Chapter 1: Elements of the Immune System and their Roles in Defense

Introduction - What is immunology?

Immunology is the study of physiological mechanisms that are used to defend the body from invasion by foreign or infectious agents.

In response to diseases caused by infectious agents, the body develops cells dedicated to defense — these form the immune system.

Definitions: Immune

Protected from future infection by that same disease

Introduction - Protective/Adaptive immunity?

Protective/Adaptive immunity takes time to develop, while microorganisms can rapidly multiply and cause disease

• Adaptive Immunity first appears in vertebrates

Introduction - Immunity involves two responses

1. Flexible but specific defenses of the adaptive immune response

2. Fixed defenses of the innate immune response

The Ubiquitous Enemy - Microbes

Microbes

• Survive on animal & plant products

• Release digestive enzymes

• Grow on living tissues (extracellular) where they are bathed in nutrients

• Other (intracellular) microbes infect animal/human cells, utilizing host-cell sources

Some microbes are harmless and some even helpful

• e.g., E. Coli in our intestines (colicins)

Many others cause disease

• human pathogens

There is a constant battle between invading microbes and the immune system

Immunity-The Immune Response

People who survive a specific infection become immune to it - protective immunity – Adaptive Cells have Memory

To provide protective immunity, the immune system must first engage the microorganism

• There is lag time between infection and protection (~7days) – Primary immune response

• The first infection (first time pathogen is engaged) is the most dangerous

• This understanding led to the concept of immunization or vaccination

• Disease is prevented by prior exposure to an attenuated/killed/subunit/RNA infectious agent (Vaccine)

  • SARS-CoV-2 vaccine uses RNA technology to SHOW your Immune system what the virus looks like so if you do come in contact with the virus in the future you can have a secondary IR.

Historical Perspective (430 BC, 15th century, and 1796)

430 BC- Thucydides recognized that only those who had recovered from the plague could nurse the sick without becoming sick again.

Fifteenth century- Chinese and Turks used dried crusts from smallpox pustules (inhaled or inserted into small cuts in the skin “variolation”) to induce immunity.

1796- Jenner realized milkmaids who had contracted cowpox (vaccinia virus), which is a virus that has mild disease symptoms compared to smallpox, were not susceptible (immune) to smallpox.

• He theorized that using fluid from a cowpox pustule would induce immunity to smallpox

• Tested theory on 8 yr old boy- inoculated boy with fluid from cowpox pustule then later injected the boy with smallpox. The boy didn’t contract smallpox.

Historical Perspective (Edward Jenner)

Origins of immunology attributed to Edward Jenner

Discovered in 1796 that cowpox “vaccinia” protected from human smallpox (Variola virus)

Procedure called vaccination

Prevents severe disease by exposing the immune system to the infectious agent in a weakened or killed state.

Provides long term protection against the real pathogen with very little risk of becoming sick

The Nature of Pathogens

Any organism with potential to cause disease is a pathogen

• Influenza and typhoid bacillus are examples of what we call a pathogen.

Opportunistic pathogens cause disease if the body’s defenses are weakened or it gets into a part of the body it isn’t normally found.

Constant evolutionary struggle between the host and the pathogen

• REPLICATION TIMES favor the PATHOGEN!!!

The Four Kinds of Pathogen that Cause Human Disease

Examples of the types of pathogen are listed, along with the diseases they cause

The virus SARS-CoV-2 causes COVID 19.

The Diversity of Human Pathogens, Refer to Figure 1.3

Commensal Bacteria

Over 1000 microbial species in the human gut (normal flora).

These bacteria typically cause no harm to the host.

Commensal = eat at the same table. Not harmful

When a round of antibiotics is taken, there is no specificity for the pathogen, so a large percentage of the bacteria (good and bad) are killed.

Skin and Mucosal Surfaces - Physical Barriers Against Infection: SKIN

Skin is first line of external defense against infection

Tough impenetrable barrier

Skin continuous with epithelia lining

• Respiratory

• Gastrointestinal

• Urogenital tracts

The impermeable skin gives way to specialized tissues that are more vulnerable to microbe attack; Known as mucosal surfaces or mucosae

Skin and Mucosal Surfaces - Physical Barriers Against Infection: MUCOSAL SURFACES

Mucosal surfaces are bathed in mucus; thick fluid containing glycoproteins, proteoglycans, and enzymes - protective

Lysozyme in tears (~ 40% of protein) and saliva – antibacterial

Respiratory tract mucus is continuously removed to clear unwanted material

Stomach, vagina, skin acidic – protective

Defensins – poke holes in the pathogen

When skin and mucosal barriers are breached - immune system responds

Physical Barriers that Separate the Body from its External Environment

Innate Immune Response Leads to Inflammation

The physical barriers have been breached. Now what?

The Innate Immune response starts to work to clear the new invader

This is the next line of defense after physical barriers are breached

Innate = determined by the genes you inherited from your parents

• Adaptive cells (T and B change the genes for their receptors)

Innate response consists of two parts

• Recognition

• Recruitment of effector mechanisms (cells)

Complement (Innate)

Series of proteins that act to tag an invader for uptake (phagocytosis) by other immune cells or destroy pathogens by poking holes in the microbe by completing the complement cascade.

Inflammation

Immune Defense-Innate Vs. Adaptive Immunity (INNATE)

1. Innate immune system

   • Is the first line of defense against infections

   • It works rapidly

   • Gives rise to the acute inflammatory response

   • Has some specificity for microbes

   • Uses different receptors to recognize pathogens

Immune Defense-Innate Vs. Adaptive Immunity (ADAPTIVE)

2. Adaptive immune system

• Takes longer to develop (~7 days)

• Is highly specific for antigens, including those associated with microbes

• Uses one type of receptor to recognize many different pathogens

• Primary immune response = first time the adaptive immune response is activated against a pathogen.

• Secondary immune response = any time the adaptive immune response is activated against a pathogen that it has been exposed to before

• Remembers that it has encountered a microbe previously

  • (i.e. shows memory)

Innate and Adaptive Immunity Work Together

The innate and adaptive immune systems work together through....

• Direct cell contact

• Interactions involving chemical mediators

  • Cytokines and Chemokines

Many of the cells of the innate immune system are the same cells used by the adaptive immune system

Vaccinations require that the innate immune system is engaged in order to provide memory.

• Innate immune system activates and aids in the adaptive immune response.

Adaptive — lymphocyte selection and proliferation

A single lymphocyte will have a receptor with a single
specificity. One cell may have many receptors (~100,000)
but all will recognize the same epitope.

When a foreign epitope is recognized by the lymphocyte
receptor (selected), the cell will proliferate (expansion).

• Clonal selection and Clonal expansion

We want a lot of that specific receptor to recognize the
invader.

• 1 receptor specificity = 1 T cell or 1 B cell

Generally takes about a week before the benefits of a
primary immune response are realized.

Innate and Adaptive

People lacking innate immunity can’t control the infection at all. Innate immunity cells are needed to activate the adaptive cells.

People lacking adaptive immunity can control the infection initially but can’t clear it.

Principle Characteristics of Innate and Adaptive Immunity, Figure 1.8

Cells of the Immune System (what 4?)

1. Lymphoid cells

2. Mononuclear phagocytes

3. Granulocytic cells – These are called granulocytes

4. Dendritic cells

Cells of the Immune System (Lymphoid cells)

Lymphoid cells –

• 20-50% of white blood cells

• T cells, B cells, and NK cells

Cells of the Immune System (Mononuclear phagocytes)

Mononuclear phagocytes –

• Monocytes that circulate in the blood and

• Macrophages found in tissues

Cells of the Immune System (Granulocytic cells)

Granulocytic cells – These are called granulocytes

• Neutrophils

• Eosinophils

• Basophils

• based on morphology and cytoplasmic staining characteristics

Cells of the Immune System (Dendritic cells)

Dendritic cells –

• Main function is the presentation of antigen to T cells

Hematopoiesis

The generation of the cellular elements of blood, including:

• Red blood cells (RBC)

• White blood cells (WBC) or leukocytes

• Megakaryocyte - Platelets

These cells originate from pluripotent hematopoietic stem cells (HSC) whose progeny differentiate and divide under the influence of various hematopoietic growth factors

HSC give rise to other cells in a process called self-renewal, becoming more mature stem cells that commit to different lineages

Types of Hematopoietic Cells

The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the

• lymphoid lineage

• myeloid lineage

• erythroid lineage

  

Development of lymphoid cells from pluripotent hematopoietic stem cells

Abundance of Leukocytes in Blood

Most abundant leukocytes are the neutrophils

Followed by lymphocytes

Leukocyte vs. Lymphocyte

Leukocytes

• A general term for a white blood cell

  • Lymphocytes, granulocytes, monocytes... are all leukocytes

Lymphocytes

• A class of white blood cells that consist of small and large lymphocytes

• T and B cells are the only cells found in lymph in large numbers, this is why they were named Lymphocytes.

Two classes of lymphocytes

1. Small lymphocyte (adaptive immunity cells)

   • B lymphocytes (B cells)

   • T lymphocytes (T cells)

2. Large granular lymphocytes

   • Natural killer (NK) cells, lymphocytes of innate immunity

     

Lymphoid Cells

Lymphocytes are divided into three classes

1. B cells (Ig’s – receptor)

2. T cells (TCR)

3. NK cells (Natural killer cells)

Naïve lymphocytes or small lymphocytes are resting cells that have not interacted with antigen

Lymphoblasts are lymphocytes that have interacted with antigen and proliferate

• Lymphoblasts eventually differentiate into effector cells or into memory cells

Effector cells eliminate antigen

• Plasma B cells that secrete antibody

• Cytokine-producing T helper cells (TH) - CD4 cell

• T cytotoxic cells (TC) – CD8 Cell

  

Natural Killer Cells

NK cells (large granular lymphocytes) are found throughout the tissues of the body but mainly in the circulation

• Constitute 5-10% of lymphocytes in human blood

• Contain cytotoxic substances which are important for protection against viruses and some tumors

• Secrete cytokines which

  • Prevent viral replication and

  • Helps to activate T cell-mediated immunity

Neutrophils

Effectors of innate immunity – specialized in the capture, engulfment and killing of microbes

• Work in the anaerobic conditions found in damaged tissue

• Are short-lived and die at site of the infection – one the major reasons for pus formation at the site of injury

  • Pus former = pyogenic

• Are phagocytic cells that contain toxic substances in intracellular granules (primary and secondary granules)

• Employ oxygen-dependent and oxygen-independent pathways to destroy pathogens