Exam 4: Immune System Flashcards
primary functions of the immune system
- protects the body from disease-causing invaders (pathogens and antigens)
- removes dead or damaged tissues and cells (inflamed cells, old blood cells)
- recognize and remove “abnormal self” cells (cancer cells)
key features of immune system
specificity: enable body to distinguish “self” from “non-self”
memory: immune response is stronger in the second stimulation
what happens if the immune system fails?
incorrect response: autoimmune diseases (type 1 diabetes or IBD
overactive response: allergies, allergic hypersensitivity reactions
lack of response: immunodeficiency diseases, AIDS, HIV
types of lymphoid tissue
primary: thymus gland and bone marrow
secondary: lymph nodes and spleen
primary lymphoid tissue
role: nurture immune cell development
naive immune cells have not encountered the proper antigens
cells involved in the immune response form and mature
secondary lymphoid tissue
role: get matured immune cells to interact with pathogens and initiate a response
categories: encapsulated and unencapsulated diffuse lymphoid tissues
bone marrow
spongy tissue inside some bones like hip and thigh bones
contains stem cells that can develop into red blood cells and white blood cells (immune cells) that can fight infections
thymus gland
on the chest between the lungs
makes T lymphocytes which help fight infection
lymph node
small bean shaped structure
filter substances that travel through the lymphatic fluid
contain white blood cells that help the body fight infection and disease
connected to each other by lymph vessels
spleen
largest lymphoid organ in the body
immune cells in the spleen monitor blood for foreign invaders
phagocytes in the spleen trap and remove old red blood cells
basophils and mast cells
release chemicals that mediate inflammation and allergic responses
granulocytes
white blood cells whose cytoplasm contains prominent granules
phagocytes
engulf and ingest their targets
cytotoxic cells
kill the cells they are attacking
antigen-presenting cells
display fragments of foreign proteins on their cell surface
neutrophils
50-70% of all white blood cells
1-2 days life span
ingest and kill 5-20 bacteria
make pus: thick fluid caused by infection that includes white blood cells and cellular debris
chemotactic migration to chemical signals such as IL-8, leukotriene that induces production of ROS such as H2O2 and inflammation
eosinophils
associated with allergic reactions and parasitic diseases
pink-orange color
1-3% of all leukocytes
life span of 6-12 hours
location: GI tract, lungs, epithelium of urinary and genital tracts, and connective tissue of skin
produce ROS (reactive oxygen species such as superoxide, peroxide), cytokines, and enzymes (elastase in asthma)
attach to large antibody-coated parasites and release substances that kill them
basophils and mast cells
located in the systemic circulation (0.5-1% of circulating WBCs)
mast cells are found in the local tissues
dark violet granules
contain chemicals that are involved in immune and allergic responses such as histamine, heparin, and cytokines
dendritic cells
characterized by long, thin processes that resemble the dendrites of the neuron
APCs: present antigens to lymphocytes to activate them
antigen-presenting cells
recognize and capture antigens
dendritic cells, macrophages, and B cells
monocytes
precursor cells of macrophages and dendritic cells
circulating version of macrophages and DC
spend ~8 hours in transit from the bone marrow to tissues where they differentiate into macrophages
macrophages
primary scavengers for the tissues
can ingest up to 100 bacteria
remove dead blood cells and dead neutrophils
antigen presenting cells
lymphocytes
responsible for acquired immune response
5% of all lymphocytes are in circulation and the rest are located in lymphoid tissues
make up 20-35% of all circulating white blood cells
t lymphocytes
cell-mediated imkmunity
b lymphocytes
antibody-mediated immunity
types of immunity
- physical and chemical barrier
- innate immune system (all animals possess)
- adaptive immune system (all vertebrates possess)
innate immune system
non-specific
begins within minutes to hours
produces general inflammatory response when pathogens penetrate physical barriers
adaptive immune system
can adapt to defend against any invader
response to a first exposure to a pathogen may take days
important when the innate immune system cannot defend against an attack
provides the immune system with “memory”
components of the innate immune system
- professional phagocytes: macrophages and neutrophils
- complement system: proteins that tag stuff for destruction
- natural killer (NK) cells: mast cells and basophils
macrophages
patrol periphery
become activated when they find an invader
when activated:
1. send signals to recruit other immune system cells (neutrophils)
2. become vicious killers (phagocytosis)
3. present antigen to adaptive immune system
what activates macrophages
chemotaxins: bacterial toxin, cell wall components
tissue injury debris: fibrin, collagen fragments
chemotactic cytokines by leukocytes
mechanism of attachment during phagocytosis
patterning recognition receptor to binding
binding to antibody
hydrophobicity
patterning recognition receptor to binding
phagocytic cells’ patterning recognition receptor can bind bacteria directly by surveilling the pathogen-associated molecular pattern
binding to antibody
phagocytic cells can bind the Fc portion of antibody
binding of several antibodies on macrophages activates phagocytosis and microbial killing
hydrophobicity
hydrophobic groups tend to attach to the hydrophobic surface of cells
may explain the recognition of damaged cells, denatured proteins, etc
mechanism of killing and digestion during phagocytosis
lactoferrin
oxygen and the oxygen burst
nitric oxide (NO)
lactoferrin
protein that inhibits bacteria by depriving them of iron which it binds with an extremely high affinity
oxygen and the oxygen burst
intracellular killing of many bacteria requires the uptake of oxygen by the phagocytic cell
reactive oxygen species are highly toxic to microorganisms
NO produced from arginine is another reactive oxygen containing compound that is highly toxic to microorganisms
complement proteins
about 30 plasma and cell membrane proteins
present in tissues and blood
attach to surfaces of bacteria and viruses
- 1. target them for destruction by phagocytes or by making pores
- 2. form membrane attack complexes
recruit other immune cells from blood
functions of complement system
opsonization and phagocytosis
lysis
agglutination
neutralization of viruses
chemotaxis
activation of mast cells and basophils
inflammatory effects
opsonization and phagocytosis
opsonins are used to tag foreign antigens and strongly activates phagocytosis by both neutrophils and macrophages
lysis
combination of multiple complement factors can directly rupture the cell membranes of bacteria or other invading organisms
agglutination
the complement products also change the surfaces of the invading organisms, causing them to adhere to one another promoting agglutination (clumping of particles together)
neutralization of viruses
complement enzymes and other complement products can attack viruses and thereby render them non-virulent
chemotaxis
chemical stimulus initiates the movement of neutrophils and macrophages
activation of mast cells and basophils
cells become activated which causes them to release histamine, heparin, and several other substances into the local fluids
inflammatory effects
- increase blood flow further
- increase the capillary leakage of proteins
- coagulate the interstitial fluid proteins in the tissue spaces, preventing movement of the invading organism through the tissues
natural killer cells
innate response against viral infection
innate immune response because they lack antigen-specific cell surface receptors
release granzyme (protease)
NK cells induce virus-infected cells to commit suicide (apoptosis)
secrete antiviral cytokines (interferons)
interferons interfere with viral reproduction in the body
release of histamine
released by mast cells and basophils
initiates inflammatory response
induce WBC recruitment from the blood stream
histamine action
- opens pores in capillaries: release of plasma protein causes local edema/swelling
- dilates blood vessels increasing blood flow: bring about hot, red, swollen area around the wound or infection site
adaptive/acquired immune system
two main components
fight pathogens outside of cells: b lymphocytes/antibody-mediated immunity
fight pathogens inside of cells: t lymphocytes/cell-mediated immunity
function of antibodies
- activates b lymphocytes
- acts as opsonins
- causes antigen clumping and inactivation of bacterial toxins
- activates antibody-dependent cellular activity
- triggers mast cell degranulation
- activates complement
b cells
lymphocytes that make antibodies
b cell receptors on the surface
100 million different types of b cells that each have different surface receptors
b cell receptors are so diverse they can recognize every organic molecule
when a b cell binds antigen…
b cells are activated and differentiated into plasma cells
plasma cells secrete antibodies at the rate of approximately 2000 molecules per second
how do T cells identify virus infected cells?
antigen presentation
all nucleated cells have major histocompatibility complexes on the surface
when virus invades the cell, fragments of viral protein are loaded onto MHC proteins
T cells inspect MHC proteins and use this as a signal to identify infected cells
MHC class I molecules
all nucleated cells
infected cells display viral antigens on MHC I
cytotoxic T cells recognize a cell with foreign antigen fragment and kills the cell
MHC class II molecules
macrophages, b lymphocytes, and dendritic cells
helper T cells recognize a cell with foreign antigen fragment on its MHC II
helper T cells secrete cytokines that enhance the immune response
lymphocytes clones and memory effects
at birth, each clone of lymphocytes is represented by only a few cells called naive lymphocytes
exposure to an antigen triggers clonal expansion and the immune response
primary immune response
clone of B and T cells are built up over the course of 1 week
when the infection is over, these cells die off and the ones that remain are memory cells
B lymphocytes become plasma cells which can secrete antibodies to treat the disease in the future
peak antibody concentration occurs about 2 weeks after exposure
secondary immune response
memory cells can activate more easily and reproduce effector and memory cells that will turn into plasma and secrete antibodies
peak antibody concentration occurs around 3 weeks post exposure, BUT antibody concentration rises immediately after exposure to yield a faster response that is also stronger
in just a few days, secondary immune response will yield the peak amount of antibodies that were secreted in the primary immune response
aka: can become stronger faster
bacteria
cells have membrane and cell wall
can survive outside the host
can reproduce without a host
can be killed or inhibited by antibiotics
how do bacteria cause disease?
invade the host
reproduce and overgrow
deplete nutrients, ions, and oxygen
secrete organic wastes
produce toxins that disturb the normal functions of cells
immune response to bacteria
complement proteins make membrane attack complex that lyses bacteria
complement proteins activate mast cells that secrete chemotaxins and histamine (chemotaxins attract circulating leukocytes that will ingest and disable bacteria or secrete antibodies)
virus
contains nucleic acid core (DNA or RNA) with protein envelope
uses the intracellular machinery to reproduce
- virus causes host cell to lyse OR viral particles will bud from the host cell surface)
cannot be killed with antibiotics
how do viruses cause disease?
virus invades the host cell
- binds to membrane receptors
- endocytosis brings virus into the cell
virus takes over the cell
- use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins
more virus is released from host cell
- virus causes the host cell to lyse OR viral particles bud from the host cell surface
immune response to viruses
MHC I presenting
- attacked by cytotoxic T and NK cells
- granzymes
- infected cell is destroyed
MHC II presenting
- macrophage ingests the virus
- secretes cytokines for inflammatory response
- macrophage presents antigen fragments
- activates helper T cell
- activates B lymphocytes
- become plasma cells that secrete antibodies
human immunodeficiency virus (HIV)
fast mutation of the viral genome
- antibodies fail to coat the viral particles for phagocytosis by macrophages
- macrophages fail to phagocytose (failed to transferred to lysosome) and virus invade macrophages
after viruses infect cells, T lymphocytes are the main defense - failed
- helper T cells are infected by the virus
- cytotoxic T cells use viral antigen-MHC I to recognize the infected cells and kill them BUT also kill T cells
- virus down regulate MHC expression to escape cytotoxic T cells
COVID 19
targets angiotensin converting enzyme (ACE2) to get into host cells
ACE2 found on apical surface of the epithelium in the lung, arteries, heart, kidney, and gut
once coronavirus binds to ACE2, complex internalizes into the cytoplasm via endocytosis
in the lung, attacks type II alveolar epithelium since it has a lot of ACE2 on the surface
disrupted type II alveolar epithelium results in reduced surfactant production –> lung malfunction
damaged type II alveolar epithelium produces multiple cytokines that recruit macrophages in the lung
mRNA vaccine
mRNA with instructions for making spike protein put into vaccine
mRNA enters the cell
virus spike protein is created
spike protein is recognized by the immune system and specific antibodies are produced
if infected, antibodies bind to the virus and stop it from replicating
sensitization
initial exposure to an allergen
allergic reaction
secondary exposure to same allergen causes more antibody binding to mast cells for release of histamine
anti-histamine
decreases vascular permeability
decreases bronchoconstriction
corticosteroids
reduce general inflammatory response
epinephrine (adrenaline)
constricts blood vessels
intramuscular or intravenous injection
autoimmune disease
immune system mistakenly attacks your body
foreign antigens that are similar to human antigens can be a trigger
- body makes antibodies BUT antibodies have enough cross-reactivity with human tissues to do some damage
multiple sclerosis
white matter of the brain and spinal cord
rheumatoid arthritis
joint lining
type 1 diabetes
the pancreas
lupus
kidneys and other organs
guillan barre syndrome
peripheral nerves
rheumatoid arthritis treatment
stimulation of the vagus nerve prevents cytokine production which reduces activation of cells which traffic to the joint
immune checkpoint inhibitor
PD-L1 on tumor cells
PD-1 on T cells
binding of PD-L1 to PD-1 keeps T cells from killing tumor cells
blocking this binding allows the T cells to kill tumor cells
- can be accomplished by inhibiting either PD-1 OR PD-L1
in the case where it is inhibited, the T cell receptor and antigen bind, but PD-L1 and PD-1 do not
chimeric antigen receptor T (CAR-T) cell therapy
white blood cells including T cells are separated out and the rest of the blood is returned to patient
T cells are engineered to find and kill cancer cells
- inactive virus inserts genes into T cells
- genes cause T cells to make CARs (special receptors) on their surfaces
- modified T cells are multiplied until there are millions of these attacker cells
CART cells put back into patient’s blood to make space and continue to multiply
CART cells identify the cancer cells with target antigens and kill them; remain in the body to prevent reemergence of cancer
CRISPR-editing for allogenic CAR-T therapy
knocks out MHC 1 and TCR for prevention of immuno-response
