THE IMMUNE SYSTEM

1
THE IMMUNE SYSTEM

• Prof. Khaled H. Abu-Elteen

2
(No Transcript)
3
Terminology

• Types of Symbiosis ( Living togathers)
• - Amensalism
• A symbiotic relationship in which one species is
  harmed, but it isdifficult to see how the other
  species benefit.
• Mutualism
• A symbiotic relationship in which both species
  benefit
• Commensalism
• A symbiotic relationship in which one species
  benefits, and the other species is neither helped
  nor harmed

4

• Types of Symbiosis (cont.)
• Parasitism
• A symbiotic relationship in which one species
  benefits, and the other species is harmed
• Generally, the species that benefits (the
  parasite) is much smaller than the species that
  is harmed (the host)

5

• Disease and Infectious Disease
• Disease
• Any deviation from a condition of good health and
  well-being
• Infectious Disease
• A disease condition caused by the presence or
  growth of infectious microorganisms or parasites

6
Immunology lingo

• Antigen
• Any molecule that binds to immunoglobulin or T
  cell receptor
• Pathogen
• Microorganism that can cause disease
• Antibody (Ab)
• Secreted immunoglobulin
• Immunoglobulin (Ig)
• A glycoprotein produced in response to the
  introduction of an antigen
• Vaccination
• Deliberate induction of protective immunity to a
  pathogen
• Immunization
• The ability to resist infection

7
TYPES OF IMMUNITY.

• Nonspecific Skin and mucous membranes,
  Phagocytosis, Inflammation, and The Complement
  System.
• Specific Humoral(Antibody-Mediated) and
  Cell-Mediated.

8
Nonspecific Immune Response

• Physical and Mechanical Barriers
• Chemical Factors
• Biological Factors
• Phagocytosis and Associated with Blood and lymph
• Defenses that protect from ANY pathogen
  regardless of type and species( Bacteria, Fungi,
  Protozoa, etc).

9
Physical and Mechanical Barriers

• THE SKIN First Line Of Defense.
• Repels many organisms difficult to get through.
• Epithelium lines all body systems exposed to
  external environments including the respiratory,
  digestive and urinary systems.
• Secretes liquid which are mildly acidic which
  hinder bacterial growth.
• Lack of nutrition for microbial growth.

10
(No Transcript)
11
DEFENSES

• Dry
• usual infection sites are wet areas, skin folds,
  armpit, groin
• Acidic (pH 3.0- 5.0)
• Temperature less than 37oC
• Some pathogens grow best lt37oC
• Lysozyme and toxic lipids
• pore, hair follicles, sweat gland
• Resident microflora
• mainly G
• Skin-associated lymphoid tissue (SALT)

12

• Tears and saliva contain lysozymes which dissolve
  the wall of bacteria.
• Cilia of respiratory tract trap bacteria in mucus.

13
SKIN AND MUCOUS MEMBRANES1st line of defense

• Mechanical Factors
• Skin.
• The Epidermis.
• Keratin.
• Mucous Membranes.
• Lacrimal Apparatus ------gt
• Cilliary Escalator mucocilliary Escalator
  Action).

14
LACRIMAL APPARATUS.
15
CILIARY ESCALATOR.
16
Flushing Mechanisms

• Epiglottis.
• Urine and Vaginal secretions.
• Sneezing, coughing, swallowing reflex
• Movement of Fluids across their surfaces
  (Saliva)
• Washing action of tears

17
CHEMICAL FACTORS.

• Sebum and fatty acids in skin ( e.g. unsaturated
  fatty acids as Olic acid).
• Gastric Juice (Low pH stomach ).
• Lyzozyme degrade the bacterial cell wall
• Antimicrobial peptides (ß Lysine) with high
  quantity of Lysine or Arginine. Act by disruption
  of plasma membrane of microorganisms.

18

• Complementcomplex of 17 proteins
  (Glycoproteins) present in normal serum) C1, C2,
  C3 ..etc. Function Lysis of microbes,
  Neutralization of viruses, Enhancement of
  phagocytosis, Damage of plasma membrane,
  Recruitment of Phagocytes,
• Interferons Family of Glycoproteins that block
  Viral Replication by rendering host cells,

19
NORMAL MICRIBIOTA AND NONSPECIFIC RESISTANCE.

• Microbial Antagonism.
• Commensalism.
• Competitive Exclusion Opportunistic pathogens.
• Natural Resistance Microorganisms has a host
  range

20
Cells of the Immune system FORMED ELEMENTS IN
BLOOD.

• Many cells of the immune system derived from the
  bone marrow
• Hematopoetic stem cell differentiation

21
Components of blood

• Serum vs. Plasma
• Serum cell-free liquid, minus the clotting
  factors
• Plasma cell-free liquid with clotting factors in
  solution (must use an anticoagulant)
• Contain protein Albumin, Globulin and
  Fibrinogen.

22
Components of blood
23
LEUKOCYTES.

• Divided into two main categories based on their
  appearance under the light microscope
• Granulocytes Versus Agranulocytes.
• Granulocytes Neutrophils(stain lilac), Basophils
  (stain blue-purple), and Eosinophils (stain red
  or orange).

24
NEUTROPHILS ( 60 of WBC)

• Commonly called polymorphonuclear leukocytes
  (PMNs).
• Multinucleated.
• Highly phagocytic and motile.
• Active in the initial stages of infection.
• Short life span (hours)
• Very important at clearing bacterial infections
• Innate Immunity

25
BASOPHILS (1 of WBC)

• Role is not clear.
• Release substances, such as histamine, that are
  important in inflammation.
• Might be blood Mast cells
• Important in allergic reactions

26
Eosinophils ( 3 of WBC)

• Somewhat phagocytic.
• Have the ability to leave the blood.
• Major function is to produce toxic proteins
  against certain parasites such as worms.
• Involved in allergic inflammation
• Double Lobed nucleus
• Orange granules contain toxic compounds

27
AGRANULOCYTES.

• Monocytes ( 5 of all WBC).
• Macrophages.
• Lymphocytes ( 30 of all WBC) .

28
MONOCYTES.

• Phagocytosis and killing of microorganisms
• Activation of T cells and initation of immune
  response
• Monocyte is a young macrophage in blood
• There are tissue-specific macrophages
• Antigen Presentation

29
MACROPHAGES.

• Maturation and proliferation of is one factor
  that is responsible for the swelling of lymph
  nodes during an infection.

30
Lymphocytes

• Many types
• B-cells produce antibodies( Humoral immunity)
• T- cells (Cellular immunity)
• Cytotoxic T cells
• Helper T cells
• Memory cells

31
Lymphocytes

• Plasma Cell (in tissue)
• Fully differentiaited B cells, secretes Ab
• Natural Killer cells
• Kills cells infected with certain viruses
• Both innate and adaptive
• Antigen presentation

32
(No Transcript)
33
TH cells play a central role in the immune system
Antigen Presenting Cell
34
Dendritic Cells

• Activation of T cells and initiate adaptive
  immunity
• Found mainly in lymphoid tissue
• Function as Antigen Presenting Cells (APC)
• Most potent stimulator of T-cell response

35
Mast Cells

• Expulsion of parasites through release of
  granules
• Histamine, leukotrienes, chemokines, cytokines
• Also involved in allergic responses

36
Other Blood Cells

• Megakaryocyte
• Platelet formation
• Wound repair
• Erythrocyte
• Oxygen transport

37
Cells, tissues and organs of the immune system

• Immune cells are bone marrow-derived,
  distributed through out the body
• Primary lymphoid organs
• Thymus T cell maturation
• Bone marrow (bursa of Fabricius in birds) B cell
  maturation
• Secondary lymphoid organs
• Lymph nodes
• Spleen
• Mucosal lymphoid tissues (lung, gut)

38
Major Tissues
2º
2º
1º
2º
2º

• Primary Lymph tissues
• Cells originate or mature
• Secondary Lymph Tissues

2º
2º
2º
1º
39
COMPONENTS OF THE LYMPHATIC SYSTEM.
40
Dendritic cell (sentinel)
41
(No Transcript)
42
The bursa of Fabricius in birds
43
ACTION OF PHAGOCYTIC CELLS.

• Wandering macrophages.
• Fixed macrophages.
• Mononuclear phagocytic (reticuloendothelial)
  system.
• During the initial infection, granulocytes,
  especially neutrophils are many and they dominate.

44
Opsonization.

• Opsonization - coating micro-organisms with
  plasma proteins aids phagocytosis.
• Complement binds to antibody-antigen targets.
• Promotes adhesion between opsonized cell
  macrophages.
• Opsonin binds to receptors on phagocyte membrane.

45
(No Transcript)
46
PHAGOCYTOSIS 2ND LINE OF DEFENSE.

• Cell Eating.
• Phagocytes Cells that perform phagocytosis.
• Are mostly types of white blood cells or
  derivatives of white blood cells.

47
THE MECHANISM OF PHAGOCYTOSIS.

• Chemotaxis.
• Adherence.
• Ingestion.
• Digestion.

48
3. Phagocytosis oxidative burst.

• Certain WBCs - phagocytosis.
• Chemotactically attracted to disease / tissue
  damage foci.
• Stages
• Engulfment of particulate matter into phagosome.
  (e.g. bacteria, virions, cell debris, etc.).
• Phagosome fuses with lysosomes phagolysosome.

49
3. Phagocytosis oxadative burst.

• Lysosomes contain enzymes degrade biomolecules.
• E.g. acid hydrolases, lysozyme, neutral
  proteases, myeloperoxidase, lactoferrin,
  phospholipase A.

50
3. Phagocytosis oxidative burst.

• Engulfed organisms killed in WBC by respiratory
  (oxidative) burst".
• Many pathogens / parasites succeed because avoid
  phagocytosis.

51
INFLAMMATION Second line of defense.

• Inflammatory response results in increased blood
  flow to infection chemical attractants and flow
  of fluid to wound ( vasodilation).
• Together these cause swelling, heat, and pain.
• Fluids include histamine and serotonine (causes
  arterioles to dilate), and plasma
  (contains clotting factors to wall off area.

52

• Kinins cause vasodilation and increased
  permeability of blood vessels.
• Prostaglandins released by damaged cells, and
  intensifies the effects of histamin and kinins.
• Leukotrienes produced by mast cells and
  basophils- Cause increased permeability, and
  attract phagocytes to pathogens.

53

• Vasodilation and increased permeability of blood
  vessels also help to deliver clotting elements to
  injured area.
• Blood clots prevent microbe from spreading, so a
  localized collection of pus results(abcess).

54
Inflammation.

• Inflammation - phagocytes complement recruited
  to site tissue invasion.
• Non-specific reaction to tissue damage.
• Cell damage initiates inflammation.

55
Inflammation.

• Vasodilation - swelling.
• Adhesion of leukocytes to endothelial cells
  migration phagocytes into tissues.
• Redness (blood flow).
• Pain (prostaglandins).
• Heat (pyrogens).
• Inflammation localised to area infection /
  injury and give pus.
• Once organisms destroyed inflammation resolves.

56
Inflammation
Figure 22.13
57
Types of Immunity
Figure 22.14
58
Types of immunity

• Innate (natural) immunity
• Phagocytes etc.
• Early, rapid responses, but limited
  non-specifc
• Adaptive (acquired) immunity
• Lymphocytes (B T cells)
• Take time but powerful - specificity memory

59
Measles attacks immunological memory
60
(No Transcript)
61
Vaccination protects us from infection by
inducing the adaptive immune response, but
bypassing the need for a primary infection
62
(No Transcript)
63
Ab basic structure
domains
64
Ab V and C regions
Fab region Antigen binding site
Fc region Activate of Complement
65
(No Transcript)
66
Figure 22.21 Antibody Structure
Figure 22.21a
67
Figure 22.21 Antibody Structure
Figure 22.21b-d
68
Actions of antibodies include

• Neutralization
• Agglutination and precipitation
• Activation of complement
• Attraction of phagocytes
• Opsinization
• Stimulation of inflammation
• Prevention of adhesion

69
Generation of immune response.

• Immunogen any molecule that stimulates immune
  response. Proteins best immunogens gt
  carbohydrates gt nucleic acids. Lipids very poor.
• Antigen molecule capable of generating antibody
  response.
• Antigen antibody generating.
• Haptan Ag incapable of stimulating immune
  response. Need carrier molecules for stimulating
  immune response

70
Generation of immune response.

• 4-7 days to generate immune response.
• gt 7 days get primary immune response.
• 1st IgM produced then IgG.
• After 3 weeks primary immune response turned
  off.
• Ab producing cells memory B cells formed.
• Memory B cells secrete ab when same agent
  encountered again.
• This is secondary immune response.
• Memory lasts weeks / years.

71
Classes of Immunoglobulins

• Large globular glycoproteins released by B cells
  in the serum of blood tissue fluids and some
  secretions.
• Specifically interact with antigens.
• 5 classes Antibodies
• 1. IgM largest 1st Ab made. Neutralisation,
  fix complement, agglutinate immobilise ags.
• 2. IgG - main serum Ab. Able to crosses
  placenta. Synthesized during secondary immune
  response. All functions. Smallest ab.

72

• IgA - mucosal / secretory ab , present in mother
  milk.
• IgD - receptor ab found on surface
  immunocompetent cells.
• IgE - binds surface mast cells degranulation
  histamine release. Allergies.

73

• The End