Host defense and Immunity Part 1 and 2

Immunology

•       The study of all features of the body’s second and third lines of defense

•       Study of the body’s response to infectious agents

•       Study of allergies and cancer

A healthy functioning immune system is responsible for the following

Surveillance of the body

•       Recognition of foreign material

•       Destruction of entities deemed to be foreign

White blood cells constantly move throughout the body, searching for potential pathogens

Recognize body cells (self)

•       Differentiate them from any foreign material in the body (nonself)

•       The ability to evaluate macromolecules as self or nonself is central to the functioning of the immune system

•       Many autoimmune disorders are a result of the immune system mistakenly attacking the body’s own tissues and organs

The immune system evaluates cells by examining molecules on cell surfaces called antigens or markers:

Consist of proteins and/or sugars

•       Allow cells of the immune system to identify whether a newly discovered cell poses a threat and should be marked for destruction:

•       Most common method of destruction is phagocytosis

•       Pathogen-associated molecular patterns (PAMPs)

Markers that many different kinds microbes have in common

•       Serve as “red flags” for phagocytes and other cells of innate immunity

•       Bacterial PAMPs: peptidoglycan and lipopolysaccharide

•       Viral PAMPs: double-stranded RNA

Pattern recognition receptors (PRRs)

Used by host cells with important roles in the innate immunity of the second line of defense

•       Recognize PAMPs

•       Nonself proteins that are not harmful are generally recognized as such and the immune system is signaled not to react or to react differently.

•       For effective immune responsiveness, the activities of one compartment must be communicated to other compartments

Mononuclear phagocyte system (MPS)

•       Phagocytic cells enmeshed in this network

  Provides a passageway between tissues and organs

•       In direct contact with tissue cells and the extracellular fluid (ECF)

•       Blood and lymphatic capillaries penetrate into these tissues

•       Allows cells and chemicals that originate in the MPS and ECF to diffuse into the blood and lymphatics

    Found in: Thymus: site of white blood cell maturation, Lymph nodes, Tonsils, Spleen, Lymphoid tissue of the mucosa of the gut and respiratory tract

 •       The MPS is loaded with white blood cells called macrophages waiting to attack passing foreign intruders as they arrive in these locations

 

innate (born with) protections

general defenses; protects against many pathogens

adaptive (develop through life)

more specific; carried out by lymphocytes

Host Defense

  Divided into first, second and third lines of defense*

First line of defense

•       Any barrier that blocks invasion at the portal of entry

•       Skin and mucous membranes: physical barrier and traps pathogens

•       Fluid secretions: tears (lysozyme), saliva, urine—flushing action to remove pathogens

•       Chemicals:  gastric acid

•       Limits access to the internal tissues of the body

What does the Human Microbiome do?

•     Forms a type of structural barrier

•     Can block the access of pathogens to epithelial surfaces

•     Creates an unfavorable environment for pathogens by competing for limited   

      nutrients and by altering the local pH

•       The first line of defense alone is not sufficient protection: inflammation, phagocytosis, and specific immune responses are also necessary

Second line of defense:

Acts rapidly at both the local and systemic levels once the first line of defense has been overcome.

what does the Second line of defense do

•       Internalized system of protective cells (phagocytes) and fluids

•       Types of phagocytes: Neutrophils, Monocytes and Macrophages

•       Survey the tissue compartments and discover microbes, particulate matter, and injured or dead cells

•       Ingest and eliminate these materials

•       Includes inflammation, fever and phagocytosis

      Rubor: Inflammation

redness caused by increased circulation and vasodilation in the injured tissue

Calor: Inflammation

warmth caused by the heat given off by the increased flow of blood

Tumor: Inflammation

swelling caused by fluid escaping into the tissues

Dolor: Inflammation

pain caused by the stimulation of nerve endings

Inflammation

 classic series of signs and symptoms:

Loss of function

Factors that elicit inflammation:

•       Trauma from infection

•       Tissue injury or necrosis due to physical or chemical agents

•       Adaptive immune reactions

Chief functions:

•       To mobilize and attract immune components to the site of injury

•       To set in motion mechanisms to repair tissue damage and localize and clear away harmful substances

•       Destroy microbes and block their further invasion

 

Stages of inflammation

1)vasodilation-

•       Increased diameter of arterioles allows more blood flow through area bringing supplies and removing debris—redness and heat

2)increased permeability of blood vessels in area

•       substances normally retained in the blood are permitted to pass out – antibodies and clotting factors—swelling and pain

•       Fluid dilutes toxic substances

3)phagocyte migration: bacteria and dead cells are removed

4)repair

Pus

-composed of cellular debris, dead neutrophils and fluid + bacteria

Pyogenic:

bacteria such as streptococci, staphylococci, gonococci, and meningococci that stimulate the formation of pus

Abscess-

excessive pus in an enclosed space

Ulcer-

inflamed tissue is shed many times at one site→open sore

Exudates

- tissue fluid and proteins collects in inflamed tissues

FEVER

•       Abnormally elevated body temperature:

•       Nearly universal symptom of infection

•       Associated with certain allergies, cancers, and other organic illnesses

•       If cause is unknown, it’s called a fever of unknown origin (FUO)

Body temperature is maintained around

37°C (98.6°F) by the hypothalamus

Low-grade fever

37.7 to 38.3°C or 100 to 101°F

High-grade fever:

40.0 to 41.4°C or 104 to 106°F

Stages of fever response:

•       pyrogens reset hypothalamus

•       hypothalamus initiates fever response

•       skin cold

•       shivering

•       stress is removed

•        crisis stage (fever breaks)

•       sweating, flushed skin

Exogenous pyrogens

•      : products of infectious agents such as viruses, bacteria, protozoans, fungi, endotoxin, blood, blood products, vaccines, or injectable solutions coming from outside the body

Endogenous pyrogens:

•       chemicals liberated by monocytes, neutrophils, and macrophages during phagocytosis

 

Function of fever:

•       high temperature inhibits bacterial growth/multiplication

increases HR to deliver WBC’s to infected site

•       phagocytes (monocytes and lymphocytes) attack bacteria more vigorously

•       Increases metabolism and stimulates immune reactions and naturally protective physiological processes:

•       Speeds up hematopoiesis, phagocytosis, and specific immune reactions

complications of a fever

•       Tachycardia: rapid heart rate

•       Tachypnea: elevated respiratory rate

•       Lowering of seizure threshold

•       dehydration, acidosis, brain damage

•       fatal above 46 Celsius (114 degrees F)

The complement system

•       proteins in blood that are activated to enhance immune, allergic and inflammatory reactions.

ANTIMICROBIAL SUBSTANCES

•       Interferon-hormone like peptides

•       produced by lymphocytes, macrophages, and fibroblasts Infected with virus

•       bind to receptors on nearby cells, cell is induced to synthesize antiviral chemicals (prevent viral replication)

•       also mediate other immune responses (phagocytosis) and prevent tumor growth

   Function of COMPLEMENT

  

•       activation of inflammation

immune adherence

binds to microbe so phagocyte can recognize it as a foreign body (attracts phagocytes)

•       Enhances  phagocytosis

cytolysis

attacks microbial membrane

Adaptive Immunity is

•       Third line of defense

Third line of defense

•       Acquired on an individual basis as each foreign substance is encountered by lymphocytes

•       Adaptive immunity acquired only after an immunizing event such as an infection

•       The reaction with each different microbe produces unique protective substances

B and T lymphocytes undergo a selective process that prepares them for reacting only to one specific antigen or immunogen

•       Formation of T and B cells

Immunocompetence:

the ability of the body to react with countless foreign substances

Antigens:

molecules that can be seen and identified by the immune system

If they provoke a response, they are called immunogens

Protein or polysaccharide molecules on or inside cells and viruses

antigen

Any exposed or released protein or polysaccharide is potentially, even those on our own cells:

Specificity:

antibodies produced against the chickenpox virus will not function against the measles virus

Memory:

lymphocytes have been programmed to “recall” their first engagement with the invader and rush to the attack once again

MECHANISM OF ADAPTIVE IMMUNITY

•       When pathogens carrying antigens cross the first line of defense:

•       Resident phagocytes migrate to the site

•       Tissue macrophages ingest the pathogen and initiate an inflammatory response

•       Phagocytic cells ingest the antigen and migrate to the nearest lymphoid organ, where they process and present antigen to T and B lymphocytes

•       When challenged with antigen, both B and T cells proliferate and differentiate:

•       A clone, or group of genetically identical cells, is created

proliferate and differentiate:

•       A clone, or group of genetically identical cells, is created

what is Cell Mediated Immunity:

How T cells respond to antigen

Helper T cells (CD4):

activate macrophages, assist B-cell processes, and help activate cytotoxic T cells

Regulatory T cells

control the T-cell response by secreting anti-inflammatory cytokines or preventing proliferation

Cytotoxic T cells (CD8)

lead to the destruction of infected host cells and other “foreign” cells

MECHANISM

ANTIGEN

→stimulate helper T cells, which become activated and specific to the antigen and divide many times forming→

MEMORY T CELLS

→remembers subsequent infection/faster the 2nd time; part of long term immunity

REGULATORY T CELLS

-stop immune response once antigen is destroyed

CYTOTOXIC T CELLS

→killer cells ; chemically destroy cell membrane and prevent virus from replicating and make cytokine, which attract macrophages.

Activated by Helper T cells or antigen/macrophage

what is Humoral Immunity

: How B cells respond to Antigen

Humoral Immunity

•       When activated, B cells divide and give rise to plasma cells

•       Plasma cells release antibodies into the tissue and the blood

•       Antibodies attach to the antigen for which they are specific, and the antigen is marked for destruction or neutralization

•       proteins; AKA-immunoglobins constitute the gamma globulin fraction of plasma specialized to react with specific parts of antigens

•       direct attachment results in agglutination, lysis,  precipitation , or neutralization

MEMORY B CELLS

-will remember the specific antigen in future, part of long term immunity-faster response 2nd time

PLASMA CELLS

-produce antigen – specific antibodies

REGULATORY CELLS-

stop immune response once antigen is destroyed

Antibody Titer:

levels of antibodies in the serum over time. Measuring specific antibodies can help determine  vaccination status against or previously infected by a certain pathogen. It can also help test integrity of  immune system

Primary Response

: the first exposure to an antigen the system undergoes

Secondary Response:

When the immune system is exposed again to the same immunogen within weeks, months, or even years

faster response

memory B (antibodies) and T cells

have Natural active-get sick; get well-results

Colostrum

: first breast secretion, appears yellow and is high in immunoglobins (IgA)

•       Protect infant against enteric pathogens (E. coli)

  Artificial passive-person

is given an injection of preformed antibodies ( gamma globulins or immunoglobulins) after presumed exposure to particular pathogen

•       Most useful in patients who have a diminished ability to mount their own immune response

•       Artificial active-body is presented with antigen and immune system responds-a vaccine stimulates production of antibodies and memory cells

sensitized helper T cells

presents the foreign antigen to B cells, which provide a strong stimulus for the activation of B cells specific for this antigen