
specific and adaptive
based on prior exposure and provides long term memory, provides future protection against same invaders
includes active and passive acquired immunity
involve proliferation of antigen-specific B & T cells
2 types: humoral & cell-mediated
External defenses of innate immunity
Skin
Gi tract: stomach acidity, normal flora
respiratory tract: mucus, cilia, alveolar macrophages
genitourinary: pH, mucosal lining, urine flushing
Internal defenses of innate immunity
1st line of defense against pathogens that get past the external defenses
phagocytes
endogenous pyrogens
interferons
complement proteins
Phagocytes
ingest and destroy pathogens/cell debris
neutrophils, monocytes, macrophages, eosinophils, basophils, NK cells
Phagocytes and infection
decrease in number of phagocytes is primary cause of increased infection risk in individuals treated with radiation or chemotherapy
neutropenia is an example
Vascular changes in injury
Transient vasoconstriction
vasodilation
increased permeability
Cellular Events in infection
margination
diapedesis and movement toward pathogen by chemotaxis
recognition and adherence
phagocytosis
Phagocytosis
foreign particle becomes surrounded by pseudopods of phagocytes
phagocytes eventually engulf antigens, form vacuole, fuses with lysosomes
Infiltration of an Inflamed Site by Leukocytes
Neutrophils are first and most intense
Monocytes are second, least intense
T-lymphocytes are third
Endogenous pyrogens
generates a fever
cytokines released by host monocytes/macrophages in response to a pathogenic signal
common: interleukin-1 (IL-1)
results in increased activity of neutrophils, production of interferon, fever, sleepiness, decreased plasma iron
Interferons
think VIRUS
released by lymphoctyes, macrophages, virally infected cells
produce nonspecific and short acting resistance
inhibit viral replication and assembly of new viruses
act as messengers, protect nearby cells
used as drug interventions
Complement system
group of plasmas proteins in blood, interstitial fluid, and mucosal surfaces that are normally dormant until they are activated by microorganisms or antigen-antibody complexes
once activated complement proteins cause 4 events–vasodilation, attraction of EBCs, opsonization, MAC
Primary Lymphoid organs
bone marrow
thymus
Secondary lymphoid
lymph nodes
spleen
peyer’s patches
tonsils
appendix
Maturity of T lymphocytes
stem cells in bone marrow
travel to thymus gland to complete development
Antibodies
produced by B lymphoctyes
only bind to specific antigens, at the epitope.
elicit immune response
help to recruit other cells to attack antigen once binded to it
types of B-cells
memory cells and plasma cells
What do B-cells do?
have surface receptors that can recognize a single specific antigen
when it binds to B-cell (and gets signal from T cell), change into protein synthesizing cells (plasma and memory cells)
B-lymphocytes
effective against bacterial infections
mature in bone marrow
high concentration in spleen, low concentration in blood
Plasma B-cells
antibody factories that secrete antigen specific antibodies
Memory B cells
identical clone of original b cell, type of acquired immunity that yields permanent resistance. important in active immunity
Opsonization
process by which targets are identified for immunologic attack
Why don’t we have a immune response with stints/grafts/joint replacements?
they don’t have epitopes, so they aren’t recognized as being foreign by the antibody
IgG
main type in circulation, production increased after immunization, secreted during secondary response, crosses placenta
5 main classes of antibodies
IgG
IgA
IgE
IgM
IgD
IgA
main type in external secretions (saliva, breastmilk) and mucous membrane surfaces
IgE
Responsible for allergic symptoms in immediate hypersensitivity reactions
Complement system
helps to directly kills antigen
although part of innate immune response, complement works with antibodies to destroy pathogens
present in plasma in inactive state until activated by antibodies
Complement and antibodies work as a team
IgG and IgM attach to antigens on invading cell membrane and activate C1
activated C1 splits into C4b which binds to invader’s cell membrane (fixation)
this triggers activation of other complement proteins until finally the membrane attack complex is inserted into the invader’s cell membrane
Membrane attack complex
C5 to C9 create large holes in membrane, causes H2O to influx into cell, causes cell death
complement proteins kill the invaders that were labeled by antibodies
Activated complement proteins go on to….
direct destruction by membrane attack complex
vasodilation
increased capillary permeability
chemotaxis
opsonization
Cell mediated immunity w/T-cells
able to recognize these hidden intracellular organisms, search them out, and destroy them on cell-by-cell basis
What do T-cells attack?
host cells infected with viruses and fungi
transplanted human cells
cancer cells
T-lymphocytes growth
originate in bone marrow, complete development in thymus gland
after thymus, enter blood and populate lymph nodes/secondary lumphoid organs
repopulation of T-cells in adulthood occurs slowly
unstimulated T cells live for months/years
Thymus gland
primary lymphoid organ that begins to shrink around puberty
types of t-cells
Cytotoxic killer T cells
Helper T cells (majority of T cells)
Suppressor T cells
Killer T-Cells/CD8
cause cell-mediated destruction
can only destroy infected host cells that present antigens in association with class-1 mhc molecules
secrete perforins that form cylindrical channels through the membrane, helps to cause osmotic cell death
defend against viral, fungal, transplants
Steps of cell-mediated immunity
virus enter the cell
abnormal peptides replicate
Class 1 MHC proteins incorporate abnormal peptides
Class 1 MHC proteins transported to cell membrane
Abnormal peptides are displayed by Class 1 MHC proteins on cell membrane
CD8 recognizes abnormal peptides bound to MHC1
CD8 secretes perfornins to kill cell
Helper/Suppressor T-cells
participate in acquired immune response by regulating responses of the B-cells and Killer T cells
Helper T-cells
must activate B cells before they differentiate into memory and plasma cells
cannot bind directly to a free antigen
antigens are presented to helper T cells by antigen presenting cells (macrophages/dendritic cells)
can only be activated by class-2 MGC presenting antigens
Suppressor T-cells
inhibit T cell and B cell activities
purpose is to moderate immune response
Steps of Helper T cells
pathogen phagocytized by antigen presenting cell (macrophage)
lysosome action produces antigenic fragments
Class 2 MHC proteins are produced
antigenic fragments are bound to MHC 2
antigenic fragments are displayed on cell brane
helper T cells bind to MHC molecule
go on to activate B cell
Tumor immunology
tumors are clones of single cells
division is not effectively controlled by normal mechanisms
tumor cells often de-differeniate, become similar to other cells
Natural killer cells
large granular non T or B cells
do not require thymus for development
back up CD8 T-cells
kill host cells & tumor cells
Active acquired immunity
person produces his own antibodies in response to the foreign organism
resistance is usually permanent
can be natural or artificial
has a primary and secondary response
Natural active acquired immunity
created after exposure
Artificial active acquired immunity
via active vaccination, provokes your immune system to make antibodies
Primary response active acquired immunity
1st exposure to pathogen
immune response is insufficient to combat disease
5-10 day latency of antibody production
Secondary response active acquired immunity
subsequent exposure to same antigen
antibody production is more rapid
max antibody concentration within 2 hours
usually prevents the disease
Passive acquired immunity
produced by transfer of antibodies from donor to recipient
donor has been actively immunized, the recipient is passively immunized
resistance is temporary
can be natural or artificial
Natural passive acquired immunity
mother to fetus during pregnancy via placenta
mother to infant during nursing via breastfeeding
disappears when infant is 1 month old, infant starts to develop immunocompetence
Artificial passive acquired immunity
passive immunization = injection of anti-serum
rabies vaccine, snake anti venom. for infections that you don’t have time to make antibodies before becomes fatal
Factors affecting immunity
aging
nutrition/malnutrition
burns
sleep deprivation
surgery/anesthesia
present of concurrent disease
Medications
Iatrogenic factors that increase exposure
Stress
Aging and immuntiy
innate = external defenses break down, phagocytes function decreases
acquired = antigen specific antibody response decrease, self antigen responses increase, # circulating T cells decrease, T cells not as responsive
Burns and immunity
increased susceptibility to severe bacterial infections due to loss of largest external barrier
Sleep deprivation and immunity
decreased neutrophils, NK, T4, T8, B cells
increased monocytes
7 hours a night
Surgery/anesthesia and immunity
suppresses T cell and B cell function for up to 1 month post op
Presence of concurrent disease and immunity
illness/disease, malignancy, diabetes, chronic renal failure, HIV infection
Metastasis
movement of cancerous cells via blood or lymph to a new distant site
Grading
histologic differentiation of cancer tissue
refers to degree of resemblance of cancerous tissue to tissue of origin
Staging
refers to degree of spread or metastasis
classification systems vary by type of cancer
Medication and immunity
immunosuppressive drugs (like glucocorticoids)
Iatrogenic factors that increase exposure to pathogens
urinary catheters, external fixation devices, chest tubes, etc
infections that result from actions of HCP
Exercise immunology
depending on intensity, frequency, type of exercise, immune system can be enhanced or suppressed
acute bouts of exercise tend to promote release cytokines, chronic exercise reduces chronic inflammation
can lessen detrimental effects of stress on immune system
What does exercise help increase
plasma concentration
activity of neutrophils
phagocytic action of macrophages
number and activity of NK cells
number of circulating WBCs
What does exercise help decrease
circulating levels of pro-inflammatory markers
Extreme exercise
suppresses lymphocyte concentration
suppresses NK cell concentration and activity
increases susceptibility to viral infections
increases circulating pro-inflammatory cytokines
deleterious oxidation of cellular macromolecules
Neck Check extra credit
when completing an intense exercise while sick with bacterial or viral infection, you should do the following:
if symptoms are above the neck, begin workout at 1/2 speed, check in 10 min. If improved, can continue. If worse, stop and get rest
if symptoms are below the neck, exercise should not be started
