41 - Innate and Acquired Immunity

Question 1

Initial Defence of Innate

Answer 1

Mechanical barrier
Skin - can be breached. Absorptive surface like GIT,RT more fragile > more mucus to compensate, also contain Langerhans cells (DC)
Moist mucus - trap debris, small particles, passively prevent adherence of bacterial cells and passage of molecule
cilia - waft mucus towards main bronchi > trachea > remove by coughing

Drainage and Irrigation
Free drainage - static fluid =nutritious site for organism. Impaired vesicouteric valve > reflux to ureter as bladder contract > recurrent infection

Chem protect
Acidic stomach
Lysozymes in tears
Bile acids

Norm bacterial flora
Non-invasive commensal bacterial imp (antibiotics can give opportunities for pathogens if not completely eradicated

Question 2

Innate immunity

Answer 2

broad
immune response are rapid
Not exhibit memory

Involve cells, inflammation, complement and

Question 3

Cells of Innate Immune sys

Answer 3

Dendritic cells - APC w/ long processes. produced continously in BM. Found in all tissue esp body surfaces. Local tissue injury > mediator > induce cells (x taken up Ag) > take up Ag by pinocytosis). PRR allow bacterial recog
Fct
- process Ag and present on MHC I or II to T cells
- Migrate to T cell rich areas of 2o lymphoid tissue where naieve and memory T cell recirc and present Ag to specific T cell
- transmit danger signal via molecule e.g. TLR to help determine T cell response

Granulocytes - short lived, facilitate destruction,

• neutrophils - kill EC bacteria and fungi via phagocytosis and NET. Granules
• eosinophils - more specialised, found in parasitic inflammed tissue and allergic process esp helminth (x phagocytic - reformed toxic mediators)
• basophils - 1o denfence for anything toxic. Release histamine and produce IL-4 and IL-3

Macrophages
derived from monocytes and mature in tissues and serous cavities
- Kupffer clls, alveolar macrophages, splenic macrophages, microglia, peritoneal macrophages
fct - phagocytose, degrade, take up Ag and present to Ag-specific T cell
- IL-1b, TNFa, IL-6, (increase perm, complement, fever) CXCL8 (recruit), il-12
- effects liver (APP e.g. CRP > complement =opsonisation0
- BM - neutrophil mob > phagocytosis
- hypothalamus - increase body temp
- fat and msc - protein + energy mobilisation > increase temp
- DC -migration, maturation >daptive response

NK cells - no ag specific recpetor, target cells w/o self MHC I (killer cell inhibitory receptor - KIR bind MHC I)
- phagocytose >granules > lysis
-death receptor mediated cytolysis
- migrate along IL-12 gradient
- stages are rolling/tethering> triggering> firm adhesion > extravasation
CR1 recptorsand Ig receptors

Natural killer Tc

• semi invariant TCr recog mammilian glycosphingolipid
• secrete cytokines iL4, ifny and target via fas-fas ligand

Mast cells - in blood tissues, surrounding BV, nerves, sin, mucosa. Sense pathogen/gying tissue > degranulation > release pre-formed mediators inc histamine and heparin> inflammation

• assoc w/ wound healing and pathogen defnense
• assoc w/ allergy

Question 4

Innate recognition of Pathogens

Answer 4

Patter recog recpetor (surface/internally) recognises PAMP

TLR - major group og PRR, recog many diff pAMPS

• surface TLR: TLR2-peptidoglycan, TLR4 - lippolysacharides and parasitic phosphates
• intracell TLR - TLR3 (viral DB strand DNA_

When PAMP binf, TLR trigger signal cascade w/i cell > activate genes > upreg inflam ctokines (mainly via MyD88 and NFkappa8) - defect = pyogenic infection
can also cause complement activation

Question 5

Complement

Answer 5

collection of sol proenzymes in blood and tissue fluid generally made in liver

3 pathways
Classical - AgAb complex (2 IgG/ 1 IgM) or CrP

Lectin bind pathway - bacteria, pathogen pamp recog by lectin in IL-1b and IL-6

Alternative pathway
- unknown pathogen ( activated by endotoxin and bacterial cell walls)

effects
mast cell degranulation, neutrophil chemotaxis, lysis, inflammation, opsonisation > phagocytosis

Question 6

Acquired Immunity

Answer 6

Supplements protection provided by innate
Provide Ag specific recptor (TCR + BCR) - precursor in BM

Mature T and B diff and prolif on Ag stim (generally 2o lymphoid organ)

Humoral immunity - via B C and circ Ab
B synth and secrete Ab by providinf cytokines
- 1o response - 1st encounter AG > ag attach to R > stim B >prolif and diff > some into plasma + some memory [helped by Th cells)
-20 response - memory cells recog ag rapid > prolif > ab > quck response

Ab fct
1) opsonisation
20 neutralisatio
3) immune complex form (phagocytosed when bound to Fc R) + complement activation
4) complement activation
5)direct cellualar activity - IgE on Fcer1 > mast cell degran, IgG on Fcyr1 >phagocytosis
6)Antibody depended cellular cytotoxicity - target opsonised by specific Ab > target for lysis

Cellular immunity - mediated by T c (not synth Ab), synth and rlease cytokines that affect other cells

1) T cell priming - leave thymus as immature > activated when bing APC T/DC w/ TCR >
2) TH1 - on MHC2/tCR w/ infected macrophage > IFNy and TNFa (enhanced by CD40+L) > induce macrophage kill by ROS, NO, lysosomal enzymes and peptides
3) CD8 - ctotoxic granules, perforine, granzymes > apoptosis + IFNy > activate macrophages

Lymphocytes recirc

BT coop
B cell bing ag > migrate to look for Th > interact > B becomes plasma

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