Immune system immunolgy

Characteristics of adaptive immunity

-Antigen specific: requires production of specific lymphocytes & antibodies against specific antigen -systemic: not restricted to initial infection site -has memory: second encounter causes more rapid & vigorous response

Inflammation

-Goal:bring phagocytes & plasma proteins to infected or injured area -isolate & destroy, remove debris, healing & repair

two semi-independent part of lymph system

-Lymph vessels:blind ended vessels originating in capillary beds contain valves -Lymph organs:house lymphocytes and phagocytic cells, allows for removal of unwanted materials from the lymph

Antigen binding activate B-cells clones to multiply & differentiate into two cells types: Plasma & memory cells.

-Most become plasma cells-actively produce & secrete igG -Memory cells:few remain dormant for future antigen exposure. basis for vaccinations.

Two types of immunity

1. Cell mediated immunity 2. Humoral immunity

Two subsets of Helper T cells augment different patterns of immune response.

1. T Helper 1 Cells(TH1): promote cell mediated(cytotoxic T cell) reponse against intracellular pathogens. 2. T Helper 2 cells(TH2): promote antibody/humoral mediated immunity by B cells & increase eosinophil activity for defense against parasitic worms.

Cytotoxic T cells(CD8) bind to self viral antigen complex and release destructive chemicals. What are the two?

1.Peforin molecules-enetrate target cells membrane & form pore like channels(similar to complement) 2.Granzymes-enter target cell through perforin pores & trigger virus infected cell to self destruct through apoptosis.

Lymph Nodes filter lymph. Its the only lymph organ that contains both ________ & ________ lymph vessels

Afferent & Efferent

The "eyes of the adaptive immune system"

BCR's & TCR's

Body defense mechanisms are aimed at eliminating abnormals cells or any foreign material that are not self

Examples: pathogens(viruses, bacteria), Worn out damaged cells, cancerous abnormal cells, allergies & autoimmune disease responses

Bacteria needs _____ to divide with lactoferrin binds to and prevents.

Iron (Fe)

Autoimmunity

Loss of tolerance to self antigens

NLR's

Nucleotide binding oligomerization domain (NOD) like receptor which recognize intracellular PAMPs. Activated NLR's trigger the formation of inflammasomes.

Clonal Selection Theory

Proposes how a matching B-cell resounds to its specific antigen.

Virulence

The disease causing power of the pathogen Ex: ebola is very virulent

Re-exposure

binding of an allergen to igE antibody triggers mast cell's granules to release chemical mediators. Most mast cells are in skin, eyes, lining of respiratory system & digestive tract

B Lymphocytes

differentiate, mature & become immunocompetent in bone marrow

Malignant tumor(cancer)

invasive & metastasize and have uncontrollable growth that competes for space & nutrients with normal cells.

Immune Complex Diseases

large antigen-antibody complexes circulate & become trapped in small vessels, cause widespread inflammation & tissue damage of kidneys, joints, brain, elsewhere.

Foreign particles are marked for phagocytosis by being coated with chemical mediators from immune system called ________

opsonins; the connection. it enhances phagocytosis by linking foreign cells to phagocytic cell. Antibodies and compliment proteins act as an opsonins.

macrophage

specific type of phagocyte

Macrophages are like warriors that wear their prey's head

true

Passive immunity

"borrowed"-transfer of antibodies actively formed by another person or animal. -Naturally acquired- mothers breast milk, placenta -Artificially acquired-injection of immunoglobulins, antiserum.

B lymphohcytes vs. T lymphocytes

*B-lymphocytes: -comes from bone marrow and matures in bone marrow -receptors for antigen are antibodies -bind with: bacteria, free viruses -active cells: Plasma cells - Has memory cells -Antibody mediated/ humoral immunity -Secretes antibodies -function: eliminate free foreign invaders(mostly bacteria) by enhancing innate immune responses -short life span *T-Lymphocytes: -comes from bone marrow and matures in thymus -receptors for antigen are T-cell receptors(highly specific) -bind with:foreign antigens associated with self antigens like virus infected cells -active cells: Cytotoxic T cells, Helper T cells, Regulatory T cells. -Has memory cells -Cell mediated immunity -Secretes cytokines -function: lyse virus infected & cancer cells, help B cells in antibody production, modulate immune responses -long life span

Self Antigen- MHC Molecules

-"self" antigens membrane bound glycoproteins found on all cells in the body. -coded by MHC genes-4 mill base pairs-128 genes. -more than 100 MHC molecules identified, person only coded for 3-6 MHC antigens "biochemical fingerprint". T cells activated when matched to specific MHC-foreign antigen combination -Class 1 MHC glycoproteins: cytotoxic T cells CD8 co receptor can only bind to class 1-on all cells. -Class II MHC glycoproteins: restricted to macrophages dendritic cells & B cells-only Helper T cells CD4 corrector can bind to class II.

Toll-Like Receptors

-12 types, each recognized different specific set of molecular patterns -recognize pathogens in the ECF -recently discovered intracellular pattern recognition receptors can recognize intracellular viruses & parasites: RLR's & NLR's -Present on phagocytes recognize & bind to foreign microbes

Complement system(antimicrobial protein)

-About 30 plasma proteins that circulate in the blood in an inactive form produced by liver -forms membrane attacking complex(MAC) that punches holes in foreign cell's membrane -acts as opsonin, chemotaxin, vasodilator, kinin activators & simulators of histamine release -activated by classical complement pathway & alternative complement pathway

Receptors on B & T-cells membrane surface

-B-cell receptors(BCR's) -T-cell receptors(TCR's) -BCR's & TCR's on plasma membrane of B & T cells -bind with specific type of antigen -BCR's & TCR's are the "Eyed of the adaptive immunity"

Immunodeficiency diseases

-Congenital:severe combined immunodeficiency disease(SCID) deficiency of B & T cells(bubble boy) -Acquired: AIDS-acquired immune deficiency syndrome. (Human Immunodeficiency virus) or HIV invades & destroys helper CD4+ T-cells.

Chemical mediators of immediate hypersensitivity

-Histamine:vasodilation, increase capillary permeability & increase mucus production -Slow reactive substance of anaphylaxis:(SRS-A) dangerous. collection of 3 related leukotrienes which induces profound & prolong contraction of smooth muscle, especially of small respiratory airways. Eosinophil Chemotactic Factor: attracts eosinophils to area which release enzymes that inactivate SRS-A to limit allergic response.

A Naive Helper T cell's future subset is determined by which cytokines the macrophages & dendritic cells secrete.

-IL2 drives Naive Helper T cells to become TH1 cells -IL4 drives Naive Helper T cells to become TH2

The body has two defense systems that differ in timing specificity yet are interactive & interdependent.

-Innate or non specific immunity -Adaptive or specific acquired immunity

Anaphylactic shock

-Life threatening systemic allergic reaction:if blood borne or large amounts of chemical mediators released in circulation -Systemic histamine & SRS releases may result in: Widespread vasodilation(hypotension/cardiac arrest) & profound bronchiolar constriction(respiratory failure) *treat with epinephrine, Iv fluids, steroids & CPR.

The triggers of the innate immunity are genetic molecular patters associated with pathogens. What are the two we are learning?

-Pathogen associated molecular pattern(PAMPS) -Damage Associate molecular patterns(DAMPS)

What two things "Milk" lymph along in the body?

-Skeletal muscle -respiratory movements

Antigen Presenting Cells

-T Lymphocytes respond only to antigens introduced to them by Antigen Presenting Cells(APC's) -APC's engulf, process & present antigens, complexed with MHC self antigen molecules on their surface to T cells. -APC's are macrophages & closely related to dendritic cells.

T- Lymphocytes- Cell mediated immunity

-T cells bind directly with targets, defend against *pathogens that hide inside cells. -killer t type cells release chemicals that destroy targeted cells they contact, virus infected cells & cancer cells. -like B receptors, T cells are clonal, antigen specific & have T cell receptors(TCR's) on surface. -Unlike B cells, the activating antigen must also have a "self antigen" known as a major histcompatibility complex (MHC). -T cells form memory pool & display both primary & secondary responses like B cells.

What happens when a Helper T cells binds to an APC?

-The APC secretes IL1 & TNF which activates attached Helper T cell -The activated Helper T cell now secretes cytokines which act in an autocrine manner on itself to stimulate clonal expansion -The cytokines also act in a paracrine manner on adjacent B-cells, cytotoxic T-cells & NK cells to enhance their responses to foreign antigen. Therefore, to be activated, T-cells must bind with foreign substance antigens presented on surface of APC's & complexed with MHC (self antigen) molecules.

Functions of lymph system

-collects excess interstitial fluid & returns it to the blood -transports of fats from digestive tract to blood -production & circulation of lymphocytes -development of immunities

Triggers of immediate hypersensitivity

-common allergens:pollen,molds,dust,foods,animal fur,bee stings, drug(PCN), & feathers

Effectors of immune surveillance

-cytotoxic T-cells -Natural Killer cells -Macrophages w/Interferon *all 3 can attack & destroy cancer cells as well as secrete interferon

Mobilization of Leukocytes(WBC's)

-from blood to tissue -margination: cytokinins from resident macrophages induce blood neutrophils & monocytes to stick to selectins and integrins(CAMS) on inner capillary wall & slow down. -Diapedesis: Leukocytes squeeze through capillary pores and crawl toward injured area. sliding under door -chemotaxis:inflammatory chemicals attract neutrophils to injury site & begin phagocytosis. -additional neutrophils are released form bone marrow in response to leukocytosis inducing factors released by injured cells. WBC count increases up to 4 or 5X! called leukocytosis.

Innate defenses(4)

-inflammation:non specific response involving phagocytic cells. -Interferon:proteins that nonspecifically defends against viral infection -Natural Killer Cells: class of lymphocyte like cells that nonspecifically lyse & destroy virus infected host cells & cancer cells -Complement System: group of plasma proteins that when activated destroy foreign cells by punching holes in their plasma membrane.

Defense cells of innate immunity: natural killer Cells

-navy seals of immune system -naturally occurring lymphocyte like cells nonspecifically destroy cancer cells & virus infected cells on first exposure to them -secrete cytotoxic chemicals such as *Perforin molecules which form pore like channels in cells -immediate and non specific -antibodies enhance killing action of NK cells

Innate immunity

-nonspecific -responds quickly -first line of defense:physical barriers such as skin, mucosa that prevent entry of pathogen -second line of defense:antimicrobial protein, phagocytes & other cells

Immunological memory-Primary immune response(slower, short lived)

-occurs on *first exposure to specific antigen -lag period of 3 to 6 days after antigen challenge -peak plasma antibody level in 10 days, then antibody levels decline

Immunological memory-Seconday immune response(quicker, longer lasting)

-occurs on *re-exposure to same antigen -sensitized memory cells respond within hours -antibody level peak in 2-3 days at higher levels than primary repossess & antibodies bind with greater affinity, level remain high in blood for weeks to months.

Lymphocytes

-originate from stem cells in red bone marrow each equipped with a unique receptor that binds specific antigen & a Major Histocompatibility Complex(MHC) molecules on plasma membrane that distinguish "self".

Interferon(antimicrobial protein)

-released by virus infected cells & binds to receptor on neighboring healthy cells. -interferon protects these neighbors by activating genes for Protein Kinase R (PKR) an antiviral protein . -PKR nonspecifically blocks viral reproduction in the cell if the cell if it becomes infected. -also slows division of tumor cells-slow growth -enhances natural killer cells

Regulatory T cells(CD4+CD25+ cells)

-suppressive regulatory T cells(T reg): about 5-10% of CD4+ cell population become T reg & suppress the immune response to keep in check. -inhibit both innate & adaptive immune responses in a check & balance fashion to minimize harmful immune pathology -regulatory B cell (B reg): performs similiar suppressive role for humoral response-B cells.

Humoral immunity

Immunity mediated by antibodies present in the blood plasma & other body fluids(B cells).

Immunocompetent B or T cells

Immunocompetent cells display unique type of receptor that resounds to distinct antigen. -Become immunocompetent before they encounter antigens that may later attack -are exported to secondary lymphoid tissue where encounters with antigens occur -Mature into fully functional antigen activated cells upon binding with their recognized antigen

Tumor

unrestricted multiplication of a clone of cells identical to original mutated cell- most benign slow growing non invasive.

Antibodies ________ destroy organisms.

Indirectly. By: -physical hindrance of an antigen: neutralization & agglutination. -Amplification of innate immune responses: to promote antigen destruction. Activate complement system(binds/activates C1), enhancing phagocytosis(igG), stimulating NK cells(act as opsonin).

___________ is innate immunity's hallmark & most important mechanism.

Inflammation, which is mediated by phagocytes.

Neutrophils secrete _______ which converts plasma proteins from liver into activated Kinins.

Kallikrein. Bradykinin(end product of kinin cascade) activate pain receptors, dilated blood vessels, and acts as powerful chemotaxin

Lymphocytes remain dormant as _____ lymphocytes until exposed to their specific antigen.

Naïve Lymphocytes

___________& ____________ are the important phagocytic specialists for innate immunity.

Neutrophils & Macrophages. they inhibit the spread of invaders throughout the body.

Lymph organs

Primary:Bone marrow & Thymus(on heart) Secondary:Spleen, tonsils, lymph nodes, & MALT/GALT tissue(Mucosal associated and Gut associated)

Lymph is like plasma but without ________ concentration

Protein. Plasma has protein wich kidneys filter, but lymph has none.

RLR's

Retinoic acid inducible gene 1 (RIG-1) like receptor

Pyrogens

Secretes by inflammatory stimulated phagocytes. Stimulated hypothalamus to elevate body's set temperature(fever). this fever can be good, and causes the liver & spleen to give up iron and zinc which is needed by microorganisms to grow and divide. It also increases rate of chemical reactions with speeds up tissue repair.

Delayed Hypersensitivity

T cell mediated immune response: usually a delayed response of the skin to an allergen exposure. -Tcell system had been previously sensitized to allergen, an asymptomatic exposure resulting in production of memory T cells _delayed skin eruption reaches peak intensity in 1 to 3 days -inflammation caused by cytotoxic T cells release of lymphokines -treat with avoidance & corticosteroids -Poison ivy, poison oak or detergent allergies

*Majority of B-cell antigens are T ________ antigens..

T dependent antigens.

Thymus is most active during fetal life, atrophies with age. It produces _________ which is a hormone needed to maintain T-cells lineage in lymphoid tissue.

Thymosin

Phagocytic cells have pattern recognition receptors such as ____-_____ __________ on their plasma membrane & cytosol that recognize & bind to PAMPS & DAMPS.

Toll-Like Receptors

Eyes of the Innate Immune system

Toll-like Receptors

______-______ __________ help phagocytes recognize & engulf infectious bacteria with standard cell wall components not found in human cells.

Toll-like receptors. Act as sign.

Neutralization

by combining with toxins or viruses they are prevented from interacting with susceptible cells

Agglutination

cross liking of multiple antibody molecules form antigen-Ab complexes with makes precipitation.

T Lymphocytes

differentiate, mature & become immunocompetent in thymus

Damps

endogenous patterns-molecules released from damages tissue such as ATP.

IL-: interleukin 1

enhances proliferation & differentiation of B & T lymphocytes

Pamps

exogenous patterns- part of bacterial cells walls that are not found in human cells- bacterial carbohydrates

Classical Complement Pathway

exposure to antibodies produced by adaptive immune response against the micro-organism

Alternative Complement Pathway

exposure to carbohydrate chains on surface of micro-organisms

phagocyte

general term to eating cell

Autoimmune disease

immune system fails to recognize & tolerate self antigens of particular tissues -possible causes: exposure of normally inaccessible self antigens, modifications of self antigens by factors such as drugs, viruses, environmental chemicals, or genetic mutation, or exposure of foreign antigens structurally similar to self antigens, and lastly persistence of fetal antigens in mothers system long after childbirth.

Cell mediated immunity

immunity mediated by activated T lymphocytes (T cells) which directly lyse infected or cancerous cells & release chemicals that regulate the immune response

hypersensitivity or allergies

inappropriate specific immune reactivity to a normal harmless environmental substance called an allergen- two categories: 1.immediate hypersensitivity-appears within 20 minutes following exposure, involves B cells & igE antibodies 2.Delayed hypersensitivity-reaction doesn't show up until a day or so following exposure, involves T cells.

Inflammasomes

multi protein complex in cytosol which brings about a potent inflammatory response.

Sensitization period

on first exposure to new allergen help T cells secrete IL 4 which activates B cells to synthesize igE antibodies specific for the allergen. No initial symptoms, memory cells are primed.

It is believed that we have more allergies to due to the decrease of __________ ________.

parasitic worms

When a B-cell's BCR binds to its specific antigen is differentiates most of the time into _______ _____. A few will differentiate into dormant _______ _____.

plasma cell & memory cells(few)

Tolerance

prevents immune system from attacking the person's own tissue.

Immunodeficiency

production or function of immune cells is lacking or abnormal

Antibodies (immunoglobulins)

proteins of which there are several antibody subclasses: -igM:serves as BCR for antigen attachment, helps bind -igG:most abundant immunoglobulin in blood -igE: fights parasited & is mediator for allergic reactions -igA: in digestive, respiratory, & urogenital secretions, found in breast milk & tears. -igD: on surface of many B-cells, unknown function.

Vaccination (immunization)

purpose is to develop memory for antigen-MMR/Hepatitis C. -thus, a strong, fast, potent secondary repossess will occur on exposure. -person is given attenuated viral particles- stripped of disease inducing capabilities(dna,rna).

4 cardinal signs of acute inflammation

redness, heat, pain, swelling

Active immunity

self generated-production of antibodies is result of exposure to an antigen.

Inflammatory response

1. Resident macrophages starts phagocytosis & release chemotaxis(leave trail) & cytokines. 2. Mast cells release histamine which cause localized arterial vasodilation for increased blood flow 3.Histamine also increases capillary permeability by enlarging their pores causing localized edema(swelling), redness, heat & pain Clotting factors activate & fibrin forms interstitial clots which helps wall of & contain the infection(like yellow tape at crime scene) 4. Migration of leukocytes within an hour after injury. Neutrophils arrive first followed by monocytes in 8-12 hours.

The two separate but overlapping branches of adaptive immunity

1. antibody-mediated or humoral immunity:involves antibody production by B lymphocytes which attack free existing invaders like bacteria 2. Cell-mediated immunity: involves activated T lymphocytes that attack virus infected cells & cancer cells.

Helper T cells (CD4) augment all aspects of the immune response by secreting regulatory cytokines. 6 main ones?

1.B-cell growth factor(IL4, IL 5, IL 6): work in concert with IL-1 from macrophages to improve B cell function. 2. T-cell growth factor(IL 2): augments cytotoxic T cells activity. 3.Chemokines: chemotaxis that lure more neutrophils & macrophages to area. 4. Macrophage migration inhibition factor: inhibits outward migration of macrohages thus keeping them in area 5. IL-5: activates eosinophils 6. IL-4: promotes igE anitbody secretion to fight parasites

8 different mechanisms involved in tolerance?

1.Clonal deletion:in thymus, apoptosis of immature cells 2.clonal anergy: two signal needed to activate T cells 3. Receptor editing:self reactive B cells are reprogrammed 4. Active suppression by regulatory cells T reg: inhibits clones 5.immunological ignorance or antogen sequestering: some self molecules are hidden from immune system-thyroglobulin 6.immune privilege: eyes & testes- contain molecules that trigger apoptosis in any approaching activated lymphocytes 7.activation induced cell death: occurs in some self reactive cells 8.release of anti-inflammatory IL-10: released by immune cells

Pathogen

A disease causing organism, bacteria & viruses are most common

Immune Surveillance

A function of the T-cell system, to recognize & destroy potentially cancerous cells.

Antigenic Determinant

A site on a complex antigen which is capable of activating T cells or B cells

dendritic cells

similar to macrophages, they have many surface projections like dendrites on neurons, phagocytes found in skin & mucosal linings. -after antigen exposure, dendritic cells migrate to lymph nodes where they cluster & activate T cells.

Plasma cells produce ________ which combine with specific antigen that stimulated the B-cell.

Antibodies

Immunoglobulin

Antibody; soluble plasma protein(gamma globulin) secreted by activated B cells called *plasma cells in response to presence of an antigen

IL-1 & IL-6 & TNf

stimulate release of acute phase proteins from liver such as C-reactice protein, a nonspecific opsonin & is a blood marker for inflammation

*TNF- tumor necrosis factor

stimulates histamine release from mast cells. *Mast cells actually secrete histamine.

Adaptive immunity-Antibody/humoral immunity

Antigens to which B cells respond to: -T independent antigens: stimulate antibody production without T cell involvement. Usually polysaccharides -T dependent antigens(majority): antigen deos not directly stimulate b cell but rather needs aid of helper T cells. Typically protein antigens.

Antigen

Any foreign substance introduced into the body that stimulates a specific immune response

Immunity

Body;s ability to resist or eliminate harmful foreign material/ microorganisms

Antibodies/immunoglobulins

Composed of 4 interlinked polypeptide chains- two long, heavy chains & two short, light chains: in shape of a Y. -two arm regions: determine specificity, what antigen antibody can bind to. -Antigen binding fragments (Fab): variable regions on the tip of each arm that bind to specific antigen -One tail region:determine functions, what the antibody does once it binds to the antigen -Constant(Fc) region: antibody's tail, contains binding sites for mediators of antibodies subclasses. Acts as opsonin.

Mediators of inflammation

Cytokines: from defense cells -nitric oxide:toxic to bacteria -lactoferrin:binds iron which bacteria needs for division Interleukin 1 (IL-1), Interleukin 6 (IL-6) & tumor necrosis factor(TNF): responsible for systemic manifestation of inflammation(body wide effect) Act as endogenous pyrogens that cause release of prostaglandins from hypothalamus and increase temperature.

3 types of T-Cells

Designated by their role or by specific surge protein given official closer of designation(CD) numbers. 1.Cytotoxic(Killer) T Cells: destory host cells harboring any foreign antigen such as virus infected cells or cancer cells. Coreceptors designated CD8-called CD8+ T cells. 2.Helper T cells: modulate or "turn on" power of other activated lymphocytes & macrophages-"Master switch". Coreceptors designated CD4-called CD4+ T cells. 3.Regulatory T cells:subset of CD4+ cells but have an additional CD25 receptor for IL-2 which promote Treg activities. Correctors CD4 & CD25-called CD4+CD25+ T cells.

Phagocytosis

Engulfs foreign material in vacuole. Enzymes from lysosomes digest the material.

Antimicrobial proteins

Enhance the innate defenses by: -attacking microorganisms directly -hindering microorganisms ability to reproduce The most important antimicrobial proteins are: interferon & complement Proteins

Adaptive specific or acquired immunity

third line of defense- mounts attack against specific foreign substances -takes longer than innate system -targets invaders that the body has previously been exposed to involves B lymphocytes & T lymphocytes -works with innate system