how long does it take the body to detect the first response to an infection?

second response?

7-10 days

3-4 days

Active adaptive immunity

Natural:

Acquired:

Natural: patient acquired, and recover

Acquired: vaccination

passive adaptive immunity

Natural:

Acquired:

Natural:breastmilk

Acquired: patient given pre formed immune components.

recognize broad paterns of cells using molecular patern recognition receptors

coded in the DNA (so unchangeable)

for example NK recognize by lack of normal expression of molecules.

identify specific antigens.  DNA can change. 

T cells

B cells

good immunogens: BIG, proteins, carbs, complex

bad immunogens: small, lipids

Doesn:t matter: charge and shape

Immunoglobulin

(ig)

part of the antibody that is reactive(γ-globulin)

1.) they can be immunogenic

domain

region

domain: repeated primary AA regions in heavy and light chains

Region: variable part where it binds to antigens.  hypervariable region contacts epitope

• quicker
• more intense, more antibodies made
• more prolonged
• primary exposure most common is IGm.  secondary exposure most common is IGg, IGa or IGe.

• usually carbs or polymers
• directly bind to Ig antigen receptors and bridge them together
• only IGm has a role
• no memory response

Titer

Antiserum

Antiglobulin

Precipiten

Agglutimin

Hemolysis

Titer: inverse of highest dilution to illicit a response

Antiserum: serum that has antibodies

Antiglobulin: part of serum protein with antibody reactive against an antigen

Precipitin: an antibody that precipitates when it encounters an antigen

Agglutimin: an antigen that reacts with a cellular insoluble antigen resulting in clumping

Hemolysis: an antibody that causes lysis of a RBC

Affinity

Avidity

Affinity: sum of atractive and repulsive forces between AB and AG

Avidity: strength of binding of AG to AB

1. AG is incubated in plate, some stay on
2. plate washed, some G remain
3. excess binding sites are blocked by proteins
4. patient diluted blood added to plate, free AB washed away
5. secondary anti-immunoglobulin AB coupled to an enzyme is added, binds to patient AB, free AB washed away
6. bound AB is detectedby dye
7. light determines concentration

1. separate proteins and denature.  put on gel for elecrofloresis to determine protein size
2. transfer proteins from gell to immobalizing nitrocellulos membrane, electrical charge done.
3. excess proteins/AG binding sites on mitrocellulose membrane are blocked.
4. overlay mitrocellulose membrane with patient specimin containing AB
5. detect bound AB using elisa

Secondary binding test

Precipitation

ouchterloney.  patient sample loaded into gel matrix in dish, AB loaded nearby.  diffusion patern determines.  can find fungus disease

radial immunodiffusion test: known AB is mixed in gel matrix, AG loaded into punched holes in gell.  diffusion occurs, rings happen.  bigger ring, more AG.  can find isotype humoral immune deficiency

Immunoelectrophoresis: serum in punched holes, elecrophoresis occurs.  good to determine gammopathies multiple myelomas.

secondary binding test

direct agglutination

Pasive agglutination

direct agglutination: AB and AG comine, clumping happens.  good for blood typing

Pasive agglutination: known AB or AG bound to insoluble item like latex bead.  combbine with serum, see clumps.

1. opsonins C3b and C4b tag things to be phagocitized
2. recruit leukocites to an area(chemotaxis)

C1INH: binds to C1r and C1s causing them to dissociate from C1q.  also prevents spontanious C1 activation

DAF CD55: acts to dissociate C4b2b to inhibit the clasical pathway

Factor I: cleaves C4b following dissociation of C4b2b by DAF

Factor H: compete with factor B for binding to surface boud C3b.  inhibits the alternative pathway

Vitronectin: inhibits insertion of MAC, prevents cytolysis

deficient in C1,4,2,3 or I: more suseptible to infection by encapsulated bacteria, dificulty clearing immune complex.  impaired clasical pathway

deficient in C5,6,7,8: trouble handling blood born infections

Type I heredetary angiodema: low on C1 esterase inhibitor  results in spontanious edema.

Factor H deficient: lysis of RBC by alternative pathway

Properdin deficient: defect in alternative pathway, infections by encapsulated bacteria

MBL deficient: more suseptible to many bacteria.

• Non professional
• kill pathogens in extracellular by releasing lysosomes

• Non-professional
• kill extracellular

• professional
• major type of myeloid cell
• rabbit
• kill intracellularly or extracellulrly
• chemotherapy drugs lower neutrophils.

• professional phagocyte
• monocytes in blood, macrophage in tissue
• tortoise
• can perform antigen presentation to T cells.

1.) Chemotaxis: phagocytes follows chemicals from compliment to a site

2.) Adherance: at the site, opsonin helps phagocyte bind to material, by C3b and iGg.  C3b+IGg=synergize.

3.) Ingestion: phagosome surounds victim

4.) Destruction: digest/killing

1.) weak binding step allows rolling adhesion

2.) tight binding that arrests rolling adhesion and allows WBC to squeeze between endothelial cells (diapedesis)

IL-1β: activates vascular endothelium, lymphocytes, local tissue distruction, increase access of effector cells.  fever, production of IL-6

TNF-α: activate vascular endothelium, increase vascular permiability, more IGg/complement/cells into tissue.  fever, mobalize metabolites,shock

IL-6: activate & increase AB production.  fever, increase acute phase protein production.  regulates Albunin, fibrinogen, hemopexin, cysteine protease inhib.

IL-8: chemotactic factor, recruits WBC, activation

IL-12: activate NK cells, induce differentiation of CD4 T cells into TH1 cells

1.) adhesion molecules expressed on vascular endothelium

2.) pavementing and diapedesia

3.) chemotaxis of leukocytes

administered with immunogen, non specifically enhance immune response.

can prevent dilution/dispersion of the immunogen

cause mild irritation to enhance antigen processing.

(eg) alum.

enzyme that breaks IGg at hinge region into 3 parts.

2 parts (FAB) can still bind

1 part binds to compliment

mutations in hypervariable region when producing clones of B cells.  specific

when the B cells encounters an antigen it can become a pasma cell or a memory B cell.  hapens only after mature B cell with IGm and IGd.  if before, the B cell is destroyed (tolerance)

• most common
• neutralize toxins
• opsonization
• compliment
• cross pacenta
• bind 2 antigens at once

• Pentamer
• J chain joins the units together
• Monamer on B cells
• no hinge region, but extra constant domain on heavy chain (4 domains)
• first IG in primary response
• important for compliment
• neutralize toxins
• can bind 5 antigens at once

• secreted as 2 piece dimer linked by J chain made by B cells.  serum as monomer
• has secretory component produced by epithelial cells that protects IGa from denature
• external secretion in fluids like milk, tears, saliva

• extra constant heavy doman (4 domains)
• responsible for alergies
• non-aglutinating
• defend from parasites

• 1 less ss bond
• not secreted by plasma cells
• coexpressed with IGm on B cells as antigen receptor

Sensitivity

Specificity

Sensative: find the diseased.  good for results that are negative to rule out.  many false +.  Eliza test.  god fro screaning

Specific: exclude the non diseased.  helpfull when test is posative to rule in. many false -.  western blot.  good to confirm.

compliment

Clasical activation pathway

C1-> C4-> C2-> C3. 

activated by IC containing (2) IGg or (1) IGm. 

1.) C1 binds to AG, and gets activated to C1'

2.) C1' atracts, and claves a C4.  C4a goes away, C4b binds to membrane

3.) C1' atracts and cleaves a C2.  C2a goes away, C2b binds to C4b on surface.

now cell surface is {C4b2b} a C3 convertase

4.) C4b2b cleaves a C3.  C3a goes away, C3b binds.

now cell surface is {C4b2b3b} a C5 convertase

terminal pathway occurs

complement

alternate pathway

(properdin  pathway)

functions in absense of AB.

first we need an activator:  something that hydrolyses C3

1.) hydrolysis of C3 happens.  C3a goes away, C3b binds to cell surface. 

2.) factor B comes and binds to C3b on cell surface.

now cell surface is factorB-C3b

3.) factor D comes and breaks factor B, so Ba goes away.

now cell surface is C3bBb

4.) properdin binds C3bBb

now cell surface {properdin-C3bBb} C3 convertase

Completment

Lectin pathway

identicle to clasical pathway exept MBL is used instead of C1

so MBL, C4, C2, C3

destruction

resperatory burst

1.) cell makes NADPH oxidase

2.) O2 becomes make super-oxide anion O₂^- which combines with H to make H₂O₂ which interacts with myeloperoxidase to make hypochalide ion OCl^- which kills bacteria

Destruction

Phagosome-lysosome fusion

O₂ independent

lysosome fuses with phagosome (phagolysosome)

Complement

:a background

• mark cells for destruction
• goal is to make C3 convertase.  C3 has short life, so is rate limiting step
• final goal is to make MAC (straw) so ions go out, water goes into cell
• "anaphylatoxins C5a>C3a>C4a"
• "margination C5a"
• "chemoatractants for WBC C5a>C3a"
• "regulation of vascular tone C2 and C2 Kinin"

C6, C7, C8.-> {C9} group up to make the straw

triggered by C5b

C1inhibitor

regulates which pathway?

what if someone lacks it?

Regulates C1 (clasical pathway)

"dissociates C1r and C1s from C1q"

can also disrupt MBL (lectin pathway)

if lacking, "type 1 heredetary angiodema".  stress-> vasodilation/adema.  cant control vascular tone.  overproduction of C2a, C2a kinin

Decay activation factor

(DAF)

CD55

what does it regulate?

breaks clasical C3 convertase

Factor I

what does it influence?

Factor H

what pathway does it influence?

what happens of deficient?

competes with factor B for binding to C3b

alternate pathway

deficient = lyse RBC, and endothelium

anaphylatoxin inactivator

serum carboxypeptidase B

vitronectin

S protein

• suseptible to encapsulated bacteria
• poor at clearing IC, so have AID

deficient in C5->C9

deficient in C5->C8

C5->C9: can't make MAC

C5->C8: can't kill gram -.  meningitis.

Properdin deficient

increased infection by encapsulated, meningitis

alternate

suseptible to many bacteria

Lectin pathway

Basophil

Eosinophil

Basophil: regulate hypersensitivity

Eosinophil: allergy/parasites

1.) chemotaxis: C5a, C3a, C4a.  chemokines (interleukins).  diapedesis happens

2.) Adherance:  binding ↑ opsonins.  IGg1, IGg3, C3b

3.) Ingestion

IL1: local tissue distruction, fever, trigger IL6

IL6: fever, induce phase protein, FIBRINOGEN

IL8: NOT ACUTE PHASE RESPONSE.  chemotactic, activate WBC

TNFα: vaso permiability, fever/shock.

1.) rolling: cell adhesion molecules "selectins"

2.) tight bind: ICAM-1 "integrin"

3.) Diapedesis: CD31

4.) Chemotacis

Th2 cells

IL-4: induce growth and isotype switching of IGg1 and IGe

IL-5: turn B cells into plasma cells, and isotype switching ti IGa

IL-6: differentiating factor can be made by macrophages, epithelial, endothelial

IL-13: growth and differentiation of B cells, and isotype switching to IGe.  works with IL-4