Immunology Introduction

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Innate (non-specific) Immune Response

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- 1st line of defense against pathogens.
- If the innate IR cannot control a pathogen, the innate immune response stimulates the specific (adaptive) IR.

- Causes inflammation at site
- Determined entirely by inheritance
- slows spread of infection while calling for lymphocytes.

Occurs in 2 steps:
1. Pathogen Recognition = Bacterial cell surface induces cleavage and activation of complement. One fragment binds to bacteria, marking it, and another recruits effector cells.
2. Recruitment of Destructive Effector Mechanisms = the complement receptor on an effector cell binds to complement fragment on bacteria. Effector cell engulfs bacteria, kills it, and breaks it down.

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Inflammation Steps

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1. surface wound introduces bacteria which activate resident effector cells to secrete cytokines.
2. Cytokines induces local dilation of blood capillaries causing skin to warm and reddens.
3. vasodilation introduces gaps between cells on endothelium making it permeable and increases leakage of blood plasma into tissue.
4. Expansion of fluid causes swelling.

Cardinal signs of inflammation are redness, swelling, heat, and pain.

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Adaptive (Specific) Immune Response

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The response of antigen-specific B and T lymphocytes to an antigen, including the development of immunological memory.

Takes over when innate immune response can't stop infection.

Specialized defense.

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Lymphocytes

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white blood cells that can be small or large.

Small = have variable cell-surface receptors for antigen and are responsible for adaptive immune responses. Includes B and T cells

Large = natural killer cells that participate in innate immunity.

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Effector Mechanism

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the physiological and cellular processes used by the immune system to destroy pathogens and remove them from the body.

Highly Specific!!!

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Clonal Selection

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The central principle of adaptive immunity.

It is the mechanism by which adaptive immune responses derive only from individual antigen-specific lymphocytes, which are stimulated by the antigen to proliferate and differentiate into antigen-specific effector cells.

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Clonal Expansion

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Occurs after the clonal selection process. This is where the selected lymphocytes go through proliferation and differentiation into many effector lymphocytes.

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Memory Cells

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After selection and expansion, some of these lymphocytes stay in the body to provide memory of an encountered pathogen. They allow subsequent encounters with the same pathogen to have a stronger, faster adaptive immune response.

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Primary Immune Response

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The first time an adaptive immune response is made to a given pathogen

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Secondary (Memory) Immune Response

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The second and subsequent times that an adaptive immune response is made. This starts sooner and builds more quickly. Is due to the presence of long-lived memory B and T-cells.

Ensures a more rapid and effective response and thereby provides lasting immunity

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Vaccination

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The deliberate induction of protective immunity to a pathogen by the administration of killed or non-pathogenic forms of the pathogen, or its antigens, to induce an immune response.

- Is the most effective means of controlling infectious diseases.
- Vaccination against a specific pathogen shortens the response time to pathogens and increases the effectiveness of the response dramatically.

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Edward Jenner

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Small Pox Vaccine

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Robert Koch

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1st Novel Prize in Medicine
- Germ theory of disease
- Basis?

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Louis Pasteur

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- Chicken Cholera
- Rabies Vaccine

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2 Branches of Adaptive (specific) Immune Response

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1. Ab-Mediated Immunity
2. Cell-Mediated Immunity

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Leukocytes (WBC's)

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- the cells of the immune system.
- originate in the bone marrow.

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2 main systems of cell development

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1. Myeloid = macrophages and granulocytes
2. Lymphoid = lymphocytes and natural killer cells

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Hematopoietic Stem Cells

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- the cells of the immune system
- they migrate through the blood and lymphatic system.

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Myeloid System Cells

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Neutrophil, basophil, eosinophil, monocyte, dendritic cell, macrophage, mast cells.

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Mast Cells

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- Resides near small blood vessels
- plays an important role in allergic responses by releasing histamine and other vasoactive substances.

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Eosinophils

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Important in defense against parasites

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Basophils

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Plays a role in allergic responses

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Monocytes

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- Circulate in the blood.
- when stimulated, they migrate into the different tissues and differentiate into macrophages.
- Macrophages are "big eaters" and monocytes are smaller eaters.
- important in defense against bacterial infections.

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Dendritic Cells

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- Antigen presenting cells that reside in the tissues.
- particularly important in presenting viral antigens.

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B-Cells

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Antigen presenting cells

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Antigen Presenting Cells (APC)

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Cells that have the ability to present Ag to t-cells
- Macrophages
- Dendritic Cells
- B-Cells

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Lymphocytes

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- The specific immune cells.
- Includes B and T-Cells

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B Cells (lymphocytes)

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- Matures in the bone marrow and differentiate into Ab producing plasma cells
- has a B cell receptor

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T Cells (lymphocytes)

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- Specialized to recognize foreign antigens as peptide fragments bound to proteins of the major histocompatibility complex.
- Matures in the thymus
- Has a T cell receptor

2 main classes: Cytotoxic and helper

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Cytotoxic T Cells (CTLs)

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- Kill target cells
- primarily anti-viral

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Helper T Cells (Ths)

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Activates other cells

Th1s activates infected cells to kill intracellular bacteria.
Th2s activates B cells to make Ab.

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Lymphoid Organs

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Primary (central) = bone marrow and thymus

Secondary (Peripheral) = spleen and Lymph nodes.

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Inflammatory Mediators

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Cytokines, Chemokines, Complement, and Histamine

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Cytokines

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Proteins released by cells that affect the behavior of other cells that bear receptors for them.

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Histamine

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Vasoactive molecule.

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Steps of Phagocytosis

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1. Attachment
2. Engulfment/Endocytosis
3. Digestion/Killing
4. Exocytosis

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Hallmarks of the Adaptive Immune Response

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1. Specificity
2. the memory, secondary, or anamnestic response.

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Two signals required for lymphocyte activation (AIR)

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1. cells must present Ag in the context of MHC
2. the second signal is a non-specific signal.

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Remembering B and T cells types

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T and B cells: types When bacteria enter body, T-cell says to B: "Help Me Catch Some!" B-cell replies: "My Pleasure!":

· T-cell types:
Helper
Memory
Cytotoxic
Suppressor
· B-cell types:
Memory cell
Plasma cell

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What determines an infections strength?

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- Number - dose - of pathogen.
- Route
- mode of transmission
- stability of infections agent outside the host.