1. Innate Immune Response

2. Acquired/Adaptive Immune Response

• always the first to respond to an attack 
• fast, 1st line of defense
• primitive, never changes 

ex. mechanical and chemical barriers, phagocytes. active innate response

MECHANICAL: tears, skin, fluids

CHEMICAL: stomach acids, lysosome in tears

NORMAL FLORA: organisms on the skin and in the mouth, urinary, genital tract, etc. that outcompete pathogens and acidify the enviornment 

1. Recognition of Pathogens

2. Effector Mechanisms (responses that kill pathogens)

• slower, takes days to weeks to respond
• adapts with time to give a better response on 2nd and 3rd exposure 
• has memory for long term immunity 
• very specific (good and bad: no overlap between certain diseases)

Activation of effector cells - these cells are preexisting in the body and are equipt with receptors to identify billions of molecules; 

They are activated by the union of antigen (Ag) with it's receptor. If this occurs, the cell is 'selected' and the number of hte receptors increases (clonal expansion). 

only selected cells replicate to create clones (always recognize the same original molecule);

this increases response and is the basis of memory

Yes - both work to fight against attacking organisms; adaptive immunity becomes smarter and has memory so that after first exposure the response is faster and more specific; 

Both induce inflammation

a localized physical condition (tissue damage or destruction) caused in response to an infection and/or damage that eliminates or walls-off the infection or damaged area

characterized by: redness, swelling, heat, pain

1. skin damaged --> bacteria enter body

2. clot forms to stop bleeding and entry of more bacteria

3. resident cells (macrophages) secrete cytokines

4. cytokines induce inflammation

What is the purpose of inflammation?

fight infection

alert person of a problem via heat, swelling, redness, and pain 

1. Local Blood Vessel Dilation(Vasodilation): increases the amount of fluid that travels through an area; leads to redness

2. Vascular Permeability Increases : the area between cells fills with fluids (swelling), proteins and cells leave the blood and enter tissue (heat), increased pressure on nerve endings (pain)

a protein produced by animals which binds specifically to a foreign chemical structure on an antigen 

though similar, ≠ immunoglobulin

Red Blood Cells

• structure: small, round, disk-shaped with no nucleus 
• function: transport oxygen and aid in immunity

aka White Blood Cells; two types: 

1. Granulocytes

2. Mast Cells

WBC's that contain granules in their cytoplasm; the granules contain toxins that kill pathogens; 

have polymorphic nuclei

• short-lived
• produced in the bone marrow
• 50-70 percent of blood leukocytes in humans 
• rapid mobilization: 1st leukocyte to enter site
• professional phagocytes (bacteria) 
• major component of pus
• stain with neutral dyes

• fairly rare: 1-3 percent of blood leukocytes
• phagocytic
• kill parasites and worms (attach to worms and focus granuoles towards the worm to burn a hole = die)
• stains with red eosin dye

• small - about the same size as a RBC
• non-phagocytic 
• extremely rare: less than 1 percent of blood leukocytes
• involved in immune response - produce histamine
• worm and parasite defense

leads to: 

• vascular permeability
• smooth muscle contraction

white blood cell NOT found in blood

• found in tissues 
• not a granulocyte
• secretes histamine
• role in inflammation, parasite defense, and allergic reactions

• phagocytic, collect and process foreign Ag to present them to adaptive immune response 

• three types: 
• monocytes, macrophages, dendritic cells

Myeloid APC

• 5-10 % of blood leukocytes, 
• bean shaped nucleus
• phagocytic

• two types: 
• inflammatory monocytes, patrolling monocytes

• enter tissue quickly for inflammation 
• produce cytokines

• crawl along capillaries/blood vessels
• become tissue macrophages

• Myeloid APC
• large irregular shapes
• have vacuoles 
• phagocytic
• long lived
• role in inflammatory response by producing cytokines
• role as an APC in the acquired response

Myeloid APC

• star shaped cells with long processes/projections
• collect Ag in tissue and take it to site of immune response (lymphnodes, spleen)
• professional APC's
• pick up "garbage" neutrophils and monocytes leave behind

• usually very small
• prominant, round nuclei 
• when activated, cytoplasmic space increases
• 20-40 percent of blood leukocytes

• three types: 
• Natural Killer Cells, B Lymphocytes, T Lymphocytes 

Lymphocyte

• aka NKC's 
• large, granular 
• recognize and kill some virus infected cells
• effector cell of innate immunity
• must have NK1.1 protein on cell surface

Lymphocyte

aka T Cell

• large, granular when activated
• small when resting (not active in blood)
• recognize Ag through T cell receptors;
• can only recognize Ag when it is presented 
• two types: Helpter T's and Cytotoxic T's

Describe Helper T Cells

(TH)

• secrete cytokines to help other cells become effector cells
• always have CD4 on surface

• have T cell receptor
• recognize and kill specific virus-infected cells
• always have CD8 on cell surface

• Immunoforescence
• Ab is tagged with a fluorescent molecule; cells with a matching receptor will fluoresce in the presence of the dye

(CD) - all surface proteins on cells that are non-polymorphic have numbers that identify them

standardized throughout world...about 350 CD proteins right now

• (B Cells) 
• Small, resting in blood
• Ig on surface
• secrete Ab's
• often activated by Ag with the aid of TH's --> plasma cells --> Ab factory (eccentric nucleus, extensive RER)

The process of producing and developing blood leukocytes; 

Occurs in bone marrow (usually)

Pleuripotent Hematopoeitic Stem Cell differentiates --> to make: Common Lymphoid Progenitor or Common Myeloid Progenitor

Common Lymphoid Progenitor --> NK Cells, T Cell Precursor (then T Cell) and B Cells

Common Myeloid Progenitor --> Granulocytes, Erythrocytes, Monocytes, Megakaryocytes

1. Primary/Central Lymphoid Tissue - lymphocytes develop and mature here 

2. Secondary Lymphoid Tissue (Peripheral LT)

• lymphoid tissues develop and mature here

• a. bone marrow: major site of adult hematopoeisis; when B cells leave here they are essentially mature

• b. Thymus: T cell precursor enter here early in life (around gestation); most of the T cells are produced, developed and matured here

sites where mature lymphocytes go; site where lymphocytes are stimulated and respond to pathogens

blood leaves heart - arteries - arterioles - capillaries - fluid leaks out - interstitial fluid bathes the cell - blind ended lymphatics - draining lymph nodes - lymphatic vessels - thoracic duct - left subclavian vein 

1. Cortex

2. Paracortex

3. Medulla 

outer most layer of LN

B cell zone and Follicular DC's 

middle layer of the lymph node

T cell zone; also houses DC's

Innermost section of the LN, 

collects filtered lymph, Abs, and plasma cells

B cells enter the blood via high endothelial venuoles where they are then attracted to follicles by chemokines. If they do not find any Ag, they move to the next antigen. If they do become find their Ag, they move to the paracortex where they are activated by T cells. 

Then they either reenter the follicles or the medulla as plasma cells. 

The spleen is an organ that assists in immunity by: 

- filtering the blood

- removing old and damaged RBC's 

The spleen has two parts: 

- Red pulp and 

- white pulp

Red pulp is an area of the spleen that is the site of destruction of RBC's. 

It contains many Macrophages that filter out antigen and pathogen. 

Has large sinusoids where exchange of cells occurs

A region of the spleen that contains T cells, B cells, macrophages, and DC's. 

Made up of several zones - periarteriolar lymphoid sheath (PALs) which contains a central arteriole; follicles (B cell zone) that contain germinal centers; and the marginal zones where B cells and macrophages are found

A removal of the spleen due to trauma or injury is okay for adults because there have already been other lymphoid tissues developed than can take over filtration. 

In children, it leads to problems because bacteria with capsules and other certain pathogens are difficult or impossible to filter. 

MALT includes any moist surface (mouth, nasal area, intestinal tract, urogenital tract, etc.)

Bronchus associated lymphoid tissue (BALT) - lungs, bronchioles, etc. 

Nasal associated lymphoid tissue (NALT) 

Gut associated LT (GALT) - tonsils, adenoids, appendix, peyer's patches

Y shaped structure contains two identical heavy (H) chains and two identical light (L) chians;the binding sites on both ends are identical 

Held together by disulfide bonds

Kappa and Lambda 

An Ab from a single B cell can be either kappa or lambda, NOT both

Constant region: all kappa have the same; all lambda have the same

Variable region: AA varies with different Ab specificity

the varying (5) types of heavy chain constant regions

Ig G A M D and E

• pentamer (flower shaped)
• 5-10% of the blood's Ig
• held together by disulfide bond and J chain protein
• on B cells as B cell Receptors 
• 1st Ig secreted in response to Ag 
• 1st Ig produced by naive B cells 
• no hinge region
• generally only binds 5 regions at a time

• the most commonly found Ab in blood (about 73%)
• also in lymph and interstitial fluid
• protects the inside of the body 
• 4 sub groups (gamma 1 2 3 4)
• longest lasting - half life of 21 days in blood

the number of disulfide bonds, 

difference in AA sequence, 

function

• dimer with J chain 
• 10-18% of Ig in blood 
• major isotype in external secretions
• protects external surfaces and mucosal surfaces
• monomeric in blood, dimeric in secretions (J chain)

very rare - 0.16% of blood Ig

major purpose: B cell receptor on naive B cells

helps in activation of naive B cells

• extremely rare in blood
• monomeric when produced
• immediately binds to mast cells and receptors on basophils
• IgE arms are non specific in mast cells and basophils with a specific Ig E receptor 
• important in anti parasite and worm immunity 
• important to the allergic reaction

• there are only 3 regions where there is variability known as Complementarity Determining Region (CDR) - there are what bind to Ag = binding sites
• the rest is known as "framework"
• there are 3 CDR's in the L chain and 3 in the H chain

• Monovalent (1 epitope)
• Multivalent (2+ epitope); can be: 
• more than one type of epitope or multiple of the same epitope
•  

multiple weak interactions: 

• van der Waals
• hydrophobic interactions
• hydrogen bonding
• ionic bonds/electrostatic forces

combine to form a very strong bond

B cell receptor: Ig as an integral membrane protein

BCR + Ig alpha and Ig beta make up signaling complex

alpha and beta portions 

variable region with binding site (Valpha, Vbeta which have CDRs), constant region, disulfide bond, transmembrane portion and short cytoplasmic tail (too short for signaling)

1 - 5 (high numbers in epithelial tissue; recognize specific bacterial compounds (lipids, glycolipids, phosphorylated antigen)

can recognize native Ag

CD4 for helper T cells: contain 4 Ig-like domains, bind to MHCR Class II

CD8 for cytotoxic T cells: alpha-beta chains held together by disulfide bonds; binds to MHCR Class I

MHC I: for Ag from within cell -- "processing" and loading of Ag or bacteria to MHC I protein then taken outside of cell. Only TCR's and CD8 can recognize MHCI + Ag. Produced by most cells. 

MHC II: for viruses, bacteria, toxins from outside cell; phagocytized by M0 or DC then processed and loaded to MHC II protein then to membrane. Only CD4 can recognize MHCII + Ag. APC's (M0, DC, B Cells) have.

LN paracortex; helps T cells to find DC where Ag may be presented

Also found in the PALs in the spleen, the folliclesan cell areas to help B cells and follicular DC interact

the paracortex - 

follicles, germinal centers are found in spleen, LN, and all lymphoid tissue

What is the follicle of the lymphoid tissue? What is a germinal center?

large accumulation of B cells; mostly made up of resting B cells 

if Bcells activated by Ag, clonal selection and expansion occur -> more cytoplasm so spread out nuclei = germinal center (active immune response occuring)

A cytokine produced by leukocyte that affects the growth and differentiation of immune and hematopoetic cells

Interleukins are specific cytokines identified as IL-#

Chemokines are a subset of interleukins

Endocrine - cytokines released from cell and move to blood stream to act on other cells over great distance

Paracrine - cytokines released from one cell act on cell nearby

Autocrine - cytokines released from cell act on itself

1. Bind to Specific Receptors

2. Are Pleiotrophic 

3. Bind with High Affinity

4. Are Redundant

5. Synergistic

6. Are Antagonistic 

7. Cascade Induction 

8. Induce Receptor Expression on Other Cells

the effect of one cytokine can induced the effects of other cytokines - snowball effect 

(i.e. IL 12 activates T cells which induces the secretion of IFN8, IL2, TRF, and others)

• secreted early on in an immune response
• produced by monocytes, M0, DC
• generally pro-inflammatory
• many subclasses

• alpha and beta forms
• activated B and T cells that have been activated previously by Ag
• increases capillary permeability
• induces cytokine/chemokine production
• systemic effects once enters blood - from liver, induces production of acute phase proteins - from hypothalamus, induces fever to inhibit bacteria 

• blocks IL1 from binding to receptor to prevent the signaling for inflammation, capillary permeability and cytokine production 
• anti-inflammatory