biology hell

Membrane bound

TLR, Dectin, LPS, Mannose, Scavenger

Inside cell

PKR, Rig-1, TLR 3, TLR 8, Nod-1

TLR

starts signal cascade

Secreted

Opsonins and complement

Inflammation

Heat, redness, swelling, pain, loss of function

Cells follow trail of what?

chemokines

Rolling

Secretins are always expressed, low affinity

Integrins

Stop rolling, high affinity, squeeze out of blood vessels

Cytokine Inflammation

IL-6, Il-1, and TNF-alpha

Chemokines

CCL2, CxCL8

Prostaglandins

Pain and cox enzymes

Vasoamines

swelling

Clotting

Fibrinogen and thrombin make fibrin

Lymphoid progenitors

NK, B, T, and dendritic cells

Myeloid progenitors

Dendritic, Macrophages, Neutrophils, Eosinophils, Basophils, RBCs

Granulocyte-monocyte progenitor

monocyte-macrophage and neutrophils

GM-CSF

growth factor for myeloid cells

Ereythropoeitin

growth factor for rbcs

IL-3

Granulocytes/macrophages

IL-2

T cell growth factor

Monocytes/Macrophages

Macrophages-tissue, apc, makes cytokines

Neutrophils

main fighters

Dendritic cells

cross-presentation (both self and non-self)

Basophils/mast cells

basophils-blood, allergies because IgE, release IL-4

Eosinophils

toxic granules, th2

NK cells

MHC class I are being expressed

Primary tissues

Bone marrow and Thymus

Secondary tissues

lymph nodes, spleen, ALTS

MHC class I

HLA-A, B, C

MHC class II

HLA-DR, DQ, DP

MHC class 1 structure

1 chain, beta-2 microglogulin

Short peptide (8-10) inside

CD8- Cytotoxic T cells

MHC class I Presentation

ImmunoProteasome

Through TAP into ER regulated by IFN-gamma

MHC I and sent to surface

MHC class II structure

2 chains

Longer peptides (20) outside

CD4- Helper T cells

MHC class II presentation

Phagocytosis

Lysosome

loaded and sent to surface

cross-presentation

exogenous antigen on MHC class I

Activates Tc cells

Phagocytosis

Attach

Endocytose

Lyse

Present antigen (APCs)

Macrophage activation

IFN-gamma

CD8 T cells activation

Recognize peptide on MHC I

Perforin makes holes

Granzyme B goes through to induce cell death via caspase3

Fas ligand

NK cell activation

Activating and Inhibitory receptor

can it bind- kill

Has mhc class I- don’t kill

Complement

opsonizes pathogens

Causes inflammation

Clears immune complexes

Links innate and adaptive immune system

Classical

Antibodies

1,4,2

4 and 2 bind to surface to make C3 convertase

Alternative

C3 is lysed

Cleaves D to cleave B

MBL

starts with PAMP, mannose-blinding lectin instead of antibodies

Convergence

C5 makes 6,7,8,9

8 sticks in membrane

9 makes the channel

MAC pore in membrane

Opsonization of pathogens

Complement control

C1 inhibitors, Factor H

DEcay Acceleration Factor

CD59 inhibits C9

B cell receptor

Ig alpha/beta on side to send signal into cell

plasma cells make antibodies

Joining fragments

Rag1/Rag2

RSS tells enzyme to stick V and J

12s only goes with 23s

Random nucleotide insertions

TdT

Affinity Maturation

B cell is activated and rapidly divides

Mutate a little more

Binds to antigen on dendrtic cell

Antibody class switching

T cell dependent

Switch from IgM to something else

IgM

low affinity, high avidity

IgD

Naive B cells

IgG

High affinity, in serum

IgA

Dimer, secretions, high affinity

IgE

Allergies, mast cells/basophils, high affinity

B cell activation

CD40-CD40L

TCR

made same way

alpha/beta chains

Co-receptors (Cd4 and Cd8)

Positive selection

Has to bind

receives signal and lives

Negative selection

Has to bind to non-self

receives signal and dies

Activation of T cells

Binds to MHC class I on some other cell

Gets second signal from some APC (Dendritic, Macrophage, B Cell) B7

Th-1 cells

Cellular immune response (macrophages/neutrophils

IFN-gamma

Th-2 cells

Humoral immune response (B cells)

IL-4, 5, 10

Th-17

Fungi

IL-17

Type 1 Hypersentisity

Allergies

IgE

Histamine

Smooth muscle constriction

Blood vessel dilation

Antihistamines, epinephrine, steroids

Type 2 Hypersentivity

Antibodies

Blood stuff with IgG

Prevent with Rhogam

Type 3 Hypersensitivy

Antibody-ception

Clumps cause inflammation

horses

Type 4 Hypersensitivity

Th cells make INF-gamma

Macrophages go in and attack tissue

Central tolerance

positive/negative selection

Peripheral tolerance

Second signal in T-cells

Lupus

Systemic

Antinuclear autoantibodies

Arthritis

Systemic

Autoantibodies

Cytokines in joints with inflammation

Diabetes

Organ-specific

Th1 cells attack pancreas

Myasthenia gravis

organ-specific

acetylocholine receptors are blocked

Muscle activation is hard

graves disease

antibodies stimulate thyroid

Viruses always have . . .

genome and a protein coat

Viruses sometimes have . . .

envelope, multiple capsids, accessory proteins

Helical Nucleocapsid

Proteins directly wrapped around genome

Triangulation number

triangle of 1 means 3 proteins per face and icosahedron has 20 faces so 60

Positive sense

immediately be translated into protein

Negative sense

must be copied into positive sense first

faster

brings an enzyme

Viruses come from . . .

transposons and maybe RNA

need a large population to sustain virus

3 problems of viruses

Replication, infection, and avoiding the immune system

Acute infection

Large spike in virus and then cleared (flu)

Acute then latent infection

large spike in virus, cleared, brought back, then cleared again (Herpes)

Acute then chronic infection

Large spike in virus then never fully cleared (Hep B)

Persistent infection

Large spike in virus, never fully cleared, second larger spike (HIV)

Chronic infection

Slow but constantly rising (Prions)

Pathogenicity

ability to cause disease compared against other viruses

Virulence

ability to cause disease compared against other strains

Cytotoxicity

Damaging cells

Tropism

What can be infected

Cellular, tissue, organism

Influenza Structure

Amorphous

Enveloped

Spikes

Influenza proteins

Polymerase

Ribonucleoprotein

Matrix protein

Hemagglutinin

Neuraminidase

influenza Genome

ssRNA

8 segments

Negative sense

Influenza pathogenesis

Infects and kills cells in respiratory area

2-day incubation

Interferon causes most symptoms

Influenza immune evasion

Mutates a lot

Blocks interferon in cells by blocking Protein Kinase R (PKR)

Influenza replication

Occurs in nucleus

Steals caps from cellular RNA

Lots of dsRNA leads to lots of interferon

Genetic drift

accumulation of mutations

genetic shift

two different strains recombine their genome in the same cell

Measles structure

amorphous

Enveloped

Fusion protein

Hemagglutinin (different than flu) that binds to CD46 (on every cell)