Day 4 Part 1: Immunology and Adaptive Immunity

What happens upon recognition? T cell

CD4 T helper 1)Antigen binds to Antigen presenting cell (in this case is a macrophage)--> CD4+ helper cell recognizes--> makes cytokines to enhance phagocytosis-->Cellular Immunity** 2) Antigen binds to Antigen presenting cell (in this case B lymphocyte)--> CD4+ helper cell recognizes--> releases cytokines to enhance B cell antibody secretion CD8+ Cytoxic 3) Cytotoxic- MHC1- can be any cell of your body that is infected with antigen- presents via MHC1 to CD8 cell--> kills infected cell-->Cellular Immunity**

3 Requirements for T cell activation

CD4 and CD8 cells 1) Antigen presentation and recognition (MHC-TCR) 2) Costimulation: B7-CD28 ** (this interaction called coreceptor) 3)Cytokines: Many (IL-12, IL-4, IL-6, etc) --APC- makes cytokines- tells t cell its time ( taking from the infected area); cytokine pool are the directions for the t cell- ONLY for CD8 cells -in some cases CD8 can get help from CD4 cells- if have activation from CD4 cells it makes cytokines that ramps up CD8 cycle

Contraction and Homeostasis

pull back down -non memory lymphocytes- die away -as have effective immune response gets rid of stimulus

Consequences of CD4+ T cell activation

CD4+ cells (T helper) - diff subsets direct immune responses by activating other cell types; subdivided based on way activated --*Subset identity is dependent on cytokines present during activation (marching orders) Cytokines- things that differentiate between WHICH CD4 subsets that we get

Consequences of CD8+ T cell activation

CD8+ cells (T cytotoxic)- eliminate cells hrboring microbes by inducing apoptosis Steps Antigen recognition and binding of CTL to target cell--> CTL activation and granule exocytosis--> apoptosis of target cell CTL- cytotic T lymphocyte What CD8 cell makes-- 1) Granzymes- gets into cell and activates enzymes that induce apoptosis 2) Perforin- perforates cell membrane

Antigen-Presenting Cells (APC):

Capture, process, and display microbial particles (antigens) for lymphocyte activation; key to get lymphocyte response

Complement:

Collection of circulating proteins that interact to modulate immune responses - not as dynamically regulated- a lot of complement floating around and get activated on occassion

Non-neutrophil Granulocytes:

Contain cytoplasmic granules with various inflammatory and antimicrobial mediators -other category- unload theri cargo quickly

After the fact

Contraction and homeostasis Non reactivity to self

Th2 cell function (allergy)

Cytokines IL-4, IL-5, IL-13 Immune Reactions -Mast cell degranulation -eosinophil activation -IgE production Role in diseases- allergic disease

Th17 cell function

Cytokines IL17A; IL-17F; IL-22 Immune Reactions Neutrophilic, monocytic, inflammation Host Defense- -Extracellular bacteria; fungi Role in Diseases Autoimmune and inflammatory diseases

Th1 cell function

Cytokines- IFNy (gamma) Immune Reactions -Macrophage activation -IgG production (for opsonization)- all antibodies can opsonize; opsonization important for phagocytosis Host Defense -intracellular microbes Role in Diseases Autoimmune diseases; tissue damage associated with chronic infections

Opsonization:

Decoration of targets to promote recognition by leukocytes

Antigen Presenting Cells (APCs)

Dendritic Cells Classic APC (BUT macrophages and B cells are other APCs) -serve as bridge between innate and adaptive immunity -multiple classes -have long dendrites used to contact and engulf materal -Prominent in skin, mucosa, tissue parenchyma Primary function- travel to lymph nodes following uptake of microbes, and display antigen for lymphocyte activation

T cell activation from dendritic cell persepctive

Dendritic cell captures antigen and leaves epithelial layer and enters lympathics--> being reprogrammed on way back (process antigen and puts on outer surface)

Cytokines:

Dynamically secreted protein mediators that coordinate immune responses -allow communication between cells of the immune system

Fab

Fab: Domain required for antigen recognition

Innate Lymphocytes:

Functionally and morphologically similar, but not antigen-specific

IgE

Help from Th2 -Allergy -defense against helminths -mast cell degranulation (hypersensitivity reactions- allergies)

Helper T cells (CD4+)

Helper T cells (CD4+) clonally expand upon activation and mobilize chemical mediators promote numerous immunological functions. -clonally expand under right conditions when activated and make chemical mediators ex: cytokines- give directions to other cells of immune system

Spleen

Highly vascularized, serving similar purpose as lymph nodes for blood-borne agents -Blood version of lymph nodes -can pull together immunological components -blood born pathogens often first recognized in spleen (in terms of adaptive immune response)

Differentiation and Effector Functions

How these cells do what it is we need them to do

Compare and contrast humoral and cellular immune responses

Humoral Extracellular pathogens; b cells and antibodies -b cell do not require APC via MHC -B cell binds to antigen- clonal diff- plasma cells that secrete antibodies- default is IgM involved in complement activated via classical pathway others are IgG, IgE, IgA, or IgD

2 types of antibodies Naive B cell express

IgM IgD

Type III

Immune Complex Diseases Antigen-antibody complexes form in circulation, possibly depositing in blood vessels and promote complement activation and inflammation ex: Lupus Antibodies that bind antigen that makes complex- displays Fc receptors all over the place- deposit on the surface of blood vessel or tissues- display all Fc portions- activate all cells in area that Fc receptors- activating cells that dont want to Antibodies bind to something they shouldn't- create aggregate of antibodies- stick themselves in blood vessel or tissue and have Fc portions sticking out which activate cells like macrophages that have Fc receptors and phagocytose for example

Phagocytes-

Ingest and destroy microbes; removal of damaged cells

Phagocytes:

Ingest and destroy microbes; removal of damaged cells; also involved in process of getting rid of waste and damaged apoptotic cells

Phagocytosis:

Ingestion of targets (microbes) for destruction. Enhanced by... Opsonization:

Types of immunity

Innate -always present -equal to all its peers -can recognize a bunch of things -respond to many foreign stimuli -very fast; less selective Adpative (acquired) -adapts to presence of a particular invader -recognize one thing -lymphocyte drive- clonal expansion that amplifies targeted response -one cell one target -slower but selective and robust -need one another -for adaptive immune to be activated it has to be turned on by aspects of innate immune system; also has to fortify components of innate immune system

Differentiate innate and adaptive immunity

Innate -less specific -cells (like MHC) recognize non self based on pattern recognition -faster; less specific Adaptive -lymph nodes -Lymphocytes; involves T cells (that matured in thymus) and B cells (that matured in bone marrow) -Receptors on the cells- built for one target -slower a few days -antibodies secreted for example can cause inflammation and recuitement of cells of innate immune system effective immune response involves integration of both

Road to defense

Innate immune system- ready and waiting; in first 2 hours of infection- all have to work with; if not enough it can deliver pathogens to adaptive immune system Adaptive immunity B or T cells,

What does Antigen presentation require?

MHC

Non-neutrophil Granulocytes

Mast Cells Basophils Eosinophils "other category"

Lymphocytes: T Lymphocytes

Mature in the thymus -Different subsets -Distinguisehd by patterns of surface markers (how differentiate?- CD) - Naïve T cells are raised against single pathogens, recognized via unique T cell receptors (B cells use antibody as receptor T cels use T receptor) 1 T cell - 1 target a) Helper T cells (CD4+) b) Cytotoxic T cells (CD8+)

Fc:

Mediates effector functions of antibody by: -Binding Fc receptors to initiate phagocytosis and leukocyte activation -Binding complement to activate classical pathway

Antigen (Ag)

Molecule (typically foreign) recognized and targeted by select leukocytes

IgA

Mucosal Environment because can cross mucosal membrane -GI and resp tracts

Rank the normal distribution of immune cells in a healthy individual

Neutrophils- most abundant- about 60% Lymphocytes- about 30% Monocytes Eosinophils Basophils General primary lymphoid organs -Bone marrow -source all hematopoietic progenitors and site B cell maturation -Thymus- site T cell Peripheral- secondary/lymph organs

Diff cell types

Phagocytes: Neutrophils Monocytes/macrophages Antigen Presenting Cells Main: Dendritic Cells B Lymphocytes Macrophages Lymphocytes B T

Type IV

Primarily caused by autoimmunity -CD4 and CD8 target parts of your body- not pathogen DTH ex: CD4 cell amking too many cytokines or CD8 cell targeting cell with self antigen

location cells

Primary/Generative lymphoid organs- where cells are made and where cells mature 2- 1) Bone marrow- source of all hematopoietic progenitors which give rise to leukocytes- every single leukkocyte requries progenitor from bone marrow (progenitors from bone marrow can go to thymus and become t cell) -site of b cell maturation 2) Thymus- -site of t cell activation

How do T cells help B cells?

Promote affinity maturation and class switching

Chemokines

specialize in directing leukocyte migraiton - category of cytokines that direct leukocyte migration (Chemotaxis) -cell that has receptor for chemikines- migrates towards the area of high chemokine concentration

Adaptive Immunity

Requires expansin and differentiation of lymphocytes in response to microbes before it can provide effective defense- it must adapt -Consists of lymphocytes and products (antibodies) 2 types -cellular (cell-mediated) -Humoral

Immunity and functions

Resistance to Disease; primary function- Prevent infections and eradicate established infections -Defense against tumors (immunotherapy) -Immune system recognies and responds to tissue grafts and newly introduced molecules (organ transplant ex) -Immune systen can injure cells and induce immunological response eX: allergies loss of function vs gain of function loss of function scenario- HIV- fewer CD4 T cells Gain of function- ramp up immune system with vaccines

Features adaptive immunity 1) Specificity

Response directed toward distinct antigens, representing different (specific) portions of a single protein, polysaccharide, or other macromolecule Epitope: recognized portion of antigen Subtle differences are considered unique (tiny part of that antigen that the t cell or b cell binds to)- where physical interaction occurs

Antibody (Immunoglobulin):

Secreted or membrane-bound glycoprotein that binds antigen "Ab" or "Ig". 5 kinds (IgM, IgD, IgG, IgE, IgA)

Non-reactivity to self

Self tolerance enabled by elimination or inhibition of self-reacting lymphocytes -development processes for t and b cells has checks and balances so dont respond to self antigens -doesnt always work (autoimmune disease)

Clusters of differentiation (CD)

Surface proteins used to define specific cell type; expressed in diff cells (including but not limited to lymphocytes) and diff stages of maturation

Th1

stimulate phagocyte-mediated ingestion and killing of microbes -macrophage activation

Lymphocytes

T cells Helper- recognize antigen that is presented to them the appropriate way (same for CD8 )- then make cytokines- go on to fortify any aspect Cytotoxic- need to recognize antigen that is presented to them- recognize infected cells- kill that cell Regulatory- can suppress immune responses B cells- uses antibody (antibody is membrane bound receptor) to illicit response-->makes antibodies Natural killer cells- can pretend to be CD4 or CD8 under correct conditions

Antigen recognition/whats required on the other side

T lymphocytes- T cell receptor (TCR) B lymphocytes- membrane bound antibody Variable (V) regions- antigen reognition domains; makes each cell unique -Constant; C- the invariant membrane proteins that antigen receptors are associated with; they deliver intracellular signals (do most of the work) Lymphocyte antigen receptor diversity is the primary factor driving diversity of the adaptive immune system (not MHC- MHC discrmininantly presents to anything around)

Antigen Receptor- T cells

T receptor -Forms of antigens recognized- peptides displayed by MHC molecules on APCs (ONLY recognize peptides not necessarily because MHC only presents peptides) -linear epitopes -Each clone has a unique specificity; potential for >10^11 distinct specifications

Humoral Immunity

Talking about B cells and antibodies -if have extracellular microbe floating around b cells can bind and respond (as long as bred to do so)-- secrete antibodies **talking about extracellular pathogens

CD4 Subsets

Th1 Th2 Th17 T helper- Th

Type I

Th2 Response Antigen is presented in association with MHC 2- given marching orders to become TH2 subset; same time B cell reaction to same antigen- find each other- b cells start making a lot of IgE (example of class switching)- Sensitization-- Fc receptors on mast cells recognize Fc portion on IgE- variable domain that recognizes allergen-- b cells stick around and make IgE-- sensitized mast cells Has early and late phase (need transcription and translation of cytokine)

Phagogyctes: Monocytes/Macrophages

Tissue resident macrophages- long lived Inflammatory macrophages- circulating monocytes derived from bone marrow precursors migrate to tissues where they mature into inflammatory macrophages -monocytes circulate they get in the tissues and become macrophages -better at cleaning waste than neutrophils -Primary function- killing via phagocytosis -other important functions- removal dead host cells, cytokine production, antigen presentation (APC)

Hypersensitivity reactions (Type I-V)

Type I- immediate hypersensitivity- ex: allergy Type II- Antibody-mediated Type III- Immune Complex-Mediated Type IV- T cell-mediated (t cells do too much) "Type V"- Subset of Type II -->antibodies bind receptors to stimulate or block functions- antibodies pretend to be receptor ligands or antagonists

Autoimmunity hypersensitivity reactions

Type II-IV

Germinal center reaction

aggregation of B and T helper cells that causes Isotype switching, affinity maturation, additional memory cells, long lived plasma cells

Phagocytes: Neutrophils

aka PMN -most abundant circulating leukocyte -circulate for hours and days (short lived 1-2 hours) -Granulocytes- ;ossess cytoplasmic granules containing enzyme and other antimicrobrial substances -segemented Primary function- killing via phagocytes

T lymphocytes- t cell receptor structure

alpha- light- yellow- Beta- heavy- green variable region at top; constant region at bottom

Leukocyte (WBC)

any cell of the immune system

Regulatory T cells

can blunt immune responses- not going to talk about much

Cytotoxic T cells (CD8+)

clonally expand upon activation and target infected cells for eradication. -CD8 can recognize cell thats been infected by intracellular pathogen and kill the cell- because cant get to pathogen

HIV

dont have CD4 T cells -importnat in helping CD8

IgG

help from Th1 -does everything

Timeline of events

if T or B cell encounters antigen T cell needs to be presented antigen- clonal expansion--> differtiate to become effector t cells, CD8,helpter etc--> t cell helping other cells or killing infected cells--> antigen eliminated--> contraction B cells can encounter antigen without antigen presenting cell--> clonal expansion--> differentiate to become plasma cells--> antibodies--> antigen eliminated--> contraction 1)Antigen recognition 2) Lymphocyte activation 3) entigen elimination 4) contraction (homeostasis) 5)memory

Way T cell help B cells

in a lymph node ahve a t helper cell responding to an antigen being presented by dendritic cell- at same time you have a b cell that has encountered this antigen and it responds (make more b cells and differentiate)- both happen at same time- as the effector cells are made and as cells respond but chemokine receptors change- change in a way that increases their movement toward each other in the lymph node-- then find each other--> if B cells present antigen to T cell T cells will secrete cytokines that will ramp up B cell response-- only twist- b and t cells find each other postactivation- as this goes on it makes germinal center reaction- then sends activated B and T cells to germinal center reaction where Isotype switching, affinity maturation, additional memory cells, long lived plasma cells different zones of lymph node- follicular and extrafollicular

Th17

induce inflammation and phagocyte recruitment for elimination of bacteria and fungi -Induces more inflammation; recruits things like neutrophils to an area -can easily have Th1 and Th17- if want neutrophils and phagocytosis

Humoral Immunity

involves B cells and antibodies -Involves macromolecules found in body fluids (humours) -Typified by antibodies (from B cells) and complement -Neutralizes and eliminates extracellular microbes and microbial toxins -Principal adaptive immune response targeting microbes with capsules containing lipids and polysaccharides -to get an apative response with a non-peptide antigen ONLY get that with B cells Why important? T cell receptor MHC interactions- PEPTIDE only

B lymphocytes receptor structure

light chain- yellow heavy chain- green variable region at top- antigen binding site Constant region- does the work- effector function

CD4 T helper cells with cytokines

with cytokines can hlep b cells an CD8 cell processes

Clonal expansion

*Important for adaptive immunity Proliferation of lymphocytes following antigen exposure Clone: Set of identical cells -Same principal applies to B and T cells -naive cells that encounter antigen rapidly divdie (clonal expansion)-

Lymph nodes

-Aggregates of tissue located along lymphatic channels -Exposed to lymph draining from blood and tissues -Concentrate antigens, APCs, and lymphocytes for immune activation -immunological rich tissue -pulling together antigen

Lymphocytes: B Lymphocytes

-B cells mature in Bone marrow -naive b cells are raised against single pathogens, recognized via unique B cell antibody receptors: 1 B cell- 1 target Primary function: -Activated B cells clonally expand and become plasma cells, which secrete antibodies that target specific microbes for eradication -Can also function as an APC** under diff surfaces b cell can activate t cell* -maturation- process when lymphocyte is told what it can respond to (have precursor then get cell that knows what it can respond to)

2 types cellular immunity

-CD4+ T cells activate phagocytes for microbial killing (leukocyte activation) CD8+ CTLs induce apoptotic death of infected cells. Induction of resposne--> antigen recognition in lymphoid organs--> differentiated effector t cells enter circulation--> migration of effector T cells and other leukocytes to site of infection--> effector t cells encounter antigens in peripheral tissues--> activation of effector t cells--> T cell effector functions (also where memory cells come from-- effector/memory) T cells are at center of everything- coordinate

Fc Receptor

-Can activate complement and elicit a lot of immune response

Antibodies (Immunoglobins)

-Composed of 2 identical heavy and light chains, with variable and constant regions Fab: Domain required for antigen recognition Fc: Mediates effector functions of antibody by: Binding Fc receptors to initiate phagocytosis and leukocyte activation Binding complement to activate classical pathway

Eosinophils

-Contain cytoplasmic granules filled with enzymes damaging parasites Potentially damaging to host tissues -can unload granules and can damage tissues due to constituents of granules

Mast cells

-Contain cytoplasmic granules filled with histamine -Responsible for many symptoms of allergic disease -Provide defense against helminths and other microbes -have granules that can unload under certain condition (like spring)- ex: histamine; responsible for symptoms of allergic disease

IgM

-DEFAULT (no Th help) -Activation of the classical pathway of complement -reason- pentomer- its conformation makes it more recognizable by complement

Peripheral (Secondary) Lymphoid organs

-Great at pulling cell together adn getting them in right place at right time -retain naive cells -can also mobilize activated cells ex: lymph noes, spleen, mucosal and cutaneois lymphoid tissue

Antigen presentation to T cells/purpose

-MHC requirement ensures T cell responses ONLY to cell-associated antigen --> reduces chance of immune response to harmless substance AND -->Brings T cell in proximity of other molecules on/near APC surface required or appropriate activation (ex: instructions) -Different processing pathways of MHC 1 and 2- intra and extracellular pathogens

Innate Lymphocytes: Natural Killer (NK) cells

-Morphologically, developmentally, and functionally similar to T cells. BUT...Do not express antigen-specific T cell receptor. Part of the innate** immune system (but can do a lot of the same things t cells can do) Unlike T cells of adaptive immunity, each NK cell recognizes the SAME repertoire of stimuli (i.e., they are all the same) -->NK cell activating receptors recognize infected cells, injured cells, and cells labeled with antibody (like a CD8 cell) -->NK activation results in cytokine production (IFNg) and/or the emptying of cytoplasmic granules which contain cytolytic enzymes.

Identify the cells of the immune system and describe the role each plays

-NK (Natural Killer)- non specific but acts like CD8- kills infected cell -APC- antigen presenting cell (for T cells)- B lymphocytes, macrophages, dendritic cells--> present via MHC 1 (CD8)-for intracellular/viruses or MHC 2( CD4) -Eosinophils: ex: mast cells -CD8/Cytotoxic T cells- Identified of CD- require MHC 1- kill via granzymes and perforin -CD4/T helper cells- identified by CD- require MHC 2- secrete cytokines-- cytokines from immune environment give it instructions to change into different subsets - Th1 cytokines-gamma ( phagocytosis- usually results with IgG if Th1 interacts with B); Th2 cytokines IL4,5,13 (allergy, defense against worms/helminths-->interacts with IgE) and Th17 Cytokines IL17,22-->recruitment of neutrophils B lymphocytes- do NOT require APC get signal-->clonal expansion-->plasma cell to secrete antibodies (IgM by default- activates complement via classical pathway), if get help from Th1-->IgG; if get help from Th2- IgE; other- IgA (all isotype switching)- requires T helper cells- go to germinal center reaction where isotype switching and affinity maturation take place Granulocytes Eosinophils, Mast cells, Basophils Phagocytes- Neutrophils- kill via phagocytosis; short lived; most abundant Macrophages/monocytes- longer lived; kill via phagocytosis; APC; also removal dead organisms, etc/clean up Dendritic cells- APC (innate immune system)- bridge between innate and adaptive

Basophils

-Similar to mast cells; have granules Constitute small percentage of circulating leukocytes Importance uncertain

Complement

-always circulates throughout body -activation of complement-proteolytic cleavage of inactive complement proteins leads to immunologically active complement components -Activated in 3 ways- Alternative pathway, lectin pathway, and classical pathway -Antibody-dependent complement activation occurs only via the classical pathway

Classical pathway**

-antibody dependent -Complement component C1 recognizes Fc portion of antibodies on microbial surface-- C1 binds to Fc portion -IgM and IgG good at it -Cascade converges at point of C3b activation- which can bind directly to bacterial surface

MHC- Major histocompatibility complex

-area of genome that determines tissue graft acceptance/rejection (-"histo"- tissue (compatibility) -called human leukocyte antigen (HLA) -most polymorphic gene- diff among individuals -not combination- hardwired into genome how relates?- low likelihood that 2 outbred individuals inherited the same MHC alleles (HLA mismatch- organ transplants) *Antigen presentation: MHC locus encodes class I and class II MHC molecules on APCs that display antigen to CD8+ and CD4+ T cells, respectively. class I MHC- presents antigen to CD8 class II MHC- presents antigen to CD4

B cell-mediated immune responses

-engagement of receptor+ other signals--> cause colonal expansion and differentiation into plasma cells -plasma cells secrete large amounts of antibody -responses to diff antigens are T-cell depdendent (protein) and T cell independent (All others) -Activation can lead to (depends on stimulus) -Class switching- release of different, perhaps more appropriate type of antibody -Affinity maturation: improved antibody binding both change the conformation and effectivenes AND require t cells

Mucosal and cutaneous lymphoid tissue:

-immunologically rich areas function like lymph node but on mucosal surface Additional concentrated areas of immunological activity Examples: tonsils, Peyer's patches(gut), respiratory tract...etc.

Cytokines

-incredibly diverse; dynamically regulated (0 to 60 very fast) Primary functions- -Growth, differentiation and/or activation of leukocytes -cause inflammation Chemokines- category of cytokines that direct leukocyte migration (Chemotaxis) -allow cells in immune system to tlak to each other

T cell circulation (from perspective of t cell being activated)

-most* T cells circulate through lymph nodes daily -naive t cells during circulation express receptors for chemokines; as going through lymph node epxress receptors for chemokines- as t cell gets to lymph node it is attracted to lymph node (chemokine gradeint)- if gets there and encounters antigen presenting cell- it gets activated--> clonal expansion--> then becomes large pool of effector cells--> escapes lymph node--> goes out to body--> has receptors for other chemokines that pull cell where it needs to be

Th2

-stimulate phagocyte-independent, eosinophilic-mediated immunity against helminths -Inhibit Th1 responses -Promote allergy by increasing IgE production and mast cell degranulation (T helpers can help B cells) What mediates immunity against helmenths and other worms

MHC Features 1)

1) Codominant epxression- both parental alleles of each MHC gene are expressed- mom and dad--> so increases # of diff MHC molecules that can present peptides to T cells 2) Polymorphic genes- many different alleles are present in the population--> ensures that different individuals are able to present and respond to diff microbial peptides 3) MHC- expressing cell types: ClassII: (only expressed by-) dendritic cells, macrophages, B cells--> CD4+ helper T lymphocytes interact with dendritic cells, macrophages, B lymphocytes Class I: All nucleated cells--> CD8+, CTLS can kill any virus infected cell

When generate immnune response really only 4 ways it kills something (primary effector mechanisms of the immune system)

1) Cytotoxicity- ex: CD8 and/or Natural killer cell- kill infected cells 2)Phagocytosis- neutrophil, macrophage- engulfs pathogen 3)Membrane attack complex- Formed by complement; if tweek complement right way it can literally poke a hole in bacteria 4)Neutralization- antibodies bind to pathogen and neutralizes it

Highlight the basic effector mechanisms controlling pathogen eradication

1) Cytoxicity (CD8) cells and NK cells- recognize infected cells and secrete granzymes and perforin 2) Phagocytosis- ex: CD4 cell secrete cytokines to assist with phagocytosis via macrophages; 3) Antibody neutralization- B cells secrete antibody that neutralizes 4) Lysis of microbe via MAC- poke hole in membrane via complement

Antibody Isotypes 5 different types (only 4 are secreted)

1) IgA (mucosal environment) 2) IgD (hangs out on surface and acts as receptor) 3) IgE (Help from Th2)- allergy 4)IgG (Help from Th1) 5) IgM (can be secreted or act as a receptor; by default and no help from T cells)

Antibody Effector functions

1) Neutralize microbes and toxins 2)Opsonization and phagocytosis of microbes (phagocytes recognize fc receptors) 3)Antibody-dependent cellular cytotoxicity (drive apopstosis) Activates complement which leads to: 1) Lysis of microbes 2)Phagocytosis of microbes opsonized with complement fragments 3)Inflammation other functions: 1)Eosinophil activation (ex: mast cells) 2)Helminth death

What does copmlement do?

1) Opsonization/phagocytosis--can opsonize and lead to phagocytosis- after cascade when C3B is bound directly to surface of microbe- opsonizes (salt) for phagocytes 2) Complement-mediated cytosis- Binding of C3b to microbe- activation of late components of complement--> Formation of MAC (membrane attack complex) that pokes a hole in the bacteria--> Osmotic lysis of microbe 3) Stimulation of inflammatory reactions-- complement fragments before and after C3b can drive inflammation--> more neutrophils--> more destruction

Immune Responses to tumors

main mechanism against tumors- cells that have CD8 Tumor cell --> tumor cells and antigens ingested by host APCs-->APC presents antigen to either CD8 via MHC 1 or CD8 AND CD4 via MHC 1 and 2--> CD4 released cytokines to help CD8 kill infected cell-->differentiation of tumor specific CD8+ T cells--> Tumor specific CD8+ CTL recognizes tumor cell

Cell mediated immunity 2 varieties

1)Macrophage+ CD4 Helper T cell-- activates cells that have engulfed microbes (ex: macrophage that has engulfed microbes- then CD4 helper cell reacts appropriately (has to be specific wit that pathogen)- releases cytokines to ramp up phagocytosis process in macrophage 2) Intracellular microbes (ex: virus) + CD8 cytotoxic cell- recognize and kills cell- induce apoptosis

MHC Features 2

4) Broad Specificity- Many different peptides can bind to the same MHC molecule- each of them can do a lot (3-4 MHC genes from each parent)- only one at a time **Can ONLY bind and present peptides 5)Each MHC molecule displays one peptide at a time--> each T cell responds to a single peptide bound to an MHC molecule 6) MHC molecules bind only peptides--> MHC- restricted T cells respond only to protein antigens, and not to other chemicals

2) Diversity

A large and diverse lymphocyte repertoire allows for an extremely wide range of antigenic specificities. ~billions specific antigens have responsive lymphocytes -Determined by different antigen receptors on T and B cell clones --Given antigen has 1,000-10,000 naïve cells (a clone) "naïve" = immunologically inexperienced; have not seen antigen

Capture and presentation of antigen to T cells

microbe lands on epithelial surface--> dendritic cell captures--> changes/morhps on way back to lymph nodes--> goes to lymph nodes where naive t cells are to display antigen -lymph nodes -spleen (blood borne)- free antigens can be picked up by Antigen presenting cells in spleen -increases likelihood certain cells interact

Th17 response

more common in extracellular bacteria -any scenario where want a lot more neutrophils

Lymphocyte clone

naive cells that are identical that can respond to one thing

Neutrophil function

Active phagocytes; number increases rapidly during short term or acute infections (Phagocytes=neutrophils)

Agranulocyte

non-granulocyte leukocyte

3 pathways complement activation

Alternative pathway lectin pathway classical pathway

DTH-Delayed type hypersensitivity

occurs 24-48 hours after a previously exposed individual encounters an antigen challenge (unlike type I) ex: PPD test for Tb is a DTH reaction

Antigen (Again)

piece of something that can elicit immune response

class II MHC-

presents antigen to CD4

class I MHC-

presents antigen to CD8

Type II: Antibody-mediated injury

Antibodies bind to self antigen on target cells/tissues to initiate 1) Fc-mediated inflammation; classcial complement cascade 2)Opsonophagocytosis 3) Binding cell surface receptors to initiate unwanted induction or inhibition of cellular processes bidn to fc receptors and try to phagocytose own cells- basically antibodies doing things shouldnt do

B cells can become

Antibody Secretion (Effector cells)- that secrete antibodies (plasma cells) Isotype Switching-(REQUIRES T HELPER) instead of expressing or secreting one antibody secrete a different type thats more specific Affinity Maturation( REQUIRES T HELPER)- (can make antibodies that bind more tightly

Memory

Antigen exposure enhances response to subsequent stimuli via generation of memory T and B cells -memory cells are ready and waiting- if encounter antigen again- response is more quick and robust the second time -NOT naive- has come from a cell that was exposed to an antigen

Antigen presentation to B cells?

B cells DO NOT require MHC for antigen presentation - B cells CAN be assissted by unprocessed (whole) antigen presentation from other cells but also and most often acts independently

Antigen receptor- B cells-

B cells- antibody (immunoglobin) Forms of antigens recognized-- macromolecules (proteins, polysaccharides, lipids, nucleic acids), small chemicals Diversity- Each clone has a unique specificity; potential for 10>9 distinct specialties

Lymphocytes:

Backbone of adaptive immunity; Launch distinct and robust responses specific to a single target (i.e., a single antigen) **Adaptive immunity

Type V

Binding cell surface receptors to initiate unwanted induction of inhibition of cellular processes -antibody stimulates receptor without hormone -makes more TSH hormone -Graves disease