1. The Lectin Pathway Originates with Host Proteins Binding Microbial Surfaces
Lectin: proteins that bind to a carbohydrate
MBL (mannose-binding lectin):
- a protein which binds to mannose residues on glycoproteins or carbohydrates on the surface of microorganisms (structurally similar to C1q)
MASP-1 & MASP-II: MBL-associated serine protease
(structurally similar to C1r and C1s)

2. MBL is induced during inflammatory responses.
After MBL binds to the surface of a microbe,
MBL-associated serine proteases, ) MASP-1 and
MASP-2,( bind to MBL.
The MBL-MASP-1&II complex mimics the
activity of C1r and C1s, and causes cleavage and
activation of C4 and C2.
Thus, the lectin pathway is Ab-independent.
It is an important innate defense mechanism comparable
to the alternative pathway, but utilizing the elements
of the classical pathway, except for the C1 proteins.

3. Q2: Why doesn’t mannose-binding lectin (MBL)
bind to host carbohydrates?
A2: Mammalian cells normally have sialic
acid residues covering the sugar groups
recognized by MBL and are not a target
for binding.

4. The membrane-attack complex can lyse a broad spectrum of cells:
Biological Effects Mediated by Complement
1. Cell lysis
The membrane-attack complex can lyse a broad spectrum of cells:
G(-) bacteria
parasites
viruses
erythrocyte
nucleated cells (tumor cells)
Because the activation of alternative and lectin pathways is Ab-independent, these pathways serve as important innate
immune defenses against infectious microorganisms.

5. 2. Inflammatory response
- Various peptides generated during activation of
complement play a role in the development
of an effective inflammatory response.
- C3a, C4a, C5a (called anaphylatoxin) bind to
complement receptors on mast cells and basophils
and induce degranulation with release of histamine
and other mediators.
- The anaphylatoxins also increased vascular permeability,
extravasation, and chemoattraction (induced by
C5a, C3a, and C5b67)

6. 3. Opsonization
- C3b is the major opsonin of the complement system, although C4b also have opsonizing activity.
binds to the surface of microbes

7. Opsonization by Ab and complement

8. 4. Viral neutralization net number of infectious viral particles.
- Formation of larger viral aggregates reduces the
net number of infectious viral particles.
- The deposits of Ab and complement on viral
particle neutralizes viral infectivity by blocking
attachment to susceptible host cells and facilitates binding of the viral particle.

9. 5. Clearance of
immune complexes

10. Innate Immunity: Complement

11. Comparison of 3 Pathways

12. Inflammation:
Inflammation is non specific response to tissue damage resulting from a variety causes, including heat, chemicals, ultraviolet light, cuts and pathogens.
There are two types:
Acute inflammation: develops quickly and is short lived, is typically beneficial and result in the elimination of whatever condition precipitated.
Chronic inflammation: develops slowly, lasts a long time, and can cause damage to tissue, resulting in disease .

13. Acute inflammation is an important part of the second line of defense because it results in:
dilatation and increases permeability of blood vessels.
migration of phagocytes ( diapedesis).
tissue repair

14. Components of Innate Immunity Inflammation
Non-specific, physiologic reaction of vascular tissue to injury and microbial invasion.
The inflammatory process can be divided into two sequential steps:
Vascular Phase - dilation and increased permeability of blood vessels with the accumulation of fluid and cells at the site of injury.
Cellular Phase - the activation of specialized blood and connective tissue cells that destroy or wall off injurious agents and clear debris so that tissue repair can take place.
Cells important to inflammation include neutrophils, basophils, eosinophils, lymphocytes, monocytes, and platelets.

15. In the skin, inflammation is recognized by the presence of
redness, swelling, heat, and pain.
Without inflammation and repair, infections would go unchecked and wounds would never heal.

16. SIGNS OF ACUTE INFLAMMATION
Heat Redness Swelling Pain Loss of function

17. Cytokines
An important group of small molecular weight polypeptides that are produced by lymphocytes, macrophages, and other connective tissue cells.
The function of cytokines is to regulate growth and differentiation of blood, lymphoid, and connective tissue cells.
They help to orchestrate many aspects of innate and acquired immunity as well as wound healing, and the production of blood cells.

18. Inflammatory cytokines: Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF)
induce the fever, fatigue, and decreased appetite.
Activate leukocytes and other inflammatory cells,
increase vascular permeability.
Activate tissue-degrading enzymes.
Activate the connective tissue cell involved in tissue repair.

19. Stages of Inflammation: 1. Vascular Phase
Vasoconstriction - Immediately following injury, tightening of blood vessels
Complement activation and mediator release –
Activated complement opsonize microbes/injured tissue and release of histamine and serotonin from nearby mast cells
Formation of bradykinin and initiation of synthesis of prostaglandins and leukotrienes
Vasodilation –
Histamine, and other vasodilators, cause relaxation of smooth muscle in arteriolar and capillaries walls.
Vessels dilate providing increased blood flow to the injured tissue.
Causes redness/heat

20. Increased vascular permeability –
endothelial cells lining blood vessels contract slightly creating gaps between the cells that allow plasma to escape into surrounding tissues.
Plasma delivers antibodies and other antimicrobial substances to the site of injury.
Fibrinogen from plasma also clots and serves as a temporary barrier to bacterial invasion.

22. Stages of Inflammation: 2. Cellular Phase
Adhesion – white blood cells (WBC’s) stick to inner surface of blood vessel walls
Diapedesis WBC's then to squeeze between the contracted endothelial cells and migrate in an ameba-like fashion into the extravascular space
Chemotaxis - Once in tissue, the WBC's begin to migrate towards the site of injury or microbial invasion. WBC's are attracted by chemotactic agents that have been released at the site of injury. WBC's apparently have surface receptors for chemotactic agents which cause them to move in the direction of increasing concentrations of the chemotactic substance.

23. Phagocytosis –
When WBC's arrive at the site of tissue injury or microbial invasion they become very active and begin engulfing bacteria (or other foreign) that have been opsonized by complement or antibodies; through various mechanisms, bacteria and other foreign substances are destroyed and degraded after phagocytosis

25. Increase permeability during inflammation

28. MECHANISMS OF INFLAMMATION

29. Emigration of Neutrophils

30. Inflammation Outcome - Resolution
Chronic Inflammation
Abscess
Sinus
Fistula
Ulcer
Acute
Inflammation
Healing
Injury

31. Fever:
is a body temperature more than 37 ºC.
- Fever results due the presence of chemicals called pyrogens.
- Pyrogens trigger the hypothalamic thermostat to reset at high temperature.

32. Pyrogens include:
- bacterial toxins
- cytoplasmic contents of bacteria that are released upon lysis Ab-Ag complexes.
- interleukin-1 a pyrogen released by phagocytes that have phogocytized bacteria

33. Steps of fever

36. Determinants of innate immunity
Innate immunity is genetically controlled and varies widely with species, race and to less extent between individuals.
Species and race:
-Man and guinea pigs are highly susceptible to diphtheria while rats are not.
-Man is susceptible to common cold while dogs are not.
-American Indian and Negro are more susceptible to tuberculosis than white races.

37. B) Individual differences:
Age: the very young and aged are particular liable to infection.
Nutrition: Malnutrition and starvation predispose to infection by decreasing the total white cell count and phagocytosis.
Hormones: Some endocrine diseases cause a decrease in resistance to infection such as diabetes mellitus, hypothroidism and adrenal dysfunction. 37