Micro Exam 3 (CH. 15,16,17)
What are Mechanisms of Pathogens to avoid antibodies?
+IgA protease: cleaves mucosal IgA, slows rush of antibodies toward pathogen, produced by Neisseria Gonorrhoeae +Antigenic variation: alter surface antigen through gene switching to stay ahead of antibody production. Allows pathogens to buy time to multiply and do damage. -EX. Neisseria Gonorrhoeae varies antigenic structure of pili, Antigenic shift of Influenza virus +Rapid turnover of Pili: Shed any bound antibody -EX. Neisseria Gonorrhoeae +Mimicking host molecules: cover surface with molecules similar to those found in host cell so they appear to be "self" -EX. Streptococcus pyogenes form capsule with hyaluronic acid, a polysaccharide found in human connective tissues such as cartilage
How is the Lectin pathway activated (complement system)?
+Lectin pathway is activated by mannos binding lectin binding to mannos on a pathogen, and they split c2 into c2a and c2b, and c4 into c4a and c4b. Then c2a and c4b join together and act as c3 convertase (remember c3 convertase is a functional property of complement proteins that can come together and split c3).
What is the Adaptive Immune System?
-Acquired specific Immunity -Specific recognition and memory -Composed of: -Third-Line Defenses: Destroy invader and memorize response (humoral and cellular immunity)
What is the Innate immune system?
-Immediate, non-specific immunity -No learning process or memory -Composed of: -First-line defenses: block or neutralize entry (Skin, mucous membranes, antimicrobial substances) -Sensor Systems: Detect Invasion -Second-Line Defenses: Slow or destroy Invader (Inflammation, fever, phagocytes)
The antibodies found in mucus, saliva, and tears are:
IgA
The presence of which of the following indicates a current new infection rather than a previous infection or vaccination? IgG IgE IgM IgD IgA
IgM, IgM indicates plasma B cell antibody production while IgG indicates memory B cell antibody production
What is the function of Helper T cells?
Immune cells that secrete cytokines to activate other immune cells such as B cells with a T-dependent antigen by secreting cytokines.
Which of the following is an effect of opsonization? increased diapedesis of phagocytes increased margination of phagocytes inflammation cytolysis increased adherence of phagocytes to microorganisms
Increased adherence of phagocytes to microorganisms
What is the difference between intoxication and infection?
Intoxication is caused by toxin itself, while infection is caused by bacteria. Know we can ingest toxin without ingesting the bacteria, in that case we would have intoxication.
Antigen processing and presentation is the way foreign cells engulf macrophages. is a way for viruses to infect cells. is a way for a cell to give information about its activities. is only accomplished by bacterial cells.
Is a way for a cell to give information about its activities
What composes the lymphatic system?
Lymph fluid + Primary and Secondary Lymphoid Organs +Primary Lymphoid Organs: Bone marrow and Thymus -Site of lymphocyte production and maturation +Secondary Lymphoid Organs: Sites throughout body where lymphocytes gather and contact antigens: -EX. lymph nodes, spleen, tonsils, adenoids, SALT, MALT (peyer's patch) -SALT = Skin Associated lymphoid tissues MALT = Mucousa Associated lymphoid tissues ex. Peyer's patch (MALT in intestine) SALT/MALT are responsible for sampling the content of the lumen of that tissue, making sure there are no pathogenic organisms in the lumen of that tissue +Inflammatory response causes more fluid to enter tissues; thus increases antigen-containing fluid entering lymphatic system, working innate system leads to lots of inflammation which builds up required precursors for adaptive response
How does the lymph aid in B and T cells finding their antigen?
Lymph node is where most B and T cells are collected. B and T cells are then exposed to lymph (fluid of lymph nodes). This is because most fluid that goes through our body is going through the lymph of the lymphatic system, and the B-cell can find matching antigens by staying in the lymph.
What is MALT and Peyer's Patch?
MALT = mucosa associated lymphoid tissue, think of it as a terminal lymph node, a lymph node that ends in the tissue. Peyer''s patch is an example of a malt that is in the small intestine.
What are MHCs?
MHC are proteins in the cytoplasm of our cells, they can pick up antigen in our cell and present it on the outside of the membrane for a T cell to bind.
Heparin is a naturally occuring anticoagulant produced by skin cells. eosinophils. macrophages. mast cells and basophils. neutrophils.
Mast cells and Basophils
What are leukocidins? Molecules that are capable of destroying phagocytes Molecules that destroy the complement proteins Molecules that can degrade IgA
Molecules that are capable of destroying phagocytes
How does the number of virulence factors correlate with the ID50 of a pathogen?
More virulence factors a pathogen has, the lower ID50 it will have as it requires less microbes to actually cause infection as it has more tools needed to overcome immune system and cause infection.
Polio is transmitted by ingestion of water contaminated with feces containing polio virus. What portal of entry does polio virus use? skin only skin and parenteral skin, parenteral, and mucous membranes parenteral only mucous membranes only
Mucous membranes only
What are Lymphocytes (lymphocytes include T + B + NK cells) ?
NK cells target infected body cells and tumor cells by releasing toxic substances (perforins or granzymes) from granules -Note: NK cells and Cytotoxic T cells both break down infected host cells and body cells, but NK cells are innate and non-specific while T cells are not -T and B cells are highly specific, play a key role in adaptive immunity -Lymphocytes target our OWN cells while AMPs target other cells
Are Exotoxins fever producing?
NO, only endotoxins are fever producing
Do the first line defenses of immunity have to be triggered?
NO, they are innate, always present (ex. skin, mucous membranes, antimicrobial substances, Normal microbiota/Flora)
Which of the following cells is NOT an APC? natural killer cells dentritic cells macrophages mature B cells None of the answers is correct; all of these are APCs.
Natural Killer cells
What is an example of serum resistant bacteria that can avoid being killed by complement proteins?
Neisseria Gonorrhoeae
Which pathogen uses Antigenic variation to avoid antibodies?
Neisseria Gonorrhoeae
Which pathogen uses rapid turnover of pili to avoid antibodies?
Neisseria Gonorrhoeae
What is Colonization?
Organism establishing itself in the host: Attachment & Growth, Normal microbiota (commensals) and pathogens (infectious) colonize
What does a phagocyte attach to on a microorganism? PAMPs PRR Nucleus TLR
PAMPs
What is the Big Picture of the Immune System?
Pathogens (Viruses, Bacteria, Fungi) -> First Line Defenses (Skin, mucous membranes, antimicrobial substances) -> Second Line defenses (Inflammation, fever, phagocytes) -> Third Line defenses (Humoral and Cellular Immunity)
What is produced by the process of clonal expansion? Plasma cells Memory B cells Plasma cells and memory B cells Plasma cells, T cells, and memory B cells
Plasma cells and memory B cells
What is Pus, Scars, Abcess, Scabs, clotting factors?
Pus: mostly the accumulation of dead neutrophils and phagocytes, as well as other debris. Scars don't occur if damage is only to the epidermis, may occur if damage occurs to the dermis. Abcess: when pus starts filling up a deeper wound. scab: dried out clot made from clotting factors (platelets) Clotting Factors: platelets
What are Pyrogens and what are the different types of Pyrogens?
Pyrogens are substances which cause fever when introduced into blood -Endogenous pyrogens: are cytokines (interleukins) -Exogenous pyrogens: such as LPS of Gram negative bacteria
How is the Complement System regulated?
REGULATION: Host cells have Complement Regulatory Proteins on their surfaces that neutralizes other complement proteins and prevent complement system activation against self -This prevents opsonization, inflammation, cytolysis of our own cells
Which pathogen prevent phagosome-lysosome fusion to avoid destruction?
Salmonella Mycobacterium tuberculosis Chlamydia trachomatis
Which of the following is NOT a step used by cytotoxic T cells to kill infected host cells? Secretion of granzyme Secretion of perforin Secreting antibody specific against the pathogen. Recognition of infected host cell using its TCR
Secreting antibody specific against pathogen
Which pathogens are known for hiding within the host cell?
Shigella and Salmonella
Which pathogen escapes from phagosome prior to fusion with lysosome to survive within phagocytes?
Shigella species cause lysis of phagosomal membrane
Which pathogens use Fc receptors to avoid adherence?
Staphyloccocus aureus Streptococcus pyogenes
Which pathogens use capsules to avoid adherence?
Streptococcus pneumoniae, Haemophilus influenza, Bacillus anthracis, Yersinia pestis
TLRs attach to all of the following EXCEPT PAMPs. AMPs. LPS. flagellin. peptidoglycan.
TLRs= Toll like receptors attach to all of the following except AMPs
Which of the following statements is FALSE? The constant region of a heavy chain is the same for all antibodies. The variable region of a light chain is partially responsible for binding with antigen. The variable region of a heavy chain is partially responsible for binding with antigen. The Fc region may attach to a host cell. All of the answers are correct.
The constant region of a heavy chain is the same for all antibodies. The constant region of a heavy chain is the same for antibodies WITHIN A CLASS not ALL.
Which of the following best characterizes clonal selection? The production of identical T cells producing the same antibody The production of identical B cells producing the same antibody The production of identical B cells producing different antibodies The production of different antigens by the same B cell
The production of identical B cells producing the same antibody post activation (antibody recognizing its antigen)
What is true of antibodies that have shorter half-lives in serum?
They are more likely present in tissue -ex. IgE has shortest half life of 2 days while IgG has longest of 23 days
What is the role of opsonins? They attract phagocytes to the location of infection. They aid in the formation of the phagolysosome. They are present on the surface of phagocytes to facilitate adherence and ingestion. They create "handles" that make it easier for the pseudopods of phagocytes to attach to the microbe invader.
They create "handles" that make it easier for the pseudopods of phagocytes to attach to the microbe invader.
All of the following are true regarding NK cells EXCEPT they are a type of lymphocyte. they release toxic substances that cause cell lysis or apoptosis. they destroy infected body cells by phagocytosis. they have the ability to kill infected body cells and some tumor cells.
They destroy infected body cells by phagocytosis
Normal microbiota provide protection from infection in each of the following ways EXCEPT they produce antibacterial chemicals. they produce lysozyme. they make the chemical environment unsuitable for nonresident bacteria. they compete with pathogens for nutrients. they compete with pathogens for space and adherence.
They produce lysozyme
Superantigens produce intense immune responses by stimulating lymphocytes to produce endotoxins. leukocidins. exotoxins. cytokines. interferons.
cytokines
Bacteria such as E. coli and Salmonella produce invasins that bind host cells, thus causing the cells to
engulf the bacteria
Phagocytes utilize all of the following to optimize interaction with (getting to and getting hold of) microorganisms EXCEPT complement. lysozyme. trapping a bacterium against a rough surface. opsonization. chemotaxis.
lysozyme
Endotoxins are associated with gram-positive bacteria. molecules that bind nerve cells. excreted from the cell. part of the gram-negative cell wall. A-B toxins.
part of the gram-negative cell wall
What is the difference between perforins (toxin) released by lymphocytes and AMPs?
perforins create hole in cell membrane, this is different than AMPs because perforins are creating a hole in OUR OWN cell membrane such that apoptosis is triggered. These lymphocytes are targeting OUR cells, not pathogens like AMPs Perforins are toxins used to break down our own cells
Which is NOT specifically employed by pathogens to avoid destruction by phagocytosis? producing a capsule forming biofilms possessing ability to replicate within a phagolysosome producing superantigens possessing ability to remain dormant within a phagocyte
producing superantigens
What are the names of the steps of the humoral Immune response?
1. Maturation: Stem cells differentiate into Mature B cells, each bearing surface immunoglobulins (antibodies) against a specific antigen 2. Clonal Selection: B cell encounters its specific antigen and proliferates, this leads to clonal expansion 3. Clonal Expansion: the proliferation of the activated B cell to give us memory cells and Plasma cells to create antibodies. these memory cells can be stimulated at a later date to become antibody-producing plasma cells. -Memory cells likely have IgG antibodies on them -Plasma cells likely have IgM antibodies on them 4. Plasma cells secrete antibodies into circulation
Correctly order the steps involved in cellular immunity: 1.The activated Tc recognizes the infected host cell 2.The Tc recognizes and interacts with epitope presented by MHC-I on the dendritic cell 3.The Tc secretes perforin and granzyme, causing apoptosis of infected cell 4.The helper T cell activates the Tc cell 4,2,1,3 2,1,3,4 2,4,1,3 1,2,4,3
2413
What type of exotoxin are Botulism, Tetanus, and Diphtheria related with?
A-B Exotoxin
Which of the following is NOT a membrane-disrupting toxin? A-B toxin leukocidin streptolysin S streptolysin O hemolysin
A-B Toxin
What are the steps of the Cell-Mediated Immune response (adaptive immune response?
Activated by INTRACELLULAR antigen presented on MHC 1. Antigen engulfed by antigen-presenting cell and displayed on MHC 2. Cytotoxic T cell binds antigen on MHC 3. Cytotoxic T cell creates active cytotoxic T cells and memory cytotoxic T cells 4. Cytotoxic T cells defend against intracellular pathogens and cancer by binding to and initiating apoptosis in infected cells or cancer cells
Which of the following is NOT a step that ultimately leads to antibody production? Immature B cells conducting surveillance for foreign epitopes Activation of cytotoxic T cells by helper T cells Differentiation of plasma B cells
Activation of cytotoxic T cells by helper T cells, this is because cell-mediated immunity doesn't produce antibodies
What must a pathogen do directly after entering an organism?
Adhere in order to Establish Infection. Adherence is the first step of infection
How is the Alternative Pathway activated (Complement system)?
Alternative pathway activated by factors B, D, P binding to microbe, and splitting c3 into c3a and c3b
What is meant by the clonal expansion of a B cell? An activated B cell divides into cells that give rise to memory B cells and plasma cells. An activated B cell will secrete perforin. An activated B cell will kill infected host cells. An activated B cell will engulf and digest anything foreign.
An activated B cell divides into cells that give rise to memory B cells and plasma cells
What is a subclinical disease?
An illness that is staying below the surface of clinical detection +Know that more than 50% of patients who get gonorrhea get subclinical disease, where to continue carrying the pathogen while not showing symptoms. Chlamydia is similar (70% of patients).
How do MHCs relate to APCs?
Antigen presenting cells will possess Major Histocompatibility Complexes which T cells will bind to
What are BCR and TCR?
B cell receptor = BCR T cell receptors = TCR -BCR or TCR are both antigen receptors BCR or TCR are antigen receptor embedded into cell membrane of B or T cell. Hundreds of BCR/TCR receptors on surface. All BCR/TCR receptors are specialized to recognize a very specific antigen/epitope. Pathogens have several antigens who are each made of several epitopes, there is a specific Antigen receptor by some B/T cell that recognizes the antigen/epitope. Epitope=antigenic determinant Antigen = combination of epitopes
Which pair of molecules do NOT directly interact with one another? CD8 and MHC-I CD4 and MHC-II BCR and epitope BCR and TCR
BCR and TCR
Which of the following statements concerning phagocytosis is true? Phagocytes ingest microorganisms by using protein transporters that are specific to the bacteria. Bacteria are digested when the phagosome fuses with a lysosome. Adherence always requires opsonization. Phagocytes cannot ingest microorganisms unless they are coated with antibodies.
Bacteria are digested when phagosome fuses with a lysosome to form phagolysosome
Botulism is caused by ingestion of a proteinaceous exotoxin; therefore, it can easily be prevented by preventing fecal contamination of food. boiling food prior to consumption. not eating canned food. administering antibiotics to patients. filtering food.
Boiling food prior to consumption
What is the mechanism and disease of Clostridium Botulinum bacterium?
Botulism, Neurotoxin prevents transmission of impulses; flaccid paralysis results
What does C3a do?
C3a is a pro-inflammatory mediator that induces changes that contribute to local vascular permeability to increase and attract phagocytes. Causes inflammation.
What are the two main CD subsets in T cells?
CD8 which are coreceptors for Tc CD4 which are coreceptors for Th
Which of the following is mismatched? abscess - a cavity created by tissue damage and filled with pus scab - dried blood clot over injured tissue pus - tissue debris and dead phagocytes in a white or yellow fluid diapedesis - movement of leukocytes between capillary walls cells out of blood and into tissue chemotaxis - chemical degradation inside a phagolysosome
Chemotaxis
What are the two main MHC classes?
Class I and Class II
Acidity is a mechanism of antimicrobial substances of the Innate immune system that kill most bacteria and toxins except for which notable exception?
Clostridium Botulinum toxin
What is Infection?
Colonization of the body by a pathogenic organism, which CAN result in disease (but not necessarily)
What is the mechanism of Competitive exclusion of pathogens by normal microbiota/flora and what pathogens is this especially effective against?
Cover binding/attachment sites and consume available nutrients, especially effective against: Salmonella, Shigella
Which pathogens can survive within phagolysosome?
Coxiella
What is Virulence?
Degree of pathogenicity by virulence factors
What is the mechanism and disease of Corynebacterium diphtheriae bacterium?
Diphtheria, Cytotoxin inhibits protein synthesis, especially in nerve, heart, and kidney cells
What are examples of Production of toxic compounds by Normal Microbiota?
E. coli synthesizes colicins in intestine (bacteriocins) Lactobacillus produce lactic acid in vagina (low pH) and hydrogen peroxide (effective against Chlamydia, Candida albicans)
How can a sufficient humoral immune response occur if a plasma cell only lives for a few days? Memory B cells can also produce antibodies. Each plasma cell can produce up to 2000 antibodies every second. T cells can also produce antibodies. Each plasma cell can proliferate into more plasma cells.
Each plasma cell can produce up to 2k antibodies
Which of the following would be the first sign of an infection that resulted in the release of endotoxin? Weakness Nausea Pain Fever
Endotoxins cause release of prostaglandins which will cause fever
If one is examining a blood smear from a patient with a parasitic worm infection, which of the following leukocytes would be found in increased numbers? lymphocytes basophils eosinophils monocytes
Eosinophils
What is the difference in Chemistry of exotoxins and endotoxins?
Exotoxins are usually PROTEINS, usually with two parts (A-B) (AB toxins exert their effects after entering host cell) Endotoxins are LIPID portion (Lipid A) of LPS of outer membrane
What is the difference in bacterial source between Exotoxins and Endotoxins?
Exotoxins from both G+ and G- bacteria, Endotoxins from ONLY G- bacteria
Which of the following statements about fixed macrophages is FALSE? They are mature monocytes. They are found in certain tissues and organs. They gather at sites of infection. They develop from neutrophils. They are cells of the mononuclear phagocytic system.
they develop from neutrophils
An example of a TLR would be peptidoglycan found in the cell wall of gram-positive bacteria. True False
False, This is an example of a PAMP
What are First-Line defenses?
First line defenses block entry through inside and outside physical and chemical barriers, we mainly focus on: 1. Skin 2. Mucous Membranes 3. Antimicrobial Substances & Normal Microbiota/Flora -Also other first-line defenses: Tears (Wash away microbes, lysozyme in tears), Large intestine (Flora protect invasion), Saliva (wash microbes away), Respiratory Tract (Mucous traps microbes, cilia sweep away trapped microbes), Stomach (acid kills organisms), Bladder (Urine washes microbes from urethra) -Part of Innate immune system
What are the portals of exit for a pathogen?
Generally the same as the portals of entry: -Mucous membranes -Skin -Parenteral route
What do Hematopoietic Stem Cells form after Hematopoesis?
Hematopoesis: division and differentiation of more cells from hematopoetic stem cell +Hematopoietic stem cells divide into Myeloid and Lymphoid Stem cells which then form red and white blood cells +Hematopoietic Stem cells are found in bone marrow
What are characteristics of Blood Cells?
+Blood cells originate from hematopoietic stem cells in bone marrow from a process called hematopoiesis -Always found in normal blood (#s change during infections) -Move around body, travel through circulatory systems -Can move against flow of blood or lymph to reach infection site -Can move through walls of capillaries (diapedesis/emigration) -Some reside in specific tissues -Three general cell categories from hematopoiesis: 1. Red blood cells (RBC/erythrocytes) which function in transport 2. Platelets (thrombocytes) which function in regulation 3. White blood cells (WBC, leukocytes) which function in protection
What is the difference between B and T cell development?
+Both begin at hemapoietic stem cell in bone marrow, which then differentiates into either B cell or T cell +HSC differentiates into B cells in adult bone marrow but HSC differentiates into T cells in thymus +Maturation then occurs to create Naive B and T cells +Naive B and T cells migrate to lymphoid tissue such as spleen, but especially LYMPH nodes where they wait until they are activated by their specific antigen and cause an immune response -Note: B and T cells typically carry many antibodies on their surface which bind to specific antigens
What does C3b do?
+C3b can act as an opsonin (opsonizing particle) and bind to microbial cells and cause opsonization -c3b is not only opsonin, ex. lectin is also opsonin +C3b can combine with other complement proteins to form C5 convertase, which splits c5 into c5a and c5b
How can Exotoxins be neutralized?
+Can be neutralized by antibodies (antitoxins) generated by host -Many fatal before adequate immune response -Toxoids are altered toxins used as vaccine (EX. Diphtheria and Tetanus) -DTAP vaccine = Diphtheria, Tetanus, Acellular pertusses vaccine
What is the difference between Direct and Indirect Damage to the Host?
+Indirect Damage: Immune response against pathogen indirectly causes damage; inflammation, tissue damage, effector Tc cells, NK cells... -indirect damage is damage by our immune system due to it trying to fight the pathogen. damage caused by immune system while trying to kill pathogen = indirect damage. +Direct Damage: Damage caused directly by pathogens, due to attachment, invasion....and mostly, by TOXINS -Toxins: Poisonous substances that can cause intoxication
What are the steps of Lymphocyte Development?
+Lymphocytes change as they develop/encounter antigen 1. Immature lymphocytes lack fully developed antigen-specific receptors -Don't have fully developed BCR/TCR depending on B or T cell. Note: Immature lymphocytes are in Bone marrow 2. Maturation: development of antigen-specific receptors 3. Mature Naive lymphocyte: Have fully developed receptors; have not yet encountered appropriate antigen. -These lymphocytes are called naive because they are not bound to any antigen yet. 4. Activation: Binding of Mature Naive lymphocyte with antigen its specialized for is the activation step. This is when a mature naive lymphocyte becomes an activated lymphocyte. 5. Activated Lymphocytes: have bound antigen and received confirmation, are able to proliferate to: -Effector Lymphocytes: descendants of activated lymphocytes, ex. B cells, Tc and Th cells, are the ones that give us adaptive immune response -Memory lymphocytes: long-lived descendants of activated lymphocytes; responsible for rapid secondary response if antigen encountered again -Memory lymphocytes remain in body until death, will deliver rapid secondary response if pathogen encountered again
What are characteristics of IgA?
+Mostly present as dimer (secretory IgA, slgA) -Secreted from important in mucosal immunity -Found mainly in GI, Genitourinary, and respiratory tracts (where mucous is) -Protects breastfed infants against intestinal pathogens -secretory peptide helps IgA/secretory peptide it stick to base of mucous membrane and prevent it from breakdown by enzymatic reactions, helps with immobilization
What is Affinity maturation?
+Natural selection which improves BCR affinity +as plasma b cells are multiplying and synthesizing antibodies, through natural selection, BCR antigen binding site is selected to become more specific/even more strongly binding for the epitope that it's meant for
What is the significance of the Lymphatic System?
+Network providing an alternate route for tissue fluid +Colorless lymph (collection of intersititial fluid in our body) flows through lymphatic vessels, which begin as microscopic lymphatic capillaries in tissues -Allows interstitial fluid to flow in but not out -Carry many antigens through lymph nodes -Empty back into blood through subclavian vein
What are Pattern-Recognition Receptors (PRRs)?
+PRRs are receptors of sentinel cells (ex. monocytes, macrophages, dendritic cells, mucosal epithelial cells) that can detect PAMPs and trigger a response against pathogen: -Phagocytosis -Releasing Cytokines to alert and recruit immune cells -Triggering an inflammatory response -Triggering activation of complement system +PRRs are receptors on our host cells that can recognize pathogenic patterns (PAMPs) which are molecular patterns on the pathogen. -especially senitel cells and phagocytes have lots of PRRs
What are Normal Microbiota/Flora?
+Part of first line of defenses of Innate Immune system +Microorganisms colonizing body surfaces in healthy humans, preventing the overgrowth of harmful microbes, provide considerable protection and resistance to disease by: -Competitive exclusion of pathogens -Production of toxic compounds +Disruption of normal microbiota (ex. antibiotic use) can predispose to infections (ex. vulvovaginitis, Candida albicans)
What are Mechanisms of Pathogens to avoid killing by complement proteins?
+Serum resistant bacteria are bacteria that can avoid being killed by the complement proteins through: -Capsule: prevent opsonization by C3b, MAC formation, and complement activation -M protein: Inactivate C3b -C5a peptidase: degrades C5a -Complement Regulatory protein: a control molecule that neutralizes C3 -EX. Neisseria Gonorrhoeae -Inactivate C3b, prevent opsonization and postpone C5 convertase formation -Can be subclinical and progress to PID: Pelvic Inflammatory Disease
What are characteristics of the Secondary Response of the Humoral Immune response?
+Significantly faster, more effective than primary: better quantity and quality of antibodies -Secondary response is different because the pathogen is activating the memory-B cell, it doesn't need to go through antigen binding of basic B cell with Th confirmation and clonal selection etc. +Memory B cells responsible: greater # present -Receptors already fine-tuned through affinity maturation -When activated, memory B cells become plasma B cells, produce antibodies: often IgG or IgA directly due to class switching from primary response +Additional exposure to antigen yields much faster SECONDARY RESPONSE due to memory B cells formed during PRIMARY response
What are characteristics of IgG?
+Smallest Ig, can exit bloodstream into tissues -Provides longest-term protection: half life 23 days -Generally 1st and most abundant serum Ig during SECONDARY response -Only antibody transported across placenta to fetus's bloodstream -Most abundant antibody in primary and secondary response
What are mechanisms of pathogens in surviving within Phagocytes?
+Some bacteria make no attempt to avoid engulfment by Phagocytes, in an attempt to hide from antibodies and be transported to other tissues: EX. Bacillus +Escape from phagosome: prior to fusion with lysosomes, SHIGELLA species cause lysis of phagosomal membrane. +Prevent phagosome-lysosome fusion: avoid destruction . -EX. Salmonella sense ingestion by macophage, produce protein that blocks fusion process, now they can multiply safely inside phagosome -EX. Mycobacterium tuberculosis, Chlamydia trachomatis +Survive within phagolysosome: Few can survive destructive environment EX. Coxiella
What are characteristics of Basophils and Mast Cells (Granulocytes)?
+Stain blue with basic dye such as methylene blue +Involved in allergic reactions, inflammation: release heparin (blood thinner), histamine & leukotrienes (increase permeability = vasodilation), this thinning of blood and vasodilation allows for greater blood and immune cell flow to inflammation site +Similar in appearance and function to Mast cells, difference is mast cells found in tissues while basophils are found in blood, thus mast cells are typically already present at site of infection since they were already at the tissue, and can recruit other immune cells (neutrophils first, then basophils) and also act to thin blood
What are characteristics of Eosionophils?
+Stain orange-red with acidic dye +Found mostly in tissues (only found in some tissues, presence of eosinophils in certain tissues of body is a sign of disease) +Involved in allergic reactions, inflammation (limited phagocytic ability) and combatting parasites +Whenever there is a parasitic infection, an increased # of eosionophils in the blood is a sign of parasitic infection
What are characteristics of Neutrophils AKA polymorphs (Granulocyte)?
+Stain poorly -> Pale lilac +Most numerous: compose around 60% of blood WBC +1st leukocyte to reach site of infection through diapedesis +Most important in inflammation +Main function is Phagocytosis +Conduct NETosis: If neutrophils detect the pathogen is resistant to phagocytosis by neutrophils, they will conduct apoptosis and spill their (NET=neutrophil extracellular trap) which is all the contents of the neutrophil which is an attempt to overpower pathogens around it with its great # of spilled digestive enzymes/toxins which it contains. Side effect of NET release is NETosis, which is killing of host cells due to NET release
What are characteristics of the Primary response of Humoral Immune response?
+Takes 10-14 days for substantial antibody accumulation +Person may be sick although immune system actively responding +B cells undergo affinity maturation and class switching
Which CD subsets bind which MHC classes?
+Tc (CD8) bind antigen presented of MHC I of ANY NUCLEATED HOST CELL -Tc cells recognize antigens presented on MHC Class I molecules -All nucleated cells present endogenous antigens on MHC class I molecules +Th (CD4) bind antigen presented on MHC II of an ANTIGEN-PRESENTING CELL (APC= dendritic, macrophages, b cells) -Th cells recognize antigens presented on MHC Class II molecules -B cells and macrophages and dendritic cells present exogenous antigens on MHC Class II molecules CD8 always associated with TCR of cytotoxic T cell, CD4 with TCR of Helper T cell Tc = CTL (cytotoxic t cell) = CD8 are all names for cytotoxic t cell Especially know that a CD8 is a cytotoxic t cell and that CD4 is a helper T cell. -Each CD is specialized to recognize a special subset of MHC. -MHC Class I is synthesized by all nucleated cells in our body, so only red blood cells and platelets as the only cells without nuclei are the only ones without MHC Class I. MHC Class II are only made by APC (antigen presenting cells), dendritic cells, macrophages, B cells. Because these cells are nucleated, they also make MHC class I. -Cytotoxic t cells, as they only recognize MHC I, are actually attacking OUR OWN cells, but just the ones that are infected. -Whenever B cell binds to T dependent antigen, they need confirmation of helper T cell. They are able to get help because they process the antigen and present it on MHC Class II so that Th can recognize it and move the B cell along in its process. Cells with MHC Class II also have MHC Class I, so they present the antigen on both MHCs, then move to lymph node and activate both Tc and Th.
What are the Key concepts of the Second Line Defenses?
+The Complement System: Which consists of a group of serum proteins (C1-C9), can detect pathogenic components, and activate a cascade of events leading to opsonization, inflammation, & cytolysis -Activation of complement system will lead to ALL 3 -these proteins are released by liver, travel through blood.. C1-C9 are named in order they were discovered. +Phagocytosis: the ingestion (endocytosis) of microbes by phagocytes (ex: neutrophils, fixed/free macrophages, dendritic cells). -Note, not all WBCs are phagocytes: neutrophils, macrophages, dendritic cells are +Inflammation: the body's response to tissue damage and infection to help contain site of damage, localize response, eliminate invader, and restore tissue function +Fever: An abnormally high body temperature in response to infection, caused by pyrogens (endogenous vs. exogenous) -pyrogens are a substance, typically produced by bacterium that cause fever -Note. these are all second line defenses of INNATE immune system as they are not specific
What is the Significance of Fever?
+The Hypothalamus, temp-regulation center, is normally set to 37C/98.6F, but raises during infection in response to Pyrogens +Moderate temperature rise increases rate of enzymes, enhances inflammatory response, phagocytic killing, multiplication of lymphocytes, production of interferons and antibodies, & release of leukocytes from bone marrow -Slight temp rise actually makes immune system more efficient and increases its rate of function +High temperature rise may compromise older people with medical conditions, can cause dehydration, seizure in children, delirium and coma. Death occurs when body temp reaches 45C/113F.
What are the 3 major types of PRRs?
+Toll-Like receptors (TLRs) are membrane bound and monitor cell's surrounding +RIG-Like Receptors (RLRs) & NOD-Like Receptors (NLRs) are soluble and monitor cell's cytoplasm -RLRs and NLRs are based in an endosome
What are the three functional categories of Blood cells & Cells of the Immune system?
+Transportation: Erythrocyte (RBC) +Regulation: Platelets (thrombocytes), regulate through hemostasis (clotting) +Protection: All leukocytes/WBCs
What do White Blood Cell counts measure?
+WBC or Leukocyte counts measure leukocytes in blood. Leukocytes coordinate efforts in controlling infections in the second and third lines of defenses +A high or low WBC indicates infection, autoimmune disease, cancer, side-effect to medication, or other medical conditions
What are characteristics of Cytokines?
+act as "voice" of cells allowing a coordinated immune response +Regulate TIMING, INTENSITY, and DURATION of immune response +Produced mostly by immune cells to induce a response +4 groups: -Chemokines -Interferons -Interleukins -Colony-Stimulating Factors (CSFs) cytokines are chemicals used to transmit messages to other immune cells. Through communication through cytokines, a coordinated immune response between different immune cells is mounted. When immune response is supposed to stop, cytokine concentration will drop, when it's supposed to start/ongoing, cytokine concentration will be high. All immune cells have cytokine receptors.
What are characteristics of the structure of Antibodies?
AKA Immunoglobulins (Ig): Structure critical for function +Antibodies (Ab) are Y-shaped compact soluble proteins (or B-bound) with 2 arms (Fab) and a Stem (Fc) -Two copies: Heavy chain & Light chain domains joined by S-S (sulfide bonds) -Two regions: Variable region V (2 specific antigen-binding sites) and constant region C (5 functional classes: IgG, IgM, IgA, IgD, IgE). -The variability in V regions is what gives us the ability to bind different antigens and varies from one antibody to another because it recognizes a different epitope. The constant region C is consistent among antibodies of a given class -Fc is directly responsible for complement system activation while Fab portion of antibody is responsible for antigen binding. However complement system cannot occur without both Fab and Fc as Fab is needed to bind the antigen in the first place
What are Monocytes?
AKA Mononuclear phagocytes, they circulate in blood and migrate into tissues to differentiate into either Macrophages (highest phagocytic activity, kidney, liver...) or Dendritic cells (skin, mucous membranes...) -Both are Antigen-presenting cells (APCs) that act as sentinel (scouts) phagocytic cells -Macrophages are huge, have highest phagocytic (Macrophage>Neutrophil>Dendritic cell in terms of phagocytic power) -Dendritic cells have many extensions/arms that are used to scout environment of these cells
Margination refers to adherence of phagocytes to the lining of blood vessels. the adherence of phagocytes to microorganisms. the chemotactic response of phagocytes. the movement of phagocytes through walls of blood vessels. dilation of blood vessels.
Adherence of phagocytes to the lining of blood vessels
Which of the following would be an example of an infection initiated via the parenteral route? An individual contracts gonorrhea as a result of unprotected sex. An individual contracts a gastrointestinal infection by consuming contaminated water. An individual contracts a hookworm infection as a result of walking around outside barefoot. An individual contracts hepatitis B from an accidental stick with a contaminated needle.
An individual contracts hepatitis B from an accidental stick with a contaminated needle
What is another name for antibodies and what is their structure?
Antibodies are Y-shaped and have two different binding sites. Another name for Antibody = Immunoglobin (Ig)
What structure on B cells are responsible for the humoral response?
Antibodies/BCRs are responsible for the humoral response, antibodies are the ones that do the work
What is an Antigen?
Antigen (Anti-body generator): any molecule that induces an antibody response/antibody synthesis. Self antigen: an antigen(molecule) that is part of our body, ex. transplantation failure is due to self antigen in one person causing a response in another non-self antigen = immunogen, can be microbial or non-microbial. A microbial one is a bacteria or virus, a nonmicrobial antigen is an allergen (food, dust, pollen), or a vaccine is also nonmicrobial as they are psuedo-microbial / artificial . Non-self antigens can be microbial or nonmicrobial. +Immunogen: non-self molecule that elicits an immune response (microbes, vaccines, pollen), and production of highly specific corresponding antibodies +Pathogenic antigens (PAMPS) can be T-dependent or T-independent +Vaccines work because they act as an immunogen in our body
Which of the following is NOT a characteristic of cellular immunity? B cells make antibodies. Cells mature in the thymus gland. T cells interact with epitopes in MHC molecules. Response to abnormal cells. The cells originate in bone marrow.
B cells make antibodies. Cellular immunity involves Th and Tc cells, while humoral immunity involves B cells
How are Granular Leukocytes (Granulocytes) named?
Based on their staining properties
How is Virulence of a microbe measured?
By ID50 = Infectious Dose for 50% of a sample population +ID50 tells us how many units of a pathogen we need in order to cause infection, this is experimentally calculated. +Cutaneous = through the skin Inhalation = through breathing, the mucous prevents easy infection Ingestion = through eating, the acidity of the stomach prevents easy function +Low ID50 = very virulent. this is how many we need to cause infection in the host.
What are Antigen-presenting cells?
Cells that are able to take up pathogen material, chop it up, and present a sample of it on the outside of the APC, thus presenting the pathogen and playing their role in communicating to the rest of the immune cells that there is an infection and an immune response is needed. Both Dendritic cells and macrophages are APCs that act as Sentinel Phagocytic cells. THESE ARE STILL NON-SPECIFIC, IT WILL PRESENT ESSENTIALLY ANYTHING. The immune system will then determine if the presented cell is indeed a pathogen or not. ex. Macrophages and Dendritic cells every cell is able to communicate in our body, but these cells specifically APCs due to the way the present. 3 total specialized APCs in our body: Dendritic cells, Macrophages, and B cells
Unbroken skin poses a substantial barrier to microbes. All of the following contribute to this barrier except _____________. the tightly-packed layer of dead, keratinized cells complement proteins found in perspiration dryness of the skin fatty acids within sebum
Complement proteins found in perspiration
What are Interleukins?
Cytokines that activate immune cell profliferation, maturation, activation, and migration during immune response
HIV directly infects T-cells. Why is this problematic for cell-mediated immunity? HIV reprograms these cells to attack the body cells. Cytotoxic T-cells begin to attack the virally infected T-cells, reducing the number of T-cells in the body. HIV transforms the T-cells into cancer cells. HIV causes cytokines to be produced at much higher levels, altering the normal function of the immune system.
Cytotoxic T-cells begin to attack the virally infected T-cells, reducing the number of T-cells in the body.
What is the difference in pharmacology (effect on body) between exotoxins and endotoxins?
Exotoxins are specific for a specific cell structure/function in host Endotoxins are general, such as fever, weaknesses, aches, and shock; all produce same effects
Antibiotics can lead to septic shock if used to treat gram-negative bacterial infections. viral infections. protozoan infections. helminth infestations. gram-positive bacterial infections.
Gram-negative bacterial infections
What is the difference between granular (granulocytes) and agranular (agranulocytes) leukocytes?
Granular leukocytes can be seen through light microscope after staining, but agranular leukocytes cannot after staining . In reality agranular leukocytes do have granules, they are just very small/not visible with light microscope after staining Granular leukocytes have very large granules and that is why they are easily stained and seen by microscope
What is the role of helper T cells in the adaptive immune response? Helper T cells produce and secrete antibodies. Helper T cells phagocytize bacteria and viruses. Helper T cells directly kill infected host cells. Helper T cells activate B cells and cytotoxic T lymphocytes to kill infected host cells.
Helper T cells activate B cells and cytotoxic T lymphocytes to kill infected host cells.
Endotoxins are also known as interleukin-1. Lipid A. cytokines. prostaglandins.
Lipid A
Based on the animation, T cells recognized the antigen displayed by what protein of the B cell? CD4 TCR Antigen MHC BCR
MHC Class II
An antibody's Fc region can be bound by macrophages. CTLs. antibodies. T helper cells. B cells.
Macrophages
Which of the following exhibits the highest phagocytic activity? erythrocytes basophils macrophages eosinophils neutrophils
Macrophages
What is Shigellosis?
Shigella takes advantage of peyer's patch mechanism of sampling antigens. It takes advantage of M cell letting in antigens by. It gets in through the M cell and is phagocytized by macrophage. Shigella can then break out phagocyte, killing the macrophage, it then uses injectosome to inject invasins into intestinal cells, causing membrane ruffling, and then shigella can be taken into the intestinal cells. It can then use actin polymerization to move from one cell to another without ever having to leave an intestinal cell/lining. As moves from cell to cell, it kills the cell by leaving a hole in it. These dying cells release their water and thus cause diarrhea. 1. M cells take up Shigella cells and transport them across the epithelium. They multiply in the macrophages that ingest them, leading to death of that host cell 2. Shigella cells attach to the base of the epithelial cells and induce those cells to take them in. From there they escape the endosome and multiply in the cytoplasm 3. Shigella cells cause the host cell actin to polymerize. This forms an "actin" tail that propels a bacterium within the host cell, some times with enough force to move it into a neighboring cell. 4. Infected epithelial cells die and slough off. An intense inflammatory response leads to bleeding and abcess formation.
Which pathogen mimicks host molecules to avoid antibodies?
Streptococcus pyogenes
Which pathogen uses M protein to avoid adherence?
Streptococcus pyogenes
Which pathogen uses exoenzyme c5 peptidase, membrane disrupting toxins streptolysin O/hemolysin, and leukocydins to prevent encounters with phagocytes?
Streptococcus pyogenes
How do Helper T-cells explain T-independent/dependent anigens?
T-independent antigen is an antigen that does not require confirmation by a helper T-cell to activate the B cell or cytotoxic T cell. T-dependent antigen is antigen that requires confirmation of a helper T-cell to activate the B cell or cytotoxic t cell and thus the humoral/cell mediated immune responses respectively
What are the representative diseases of Exotoxins?
TETANUS, BOTULISM, DIPHTHERIA, Scarlet fever
Which of the following recognizes antigens displayed on host cells with MHC II? TH cell natural killer cell basophil B cell TC cell
TH Cell
What is the mechanism and disease of Clostridium Tetani bacterium?
Tetanus, Neurotoxin blocks nerve impulses to muscle relaxation pathway, results in uncontrollable muscle contractions
What is Pathogenicity?
The ability of an organism to cause disease by overcoming host defenses. Mechanism includes causes & effects
What complement proteins form c5 convertase?
c2bc3bc4a, or c3b and factor B
What are characteristics of endotoxins?
endotoxins are part of bacteria, endotoxin doesn't mean INSIDE bacteria, but rather a structure OF bacteria. +Within Lipid A of Lipopolysaccharide (LPS) of Gram-negative bacteria ONLY -Heat stable/resistant -Released during multiplication, lysis & antibiotic treatment, thus why killing a lot of a pathogen will make things worse before getting better as toxins must be cleared too -Symptoms worsen before improvement (fever = early sign), as liver lipases clear out endotoxins -Usually T-independent antigens -> might overstimulate immune system -Can have similar effect to superantigen, which can lead to septic shock. Whenever septic shock is caused by endotoxin specifically, we call it endotoxic shock. Endotoxic shock caused by release of TNF by macrophages which has effects as shown on slide. this drop in blood pressure can cause organ failure, brain damage, etc. +All endotoxinsProduce same signs and symptoms: chills, fever (exogenous pyrogens), weakness, and in some cases, miscarriage, shock, or even death -Endotoxic shock is a result of excess cytokine release by macrophages (Tumor Necrosis Factor TNF) which damage blood capillaries -> increase their permeability -> drop in blood pressure -EX. SALMONELLA (Salmonellosis, typhoid fever), E. Coli (UTI)
The swelling associated with inflammation decreases when the fluid is lost as perspiration. goes into lymph capillaries. is excreted in urine. returns to the blood. is transported into macrophages.
goes into lymph capillaries
All of the following are methods of avoiding host antibodies EXCEPT invasins. membrane-disrupting toxins. antigenic changes. inducing endocytosis. IgA proteases.
membrane-disrupting toxins
Which of the following contributes to the virulence of a pathogen? toxin production numbers of microorganisms that gain access to a host, evasion of host defenses, and toxin production numbers of microorganisms that gain access to a host evasion of host defenses numbers of microorganisms that gain access to a host and evasion of host defenses
numbers of microorganisms that gain access to a host, evasion of host defenses, and toxin production
How do microbes avoid/overcome host defenses?
+Although some pathogens can cause damage on the surface, most must penetrate tissues to cause disease +Through various mechanisms, and virulence factors, microbes have evolved mechanisms to avoid/overcome the host's defenses: 1. Avoiding destruction by phagocytosis 2. Avoiding antibodies 3. Avoiding the complement system 4. Hiding within a host cell
What are Epitopes?
+Antigenic determinants, epitopes are the smaller, specific piece of the antigen that our receptors bind to. +Stretches of AA/3D regions of antigen +Recognized by specific receptor (PRRs) +Bacterial cell has multitude of different epitopes +Each antibody specifically binds to one epitope Every epitope has its own antibody, has its own receptors.
What is the correct sequence of events for activation of a B cell by a T-dependent antigen? (1) The T cells bind to an antibody on the B cell. (2) The T cell secretes cytokines. (3) The B cell binds the antigen. (4) The B cell is activated by binding to the antigen. (1) Identical repeating subunits on the antigen bind to many of the antibodies on the surface of the B cell. (2) This activates the B cell. (1) Immunoglobulin receptors on the B cell recognize and bind the antigen. (2) An antigen fragment in complex with MHC class 2 is displayed on the B cell's surface. (3) The MHC-antigen complex binds a receptor on a TH cell. (4) The TH cell secretes cytokines that activate the B cell. (1) The B cell binds to a cytokine and then interacts with the TH cell. (2) This causes the B cell to bind the antigen, and then the B cell is activated.
(1) Immunoglobulin receptors on the B cell recognize and bind the antigen. (2) An antigen fragment in complex with MHC class 2 is displayed on the B cell's surface. (3) The MHC-antigen complex binds a receptor on a TH cell. (4) The TH cell secretes cytokines that activate the B cell.
What are characteristics of Adherence (Establishing Infection?
+Adherence is necessary to establish infection +Pathogens use Adhesins to attach to complementary receptors of certain host tissues -Adhesins are on the outside of the bacteria, and are used by the bacteria to bind to the host receptors. Adhesins match receptors that can only be found through some portals of entry, this is why portal of entry is very important. +Adhesins (glycoproteins or lipoproteins) on pili, fimbriae, flagella, capsule, cell wall... +Host receptors of specific tissues can recognize matching adhesins, thus pathogens have preferred portals of entry
What is the mechanism of pathogens to hide within the host cell?
+Allows avoidance of complement proteins, phagocytes & antibodies +Microbes attach to host receptor by adhesins and assemble a specialized secretion system (injectisome) to deliver effector proteins (invasins) into host that trigger actin rearrangement in the host cell cytoskeleton, leading to membrane ruffling and uptake of microbe -Used by SHIGELLA and SALMONELLA -membrane ruffling is chaos in the membrane that allows bacteria to get into the "ruffle/disorder" and allows the bacteria to sink into/ endocytose into the host cell. -note Shigella and Salmonella use injectisomes and invasins, know the examples.
What do Lymphoid Stem cells derivate into?
+3 Agranular leukocytes (WBCs): All function in protection -T cell -B cell -Natural Killer Cell +In general, all Leukocytes/WBCs function in protection +Only B and T cells are part of adaptive immune system (3rd line of defensive), all other leukocytes/WBCs are part of innate immune system
What are the different classes/Isotypes of Antibodies?
+5 classes: IgG, IgM, IgA, IgD, IgE +Have same basic monomeric structure, some form multimers +Each class has distinct functions and role in immune response +The constant region is the same for all antibodies of a particular class, but different amongst the different classes
How is the Complement system activated?
+Activated by 3 different pathways leading to the formation of C3 convertase (C2aC4B or Factors BDP) that splits C3 into C3a and C3b. +C3 convertase is a function, not a structure, C3 convertase is composed of a group of molecules (c2ac4b or Factors BDP) that come together and can now convert c3 into c3a and c3b. +This formation of C3a and C3b is what leads to outcomes of complement system (opsonization, inflammation, cytolysis) +3 different pathways: -Classical -Alternative -Lectin -All 3 pathways will lead to activation of rest of complement system and all 3 outcomes +Regulated by Complement Regulatory Protein
What are the different types of adaptive immunity?
+Active Naturally acquired immunity: Antigens enter the body naturally; body induces antibodies and specialized lymphocytes +Passive Naturally acquired immunity: Antibodies pass from mother to fetus via placenta or to the infant via milk +Active Artificially acquired immunity: Antigens are introduced in vaccines; body produces antibodies and specialized lymphocytes +Passive Artificially acquired immunity: Preformed antibodies in immune serum are introduced by injection
What does c5a do?
+Acts as pro-inflammatory mediator +Acts as chemoattractant, meaning it chemically attracts phagocytes to site of infection
What is the difference between Acute and Chronic Inflammation?
+Acute inflammation caused by short term injuries/irritants: ex. stubbing toe/chemical irritant/frostbite +Chronic Inflammation caused by long term diseases or depression. ex. cancer/depression/Autism/heart disease/Arthritis
What are mechanisms of pathogens in Avoiding Adherence (direct or indirect)?
+Capsule: interfere with complement activation, phagocytic adherence and opsonization (EX. Streptococcus pneumoniae, Haemophilus influenza, Bacillus anthracis, Yersinia pestis) -capsules have complement regulation ability, it has complement regulatory protein which allows it to bind to C3 and to neutralize it, thus preventing complement system activation and thus phagocytosis and opsonization, and thus adherence. Our host cells use this to get complement system under control. +M protein: heat and acid resistant protein, used to adhere to host cells, can inactivate c3b and interfere with opsonization (EX. Streptococcus pyogenes) +Fc receptors: bind Fc region of antibodies, invert their orientation (Ex. Staphylococcus aureus, Streptococcus pyogenes) -Fc receptor is a receptor on the bacteria that bind to Fc portion of our antibodies. Fc receptor is part of the pathogen. By binding to the Fc region of the receptor, it inverts the antibody's orientation and prevents binding of antibodies. LOOK AT DIAGRAM. Fc of antibody is what our immune system recognize as sign to carry out immune response, Fab region is what needs to bind to the pathogen itself. By binding Fc region, the pathogen prevents Fab binding and the Fc region can't bind other immune cells to ellicit a response against that pathogen, essentially making the pathogen unnoticed/marked by immune system.
What are characteristics of Cell-Mediated Immunity (Cellular Immunity)?
+Carried out by T cells, which combat intracellular pathogens (ex. viral protein within cell, phagocytized molecules) +Helper T cells (Th) and Cytotoxic T cells (Tc) have T-cell receptors (TCR), which with thecorresponding CD (Cluster of Differentiation = co-receptor), can recognize epitopes presented on MHC of other cells +TCR + CD interact with antigen only when presented on MHC -A specific CD subset can only bind with a specific class of MHC
What are characteristics of the Humoral Immune Response?
+Carried out by antibodies against free antigens +Each naive B cell carries highly specific immunoglobins/antibodies (BCRs) on its surface +Can be activated directly by a T-independent antigen, or require helper-T cell confirmation for activation by T-dependent antigen
How is the Classical Pathway Activated (complement system)?
+Classical pathway activated by antibodies binding to microbe. Two antibodies recruit a C1 which then splits c2 and c4 into c2a, c2b, c4a, c4b. c2a and c4b then function as c3 convertase and split c3 into c3a and c3b.
What does c5b do?
+Combines with complement proteins c6,c7,c8, and c9 to form membrane attack complexes (MAC) that insert into cell membranes -This complex is called a MAC complex (membrane attack complex) which insert into cell membranes of pathogens and cause cytolysis
What is true of the Skin (Physical and Chemical Barrier)?
+Difficult for Microbes to penetrate; impermeable, inhospitable +Dermis: Inner, connective tissue -Sweat, Sebaceous glands-pH +Epidermis: outer, tightly packed layers of epithelial cells -Outermost: dead, repels water, filled with Keratin, continuously shedding -Dead, dry skin in places like the bottom of your foot are important as moist skin is more hospitable to microbes, and leads to higher skin infections such as athletes foot -Part of first line of defenses of Innate immune system
What is true of Mucous Membranes?
+Epithelial layer bathed in mucous lining in digestive, respiratory, genitourinary tracts +Mucous moistens tracts while trapping & washing off pathogens, contribute to ciliary escalator and peristalsis -Ciliary escalator: Beating action of cilia of respiratory tract propels microbes upwards away from lungs -Peristalsis: Muscular contraction of intestinal wall resulting in movement of content into the rectum, resulting in defecation -Part of first line of defenses of Innate immune system
What do Myeloid Stem Cells derivative into?
+Erythrocyte (RBC), function in transport of O2 +Megakaryocyte->Platelets (fragments of megakaryocyte), platelets AKA Thrombocytes function in regulation through hemostasis (clotting) +4 Granular leukocytes (WBCs):All function in protection -Mast Cell -Eosionophil -Basophil -Neutrophil +1 Agranular leukocyte, Monocyte -> Macrophage or Dendritic celln (Both protection)
What are mechanisms of STREPTOCOCCUS PYOGENES to Prevent Encounters with Phagocytes?
+Exoenzyme c5a peptidase: degrades chemoattractant c5a, released to surrounding of bacteria, destroys c5a that's around so it can slow down chemotaxisis step of phagocytosis by preventing c5a to bind to it. +Membrane-disrupting toxins: -Streptolysin O AKA hemolysin: inserts itself into membrane of phagocyte and kills phagocyte.Is considered a hemolysin, so it can also kill eryhtroycytes -Leukocidins: inserts itself into membrane of phagocyte and kills phagocytes
How does the Immunology (relation to vaccines) of Exotoxins and Endotoxins compare?
+Exotoxins can be converted to toxoids to immunize against toxin; neutralized by antitoxin +Endotoxins not easily neutralized by antitoxin; therefore effective toxoids cannot be made to immunize against toxin
How do Exotoxins and Endotoxins compare in Toxicity (ability to cause disease) and lethal dose?
+Exotoxins highly toxic, low lethal dose +Endotoxins have low toxicity, much higher lethal dose
What occurs in the T-independent Humoral response (10% of all humoral responses)?
+Extracellular antigen binds BCRs directly and activates B cells, triggering clonal selection and expansion -Molecules with numerous identical evenly spaced epitopes can cross-link many BCRs at once -this results in a strong activation signal -No Th confirmation needed -No memory cells produced, e.g. polysaccharide capsules, LPS -T-independent antigens are NOT very immunogenic(don't result in big immune response) in young children -> more susceptible to pathogens -EX. Encapsulated bacteria Haemophilus Influenza type b (meningitis) -> Hib vaccine (1st dose) at 2 months old
What is the significance of the Complement System?
+Functions as SENSOR system and SECOND LINE DEFENSE through the complement proteins (C1-C9) activated by being split (a,b) +Complements/Enhances activities of adaptive immune system through the classical pathway +Produces 3 major outcomes: 1. Inflammatory Response: Induced by C3a and C5a 2. Opsonization by C3b -> Phagocytosis 3. Cytolysis: lysis of foreign cells by the membrane attack complexes (MACs) formed by C5b, c6, c7, c8, c9,
What are characteristics of Antimicrobial Substances (Chemical Factors)?
+Part of first line of defenses of Innate immune system, all of the following defend against pathogens -Sebum, oily secretion of sebaceous glands, (Skin, ear) rich in fatty acids, result in low pH -Lysozyme, enzyme that destroys cell walls of bacteria, (sweat, tears, saliva, urine) degrades pathogen -Acid (ex. stomach acidity) kill most bacteria & toxins, EXCEPTION: Clostridium botulinum toxin -Lactoferrin protein antioxidant (saliva, tears, mucous) protects against pathogens -AMPs: broad spectrum antimicrobial peptides produced by our cells in response to microbial components -ex. Defensin proteins form pores/holes in microbial membranes causing Cytolysis (dissolution of cells)
What are characteristics of Colonization and Infection?
+Pathogen compete with Flora for nutrients (siderophores) and space -siderophores are virulent factors synthesized by pathogens in order to complete with flora for ions such as iron, they are even capable of taking iron for erythrocytes +Pathogen must overcome toxic compounds produced by Flora +Pathogen must compete with host proteins for circulating ions +Pathogen must tolerate, avoid, or overcome host's defenses +Colonization can occur with or without invading host cell +Pathogen can grow in biofilms -Know for infection to take place, we need many things such as correct portal of entry, correct # of microbes, adherence etc.
What are Pathogen-Associated Molecular Patterns (PAMPs) and how are they involved in Detection by Pattern Recognition Receptors (PRRs)?
+Pathogen-Associated Molecular Patterns (PAMPs) are microbial components that remain unchanged over the course of evolution: -ex. cell wall components (LPS, PG) -ex. Bacterial peptides (flagellin) -ex. Bacterial and viral DNA or RNA +PAMPS can be detected as "non-self" by PRRs of sentinel cells of the innate immune system (dendritic + macrophages), triggering a response against pathogen
What are characteristics of IgM?
+Pentamer (5 subunits = 10 binding sites) -FIRST class produced during primary response -Large size prevents crossing from bloodstream (bloodstream infections) -10 antigen-binding sites mean they're important for catching the pathogen right away. Helps contain the infection from spreading far into blood.
What is Class Switching?
+Process B cells undergo during Primary response of Humoral Immune response +IgM is the first antibody isotype produced by plasma B cells +Th cells can induce activated B cells to secrete other antibody classes by switching gene activation -B cells in lymph nodes usually switch to IgG -MALT B cells switch to IgA
What is the significance of the Inflammatory Response?
+Protective biological response tirggered by inflammatory mediators released by host cells (e.g. cytokines, histamine, prostaglandins) in response to tissue damage or infection -prostaglandins are stress chemicals released by injured cells +Helps contain site of damage, localize response, eliminate invader, and restore tissue function +Results in: - pain (caused by chemicals, nerve damage) -swelling (caused by edema or fluids in tissue), -redness due to (erythema or vasodilation) -heat (caused by vasodilation), -sometimes loss of function (severe cases)
What are Exotoxins?
+Proteins with highly specific damaging effects released into surrounding from gram-negative (mostly) and gram-positive pathogens -Majority of exotoxins destroyed by heat -Soluble -> can easily diffuse to blood (toxemia = toxins in blood), transported throughout body -Enzymatic toxins are the most harmful, even in small amounts, as they can be reused and continue damage antibodies for toxins (antitoxins) are synthesized -Highly specific in their effects on body tissues (neurotoxin, cytotoxin, enterotoxin, hepatotoxin, cardiotoxin) -Streptolysin/Leukocydins are both cytotoxins -3 types: AB Toxins, Membrane-disrupting Toxins, Superantigens ( have ability to overstimulate immune system until there is such chaos that immune system cannot attack toxin, can lead to septic shock) -These toxins are categorized based on structure-function relationship
What are the Effector Functions of Tc (CD8+) cells?
+Recognize antigen presented on MHC Class I of infected cells +Tc induces apoptosis by releasing digestive enzymes (perforins and granzymes), and also releases cytokines that alert neighboring cells -apoptosis of infected cells ensures any pathogens left inside will also be killed +Memory Tc cells ensure faster secondary response
What are the Effector Functions of Th (CD4+) cells?
+Recognize antigens presented on MHC Class II of APCs +Secrete cytokines that: 1. Activate B cells and induce B cell clonal expansion 2. Activate macrophages to increase power and fuse to form giant cells 3. Direct and support T cells proliferation and differentiation
What are characteristics of T lymphocytes or T cells?
+Responsible for Cell-Mediated Immune Response, NOT humoral +Form in bone marrow and mature in thymus into helper (Th) or cytotoxic (Tc) T cells +Each T cell expresses TCRs, which all recognize a specific intracellular antigen only when presented on Major Histocompatibility Complex (MHC) -TCR only has one antigen binding site as opposed to 2 of antibodies/BCR, so it only binds to one specific epitope with the help of a coreceptor -TCR cannot recognize extracellular antigen. Can only bind to an intracellular antigen that is presented on our MHC (MHC are proteins synthesized by our cells that are able to take a fragment of our processed pathogen and present it on the outside of the cell) +Maturation in Thymus involves: -Negative selection of self-reactive T cells, removal of t cells which bind our own cells -Positive/Thymic Selection: Selection for T cells that bind self MHC, Keeping T cells that recognize self MHC. T cells have to recognize the MHC and the antigen presented on it. Also rephrased as Thymic selection: Removal of T-cells that do not recognize our own/self MHC. -We want the T cells to recognize the MHC because it will be displaying the antigen that it has broken down -95% of developing T cells undergo apoptosis due to failing negative and positive selection +Travel to lymph nodes as naive T cells, activated by recognizing matching intracellular antigen presented on MHC (of APCs or other host cells)
What are characteristics of B lymphocytes or B cells?
+Responsible for Humoral Immune response (Humoral = fluid) +Form and mature in bone marrow: Maturation involves negative selection of self-reactive B cells before release (B cells which mount responses against cells in our own body) +Each B cell expresses several B-Cell receptors (BCRs) AKA antibodies, all recognizing the same specific epitope -More than 100M in our own body -Each BCR recognizes a specific epotope, but ALL BCR on a specific B Cell recognize the same specific epitope. SO ALL BCR on 1 given B cell can recognize the same epitope on 1 pathogen. look at figure to right. +Travel to lymph nodes as naive B cells, activated by recognizing matching extracellular antigen
What are the Protective Outcomes of Antibody-Antigen Binding?
1. Agglutination: cross-linking, immobilizing pathogens -One antibody binds to two epitopes of two different pathogenic cells/bacterium to immobilize pathogens and reduce their function. This also reduces the # of infectious units to be dealt with 2. Opsonization: enhance phagocytosis. remember opsonization is like marking a pathogen for phagocytosis 3. Neutralization: Prevents toxins, viruses , bacteria from binding to cell and causing infection/intoxication 4. Complement system activation: remember classical pathway requires antibody binding 5. Antibody-dependent cellular cytotoxicity (ADCC): infected host cell or pathogenic cell targeted for destruction by immune cells (NK cells, eosinophils & macrophages) through perforin and lytic enzymes
What occurs in the T-dependent Humoral Response?
1. BCRs recognize and attach to antigen 2. Antigen is internalized (thru receptor mediated endocytosis) and degraded into fragments 3. Antigen fragments are displayed on MHC class II on B cell, attracting a matching helper T cell 4. Th cell secretes cytokines, activating B cell. (Clonal Selection) 5. The activated B cell begins clonal expansion, producing antibody-producing plasma cells and memory cells (clonal expansion).
What are the steps of Phagocytosis?
1. Chemotaxis by chemoattractants: the attracting of phagocyte to location of pathogen by chemoattractants. there are a variety of chemoattractants 2. Adherence (direct vs. indirect): indirect attachment is through opsonization, where phagocytes attach to opsonins that are bound to pathogen direct attachment is when the phagocyte directly binds the pathogen 3. Ingestion of microbe by phagocyte 4. Phagolysosome formation: phagosome (phagocytic vesicle) is made around the ingested microbe. Lysosomes are then fused with phagosome to create phagolysosome. remember lysosomes carry digestive enzymes. 5. Digestion 6. Elimination (exocytosis) + antigen presentation on MHC (Major Histocompatibility Complex)
What are the steps of Cell-Mediated Immunity?
1. Clonal Selection: Antigen Presenting cells (dendritic/macrophage) migrate through the lymph and present epitope to mature naive T cells 2. Clonal Expansion: Activated T cells proliferate & differentiate into effector T cells and memory T cells. -Activated Tc (CD8+) cells, by MHC I-bound antigen, differentiate into Cytotoxic T cells (Tc) & memory T cells -Activated Th (CD4+) cells, by MHC II-bound antigen, differentiate into helper T cells (Th) & memory Th cells cytotoxic t cells go around body looking for cells with MHC I displaying antigenic process which means the host cell is infected, and then kill the host cell and release cytokines to alert other immune cells.
What are the steps of the Inflammatory Response?
1. Skin is breached (1st line of def.) 2. cells that are injured are releasing prostaglandins, macrophages on site use their PRR to sense pathogen and start phagocytosis while releasing cytokines to alert neighboring cells and chemokines to recruit other immune cells. Mast cells are also noticed by cytokines and start pro-inflammatory response which result in vasodilation. 3. Vasodilation and Increased permeability of blood vessels 4. Margination 5. Diapedesis 6. Phagocytosis 7. if neutrophils feel phagocytosis is ineffective, they release their NETs
What are the steps of the Humoral response (adaptive immune response)?
Humoral response = ACTIVATED by EXTRACELLULAR ANTIGEN 1st. exposure: 1. Antigen bound by Antibodies/BCR of B cell 2. B cell activates 3. B cell multiplies to create Plasma cells 4. Plasma cells make antibodies 5. Antibodies bind to pathogenic antigen, neutralizing pathogens or making them better targets for phagocytes and complement proteins 6. Antigens can also be used to defend against pathogen for a long time 2nd exposure: 1. Antigen noticed by memory B cells which create Plasma cells which then secrete more antibodies. Through memory B cells you can avoid maturation/activation steps of B cell that happen in 1st exposure in a primary response (1st exposure) you would feel the side effects/symptoms, but in secondary response (2nd exposure), memory by antibodies would make it so you wouldn't really feel side effects/symptoms.
Why is a release of endotoxin into the bloodstream potentially deadly? Endotoxin can quickly enter the brain from the bloodstream, causing brain damage. It results in dehydration of the patient. It causes necrosis of the liver. It can lower blood pressure and cause the patient to go into shock.
It can lower blood pressure and cause the patient to go into shock
Do both T-independent and T-dependent antigens prompt memory cell production in B cells?
NO, T-independent antigens do not prompt memory cell production by B cells, while T-dependent antigens do. Thus, a primary response is needed every time T-independent antigens are present. T-independent antigens tend to be high virulent/pathogenic. Children tend to not respond to T-independent antigens, this is why vaccination is crucial. Need multiple doses at young age because you have to protect the baby until the baby is able to produce its own primary response.
Which pathogen uses IgA protease to avoid antibodies?
Neisseria Gonorrhoeae, cleaves mucosal IgA, slows rush of antibodies
What is Opsonization?
Opsonization is a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte . The process of opsonization is a means of identifying the invading particle to the phagocyte.
Digestion of microorganisms occurs in ________________ Phagosomes Phagolysosomes Lysosomes Complement proteins
Phagolysosomes
What is the Immune system?
The internal defense mechanism against pathogens -Split into Innate and Adaptive Immune systems
Consider a helminthic infection in which an individual is colonized by a parasitic worm. The worm is too big to be engulfed by a phagocytic cell. How does the immune system respond? The worm gets coated with antibodies, which activate other cells in the immune system to secrete chemicals that kill it. Blood flow is reduced to the area, which starves the worm of nutrients. Numerous phagocytes work cooperatively to ingest the worm. Antibodies bind to the worm and disrupt its plasma membrane.
The worm gets coated with antibodies, which activate other cells in the immune system to secrete chemicals that kill it. (dropping NETs)
Which of the following statements concerning antigen-presenting cells is true? View Available Hint(s) Which of the following statements concerning antigen-presenting cells is true? They are found only in lymphoid tissues. They are a type of T cell. They are involved in activating T cells. They transport antigens to the liver, where they can be degraded.
They are involved in activating T cells
Which of the following is NOT a characteristic of B cells? They recognize antigens associated with MHC I. They have antibodies on their surfaces. They are responsible for antibody formation. They are responsible for the memory response. They originate in bone marrow.
They recognize antigens associated with MHC I, B cells recognize free extracellular antigens, Tc cells recognize antigens associated with MHC I
How is the Potency of a toxin measured?
Through LD50 = Lethal Dose for 50% of a sample population +LD=lethal dose is the dose needed to kill an organism. +Lower lethal dose = more potent. In this case we are talking about the toxin itself, NOT the presence of the organism.
What are Portals of Entry?
To establish infection, pathogen must first invade or breach host: +Skin: openings such as sweat glands, hair follicle, or grows on. +Mucous membranes: route for most pathogens through air, food, water, sexual contact ex. respiratory tract, GI tract, genitourinary tract, conjunctiva +Parenteral route: access through injury/injection; bites, surgery, dry cracking skin, IV. etc. essentially just a way for pathogen to get in under skin
The function of the "ciliary escalator" is to trap microorganisms in mucus in the upper respiratory tract. remove microorganisms from the gastrointestinal tract. remove microorganisms from the lower digestive tract. trap inhaled dust and microorganisms in mucus and propel it away from the lower respiratory tract. propel inhaled dust and microorganisms away from the mouth, toward the lower respiratory tract.
Trap inhaled dust and microorganisms in mucus and propel it away from the lower respiratory tract
What are Interferons?
Type of antiviral cytokines that alert neighboring host cells, stimulate NK cells Interferons: tell other cells (not just immune cells) that there is a pathogen around. Stimulate Natural Killer cells
What are Colony-Stimulating Factors (CSFs)?
Type of cytokine that go to bone marrow, go to hematopoetic cells and induce hematopoiesis to produce more WBCs
What are Chemokines (Cytokines)?
Type of cytokines that work to attract/recruit other immune cells. Conduct Chemotaxis (chemical transport) of phagocytes (leukocytes) to site of infection.
What are the representative diseases of Endotoxins?
Typhoid Fever, UTIs from E.Coli, Meningococcal meningitis, Salmonellosis
What is the general composition of blood?
Typically the vast majority of blood is Plasma, a good amount is RBCs, a very minimal amount is WBCs
All of the following occur during inflammation. What is the first step? phagocyte migration vasodilation repair diapedesis margination (process in which free-flowing leukocytes exit the central blood stream)
Vasodilation
Are BCRs antibodies/Immunoglobin?
YES, BCRs are comprised of immunoglobin molecules that form a receptor protein TCR has a different structure than antibodies in that it only has one receptor site per chain while BCR are Y shaped with 2 receptor sites on each chain like antibodies
Can Foodborne intoxication (vs. infection) result from toxic consumption?
YES, Foodborne intoxication (vs. infection) can result from toxin consumption (without pathogen itself) -EX. Botulinum toxin by CLOSTRIDIUM BOTULINUM -Results in flaccid paralysis (vs. spastic paralysis with tetanus) -Is the most powerful enzymatic toxin -in tetanus muscles are stuck in contracted position, in botulism muscles are stuck in relaxed position and patient is not able to contract muscles. Know that botulism and tetanus are neuromuscular toxins. Know botulinum toxin is most potent enzymatic toxin known, just 1 toxin can cause signs of paralysis. This is what used in botox. Botulinum toxin thrives in canned food and honey, this is why we don't give babies honey, as their immune system is weak.
Is a mature B cell an APC?
YES, mature B cells can display their T-dependent antigen to Th cells for activation
Why do we have to get new vaccinations every year for the flu?
reason we have to get new vaccinations every year for flu are due to flu virus mutations that cause antigenic shift that prevents our current antibodies from recognizing and binding it.
What do we mean when we say we need an organ donor match?
we say we want a similar MHC match so cells will recognize MHCs as self. Transplantation relies heavily on matching of MHCs.
