1. Lec-3 Basic Immunology
Romana Siddique

2. Blood cells

5. Cells of the Immune System
White Blood Cells
I. Granulocytes:
characterized by the presence of granules in their cytoplasm.
they are also called polymorphonuclear leukocytes ( PML) because of the varying shapes of the nucleus.
All of them are phagocytes mainly carry out innate immune response
There are three types of granulocytes
Neutrophils (polymorphonuclear neutrophils- PMN)
Eosinophis
Basophils

6. Granulocytes
Neutrophil
Eosinophil
Basophil

7. II. Agranulocytes:
characterised by the absence of granules in their cytoplasm.
There are two types of agranulocytes:
Lymphocytes
Monocytes
The blood has three types of lymphocytes: B cells, T cells- adaptive response and NK cells but NK cells carried out innate immune response
monocytes move from the bloodstream out into the body tissues, they undergo changes (differentiate) allowing phagocytosis and are then known as macrophages.

8. III. Fixed leukocytes Mast cell:
Some leukocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood
Mast cell
Dendritic cell
Mast cell:
contains many granules
rich in histamine
best known for their role in allergy and inflammation
Professional phagocyte
they function as antigen-presenting cells to TH cell

9. Origin and Development of Macrophages

10. Monocyte
Activated Mac

11. Dendritic Cells Transport Antigens to L. nodes
Initiation of T Cell Responses

12. Dendritic Cell Subsets

13. Innate immunity
 Innate immunity is an antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

14. Component of Innate Immunity
Innate Immune system
First line Second line
1) Mechanical barriers A- cells
2) Chemical & biochemical inhibitors Natural killer
3) Normal flora Phagocytes
B- Soluble factors
C- Inflammatory barriers

15. Innate immunity can be divided into immediate innate immunity and early induced innate immunity.
a. Immediate innate immunity
Immediate innate immunity begins hours after exposure to an infectious agent and involves the action of soluble preformed antimicrobial molecules that circulate in the blood, our found in extracellular tissue fluids, and are secreted by epithelial cells. These include:
antimicrobial enzymes and peptides;
complement system proteins; and
anatomical barriers to infection, mechanical removal of microbes, and bacterial antagonism by normal flora bacteria

16. b. Early induced innate immunity
Early induced innate immunity begins hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS  binding to pattern-recognition receptors or PRRs . These recruited defense cells include:
phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages ;
cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells ; leukocytes such as basophils and eosinophils; and
natural killer cells (NK cells).

17. PAMPs:Pathogen-associated molecular patterns are molecules unique to microorganisms that are not associated with human cells. They include LPS, peptidoglycan, lipoteichoic acids, mannose, flagellin, pilin, bacterial DNA, and viral double-stranded RNA.
In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)

18. Most body defense cells have pattern-recognition receptors or PRRs for these common PAMPS  and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 of these microbial molecular patterns.

19. Innate Immunity
1. Provides a anatomical barrier barrier to prevent the spread of infection
Mechanical (tight junctions, movement)
Chemical (fatty acids, enzymes, pH, antimicrobial peptides)
Microbiological (normal flora)
Mucosal surfaces
Nasopharyngeal, Oral, Respiratory, Intestinal tract
Urogenital tract
Skin (epithelial cells)
Wounds, burns, insect bites
Prevents the pathogen from colonization
-To establish an infection the organism must attach the epithelial surfaces.
-Infectious disease occurs when a microorganism succeeds in evading or overwhelming innate host defenses to establish a local site of infection and replication that allows its further transmission.
Mechanisms
-Movement: mucin, cilia, perisalsis
-Enzymes: lysozyme, pepsin
-Antimicrobial peptides discussed in a later lecture

20. Innate Immunity 2. Identifies and eliminates pathogens
Factors released by immune cells = cytokine/chemokines
Factors present in circulatory system = plasma proteins (C’ Dr. Morrison)

21. Recognition of pathogen

22. Innate Immunity 3. Initiates an inflammatory response
Reaction to injury or infection
Trauma to tissues or cells
Presence of foreign matter (self vs. non-self)
Infectious agents (viruses, bacteria, fungi)
Delivers effector molecules & immune cells to the site of infection
Components
Leukocytes & secreted factors
Blood vessels
Plasma proteins
Innate Immunity can also be referred to as an “Inflammatory Response”.

23. Innate Immunity
4. Provides signals to activate and regulate the type of adaptive immune response generated.
Sometimes this can lead to immune-mediated pathology.

24. Inflammation- innate immunity
“rubor et tumor cum calore et dolore”
(redness and swelling with heat and pain)
Inflammation is one of the first responses of the immune system to infection
Inflammation is a response to noxious conditions (infection and tissue injury)--an attempt to restore homeostasis and it is characterized by
increased blood flow to the site of injury
increased temperature,
redness,
swelling, and
Pain
edema

25. Objective of inflammation
Destroy the agent causing injury or infection
Limit the affect of injury or infection on rest of the part of body
Repair and replacement of injured or infected tissue

26. Inflammation process Tissue injury or infection Chemotaxis:
Mast cells and injured cell:
release histamin, leukotrienes, prostaglandins cause chemotaxis of leukocytes towards site of injury/infection
Prostaglandins cause relaxation of smooth muscle for increasing the permeability of blood vessel
Prostaglandin –increase temperature and pain

27. Blood vessel endothelium

28. III. Vasodilation :
histamine released by mast cell binds to enothelial cell receptor
Dilation of blood vessel
Impact
Increased blood flow-redness
Leakage of plasma and blood proteins , nutrients and oxygen-swelling
Leakage of blood proteins are the cause of pain and edema

30. Mast cell Red blood cells
Figure
Pathogen
Splinter
Macro- phage
Movement of fluid
Signaling molecules
Mast cell
Capillary
Phagocytosis
Figure 43.8 Major events in a local inflammatory response.
Red blood cells
Neutrophil

31. Inflammation

32. IV. Extravasion : circulation of leukocytes by interraction with endothelial cells following a specific leukocyte adhesion cascade
V. Destruction of injury or infection causing agent by phagocytosis
VI. The healing of injury

33. Leukocyte adhesion cascade

36. Phagocytes-innate immunity
Produced throughout life by the bone marrow
Scavengers – remove dead cells and microorganisms
Main phagocytic response are carried out by-
All granulocytes
agranulocyte includes macrophage,
Fixed leukocyte -dendritic cells, mast cell
Two types
Professional phagocytes – key function phagocytosis
Non-professional phagocytes-phagocytosis is not key function

37. The professional phagocytes are the
monocytes,
macrophages,
neutrophils,
tissue dendritic cells and mast cells
The non-professional phagocytes are-
Natural killer cell
2.Endothelial cells and Epithelial cells

38. Professional phagocyte
Neutrophils
60% of WBCs
They are most abundantly found in blood and tissue
Large numbers are released during infections
Short lived – die after digesting bacteria and fungus
Dead neutrophils make up a large proportion of puss during inflammation.

39. Professional phagocyte
Macrophages
Less abundant than neutrophils
They can able to ingest microbes both in blood and in tissues
Made in bone marrow as monocytes and circulate in blood , but differentiated to macrophage in tissue
Long lived

40. Name of macrophage varies with its location
Lungs= Alveolar macrophage
Liver =kupffer cell
Kidney=mesangial cell
Connective tissue=histiocytes
Brain=microglial cell
Bone=osteoclasts

41. Non-professional phagocyte
Natural killer cell/NK cell:
NK cells are defined as large granular lymphocytes
a type of cytotoxic lymphocyte that constitute a major component of the innate immune system
NK cells play a major role in the rejection of tumors and cells infected by viruses by apoptosis

42. Phagocytic process
Chemotaxis: Phagocytes are chemically attracted to site of infection.
Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material
Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome.
Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome initiate the digestion of target pathogen

43. How phagocytosis occur

44. Methods of killing Oxygen-dependent
When a phagocyte ingests bacteria (or any material), its oxygen consumption increases.
increase in oxygen consumption, called a respiratory burst
produces reactive oxygen-containing molecules that are anti-microbial
two types-
oxygen-dependent production of a superoxide
use of the enzyme myeloperoxidase

45. oxygen-dependent production of a superoxide
The superoxide is converted to hydrogeen peroxide and singlet oxygen by an enzyme called superoxide dismutase
Superoxides also react with the hydrogen peroxide to produce hydroxyl radicals which assist in killing the invading microbe

46. use of the enzyme myeloperoxidase
enzyme myeloperoxidase derive from granules
this enzyme uses hydrogen peroxide and chlorine to create hypochlorite
hypochlorite is extremely toxic to bacteria

47. Oxygen-independent
four main types of proteins and enzymes involved
electrically charged proteins defensins -damage the cell membrane.
lysozymes-break down the bacterial cell wall.
lactoferrins, - remove essential iron from bacteria.
proteases and hydrolytic enzymes-digest the proteins of destroyed bacteria

48. Role of NK cells in innate immunity
NK Cell Interacting with a Normal Body Cell

49.  NK Cell Interacting with a Virus-Infected Cell or a Mutant Cell Not Expressing MHC-I Molecules

50. NK cell killer function
Apoptosis induction in infected and tumor cells
Killing mechanisms same as in cytotoxic T-cells
- Perforin and granzymes
granzymes
Infected or tumor cell
apoptosis
NK cell
perforin