Topic 11 Fundamental Immunology

The immune system provides two forms of defense against invading microbes and, pathogen-infected cells, and tumor cells.

Homeostasis in the context of immunology results in the destruction of abnormal or dead cells.

11.1 Innate Immunity

This is the first line of response - it relies on already formed components and hence, has rapid response times (i.e., within minutes of an initial infection).

However, the innate immune system is not specific (i.e., cells respond to a large range of pathogens), has no memory, and doesn’t lead to clonal expansion.

11.1.1 Mechanisms of innate immunity

Figure 11.1: Cells Involved in Innate Immunity

Some natural defenses include:

1. Physical barriers

   For instance, the skin, stomach acid (which has a low pH - this kills most pathogens, but some like H. pylori can bypass this mechanism), and mucosal protection (mucous has anti-microbial properties).

2. Cellular defense mechanisms

   Including natural killer cells: neutrophils, macrophages, mast cells, basophils, and eosinophils.

   1. Neutrophils

      This is a phagocytotic leukocyte that engulfs and digests pathogens. It is also attracted to infected tissues.

11.2 Adaptive Immunity

This is the second line of defense. Unlike the innate immune system, this immune system responds slowly over days, relying on genetic events and cellular growth in the process.

The adaptive immune system also has the following properties:

1. Specific

   Each cell responds to a single epitope on an antigen. Antigens are typicaly proteins, polypeptides, and polysaccharides.

2. Has memory

   Repeated exposure of the adaptive immune system to a pathogen leads to a stronger, faster response.

Furthermore, this immune system leads to clonal expansion.

11.2.1 Mechanisms

There are two main ones here:

1. Cell-mediated immune response

   

   Figure 11.2: Sites of T-Cell Production

   T-cells are the main cells here: Helper T cells and Cytotoxic T cells.

   Note that T-cells are generally made in the thymus, the bone marrow, the spleen, and the lymph nodes.

2. Humoral immune response

   B-cells are the main ones here: these are antibody-producing cells.

11.2.2 Comparisons between the innate and the adaptive immune system

Figure 11.3: Differences Between Adaptive and Innate Immune System

11.3 Humoral Immune Response

Figure 11.4: Structure of an Antibody

Antibodies are Y-shaped polypeptides with:

1. 2 identical heavy chains
2. 2 identical light chains

There are also five kinds of antibodies to note:

1. IgG
2. IgM
3. IgA
4. IgD
5. IgE

Figure 11.5: Effector Regions of Antibodies

Antibodies also have different effector functions.

11.4 Cell-Mediated Immune Responses

A T-cell recognizes the peptide antigen on an antigen presenting cell (i.e., APC) in association with major histo-compatibility complex class II (i.e., MHC-II) proteins.

T-cells also recognize peptides on MHCI cells (which help to identify similar cells with non-similar cells).

11.4.1 T lymphocytes

There are two kinds of lymphocytes examined in BS2004:

1. Helper T-lymphocytes

   

   Figure 11.6: Mechanism for Peptide Presentation on MHC

   CD4+ T cells activate phagocytes to kill microbes and activate B cells (and other immune cells).

   The figure above also shows the mechanism by which peptides are generated to be shown on a MHC.

2. Cytolytic T-lymphocytes

   CD8+ T cells destroy infected cells that contain microbes and / or microbial proteins.

Figure 11.7: Clonal Expansion

Also note the mechanism by which T-cells become clonally selected.

11.5 Immune Responses Against Infection

There are two kinds of responses:

1. Primary response

   This is the production of specific clones of memory clones and effector cells.

   This response doesn’t curb the infection and can occur over several days.

2. Secondary resopnse

   This is faster and more pronounced; this is also more effective at curtailing an infection.

Figure 11.8: Faster Immune Responses After Initial Infection

When the organism in question becomes infected with the same pathogen the second time, a more vigorous reaction is observed.

11.6 How do Vaccines Work?

Figure 11.9: Types of Vaccines

Vaccine particles are first uptaken by dendritic cells that activate the adaptive immune response when T-cells become activated.

Vaccine particles also activate B-cells - active B-cells also aid in T-cell activation and antibodies are produced.

Memory T and B cells are formed and the host is then prepared to face the actual infection.

11.6.1 Influenza vaccines

Figure 11.10: Schematics of the Influenza Virus

The Influenza virus has two proteins worth noting:

1. Hemagglutinin (i.e. HA)

   This helps the virus bind to target cells.

2. Neuraminidase (i.e., NA)

   This releases new virus from target cells.

11.6.2 Types of Influenza virus

Types A and B are related to seasonal epidemics; type C causes mild symptoms.

Subtypes of influenza A are based on viral surface proteins

Influenza B has two lineages: Victoria and Yamagata

The CDC follows internationally accepted naming conventions for influenza viruses.

11.7 A Review of Immune Cells and Their Roles

11.7.1 Cells to note

1. Monocytes

   These are cells that develop into macrophages and are found in the bloodstream and bodily tissues.

2. Neutrophils

   These are cells that aggregate to a site of local tissue injury. Their coordinated movement then recruits other cells: macrophages and monocytes to the site to form a seal.

3. Dendritic cells

   These are antigen-presenting cells that can develop from monocytes. Antigen-presenting cells process large molecules into “readable” fragments (i.e., antigens) that can be recognized by B cells and T cells.

4. Natural killer cell (i.e., NK cell)

   These cells play roles in innate and adaptive immunity - these cells kill tumor or virus-infected cells.

11.7.1.1 Cells of the adaptive immune system

1. B cells

   These are cells that present antigens to T cells, but more importantly, produce antigens to neutralize infectious microbes.

2. T cells

   These can be cytotoxic or helper T cells (based on the proteins on their surface). T-cells carry out multiple functions.

11.7.2 Flowchart of immune response

Figure 11.11: Flowchart of Immune Response (from Innate to Adaptive)