Ch. 14 & 15: Immune System

Three main antigen-presenting cell types?

1 ) Dendritic cells 2) Macrophages 3) B- Lymphocytes

How can bacterial cells evade phagocytosis?

1) By avoiding contact w phagocytes The bladder & unbroken skin are not patrolled by phagocytes 2) Inhibit phagocyte chemotaxis Mycrobacterium tuberculosis can inhibit phagocytic migration 3) Inhibition of phagocytic engulfment: Polysaccharide capsules of s. pneumonias, klebsiella pneumoniae 4) Survival inside of Phagocytes Mycrobacterium tuberculosis

What are the major events in inflammation?

1) Immediate reactions: Vasoconstriction; Plug up damaged blood vessels,stop excessive bleeding/pathogens entering bloodstream 2) Vascular reaction: vasodilation delivers leukocytes (neutrophils) and bloodto site of injury. Leukocytes fight off invaders. Increased blood flow raisesthe temperature which may restrict microbe metabolism. 3) Edema/pus: Fluid fills interstitial area of inflammation. Sequestersforeign invaders. Dilutes toxins 4) Resolution: macrophages and lymphocytes clean up the mess.Stimulate tissue regeneration to prevent further infection

Fever

1) Inhibits multiplication of temperature sensitive microbes 2) Reduces availability of iron; macrophages stop releasing iron 3) Increases hematopoiesis (blood cell production), phagocytosis and specific immune reactions

Why can fever be good at helping to retard infection?

1) Inhibits multiplication of temperature sensitive microbes 2) Reduces availability of iron; macrophages stop releasing iron 3) Increases hematopoiesis (blood cell production), phagocytosis and specific immune reactions

Major Events of Inflammation

1) Migration of cells out of blood vessels into tissues =Diapedesis 2) Migration in response to specific chemicals at the site of injury or infection = Chemotaxis

What are the four types of leukocytes (white blood cells) we talked about? What is their primary function?

1) Neutrophil -- NEVER *Considered the first cells to defend infection (make it to the battlefield) bc they're plentiful = Granulocyte a type of leukocyte that contain granules in their cytoplasm containing enzymes - 50-90% of white BC - General phagocytosis - 2nd Line 2) Lymphocytes -- LET - 20- 35% of white BC - Specific (acquired) Immunity - 3rd Line 3) Monocytes -- MONKEYS - 3-7% of white BC - Phagocytosis, followed by final differentiation into macrophages & Dendrific cells - 2nd Line 4) Eosiniphils -- EAT = Granulocyte a type of leukocyte that contain granules in their cytoplasm containing enzymes - 1-3% of white BC - Destruction of parasitic worms/ mediators of allergies - 2nd Line 5) Basophils -- BANANAS = Granulocyte a type of leukocyte that contain granules in their cytoplasm containing enzymes - 0.5% of white BC - Active in allergy, inflammation, parasitic infections - 2nd Line

What characteristics contribute to effective vaccines?

1) Should have a low level of adverse side effects or toxicity & not cause serious harm 2) Should protect against exposure to natural, wild forms of pathogens 3) Should stimulate both antibody (B-Cell_ response & mediated (T-Cell) response 4) Should have long-term, lasting effects (produce memory) 5) Should not require numerous doses or boosters 6) Should be inexpensive/ long shelf-life/ Easy to administer

How is the lymph system involved in immunity?

1) Surveillance, recognition & protection against foreign material 2) Acts as a drain-off system for the inflammatory response fluid to circulatory system

How does each system protect us from pathogens? 2nd Line

(If pathogens break through 1st line of defense) Protective cells and fluids; inflammation and phagocytosis - nonspecific Lymphatic System / Inflammatory response Surveillance/recognition of invaders + drain-off system Lymphoid Organs & Tissues Primary Lymphoid Organs: Sites of Lymphocytic origin & maturation (B & T cells) -- Thymus = T cell + Bone marrow = B cells Secondary Lymphoid Organs & Tissues: Circulatory-based locations such as spleen & lymph nodes (filters)/ sites of immune activation

How does each system protect us from pathogens? 3rd Line

(If pathogens break through 2nd line of defense) Acquired with exposure to foreign substance; produces protective antibodies and creates memory cells - specific Here is the production of two types of lymphocytes (B and T cells) which are specific to the invading particle. Leukocyte present here = Lymphocytes / 20-35% of white blood cells

Non-Specific (Innate) immunity

- 1st + 2nd Line of Defense - The defense system with which you were born - Involves barriers that keep harmful materials from entering your body Innate immunity -nonspecific resistance; -the body response to the pathogens is the same each time the body is exposed; - No specificity - No memory -it is accomplished by physical barriers (skin, tears, urine,..), chemical mediators, white blood cells and the inflammatory response.

How do antibodies help clear infections?

- Agglutinating pathogens - Neutralising toxins - Preventing the pathogen binding to human cells They work to destroy disease causing pathogens & prevent them from binding (If an antigen enters the body and B-cells recognize it (either from having had the disease before or from being vaccinated against it), B-cells will produce antibodies - When antibodies attach to an antigen (think a lock-key configuration), it signals other parts of the immune system to attack and destroy the invaders)

Another definition of Antigen

- Anything that causes an immune response - Antigens can be entire pathogens, like bacteria, viruses, fungi, and parasites, or smaller proteins that pathogens express - Antigens are like a name tag for each pathogen that announce the pathogens' presence to your immune system

Why is clonal deletion necessary?

- Cells go through this & some get murdered except for VERY specific ones - Deletes the cells that would bind & kill OUR cells - Our own cells screen these - Then the Thymus kills the bad ones

What is Herd Immunity?

- Each microorganism requires a certain density of susceptible individuals (herd) to be transmissible - With a sufficient number of immune individuals, the microbe does not spread - Collective immunity through mass immunization confers indirect protection on non-immune members

Functions of the Spleen

- Macrophages present in the spleen engulf or phagocytize and destroy worn out blood cells, live or dead pathogens, cell debris etc.

Antibodies

- Proteins in the Y shape - Membrane-bound on B cells - Have an antigen binding area where they bind a specific antigen - Found in blood and also found in mucus, breastmilk, saliva etc - Different classes of antibodies-- Ex. IgE can protect against parasitic worms - They are very specific so there must be an antibody that is able to bind to an antigen - * When antibodies bind an antigen, they can deactivate the pathogen - And activating these B cells is what causes the antibodies to be produced! ---> which is part of the 3rd Line of Defense / part of the Humoral response (Sometimes they are referred to as "Immunoglobulins")

What makes Specific Immunity (Acquired) special?

- Specificity - Diversity - Inducibility (only turned on when triggered) - Clonality - Tolerance - Memory

Brief intro of B & T cells

-2 main types lymphocytes: T cells and B cells - B cells produce antibodies that latch on & destroy invading viruses or bacteria - T cells are direct fighters of foreign invaders and also produced cytokines, which are biological substances that help activate other parts of the immune system

B Cell Overview

-Humoral Immune Response 1) binding of antigen receptor to antigen activates B 2) gives rise to cells that secrete antibodies 3) antibodies defend against pathogen rather than B Each B cell has only one type of antigen binding antibody on it & its antibodies are membrane-bound (antibodies are the Y shaped receptors made of protein) - Also, each antibody has the SAME variable portions on it per each B cell/ so diff on each B cell but all antibodies on one B cell have same variable portions - 10^10 variable portion combinations at first but then the "self-responding" ones get eliminated so less than that but the point is a really big amount of them exist - Sooo many possibilities is good: Say a crazy, "new" to us pathogen comes along; there is a good chance that there will be a B cell w the proper antibody receptor bc so many variables so luckily the pathogen will find it and bind to it then the B cell becomes activated (need help from Helper T cells to truly bind though so keep that in mind) - Then clonal selection occurs bc the chosen one is needed - Then they DIFFERENTIATE = Tale on particular roles!! Roles = Two forms of differentiation: 1) Become Memory Cells 2) Fight (Effector Cells) also sometimes called Plasma cells- they're antibody factories - Those antibody factories start spitting out the exact antibodies w the special variable combo that will fight the invader/ they're uniquely able to bind to the pathogen - They'll go & find all the viruses & TAG the pathogens - Then the tags are an indicator to the phagocytes that they need to be eaten! Called OPSONIZATION when they get tagged by the antibodies - The tagged antibodies on the pathogen make it hard for the pathogen to function too while they wait to get eaten https://www.youtube.com/watch?v=Z36dUduOk1Y

Another way to look at: 3rd Line of Defense

Includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells: - B cells - T cells

What is the difference between Specific (Adaptive Immunity) and Non-Specific (Innate) immunity?

Innate immunity is nonspecific resistance of the body, that does not have characteristics such as specificity and memory, unlike the adaptive immunity. That is their main difference.

Lymphoid Organs:

Lymphoid organs are those organs where the maturation and proliferation of lymphocytes takes place

Cell Lysis (The Complement system)

Lysis is the breaking down or destruction of the membrane of a cell

Monocytes move from the systemic circulatory system into general connective tissues, where they differentiate into what phagocytic cell type?

Macrophages

Cytokines

Molecules that are used for cell signaling, or cell-to-cell communication * Innate/Non specific

Natural Killer cells

Natural Killer cells do not attack pathogens directly. - Instead, natural killer cells destroy infected host cells in order to stop the spread of an infection

What are opsonization, inactivation, agglutination, antitoxin?

Neutralization: Antibodies block pathogenic activity Agglutination: Antibody molecules aggregate multiple pathogens Opsonization: Phagocytes engulf pathogens bound to antibodies Antitoxin: Antibody that counteracts a toxin

Neutrophils

Neutrophils are phagocytic cells that are also classified as granulocytes because they contain granules in their cytoplasm. - These granules are very toxic to bacteria and fungi, and cause them to stop proliferating or die on contact.

1st Line of Defense

Nonspecific bc it's not selective about what it chooses to block

Regulatory B Cells

Regulation of the immune response including anti-inflammatory responses

Memory T cells

Remember antigen and react quickly to second appearance

Memory B cells

Remembers the infection and can produce antibodies more rapidly with second infection

Plasma Cells

Secrete antibodies

Antimicrobial Proteins: Antimicrobial Peptides

Short proteins capable of inserting themselves into bacterial membranes - Between 12 and 50 amino acids Ex: Bacteriosins, defensin, magainins, protegrins

Primary Lymphoid Organs

Sites of lymphocytic origin and maturation (B and T cells) - thymus and bone marrow

How are lymph nodes involved in immunity?

Small organs stationed along lymphatic channels & large blood vessels of the thoracic & abdominal cavities - Filters lymph - Site of adaptive immune cell activation

Characteristics of Antiviral Interferon

Small protein produced naturally by certain WBCs and tissue cells. • Warning molecules for defense of adjacent cells • Produced industrially as a treatment for virus infections

How is the spleen involved in immunity?

Structurally similar to lymph nodes - Filters circulating blood - To remove worn out RBCs & pathogens - filters pathogens for phagocytosis

Regulatory T cells

Suppress reactions to self; modulate auto-immuneresponse

Another way to look at: 1st Line of Defense

Surface protection composed of anatomical & physiological barriers: - Physical barriers - Microbiota barrier - Chemical barriers

How and where do B cells and T cell differentiate?

T Cells: - Produced in the bone marrow, but they subsequently migrate to the thymus, where they mature and develop the ability to recognize specific antigen - T cells are responsible for cell-mediated immunity - Their job is to kill the pathogen/ help other immune cells fight the infection B Cells: - Mature in the bone marrow - Responsible for antibody-mediated immunity - Their job is to produce antibodies

How does VDJ recombination create a LARGE number of B & T cell variation?

The Immune system has a precursor B or T cell - Where the DNA recombines - Making diff RNA - All cells have SAME DNA, just diff expressions - V, D and J categories of variable genes - Then they get recombined - 40 V options, 25 D options, 6 J options - So can make TONS of diff variations

Specific (Adaptive Immunity)

The adaptive immune system takes over if the innate immune system is not able to destroy the germs. - 3rd Line of Defense - It specifically targets the type of germ that is causing the infection. But to do that it first needs to identify the germ. - Involves specialized immune cells & antibodies that attack & destroy foreign invaders and are able to prevent disease in the future by remembering what those substances look like ----- - specificity (the adaptive immunity can distinguish among various kinds of bacteria) - memory (adaptive immunity remembers previous encounters with a particular substance, so future responses will be faster, stronger and longer-lasting); -it is accomplished by B-cells and T-cells.

Chemotaxis (The Complement system)

The attraction and movement of macrophages to a chemical signal

Humoral Response

The branch of acquired (specific) immunity that involves the activation of B cells and that leads to the production of antibodies, which defend against bacteria and viruses in body fluids. - Main diff here is that the Humoral immunity produces antigen-specific antibodies whereas cell-mediated does not Aka Response to things floating around (B cells most active here)

What does the complement system do?

The complement system is made of a variety of proteins that, when inactive, circulate in the blood - When activated, these proteins come together to initiate the complement cascade, which starts the following steps: 1) Opsonization = A process in which foreign particles are marked for phagocytosis 2) Chemotaxis = The attraction and movement of macrophages to a chemical signal 3) Cell Lysis = Lysis is the breaking down or destruction of the membrane of a cell 4) Agglutination = Agglutination uses antibodies to cluster and bind pathogens together, much like a cowboy rounds up his cattle... ** The steps of the complement cascade facilitate the search for and removal of antigens by placing them in large clumps, making it easier for other aspects of the immune system to do their jobs.

What is the difference between the first, second and third line of defenses? 2nd Line

The non-specific immune response, which includes: - Cell recognition - Phagocytosis of foreign bodies - Inflammation/fever - Interferon system - Dendritic cells. (Know how all of these contribute to immune function)

Critical Thinking: Individuals who smoke have much higher rates of lung infection. Explain which first-line defense mechanisms may be impaired by smoking, allowing pathogens to more readily enter the lower respiratory tract.

The respiratory epithelium constitutes the first line of defense against inhaled pollutants and pathogens - Cigarette smoke can directly damage the airway epithelial barrier, including ciliated cells, goblet cells, basal cells, and submucosal secretory glands Lung First Line of Defense: Alveolar macrophages AMs, the resident mononuclear phagocytes of the lung, provide the first line of defense against organisms or particles reaching the lower airways - They must neutralise the invading pathogens or recruit neutrophils and other mononuclear cells.

Cell-Mediated Response

The response of T-cells to antigens (T cells most active here) - Main diff here is that the Humoral immunity produces antigen-specific antibodies whereas cell-mediated does not

What is the difference between the first, second and third line of defenses? 3rd Line

The specific immune response

How do vaccines work?

The vaccine inserts dead or weakened pathogen to produce a primary immune response - Dead pathogens or antigens injected into body ; they DO NOT cause disease; they DO stimulate the production of memory cells

Define B and T cells

There are two main types lymphocytes: T cells and B cells B Cells Produce antibody molecules that can latch on and destroy invading viruses or bacteria. T Cells Direct fighters of foreign invaders and also produced cytokines, which are biological substances that help activate other parts of the immune system

Types of Lymphoid Organs

There are two types of lymphoid organs: primary lymphoid organs and secondary lymphoid organs Primary lymphoid organ: It includes bone marrow and thymus. Secondary lymphoid organ: It includes lymph nodes, spleen, tonsils, Peyer's patch and mucosal associated lymphoid tissues.

Why are Dendritic cells special?

They bridge the innate and adaptive immunity (- Presents antigen to Helper T Cell) (- The Helper T cell activates!)

Critical Thinking: Myasthenia gravis is an autoimmune disease caused by T cells attacking healthy tissue. When the disease is diagnosed in early childhood, the treatment often involves removal of the thymus. Discuss why this treatment is therapeutic for this condition based on your knowledge of basic immunology.

Thymus role recap: -The thymus makes white blood cells called T lymphocytes (aka T cells) - The thymus plays an important role in the development of the immune cell pool; it serves as the primary location for T-lymphocyte maturation - The thymus gland grows to its largest size during childhood and makes all the T cells we need before we become teenagers) ------- - People with the disease typically have clusters of immune cells in their thymus gland and may develop thymomas (tumors of the thymus gland) - Thymomas are most often harmless, but they can become cancerous - Thymectomy eliminates the primary location where T cells differentiate and mature - In humans, a neonate is born with an already functioning thymus and developed immune cells, even though human thymus achieves optimal effectiveness as late as during puberty - Lessens antibody production/ B cells... Lessens attacks bc less T cells - Can remove it to relieve some attacks

What is herd immunity?

When a majority of a population are vaccinated against a disease, this means that even people who have not been vaccinated are less likely to get it because there are fewer people to catch it from / Immunity in most of a population

4 major events of Inflammation:

a) Immediate Reactions: Vasoconstriction; Plug up damaged blood vessels, stop excessive bleeding/pathogens entering bloodstream. b) Vascular Reaction: vasodilation delivers leukocytes (neutrophils) and bloodto site of injury. Leukocytes fight off invaders. Increased blood flow raisesthe temperature which may restrict microbe metabolism. c) Edema/pus: Fluid fills interstitial area of inflammation. Sequesters foreign invaders. Dilutes toxins d) Resolution: macrophages and lymphocytes clean up the mess.Stimulate tissue regeneration to prevent further infection

What is Clonal Selection

https://www.youtube.com/watch?v=EsQyCHs4IBY With B & T Cells: STEP 1: B/T cell reproduction Ex. B cells have daughter B cells, each with their own uniquely shaped receptor- - Their receptors are VERY specific towards pathogens - It's those receptors that find antigens from antigen presenting cells - Happening in the bone marrow bc B cells - Same exact thing happening to T cells except in the Thymus - End up w genetically tons of diff B & T cells each one special w its very own unique receptor STEP 2: When the infection occurs & the right B & T Cells are Alerted - They migrate to Lymph nodes both B & T cells - Say the end up in your armpit node, and that is where they await their special pathogen to stick to their receptor - Say there is an infection in some tissue near your arm pit/ the Dendritic cells are doing their best to eat all the say bacteria - Then the dendritic cells bump around to FIND the B & T cells w their unique receptors to bring the bad bacteria with them and present them to B & T cells - Dendritic cells = antigen presenting cells !! - You get some of the bacteria swept into the lymph node as well with the Dendritic cells - The dendritic cells have a protein on them called MHC that present pieces of that bacteria on it to the special B/T cell receptors - (The B/T cells can't just get a free floating bacteria- they need a dendritic cell to present it to them) - Okay now the T cell receptor will take the presented pathogen from dendritic cell & realize that the one pathogen he was created for to kill is somewhere out there in the body - As for the B cell, he can react directly when it finds the bacteria that will bind to its specific receptor- doesn't need a dendritic cell to present it to him - All the other B/T cells in that node have no idea what's going on bc they can't bind Step 3: The Fight - Activation of those B & T cells - Now they are going to start replicating like CRAZY - Those 2 winners know they're useful for the fight now so they begin replicating - They'll have the same receptors bc that was the useful one - Some will go on to become memory cells & won't actually fight rn but will fight the next time the pathogen comes around - Some will stay in lymph node & some will travel out to wherever the battlefield is

VDJ

10^11 - 10^14 amount of variations - So we get tons of diff receptors to make for pathogens - Recombine - Makes the mRNA - Makes protein receptor - Each cell has just one receptor - Can't have all these w receptors running around so clonal deletion occurs

How is the spleen, thymus, bone marrow and the lymph system involved in immunity?

2nd Line of Defense: Innate/ Non-Specific

Another way to look at: 2nd Line of Defense

A cellular & chemical system that comes immediately into play when microbes break past protective surface layer: - Phagocytosis - Inflammation - Fever - Antimicrobial products

The Complement System

A mechanism that complements other aspects of the immune response. - ** Typically, the complement system acts as a part of the innate immune system

Opsonization (The Complement system)

A process in which foreign particles are marked for phagocytosis

Antigen

A protein that, when introduced in the blood, triggers the production of an antibody - Aka something the body recognizes as "non-self" & in this case, it is something that would be a PART of the pathogen

Chemokines

A type of cytokines that are released by infected cells - Infected host cells release chemokines in order to initiate an immune response, and to warn neighboring cells of the threat * Innate/Non specific

Helper T cells

Activate macrophages, B cells and T cells

Agglutination (The Complement system)

Agglutination = Agglutination uses antibodies to cluster and bind pathogens together, much like a cowboy rounds up his cattle...

How does clonal variation generate B and T cells that can recognize antigens with no prior exposure?

Aka how do they recognize antigens they have never encountered before??? - Because infected cells display on their surface peptide fragments derived from the pathogen's proteins - These foreign peptides are delivered to the cell surface by specialized host-cell glycoproteins.

How is bone marrow involved in immunity?

All blood cells arise here (Hematopoiesis) including B-Cells

Humoral immunity is a type of adaptive immunity that results in the circulation of which of the following throughout the blood?

Antibodies

Major histocompatibility complex (MHC) refers to a large group of genes that code for proteins that play an essential role in which of the following?

Antigen presentation to T lymphocytes

How does each system protect us from pathogens? 1st Line of Defense

Any barrier that blocks invasion at the portal of entry - nonspecific• Physical (ie. skin) and chemical barriers (ie. lysozyme), genetic barriers Physical Barrier: 1) Skin & Mucous membranes 2) Respiratory, Urogenital, Eyes, Digestive Tract 3) Epithelial cells compacted/cemented together- keratin; few pathogens can penetrate 4) Hair follicles/ shaft are shed 5) Vomiting & pooping Chemical Barrier: 1) Sebatious secretions 2) Lysozyme: Enzyme that degrades the peptidoglycan layer 3) Lactic acid & electrolyte concentration in sweat 4) Skin's acidic pH 5) Hydrochloric acid in stomach Resident Microbiota: 1) Proved microbial antagonism 2) Blocks access of pathogens to epithelial surfaces 3)*Creates unfavorable environments for pathogens/ competes for nutrients & alters local pH

Which cells produce antibodies?

B cells (lymphocytes)

Which cells are important in protecting against a second infection from the same microbe?

B/T Memory

Which of the following cell types of the innate immune system does not perform phagocytosis?

Basophils

Basophils

Basophils are also granulocytes that attack multicellular parasites - Basophils release histamine, much like mast cells. The use of histamine makes basophils and mast cells key players in mounting an allergic response

Cytotoxic T cells

Can kill virally infected or cancerous cells with perforins and granzymes (Killer cells)

Secondary Lymphoid Organs & Tissues

Circulatory-based locations such as spleen and lymphnodes (filters) - Sites of immune cell activation

Antimicrobial Proteins: Complement

Crippling C3b - binds to bacteria/virus preventing infection; also initiates complement cascade Activating C3a - released from site of infection; activates phagocytes Ripping Membrane attack complex - places pour in bacterial membrane Complement overview: https://youtu.be/BSypUV6QUNw

Dendritic cells

Dendritic cells are antigen-presenting cells that are located in tissues, and can contact external environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines - Since dendritic cells are located in tissues that are common points for initial infection, they can identify threats and act as messengers for the rest of the immune system by antigen presentation - *** Dendritic cells also act as bridge between the innate immune system and the adaptive immune system

Helper T Cells (Th cells)

Don't directly kill cells; help activate T cytotoxic and macrophages - Assist to activate of B & T cells

Eosiniphils

Eosinophils are granulocytes target multicellular parasites (worms) - Eosinophils secrete a range of highly toxic proteins and free radicals that kill bacteria and parasites

What is the difference between the first, second and third line of defenses? 1st Line of Defense

First line of defense is composed of physical chemical and genetic barriers - Any barrier that blocks invasion at the portal of entry --> Non-specific - Physical barriers (skin) -Chemical barriers (Lysozyme)

Mast cells

Found in the connective tissue of the dermis; respond to injury, infection, or allergy by producing and releasing substances, including heparin and histamine - important for wound healing and defense against pathogens via the inflammatory response - When mast cells are activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade. * Innate/Non specific

How is the thymus involved in immunity?

High rate of growth & activity until puberty, then begins to shrink - Site of T-Cell maturation