Lecture 11 - Immune System Flashcards
Three Stages of Defense
- recognition phase
- organism distinguishes from self and non-self - activation phase
- recognition leads to mobilization of cells and molecules to fight the invader - effector phase
- mobilized cells and molecules destroy the invader
Two Types of defense mechanisms
- Innate immune system
- nonspecific defenses
- first line of defense
- recognize a broad class of organisms or molecules
- act very rapidly (minutes to hours)
- several forms (skin, molecules toxic to invaders, phagocytotic cells that digest invaders) - adaptive immune system
- specific defenses
- aimed at specific pathogens
- slow to develop (days, weeks) and long lasting
- humoral immune response (b-cells produce antibodies)
- cellular immune responce (killer t cells)
Innate Immune System In General
- nonspecific defenses
- first line of defense
- “ready to go”
- recognize a broad class of organisms or molecules
- act very rapidly (minutes to hours)
- several forms (skin, molecules toxic to invaders, phagocytotic cells that digest invaders)
Adaptive Immune system
- specific defenses
- aimed at specific pathogens
- slow to develop (days, weeks) and long lasting
- humoral immune response (b-cells produce antibodies)
- cellular immune responce (killer t cells)
Lymph
- fluid in intracellular spaces throughout the body that circulates through lymphatic vessels
- when blood exchanges nutrients and metabolites with tissue, it does so via the interstitial fluid
- some of the fluid is reabsorbed into blood vessels
- some is collected into lymph capillaries where it moves slowly through vessels of lymphatic system as lymph
Lymph Nodes
- sites along lymph vessels that contain white blood cells embedded in connective tissue
- as lymph passes through a lymph node, white blood cells encounter foreign cells and molecules that have entered the body and can initiate an immune response
White blood cells
several types
- circulate through blood and lymph
- originate from stem cells in bone marrow
Types:
- phagocytes (macrophages, dendritic cells)
- Lymphocytes (b cells, t cells, natrual killer cells)
Antibodies
- proteins that bind specifically to certain substances that are non-self
- can inactivate the pathogen
- can act as a tag to make it easier for immune system to attach
- produced by b cells
Major histocompatibility complex
- proteins found on surface of most cells of the body
- self-identifying labels
- can present non-self substances
- coordinate interactions between lymphocytes and macrophages
T cell Receptors
- membrane bound proteins on surface of t cells
- recognize and bind to non-self substances presented by MHC molecules on surface of other cells
Cytokines
- soluble signaling proteins that are released by many cell types
- bind to cell surface reseptors
- can activate or inactivate B cells, macrophages, T cells
Physical Barriers of the innate immune system
SKIN
- difficult for pathogens to penetrate skin
MUCUS
- traps airborne microorganisms
- contains the enzyme lysozome (destroys bacteria by breaking down their cell walls)
- contains the peptide defensin (hydrophobic peptides that insert into cell wall of microorganism and make the membranes permeable)
TEARS, SALIVA
- lubricate and cleanse
GASTRIC JUICE
- very acidic (HCl)
- proteases
cellular and chemical defenses of innate immune system
once pathogen has penetrated the body, it encounters defenses such as the activation of defensive cells and secretion of various defensive proteins
- compliment proteins
- interferons
- normal bacterial flora of the body
- phagocytes
- natural killer t cells
Compliment Proteins
- more than 20 different proteins
- bind to microbe to help phagocytes recognize and destroy it
- activate inflammation response and attract phagocytes to site
- lyse invading cells
interferons
- type of cytokine
- increase resistance of neighboring cells to infection
- stimulate cells to hydrolyze bacterial or viral proteins
- inhibit viral replication if cells are subsequently infected
Normal Bacteria Flora
(defensive cells)
- some bacteria normally live in our body without causing disease
- compete with pathogens for space and nutrients
phagocytes
(defensive cells)
- Ex: macrophages
- pathogenic bacteria and viruses can be recognized by phagocytes and ingested
Natural killer cells
(defensive cells)
- type of lymphocyte
- can distinguish virus-infected cells and some tumor cells from thrig normal counterparts
- initiate apoptosis or lysis of these target cells
Defense from inflammatory response
- coordinated defense response to infection or injury
- tissue damage recruits mast cells
- mast cells release histamine and prostaglandins (cause blood vessels to dilate and become leaky –> heat and inflammation)
- complement proteins leave blood vessels and attract phagocytes
- phagocytes engulf invading pathogen and dead cells
- produce cytokines (signal barin to produce fever, stimualtes immune cell production and function)
Why is inflammation painful?
- increased pressure due to swelling
- prostaglandins increase sensitivity of nerve endings to pain
- aspirin: inhibits prostaglandin synthesis
Four main features of the adaptive immune system
SEPCIFICITY
- antibodies (produced by B-cells) and t-cell reseptors recognize and bind to sepcific sites (epitopes) on sepcific pathogens –> antigens
DISTINGUISHING SELF FROM NON SELF
- important to not attack the cells of the own body
- aby b or t cells that show potential to mount immune response against self-proteins are killed early on in that cells development
DIVERSITY
- pathogens can take many forms (many strains of ciruses, bacteria, protistsm fungi, parasites)
- humans can respond to ~ 10 million different atigens
IMMUNOLOGICAL MEMORY
- after responding to a particular pathogen once, immune system can respond more rapidly and powerfully to the same threat in the future
Two Major Types of Specific Responses (Adaptive immunity)
HUMORAL IMMUNE RESPONSE
- produces antibodies
- with goal of destroying the pathogen itself
- main player: B-cells (produce antibodies)
CELLULAR IMMUNE RESPONSE
- destrosy infected cells
- main player: cytotoxic (killer) T cells
- operate simultaneously
- share many mechanisms
Antigen Presentation and Helper T Cells
first step in adaptive immunity
(first step for both humoral and cellular response)
Antigen presenting cell (APC)
- includes dendritic cells and macrophages
- T-cells cannot recognize free-floating antigen
- APCs capture antigens and enable their resognition by “presenting” them
- antigen is take up by an APC cell and processed (digested)
- a piece of this digested pathogen (antigen) is displayed by the APC outside the APC cell on a major histocompatibility complex (MHC molecule)
T Helper Cell
- binds to the antigen on APC
- releases cytokines
- Th cell stimulates both the humoral and cellular immune responses
Major histocompatibility complex (MHC) proteins present antigens (second step in adaptive)
- cell surface protein that presents antigens to T cells
- T-cells only recognize presentation of non-specific cells
- aldo used to ID whether the cell itself is from the host (many different MHC alleles, transplant rejection)
Types of MHC cells
Class I MHC Complex
- present on surface of all cells in the body
- when cellular proteins are degraded, fragments are carried to plasma membrane and presented on MCI outside of cell
- sampling of all components in the cell, normal or not
- detects infections of mutations
- recruits cytotoxic (killer) T cells
Class II MHC compelx
- found on surface of APCs
- when the APC ingests a pathogen through phagocytosis, the pahtogen is broken down and a fragment is carried to the cell surface
- recruits helper T cells
Humoral Immune Response
- B cells make antibodies (can secrete them or express them on cell surface, bind to specific antigen)
- first time antigen is encountered, it is detected by binding to the antibody receptors on the B-cell surface (with help from Th cells)
- activates B-cell to make and secrete multiple copies of the antibody
Antibodies
- all have a common structure
- tetramer of 4 polypeptide chains
- two are identical light chains
- 2 are identical heavy chains
Each chain has 2 regions
- constant regions
- shared amino acid sequences
- determine whether it will be an integral membrane receptor or a soluble antibody secreted into the blood stream - variable regions
- different for each type of antibody
- specificity of antigen binding
- two identical antigen binding sites on each antibody
Selective proliferation of B-cells
- one B-ell makes a specific type of antibody
- enormous diversity of different B-cells exist, each of which makes a different type of antibody
- one antibody reacts with a specific antigen
Proliferation
- when an antigen binds to a B-cell, it (with Th cells) stimulates it to proliferate to form a group of identical C cells
- all of these clones produce and secrete antibpdies with that same sepcificity as the activated B-cell
Humoral Immune Response: Part I
Activation: sepcific Th cells are activated and proliferate
- APC presents antigen via Class II MHC complex
- T helper cell binds to APC
- specific receptor that binds specific antigen
- Th cell releases cytokines
- cytokines activate Th cell to proliferate, producing clones of Th cells with the same specificity
Humoral Immune Response: Part II
Effector phase: activated Th cells activate specific B cell to proliferate and produce antibodies for secretion
B Cells act as APCs
- B cells have antibodies bound to cell surface that serve as receptors to which antigens can bind
- pathogen binding to this antibody is internalized and broken down and antigen is displayed by MHCII complex of B cell
- activated Th cell binds to a Bcell that is presenting the correct antigen (same antigen as it originally encountered in the initial APC)
- cytokines released by Th cells activate B cells
- activated B-cell proliferates and synthesizes antibodies
Humoral Immune Response Part III
Th cell stimulates B Cell to divide, differentiate and produce antibodies
Gives rise to two types of B cells:
- effector B cells (plasma cells)
- secrete antibodies into bloodstream
- all effector cells arising from a given B cell produces antibodies that are specific for the antigen that originally bound to the parent B cell - Memory cells
- long lived stand by’s that are ready to amp-up the immune system quickly if re-exposed to a pathogen
- allow for lasting immunity against pathogen
Antibody function
OPSONIZATION
- antibody stimulates removal of pathogen by macrophages
- tag a microbe or an infected cell for phagocytosis
NEUTRALIZE TARGET
- block pathogen’s ability to enter cells
AGGLUTINATION
- link pathogens together into large complexes
- become easy targets for phagocytes
TRIGGERING OTHER IMMUNES PATHWAYS SUCH AS COMPLEMENT SYSTEM
- marks pathogen for phagocytes
- helps kill the pathogen directly
Cellular Immune Response Part I
- cell that has been infected by a virus or undergone mutations will contain foreign or abnormal peptides
- will present these on cell surface as Class I MHC complex
- Cytotoxic T cells recognize and bind to this comples
- Tc cell activation and growth is promoted by activated T cells
- activation of a specific T cell triggers selective proliferation of that type of T cells
- these activated Tc cells now bind to any cell tha tis displaying an antigen on its Class I MHC receptor (and therefore is infected)
Cellular Immune response Part II: TC cells kill infected cells
CELL LYSIS
- activated Tc cells produce a substance called perforin
- peprforin lyses the cells that the Tc cell has bound to via MHC I complex
PROGRAMMED CELL DEATH
- Tc cells can also bind to a different receptor on the target cell that initiates apoptosis in that cell
- work together to eliminate antigen containing host cell
- help rid body of its own virus-infected cells
What allows for long Lasting Immunity
- activated lymphocytes (B or T cells) divide and differentiate to produce two types of daughter cells
EFFECTOR CELLS
- carry out attack on antigen
- effector B cells secrete antibodies
- effector t cells secrete cytokines and other molecules that destroy pathogen cell
- only live a few days
MEMORY CELLS
- long lived cells
- retain ability to start dividing on short notice to produce more effector and memory cells
- many survive in body for decades
Two stages of immune response to an antigen
- Primary
- when body first recognizes an antigen, naive lymphocytes that recognize the antigen proliferate
- lag time - takes a while for number of B and T cells to slowly increase - Secondary
- subsequent encounters with the same antigen
- memory cells bind antigen and rapidly proliferate
- launch army of B and T cells
- much more rapid and powerful response
Where does immunity come from?
- can come from previous exposure to pathogen
- can come from vaccines
Immunity from Vaccines
introduction of the antigen into the body in a form that doesnt cause disease
Ways:
INACTIVATION
- kill pathogen with heat or chemicals
ATTENUATION
- live but not toxic
- cultured in the lab to get mutations that make it harmless
PEPTIDE SUBUNIT
- recombinant DNA technology
- do not introduce a whole microorganism to the immune system, just a part of the antigen protein
- peptide fragments that can bind and activate lymphocytes but do not have the harmful part of a protein
Then:
- initiate primary immune response, generating memory ells without making the person ill
- memory cells already exist if person encounters pathogen later
What happens when the immune system malfunctions?
- overreact (allergic reaction)
- attack self antigens (autoimmune)
- function weakly (immune defficiency)
Allergic reaction
- immune system overreacts to a dose of antigen
- exposure to an antigen causes B-cells to make a large amount of a specific type of antibody that takes up residence in cell membrane of mast cells
- if individual is re-exposed to that allergen, the allergen binds to these antibodies on the mast cells
- causes the mast cells to secrete a large amount of histamine
- dilation of blood vessels, inflammation
autoimmune disease
T cells or antibodies that bind self-antigens
- during development of lymphocytes, cells that make antibodies against self antigens that should have been destroyed were not
- molecular mimicry - T cells that are designed to recognize a non-self antigen may accidentally recognize something in he self antigen that has a similar structure
Immune deficiency disorder
- highly vulnerabel to infections and cancer
- B or t cells never form
- B cells lose ability to give rise to effector cells
- HIV (aids)
- infects and destorys helper T cells
- killed by both the virus itself and Tc cells the destroy infeted cells
Examples of autoimmune disease
Lupus
- b cells produce antibodies against the body’s own nuclear proteins
rheumatoid arthritis
- inability to shut down a t cell response
- inflammation in the joints
hashimoto’s thyroiditis
- immune cells attack thyroid tissue, resulting in fatigue, depression, weight gain
type i diabetes
- immune reaction against cells in pancreas that produce insulin
MS
- immune system attacks and damages myelin
myasthenia gravis
- antibodies block acetylcholine receptors on muscle cells
- muscle weakness
