Innate Immune System

Question 1

Innate Immunity

Answer 1

This is the first response, its fast, there is no specificity or memory

Question 2

Physical barriers in innate immunity

Answer 2

Skin and epithelial mucosa: Resp/GI/GU tracts
Cilia – muco-ciliary escalator

Secretions: sweat, tears, saliva, gastric acid, sebaceous glands, mucus, breast milk
Saliva: lysozyme, IgA, IgG, lactoferrin

Normal flora
Commensal bacteria – compete for nutrients, prevent attachment, release fatty acids and antibacterial proteins, prevent invasion
Lactobacilli in vagina – cause acidic pH (4.0-4.5)

Physiological
Temperature (fever), pH, location of immune cells within the bloodstream – can readily attack when and wherever microbes invade

Question 3

Cells of the innate immunity

Answer 3

phagocytes, eosinophils, basophils, mast cells, Natural Killer cells (NK)

Question 4

Complement in the innate immune system

Answer 4

acute phase reactants, cytokines, chemokines, matrix metallo-
proteinases, defensins

Question 5

Pattern-recognition receptors the innate immune system

Answer 5

recognition receptors such as toll-like receptors (TLR) binding to PAMPs
(pathogen associated molecular patterns) or DAMPs (damage associated molecular patterns to stimulate a response by cells of the innate immune system.

Question 6

Mechanisms of the innate immune system

Answer 6

Inflammation

Recruitment of immune cells

Activation of complement

Opsonisation

Phagocytosis (and endocytosis)

Question 7

Inflammation

Answer 7

Vasodilation
Loosening of endothelial tight junctions
Increased cell adhesion molecules
Chemotaxis
Smooth muscle contraction

Resulting from damage to tissue (prostaglandin and leukotriene release), allergens (mast cell degranulation, histamine release), microbial infection (release of endotoxins, exotoxins, TLR’s, Interleukins, nitric oxide), complement activation (C3a, C5a), autoimmunity (immune complexes, complement, T-cell)

Question 8

Phagocytosis

Answer 8

1. Phagocyte moves towards the microbe
2. Phagocyte attaches to microbe via opsonin
3. Endocytosis of microbe with phagosome
4. Phagosome fuses with lysosome
5. Oxygen-dependent species result in microbe death (lyzozymes, lipases, proteases, RNAses and DNAses)
6. Release of microbe products

Question 9

Cells that carry out phagocytosis

Answer 9

Macrophages, neutrophils, eosinophils, dendritic cells

Question 10

Chemostaxis of phagocytes

Answer 10

Chemically attracted to the site of infection

Question 11

Opsonization

Answer 11

Coating process with opsonins that facilitates attachment.

Question 12

Opsonins

Answer 12

Complement
Antibodies
Plasma Proteins

Question 13

Complement System

Answer 13

Large group of serum proteins that participate in the lysis of foreign cells, inflammation and phagocytosis

Question 14

Classical Pathway Complement System

Answer 14

Initiated by an immune reaction of antibodies

Question 15

Alternative Pathway Complement System

Answer 15

Initiated by direct interaction of complement protiens with microbial polysaccharides

Question 16

Consequences of Complement Activation

Answer 16

Cytolysis due to the formation of a membrane attack complex (C3b-C5-C5b) which produces lesions in microbial membranes

Inflammation due to complement components (C3a and C5a) triggering the release of histamine which increases vascular permeabilty

Opsonisation

B cell activation

Immune complex clearance

Question 17

Membrane Attack Complex

Answer 17

1. Antibody molecules attach to the antigens on the pathogens plasma membranes
2. Complements proteins link two antibody molecules
3. Activated complement proteins attach to pathogens membrane
4. MAC pores in the membrane and causes cell lysis

Question 18

Life span neutrophils

Answer 18

Few days

Question 19

Main function neutrophils

Answer 19

Phagocytosis

Degranulation release of bacteriocidal components (peroxidase, defensins, acid and alkaline phosphatases)

Question 20

Main targets of neutrophils

Answer 20

Bacteria and fungi

Question 21

Receptors Neutrophils

Answer 21

Toll like receptors
Complement
IgG 
Chemokine IL-8
Chemoattractant C5a
ICAM + VCAM - adhesion to endothelium

Question 22

Life span eosinophils

Answer 22

8-12 days

Question 23

Main function of eosinophils

Answer 23

Extracellular killing via degranulation of peroxidase, major basic protein (induced mast cell and basophil degranulation), IL-8 and cytokines

Question 24

Main targets of eosinophils

Answer 24

Parasites

Question 25

IL-5 and IL-3 stimulate

Answer 25

Production and release of eosinophils from basal membrane Expression of IgE receptors on eosinophils

Question 26

Main function of basophils

Answer 26

Degranulation release of histamine, prostaglandins and leukotrienes and cytokines (IL-4, IL-13)

Question 27

Main targets of basophils

Answer 27

Parasites

Question 28

Receptors of basophils

Answer 28

Surface bound IgE C3a, C5a anaphylatoxins Toll-like receptors

Question 29

Mast cells are present in

Answer 29

Tissues exposed to the external environment

Question 30

Main function of mast cells

Answer 30

``` Degranulatin through cross-linkage of IgE receptors Histamine Proteases Reactive oxygen species Cytokines – TNF alpha, IL-4, IL-13 Leukotrienes and prostaglandins ```

Question 31

Receptors on Mast cells

Answer 31

``` Surface bound IgE C3a and C5a Damage associated molecular patterns Toll like receptors Complement Others: that can bind drugs e.g. opioids / antibiotics ```

Question 32

Tissue based monocytes

Answer 32

Kupffer (liver), Microglial (brain), Mesangial (kidney)

Question 33

Life span of macrophages

Answer 33

Months to years

Question 34

Main function of macrophages

Answer 34

Phagocytosis Antigen presentation to T cells Release of TNF-alpha, IL-2, IL-6

Question 35

Receptors on macrophages

Answer 35

Toll like receptors Fc for IgG and IgA C3b MHC class I and II

Question 36

Dendritic cells

Answer 36

Present in tissues exposed to the external environment. Once activates migrate to the lymphoid tissues.

Question 37

Main function of dendritic cells

Answer 37

Phagocytosis Antigen presentation to CD4+ T cells via MHC II Shape enhances activation Secrete TNF alpha, IL-12, IL-23

Question 38

Follicular Dendritic Cells

Answer 38

Mesenchymal origin Within follicles of lymphoid tissue Do not express MHC II but interact with B cells

Question 39

Natural Killer Cells are activated by

Answer 39

IFN and macrophage derived cytokines

Question 40

Main functions of natural killer cells

Answer 40

Bind to and kill virus-infected and cancerous cells –reduced MHC I expression Release of perforin + granzymes from granules Perforates cell, inserts proteolytic enzymes, induces apotosis Also induce apotosis by binding to FasL molecules on virus Release IFN gamma and TNF alpha Are inhibited by normal ‘self’ signal via MHC I

Question 41

Receptors present on NKC's

Answer 41

``` Killer activation receptors Killer inhibitory receptors – recognise MHC class I Toll-like receptors Fc receptors Adhesion molecules FasL ```