Overview of Innate/Adaptive Immune System

Question 1

Innate Immune System

Answer 1

1. Epithelial Barriers
2. Phagocytes
3. NK Cells
4. Complement

Question 2

Epithelial barriers

Answer 2

Produce natureal antibiotics

i.e. defensin

Question 3

Phagocytes

Answer 3

Macrophages, PMNs, Dendritic Cells
Neutrophils DO NOT communicate to adaptive immune system.
These cells do not need to be activated; always available

Question 4

Complement

Answer 4

Major humoral effector mechanisms
Family of proteins that exist in body fluids
Consists of
* Classical Pathway (uses peices of adaptive)
* Alternative Pathway
*Mannose Binding Lectin pathway

Question 5

NK Cells

Answer 5

Bone marrow derived cells
Involved in viral infection
Derived from lymphoid progenitor cells
Dont need series of activation
Recognize immuno comprimised cells that are not expressing MHC I

Question 6

PRR and DAMP/PAMP

Answer 6

PRR = Patern Recognizing Receptor
PAMP = pathogen associated molecular pattern
DAMP = Damage associated molecular patter

PRR recognize PAMPs/ DAMPs

Question 7

Clonal Selection

Answer 7

When T-helper cell gets activated by MHC II the cell rapidly divides
Each cell has SAME specificity for antigen

Question 8

B cells need _____ to undergo clonal expansion

Answer 8

recognition of antigen via surface MHC II by T-helper cell

Question 9

Extracellular Pathway

Answer 9

B cell and their products are hummeral immunity

Question 10

Intracellular pathway

Answer 10

Internal pathogens like virus
Cytotoxic T-cell recognizes MHC I
Cytotoxic T-cell expresses CD8+
Cytotoxic T-cell kills infected INTRACELLULAR cell

Question 11

HIV mechanism

Answer 11

HIV docs on CD4+ T-helper cells

HIV infects Th and inhibits production of cytotoxic T cells and Plasma cells from producing antibodies

Question 12

Examples of PRRs

Answer 12

TLR: toll like receptors
3: Recognizes DS RNA (endosomal)
5: Recognizes Flagella
4: Recognizes LPS
TLRs are upregulated by NFk-B

NOD: (Cytosolic) Nuclootide-binding oligomerizing domain
Activated by stress proteins within the cell

Mannose Receptor: only recognizes mannose as terminal sugar (bacteria put manose on terminal sugar
Activates manose binding lectin domain

Question 13

Activation of NK cells

Answer 13

KAR: killer activating receptor
recognizes stress proteins due to viral, tumor transformations
binding of receptor activates NK cell and kills target
i.e. NKG2D
CD16 of NK cell binds to Fc Portion of antibody on virus
CD16 is antibody dependent!!

Question 14

Inhibition of NK cells

Answer 14

Killer Inhibiting Receptor (KIR)

Receptor engages MHC I and inhibits activation

Question 15

T or F

PMNs are professional APCs

Answer 15

FALSE

PMNs ARE NOT ANTIGEN PRESENTING CELLS

Question 16

Professional APCs

Answer 16

Macrophages, Dendritic Cells - phagocytic

B cells- pinocytic and then present antigen

Question 17

MHC II

Answer 17

Made in ER
Made up of 2 polypeptide chains alpha & beta
embedded in membrane
multi-geneic complex
alpha1, beta 1 domain binds to bacterial peptide
anchor site binds 15-20 AA of bacterial peptide
In ER MHC II is inactivated by Invariant chain

Question 18

Activation of MHC II

Answer 18

In ER MHC II is covered by invariant chain
As MHC II migrates to late endosome invariant chain gets digested to small fragment that remains on MHC II called CLIP (CLass II Invariant chain associated Protein)
HLA-DM removes CLIP from MHC II to interact with digested bacterial polypeps in late endosome

Question 19

Genese of MCH II

Answer 19

HLA Genes (Human Leukocyte Antigen)
DP, DQ, DR
get two sets (one mom, one dad)
each gene is codominantly expressed
each loci has two genes one for alpha portion and one for beta portion
genes are constitutively expressed in APCs

Question 20

Cell mediated

Intracellular Pathway

Answer 20

Utilizes MHC I / CD8+ cells

Question 21

Activation of MHC I

Answer 21

Viral poly-peps (pp) get ubiquinated and taken to proteosome for degredation
Degraded viral pp get transported into RER via TAP (transporter associated-antigen presentation) (ATP Dependent transporter)
MHC I binds to viral PP and expresses on cell surface to get destroyed
MHC I binds to up to 9AA of viral PP
cells make MHC I constitutively

Question 22

Genetics of MHC I

Answer 22

HLA-A, HLA-B, HLA-C
On chromosome goes B, C, A
Multigeneic, multi-allelic and codominant
genes code for alpha 1, 2, 3 portion

Beta 2 microglobulin
Attached to alpha1 portion
Coded for on another chromosome but REQURED for transport of MHC I to outside of cell

Question 23

Ternary Complex

Answer 23

Complex that contains alpha1, alpha2, alpha3 from HLA-A, HLA-B, or HLA-C with beta2 Microglobulin
(MHC I)
The MHC I is also bound to viral PP

Question 24

Bacterial Poly Peptides that create response are called ________

Answer 24

immunodominant

Question 25

Why is it difficult to find a donor/ recipient in regards to MHC I?

Answer 25

Each person expresses at least 6 different MHC I genes
i.e. HLA-B26, HLA-C3, HLA-A2 from mom
HLA-B3, HLA-C16, HLA-A9 from dad

Question 26

Who expresses MHC I?

Answer 26

Cells that are infected with viral pp express MHC I with viral pp bound
Other HEALTHY cells express MHC I with self pp and are not destroyed

Cytotoxic T cells with CD8+ recognize infected target cell with MHC I and KILL