Understanding the Immune System

The Immune System

• The immune system is a collection of structures and processes that protects the body against disease and potentially damaging foreign bodies.
• Functioning immune systems are essential for survival, to identify a variety of threats (viruses, bacteria, parasites).
• The immune system helps guard against disease and tissue damage.
• Immune cells are distributed throughout the body but highly concentrated in blood and lymphatic tissue.
• The immune system has functions for: defense against invading organisms, clean up and removal of damaged tissue, and surveillance to identify and destroy abnormal body cells.
• Major components of the immune system include: lymph nodes, spleen, bone marrow, lymphocytes, thymus, and leukocytes.
• Lymphocytes include; B-cells to make antibodies, T-cells, to kill pathogen infected or damaged cells, and helper T-cells to determine immune responses made against a particular pathogen.
• Everyone has an immune system that starts to develop in utero and is always working.

Why We Need an Immune System

• The immune system protects us from external threats such as bacteria, viruses, pollution, and allergens (pets, dust).
• The immune system protects us from internal threats like pathogens.

The Immune System: Layers of Defense

• First line of defense: Innate (Nonspecific) Immunity barriers at the body surface.
• Second line of defense: Innate (Nonspecific) Immunity defense.
• Third line of defense: Acquired (Specific) Immunity.
• First line defense includes: skin, mucous membranes, secretions, reflexes, and normal microbiota.
• The first line of defense has mechanical and chemical barriers, such as skin and mucous membranes, HCL acid, tears and saliva, cilia, and ear wax.
• Second Level defense includes: inflammation, phagocytes, fever, complement system, and interferon.
• Key parts of the second line of defense include: phagocytes (WBC that eat pathogens), inflammation (bodies response to infection), pyrogens (produce a fever), cytokines (stop the spread of virus), and complement proteins (enhance action of antibodies.
• Important phagocytes in the second line defense include neutrophils and macrophages.
• Third line defense includes: T cell lymphocytes, B cell lymphocytes, and antibodies.
• Normal Microbiome: Body surfaces are colonized with a combination of bacteria and fungi that is unique to the particular location, and individual.
• Normal Microbiome will not cause disease if a person's immune system is working.
• Opportunistic Infections can occur if the immune system is not working properly.

Inflammation and Wound Healing

• Body's attempt to self-protect to remove harmful stimuli and begin healing is inflammation.
• Infections, wounds, and damaged tissue would not be able to heal without an inflammatory response.
• Chronic inflammation can eventually cause several diseases and conditions.
• Local effects of inflammation: capillary dilation, increased blood flow/warmth/redness, increased capillary permeability, attraction of leukocytes to the injury site.
• Systemic effects of inflammation: fever and leukocytes
• Phases of Wound Healing: Inflammatory, Proliferative, and Maturation.
• Inflammatory phase begins when a wound develops and lasts for 4-6 days.
• An inflammatory stage is marked by oedema (swelling), erythema (redness), inflammation and pain.
• The inflammatory phase includes a triggered healing process and the immune system preventing microbial colonization.
• The proliferative phase lasts another 4-24 days where granulation tissue fills the wound.
• Fibroblasts lay collagen in the wound bed in the proliferation stage, by strengthening new granulation tissue and wound edges beginning to contract.
• Epithelial cells migrate from the wound margins in the proliferation stage.
• The maturation phase can last from 21 days to 2 years.
• Length of time depends on patient- and wound-related complicating factors (duration of wound, patient comorbidities, wound infection status).
• A filled-in wound is covered and strengthened and scar tissue forms.
• Dysfunctional would healing involves: impaired collagen matrix assembly, impaired epithelialization, impaired contraction, and wound dehiscence.

Adaptive Immunity

• Adaptive Immunity: Humoral vs cell mediated immunity.
• Humoral immunity involves intact antigens and antigens that are engulfed and displayed by phagocytes.
• B cells, plasma cells, and memory B cells are part of Humoral immunity.
• Cell mediated immunity involves antigens displayed by infected cells.
• TH cells, TC cells, memory TH cells, memory TC cells, and active TC cells are part of cell mediated immunity.
• Humoral Immunity function: secrete antibodies that defend against extracellular pathogens.
• Cell-mediated Immunity function: defend against infected cells, cancers, and transplant tissues.
• The third line of defense is specific and has acquired immunity, which is WBCs that take out specific pathogens.
• types of Lymphocytes: T cells (from thymus gland) and B cells (from bone marrow).
• Both types of lymphocytes need to see the pathogen first before they respond.
• Both types of lymphocytes develop memory to what they have destroyed.
• T cells recognize what is wrong and target/destroy cells.
• B cells produce AB and proteins that bind to foreign material.
• Active Immunity Immunity gained by actively engaging with the antigen through invasion or vaccination.
• Passive Immunity Immunity gained by receiving antibodies made outside the body by another person, animal, or recombinant DNA.
• Surface molecules expressed on cells of the immune system that play key roles in immune cell-cell communication are CD Molecules.
• CD molecules are essential markers for the identification and isolation of leukocytes and lymphocyte subsets.
• IgG has the highest opsonization and neutralization activities and is classified into four subclasses (IgG1, IgG2, IgG3, IgG4).
• IgM is produced first upon antigen invasion and increases transiently.
• IgA is expressed in mucosal tissues and forms dimers after secretion.

Alterations in Immunity and Inflammation

• Disorders of the immune system include: allergies, immune deficiency, autoimmune diseases, sepsis, and cancer.
• Hypersensitivity: Body responds to a particular substance (antigens/allergens) in an exaggerated fashion where it does not happen in normal circumstances.
• Hypersensitivity results in inflammation and destruction of healthy tissue and can be immediate or delayed.
• There are 4 types of reactions that can be produced by the immune system due to hypersensitivity.

The 4 main types of Hypersensitivity Reactions:

• Type I (IgE-Mediated)= Allergen binds to IgE, which releases mediators and leads to anaphylaxis.
• Type II (Tissue Specific)= IgG or IgM reaction with an antigen on the cell resulting in cell lysis or blood transfusion reaction.
• Type III (Immune Complex Mediated)= Antigen-antibody complexes accumulate and become deposited in tissues.
• Type IV (Cell Mediated)= Delayed processing of the antigen by macrophages, TB test, transplant reaction, or contact dermatitis.
• Type 1 Hypersensitivity is immediate and involves allergies.
• Type 2 Hypersensitivity is cytotoxic reaction like blood transfusion.
• Type 3 Hypersensitivity is an immune complex reaction with autoimmune disorders.
• Type 4 Hypersensitivity is a delayed reaction.
• Treatment for allergies/hypersensitivity: Desensitization through allergy injections or blocking antibodies.
• Autoimmune Disorders happen when normal defenses become self destructive and perceive self as foreign.
• SLE (Systemic Lupus Erythematosus) is a chronic inflammatory autoimmune disorder that can affect connective tissues.
• B cells are activated for unknown reasons to produce AB and AG which combine to form immune complexes (IC).
• These IC fight against the body's own tissue.
• Diagnostic criteria for SLE includes having four or more of the following: butterfly rash, skin rashes, photosensitivity, mucous membrane ulcers, joint inflammation, fever, pain, fatigue, arthritis, Pleuritis or pericarditis (chest pain), or renal abnormalities.
• Treatment for SLE includes: checking Inflammation markers, ruling out other things, and stress management.
• Graft: Any tissue that has been taken from one part of the body and used in another part making the best match of tissue antigens.
• Donor sources for Grafts may be living or cadaver.
• Graft types include: autograft (same person), isograft (identical twin), allograft (same species), xenograft (different species).
• Causes of transplant reactions is when the donor organ may not work well, non adherence, or rejection (based on timing).
• Rejection comes in 3 types: hyper-acute, acute, and chronic.

Rejection Reactions

• Host verses Graft rejection- The host is fighting the graft
• Graft verses Host rejection- The graft fights the host
• Failure of organ most common first sign!
• Treatment: Prevention First & Immunosuppressive Therapy

Immunodeficiency

• Immunodeficiency is a diminished or absent immune response that increases susceptibility to infections.
• Primary Immunodeficiency is a defect within the immune system, a genetic loss of one or more lines of defense, or being born with the conditions of having more than 2 infections of the same type in a year.
• Immunodeficiency Predispose patients to Opportunistic Infections and/or can be diagnosed by measuring Immunoglobin levels, WBCs and Lymphocytes.

Immunodeficiency Treatment

• Gamma Globulins (AB)
• Bone Marrow Transplant
• Reverse isolation precautions
• Hand washing
• Limiting visitors
• Avoiding flowers (pathogens)
• Individuals at risk for Immune Dysfunction include: the very young/old, people with poor nutrition, impaired skin integrity, circulatory issues, alterations in normal flora, chronic diseases, corticosteroid therapy, chemotherapy, smoking, alcohol consumption, and immunodeficiency states .
• Strategies to build a better Immune system: increasing fluid intake, eating a well-balanced diet, eating antioxidants and protein, getting adequate sleep, avoiding caffeine and refined sugar, spending time outdoors, and reducing stress.

Replacement Therapies For Immune Deficiencies

• Gamma Globulin Therapy
• Transplantation and Transfusion

Infection Stages

• Incubation period: organisms growing and multiplying
• Prodromal stage: person is most infectious, vague and nonspecific signs of disease
• Full stage of illness: presence of specific signs and symptoms of disease
• Convalescent period: recovery from the infection

Infection Invasion

• Fungal infection is called mycosis.
• Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes.
• HIV (Human immunodeficiency virus) is a virus spread through certain body fluids that attacks the body's immune system, specifically the CD4 cells (T cells).
• AIDS (Acquired immunodeficiency syndrome) is a deadly, sexually transmitted disease caused by the HIV.
• Stages of Progression to AIDS: Acute HIV Infection, Clinical Latency, and AIDS.
• Aids is dx by a CD4 count < 200 cells/mm or presence of an opportunistic infection.
• People may not know they are infected because they don’t show symptoms.
• Condoms are the best way to protect spreading HIV disease.
• HIV Diagnosis: blood test & polymerase chain reaction (PCR).
• There is no cure for HIV, but combination therapy works best highly active antiretroviral therapy (HAART).