Francis Ian L.

Salaver, RMT BMLS 3CDE

Types of Immunity
1. Natural/Innate/Nonspecific Immunity 2. Adaptive/Acquired Immunity

The immune system

Immune system
Innate (non-specific) immunity Adaptive (specific) immunity

Anatomic barriers (Skin,mucous membranes) Physological barriers (temperature, pH) Phagocytic Barriers (cells that eat invaders) Inflammatory barriers (redness, swelling, heat and pain)

Antigen specificity Diversity Immunological memory Self/nonself recognition

Humoral and cellular immunity

(antibody mediated or cellular)

Seminar Winter Semester 2002/2003

Pierre Dnnes pierre@bioinf.uni-sb.de

Andreas Hildebrandt anhi@bioinf.uni-sb.de

Annette Hglund annette@bioinf.uni-sb.de

Component of Innate Immunity

Innate Immune system
First line
1) Physical Barrier
2) Chemical & biochemical inhibitors 3) Normal flora

Second line
A- cells
1- Natural killer 2- Phagocytes

4) Mechanical barrier

B- Soluble factors
C- Inflammatory barriers

Important components of innate immunity

Factors that limit entry of microorganisms into the body
Factor Mode Of Action

-Keratin layer of intact skin -Acts as mechanical barrier -Lysozyme in tears and other secretions -Degrades peptidoglycan in bacteria cell wall -Respiratory cilia -Elevate mucus containing trapped organisms -Low pH in stomach and vagina; -Retards growth of microbes fatty acids in skin --Defensins (cationic peptides) -Create pores in microbial membrane -Normal flora of throat, colon -Occupy receptors which prevent and vagina colonization by pathogens

First line of defense

1) Physical barriers Intact skin Cilia Mucous secretion

First line
1) Mechanical barriers Blinking reflex and tears Coughing and sneezing reflex Urination Defecation Vomiting

First line
2) Chemical & biochemical inhibitors
- Sweat and sebaceous secretion
- Hydrolytic enzymes in saliva

- HCl of the stomach

- Proteolytic enzyme in small intestine

- Lysozyme in tears (damages cell wall)

- Acidic pH in the adult vagina

First line
3) Normal bacterial flora - Competition for essential nutrients - Production of inhibitory substances

Done with the First line Before we will proceed to the Second line of defense

What if..

Important components of innate immunity

Factors that limit growth of microorganisms within the body
Natural killer cells Neutrophils Macrophages and dendritic cells Inferons Complement Kill virus infected cells Ingest and destroy microbes
Ingest and destroy microbes, and present antigen to helper T-cells

Transferrin and lactoferrin Fever Inflammatory response

Inhibit viral replication C3b is an opsonin, membrane attack complex creates holes in bacterial membranes Sequester iron required for bacterial growth Elevated temperature retards bacterial growth Limits spread of microbes

Second line
A) cells
1- Natural killer (NK)

Definition:

Large granular lymphocytes Innate cytotoxic lymphocytes

Function : Provides non specific response to viruses and tumor cells

Natural Killer Activation Receptor

Natural Killer Cell Inhibition Receptor

Second line
B- Phagocytes
What are the two most important phagocytes ?

Mechanism of Phagocytosis

Macrophage

Opsonins

Types of Opsonins

Question!!
How does a phagocyte recognize self from nonself???????

Phagocytosis
Killing (two microbicidal routes) a- Oxygen depended system (powerful microbicidal agents) Oxygen converted to superoxide, anion, hydrogen peroxide, activated oxygen and hydroxyl radicals. b- Oxygen-independent system (anaerobic conditions) Digestion and killing by lysozyme. Lactoferrin, low pH, cationic proteins and hydrolytic and proteolytic enzymes

What if the Bacterium is AEROBIC??

What if the Bacterium is ANAEROBIC??

C) Inflammation
Reaction of tissues to injury, characterized clinically by: heat, swelling, redness, pain, and loss of function.

Pathologically by : vasoconstriction followed by vasodilatation, stasis,

hyperemia, accumulation of leukocytes, exudation of fluid, and

deposition of fibrin.

Pathogenesis: Three main processes occur at the site

of inflammation, due to the release of chemical mediators :

Increased blood flow (redness and warmth).

Increased vascular permeability (swelling, pain & loss of function). Leukocytic Infiltration.

Inflammatory Response

Histamine & prostaglandins released

Capillaries dilate Clotting begins

Chemotactic factors attract phagocytic cells

Phagocytes consume pathogens & cell debris

Cardinal Signs of Inflammation

Redness : Hyperaemia.

Warm : Hyperaemia.
Pain : Nerve, Chemical

mediators.
Swelling : Exudation

Loss of Function: Pain

Second line
D- Soluble factors 1- Acute phase protein (Plasma protein, CRP=C Reactive Protein, Fibrin.) 2- Complement (proteins in serum, body fluids) 3- Interferons (Proteins against viral infections) 4- Properdin (Complement activation)

Second line
B- Soluble factors 5- Beta lysine (Antibacterial protein from Platelets) 6- Lactoferrrin; Transferrin ( Iron binding protein) 7- Lactoperoxidase 8- Lysozyme (Saliva & Milk) (Hydrolyze cell wall)

Interferons
Proteins usually produced by virally infected cells * Types of interferons: 1- Alpha interferon
Secreted by Macrophages Induced by Viruses or Polynucleotide Secreted by Fibroblasts, Viruses

2- Beta interferon

3- Gamma interferon T- lymphocytes, Specific antigens

Interferons
Protective action of interferons: 1) Activate T-cells 2) Activate macrophages 3) Activate NK

Third Line of Defense Specific Immune Response

This is a specific response to a specific pathogen/antigen. The response involves the creation of Antibodies.

SPECIFIC OR ADAPTIVE IMMUNE RESPONSE

Specific Immune Response Characteristics

Specificity Heterogeneity memory

Specific Immune Response Mechanisms

Humoral Immune Response or Antibody-Mediated Immunity (AMI) Cell Cellular Immune Response or CellMediated Immunity (CMI)

The Pathway of Specific Immune Response

Step 1 Pathogens eaten by Macrophage

Step 2 Displays portion of Pathogen on surface

Step 3

Pathogens

Helper-T cell recognizes Pathogen

Cellular Immunity .vs. Antibody Immunity

Cellular Immunity Antibody or Humoral Immunity

Carried out by T-Cells Infected cells are killed by Cytotoxic T Cells.

Carried out by B-cells Antibodies are produced and dumped into blood stream. Antibodies bind to antigens and deactivate them.

Humoral (Antibody-Mediated) Immunity

Iof antibodies against Involves production
foreign antigens.
Antibodies are produced by a subset of lymphocytes called B cells.

B cells that are stimulated will actively secrete antibodies and are called plasma cells.

Antibodies are Produced by B Lymphocytes

Antibodies are Proteins that Recognize Specific Antigens

Cell-Mediated Immunity
Consist of immune activities different from antibody-mediated immunity is moderated by the link between T lymphocytes and phagocytic cells (macrophages)

Cell Mediated Immunity

Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues:
Helper T cells

Cytotoxic T cells

T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc.