UAMS Immunology Exam 1

Study of host reactions when foreign substances are introduced

Immunology

Study of non-cellular components in the blood (antigen and antibody)

Serology

Substance that induces an immune response

Antigen

Glycoprotein; made in response to antigen

Antibody

Antibody binding site

Epitope

The ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells

Immunity

The Role of the ______________________________ (2 words):

*Confer health by effective elimination of infectious agents

*Designed to interact with environment to protect the host against pathogenic invaders

*Recognize and respond to tissue grafts/newly introduced proteins

*Defend against tumors

Immune System

Properties of the _________________________ (2 words)

*Distinguish between self and non-self

*Two overlapping systems

*Specificity

*Diversity

*Clonal selection

*Memory

*Regulation

Immune System

____________ ____________ confers health by responding and controlling infection with moderation.

Immunological homeostasis

Immune response is ABSENT from the host, leading to illness

*SCID-severe combine immmunodeficiency (bubble baby)

*HIV/AIDS-Destruction of T helper cells leads to vulnerability of host by opportunistic infections

Deficiency: Hyporeactivity

AUTOIMMUNITY/ALLERGIES

Immune system reacts by error resulting in active response that damages host tissue

*Rheumatoid arthritis

*Allergies

IMMUNOPATHOLOGY/IMMUNOPROLIFERATIVE

Absence of protective response or excessive uncontrolled response

*Multiple myeloma

Dysregulation: Hypereactivity/Hypersensitivity

What are the two overlapping immune systems?

Innate/Natural and Adaptive/Acquired

*"Non-specific" recognition of substances (obviously) different from self

*Always present in healthy individuals

*First line of defense

*Examples: epithelial barriers, phagocytes, and inflammation components

Innate/Natural Immunity

*Recognition with "specificity" to usually non-self (foreign) substances

*Stimulated by microbes that invade tissue

*Adapts to defend against specific invaders; protection result of prior experience with AGN

*Involves lymphocytes and their products

Adaptive/Acquired Immunity

Which type of immunity is:

*very primitive (can be found in most multicellular animals)

*always present and active as part of the tissue

*rapid response

*does not exhibit memory the way acquired memory does

Innate/Natural Immunity

Which type of immunity is:

*found only in vertebrates (fish, amphibians, birds, and mammals)

*must be induced to be active against infections or tumors

*induces immunological memory

*TWO TYPES

Humoral

Cell-mediated

*Two ways to get it

Active

Passive

Adaptive/Acquired Immunity

What are the two types of acquired immunity?

humoral immunity and cell-mediated immunity

What type of acquired immunity does the following describe?

*B-lymphocyte

*produces antibodies

*Neutralizes and eliminates EXTRACELLULAR microbes/microbial toxins

Humoral immunity

What type of acquired immunity does the following describe?

*T-lymphocyte

*produces cytokines and other substances

*Activates phagocytes to destroy INTRACELLULAR microbes

Cell-mediated immunity

Active or Passive Immunity?

*antibodies are made by self

*immune system responds and creates products after exposure due to infection or vaccination

*long-term immunity

Active immunity

Active or Passive Immunity?

*antibodies are made by ANOTHER immunized individual or animal

*immunity is transferred from source to individual in need of products

*short-term immunity

Example: mother's milk (ab) transmitted to the nursing baby

Passive Immunity

What is clonal selection?

A small number of B and T cell clones bind to the antigen with high affinity and undergo:

*Activation

*Proliferation (clones)

*Differentiation

-Plasma cells (for the B cells)

-Activated T cells

-B & T memory cells

What does the following describe?

A small number of B and T cell clones bind to the antigen with high affinity and undergo:

*Activation

*Proliferation (clones)

*Differentiation

-Plasma cells (for the B cells)

-Activated T cells

-B & T memory cells

What is clonal selection?

All lymphocytes start as a __________ __________ (two words)

Stem cell

Stem cell

All lymphocytes start as a __________ __________.

What are the two kinds of immune response?

Primary and secondary immune response

*Response to 1st exposure to antigen

*Mediated by naive lymphocyte

Primary immune response

*Also referred to as anamnestic response

*Subsequent encounters with same antigen

*Mediated by "memory" lymphocytes

*Higher level response

Secondary immune response

Foreign susbtance that induces an immune response

Antigen

Glyco-protein; made in response to antigen

Antibody (immunoglobulin)

Antibody binding site; single antigen site

Epitope

TRUE or FALSE

The immune response that causes immunity is associated with natural immunity.

FALSE

TRUE or FALSE

A key characteristic of acquired immunity is being antigen specific.

TRUE

Regulation

Adaptive immune system has mechanisms to control and inhibit self-reactive or over-reactive lymphocytes. What are the 3 mechanisms?

1. Elimination

2. Permanent inactivation

3. Inhibition

Defends against intracellular microbes through lymphocytes and their products

Cell-mediated immunity

Immediately protects the newborn

Passive immunity

Occurs as response to 1st exposure to antigen

Primary response

Activation, proliferation, differentiation

Clonal selection

Born with, non-specific immunity

Natural immunity

Mediated by memory lymphocytes

Secondary response

Must be induced, specific, adapts to defend

Acquired immunity

Defends against extracellular microbes, mainly through antibodies

Humoral immunity

Can be induced by a vaccine

Active immunity

Passive or Active Immunity

An immunized cow and a nonimmunized cow and calf

*Immunized cow has _____________________ immunity.

*Nonimmunized calf consumes 1st milk from immunized cow. Therefore the calf has ____________________ immunity.

*Nonimmunized cow receives an injection of serum from the immunized cow. This inoculated cow now has __________________ immunity.

*Immunized cow has active immunity

*Calf and inoculated cow have passive immunity

What constitutes Natural Immunity?

*System present from birth prior to onset of infection

*Constitutes non-specific mechanisms of defense (hold off invasion until specific immune response is generated

*Components recognize frequent molecules and invading pathogens

*Two mechanisms of protection:

External and Internal

*System present from birth prior to onset of infection

*Constitutes non-specific mechanisms of defense (hold off invasion until specific immune response is generated

*Components recognize frequent molecules and invading pathogens

*Two mechanisms of protection:

External and Internal

What constitutes Natural Immunity?

External or Internal defense mechanism?

Function: designed to keep microorganisms at bay and impedes entry into the body

Categories: benign flora and anatomic/physiologic

External defense

External or Internal defense mechanism?

Function: deals with breach of any barrier through difficult mechanisms

Categories: inflammatory, phagocytic/endocytic, and cells

Internal defense

Surface barriers protect at common portals of microbial entry:

Skin: impedes entry of foreign material

Mucous membranes: trap organisms at entryways

Provide physical and chemical barriers

Example: mucus secretions and cilia

External defense - Anatomic

List the physiologic barriers of EXTERNAL DEFENSE

*Temperature: impairs multiplication when temp is elevated

*Low pH: acidity in stomach discourages organism growth

*Antimicrobial substances: complement components attack bacterial membranes; lysozomes degrade bacterial membranes

List the 4 signs of inflammation

Redness

Swelling

Heat

Pain

What are the 4 signs of inflammation also called?

redness, swelling, heat, pain

Redness - RUBOR

Swelling - TUMOR

Heat - CALORE

Pain - DOLORE

What are the two types of inflammation?

acute and chronic

Describe the two types of inflammation:

Acute

Chronic

Acute inflammation: most common cell is neutrophil, function usually returns to normal

Chronic inflammation: macrophages and lymphocytes involved; prolonged, may adversely affect function

What are the sequence of events in inflammation?

1. Increased blood supply

2. Increased vascular permeability

3. Influx of phagocytes

*Increased blood supply due to dilation of blood vessels

*Chemical mediators (such as histamine) from injured cells

*Redness and heat

Vasodilation

*Caused by retraction of endothelial cells lining blood vessels

*Allows fluid in plasma to leak to tissues

*Swelling and pain

Vascular permeability

*PMNs move from vessel into tissues (diapedesis)

*Attracted to site of injury/infection by chemotaxins

*PMNs mobilized first (30-60 minutes)

*Several hours later macrophages arrive and clear the area through phagocytosis

Influx of phagocytes

Vasodilation

*Increased blood supply due to dilation of blood vessels

*Chemical mediators (such as histamine) from injured cells

*Redness and heat

Vascular permeability

*Caused by retraction of endothelial cells lining blood vessels

*Allows fluid in plasma to leak to tissues

*Swelling and pain

Influx of phagocytes

*PMNs move from vessel into tissues (diapedesis)

*Attracted to site of injury/infection by chemotaxins

*PMNs mobilized first (30-60 minutes)

*Several hours later macrophages arrive and clear the area through phagocytosis

Name important inflammation agents

Acute phase reactants

CRP

HsCRP

Complement

*Measured in the laboratory

*Increase rapidly with infection, surgery, or other trauma

*Normal serum constituents (most made in liver)

*Nonspecific response: same response whether bacterial infection, hip replacement, etc.

Acute phase reactants

*Most widely used indicator of acute inflammation

*Functions include: opsonizes, activate complement

*Increased rapidly after stimulus

-Increases 100-1000 fold (peaks @ 24-72 hrs)

-Declines very quickly

C-reactive protein (CRP)

Used to predict a healthy person's risk of cardiovascular disease

High-sensitivity CRP

*group of approximately 25 serum proteins

*inactive form under normal circumstances

*at 1st activation, each component acts on next in specific sequence (known as complement cascade)

*very powerful INNATE mechanism

Complement

Functions of complement

-Cell lysis: membrane attack complex- punch hole in cell

-WBC chemotaxis: attracts phagocytes

-Opsonization or immune adherence: enhanced phagocytosis

-Inflammation: heat, pain, swelling

Functions of complement

-Cell lysis: C5b-C9

-Opsonization: C3b

-Inflammation: C3a, C5a

-Clearance of Immune complexes: C3b

-Viral neutralization: C3b, C5b-C9

Functions of complement

*direct cytolysis of foreign organisms

*opsonization of foreign organisms by coated (targeting for destruction by phagocytosis)

*directs phagocytes to site of infection by releasing part of the protein which acts as an attractant

CRP

Complement

HsCRP

D-Dimer

Alpha-1 antitrypsin

Fibrinogen

Haptoglobin

Acute Phase Reactants

Acute phase reactant that:

-responds in 6-10 hours

-increases 1000x

-opsonization

-complement activation

CRP

Acute phase reactant that:

-responds in 48-72 hours

-increases 2x

-opsonization

-lysis

C3

What are acute phase reactants?

Serum proteins that increase rapidly due to inflammation

Serum proteins that increase rapidly due to inflammation

acute phase reactants

What affects the levels of Acute Phase Reactants?

infection

surgery

trauma

Inflammation occurs in what order?

1. increased blood supply to area

2. increased capillary permeability to allow PMN to slip through vessels

3. PMNs migrate to affected area

4. Macrophages arrive at the site of injury

Immune system cells are derived from:

Pluripotent hematopoietic stem cells

Leukocytes or WBCs provide either ____________ or ____________ adaptive immunity.

Leukocytes or WBCs provide either INNATE or SPECIFIC adaptive immunity.

In innate immunity, myeloid cells provide non-specific immunity. Name these cells involved in the first line of defense.

*Neutrophils

*Eosinophils

*Basophils/Mast cells

*Monocytes/Macrophages/Dendritic cells

What are cytokines?

chemical messengers produced in response to a stimulus

What are cytokines?

Secreted proteins responsible for communication between cells

*acts as a chemical messenger

*aids communication between cells

*prevents viral infections

Cytokines

List a few of the important cytokines:

Interleukin

Interferon

Chemokines

Tumor Necrosis Factor (TNF)

Colony stimulation factors

...and many, many more

internal defenses of innate immunity

2nd line of defense; phagocytes (neutrophils, monocytes), WBCs, NK cells, antimicrobial proteins, inflammation, fever

Internal defense - Phagocytic/Endocytic

Blood monocytes, tissue macrophages, dendritic cells and neutrophils phagocytose and kill microorganisms via complex digestion mechanisms.

-bacteria are ingested into phagocytic vesicles

-phagosomes fuse with lysosomes

-lysosomal enzymes digest captured organisms

-debris is released by exocytosis

Define chemotaxis

following the concentration gradient of a chemical attractant

What are opsonins?

Chemicals which bind to pathogens and tag them. Phagocyte receptors bind to opsonins.

Serum molecule that attaches to foreign material and enhances phagocytosis

Opsonin

ex. complement (esp. C3b) and antibody (esp. IgG)

What are the most important phagocytes of innate immunity?

Neutrophils

Macrophages

Dendritic cells

Natural killer cells

What function do cytokines perform?

-stimulate inflammation

-activate NK cells and macrophages

-prevent viral infections

What are cytokines?

chemical messengers used by cells

What are the primary phagocytic cells?

-neutrophils

-monocytes

-macrophages

-dendritic cells

What is the function of opsonins?

enhance phagocytosis

Give two examples of opsonins

antibodies and complement

-First to arrive and act to get the situation under control

-The MARINES

-Action mechanism: PHAGOCYTOSIS (engulfs and fills invading microbes)

-very effective killers (except against fungi and parasites)

Neutrophils

-PMNs

-make up 40-75% of circulating WBCs

-Half are circulating in the blood stream and other half are in marginating pool (on blood vessel walls)

-Enter tissues at random or if attracted by chemotaxins

Neutrophils

-make up <5% of circulating WBCs

-can phagocytize butnot as effectively as PMNs

-most important functions are to neutralize basophil and mast cell products and kill some parasites

Eosinophils

-make up <5% of circulating WBCs

-very short life (only hours)

-releases histamines and heparin

-binds to IgE

Basophils

-found in connective tissue, esp. around blood & lymphatic vessels

-important in hypersensitivity reactions

-binds to IgE

-releases histamines

-lives 9-18 months

Mast cells

-up to 12% of circulating WBCs

-stay in circulation up to 70 hours, then migrate to tissue to become macrophages

Monocytes