Introduction to Immunology

Dr. Catherine Gerald Mkindi

MVM, BVM, SUA

What is immunology?

Immune (Latin- “immunus”)To be free, exemptPeople survived ravages of epidemic diseases when faced with the same disease again

The study of physiological mechanisms that humans and other animals use to defend their bodies from invading organisms

Bacteria - VirusesFungi - Parasites - Toxins

Immune response• The immune response is the host reaction to

infection/invasion.• The body is under constant attack by microorganisms in

the environment.

• pathogen : an infectious agent that causes disease• Infectious disease occurs when a microorganism

succeeds in evading or overwhelming host defenses to establish a local site of infection and replication. In order for a pathogen to enter the body it must first overcome the innate immune response and the adaptive immune response.

Types of Immunity

• Innate Immunity– Host defense mechanisms that act from the

start of an infection but do not adapt to a particular pathogen

– Recognize “patterns’ of a.a., saccharides, etc..

• Adaptive Immunity– Response of an antigen specific B and T

lymphocytes to an antigen– Immunological memory

Types of Immunity

• Humoral immunity– Immunity that is mediated by antibodies– Can be transferred by to a non-immune

recipient by serum

• Cell Mediated Immunity– Immune response in which antigen specific T

cells dominate

Humoral and cellular immunity (antibody mediated or cellular)

Immune System

Innate/Nonspecific

Adaptive/Specific/Acquired

Protects/re-exposure

Cellular Components Humoral ComponentsHumoral ComponentsCellular Components

Development of the Immune System

• Many cells of the immune system derived from the bone marrow

• Hematopoetic stem cell differentiation

Cells of the immune system

Lymphocytes

Important in bothhumoral and cellmediated immunity

B-cells produce antibodiesT- cells– Cytotoxic T cells– Helper T cells

Memory cells

• Natural Killer cells– Kills cells

infected with certain viruses

– Both innate and adaptive

– Antigen presentation

Monocytes/Macrophage

• 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

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

Mast Cells

• Expulsion of parasites through release of granules

• Histamine, leukotrienes, chemokines, cytokines

• Also involved in allergic responses

Neutrophil

• Granulocyte– Cytoplasmic granules

• Polymorphonuclear• Phagocytosis• Short life span (hours)• Very important at

“clearing” bacterial infections

• Innate Immunity• CD 66 membrane

marker

Eosinophils

• Kills Ab-coated parasites through degranulation

• Involved in allergic inflammation

• A granulocyte• Double Lobed nucleus• Orange granules

contain toxic compounds

Lymphoid organs

Function of the Immune System(Self/Non-self Discrimination

• To protect from pathogens• Intracellular (e.g. viruses and some bacteria

and parasites)• Extracellular (e.g. most bacteria, fungi and

parasites)

• To eliminate modified or altered self

Innate immune responses

Anatomical barriers– Mechanical factors– Chemical factors– Biological factors

• Humoral components– Complement– Coagulation system– Cytokines

• Cellular components– Neutrophils– Monocytes and macrophages– NK cells– Eosinophils

Anatomical Barriers - Mechanical Factors

System or Organ Cell type Mechanism

Skin Squamous epithelium Physical barrier

Desquamation

Mucous Membranes Non-ciliated epithelium (e.g. GI tract)

Peristalsis

Ciliated epithelium (e.g. respiratory tract)

Mucociliary elevator

Epithelium (e.g. nasopharynx)

Flushing action of tears, saliva, mucus, urine

Anatomical Barriers - Chemical Factors Anatomical Barriers - Chemical Factors

System or Organ Component Mechanism

Skin Sweat Anti-microbial fatty acids

Mucous Membranes HCl (parietal cells)

Tears and saliva

Low pH

Lysozyme and phospholipase A

Defensins (respiratory & GI tract)

Antimicrobial

Sufactants (lung) Opsonin

Anatomical Barriers - Biological Factors

System or Organ Component Mechanism

Skin and mucous membranes

Normal flora Antimicrobial substances

Competition for nutrients and colonization

Humoral Components

Complement Lysis of bacteria and some viruses

Opsonin

Increase in vascular permeability

Recruitment and activation of phagocytic cells

Coagulation system Increase vascular permeability

Recruitment of phagocytic cells

Β-lysin from platelets – a cationic detergent

Lactoferrin and transferrin

Compete with bacteria for iron

Lysozyme Breaks down bacterial cell walls

Cytokines Various effects

Cellular Components

Cell Functions

Neutrophils Phagocytosis and intracellular killing

Inflammation and tissue damage

Macrophages Phagocytosis and intracellular killing

Extracellular killing of infected or altered self targets

Tissue repair

Antigen presentation for specific immune response

NK and LAK cells Killing of virus-infected and altered self targets

Eosinophils Killing of certain parasites

Adaptive/ Acquired/ Specific Immunity

Key characteristics of the adaptive immune responses

• Specificity

• Adaptability

• Memory

Types of Acquired Immunity

I. Naturally Acquired Immunity: Obtained in the course of daily life.A. Naturally Acquired Active Immunity: – Antigens or pathogens enter body naturally. – Body generates an immune response to antigens.– Immunity may be lifelong (chickenpox or mumps) or

temporary (influenza or intestinal infections).B. Naturally Acquired Passive Immunity: – Antibodies pass from mother to fetus via placenta or breast

feeding (colostrum).– No immune response to antigens.– Immunity is usually short-lived (weeks to months).– Protection until child’s immune system develops.

Types of Acquired Immunity (Continued)

II. Artificially Acquired Immunity: Obtained by receiving a vaccine or immune serum.1. Artificially Acquired Active Immunity: – Antigens are introduced in vaccines (immunization). – Body generates an immune response to antigens.– Immunity can be lifelong (oral polio vaccine) or temporary

(tetanus toxoid).2. Artificially Acquired Passive Immunity: – Preformed antibodies (antiserum) are introduced into body

by injection. • Snake antivenom injection from horses or rabbits.

– Immunity is short lived (half life three weeks).– Host immune system does not respond to antigens.

Cells of adaptive immune responses

B lymphocytes

Cell group Surface components

Function

T-lymphocytes CD3 molecule

B-cell receptor (BCR, Ag recognition)

Involved in humoral

T-lymphocytes

Cell group Surface components

Function

T-lymphocytes CD3 molecule

T-cell receptor (TCR, Ag recognition)

Involved in both humoral and cell-mediated responses

T helper cells (CD 4+ cells)

Cell group

Surface components

Function

Helper T-cells (TH)

CD4 molecule 1. Recognizes antigen presented within Class II MHC

2. Promotes differentiation of B-cells and cytotoxic T-cells

3. Activates Macrophages

Cytotoxic T cells (CD 8+ cells)

Cell group Surface components

Function

Cytotoxic T-cells (CTL)

CD8 molecule Recognizes antigen presented within Class I MHC

Kills cells expressing appropriate antigen

T Suppressor Cells (CD 8+ cells)

Cell group Surface components

Function

Suppressor T-cells (TS)

CD8 molecule Downregulates the activities of other cells

Macrophages

Cell group Surface components

Function

Macrophages 1. Immunoglobulin Fc receptor

2. Complement component C3b receptor

3. Class II MHC molecule

Bind Fc portion of immunoglobulin (enhances phagocytosis)

Bind complement component C3b (enhances phagocytosis)

Antigen presentation within Class II MHC

Secrete IL-1 (macrokine) promoting T-cell differentiation and proliferation

Can be "activated" by T-cell lymphokines

Dendritic Cells

Cell group Surface components

Function

Dendritic cells Class II MHC molecule

Antigen presentation within Class II MHC

Primary and Secondary Immune Responses

1o and 2o immune responses

[Ab]in serum

Time (days)10 20 60 70 80

1st injection of Ag A2nd injection of Ag A

React only withA, not B, C, etc

1o

2o

• The figure illustrates the production of antibody in response to antigenic substances. In this figure, an animal was injected with Antigen A at day 0. Antigen A invokes a primary response beginning about day 4, as indicated by a rise in the specific antibody titer (titer = measure of the amount of antibody in the animal's serum per unit volume). Initially, this antibody is mostly IgM (and some IgG). After a peak titer between days 7 and 10, the response decreases rapidly. If the animal is then reinjected with Antigen A at day 28, the production of antibody begins almost immediately and reaches a level 1000-fold greater that that seen in the primary response. This is known as the secondary response and the principal antibody produced is IgG. If a second antigen (Antigen B) is also injected at the same time as the reinjection of Antigen A, however, only a primary response to Antigen B is observed. These results demonstrate that:

• The immune response is specific. • The immune response has memory.

Comparison of Innate and Adaptive Immunity

• Innate Immunity:• Fast-acting • Less specific recognition• Early during evolution • e.g. phagocytes, barriers to infection

such as skin and mucus surfaces• Adaptive Immunity:• Specificity• Distinguish antigens sometimes present

from those always present• Memory and Recall