Ch. 4 - Immunity

innate immunity

• Is the first responder to insult; this immune response is rapid and can be initiated by many different pathogens w/o prior exposure 

• Primary cell types: macrophages, neutrophils, and dendritic cells 

  • The rapid responders to microbes that pose a threat of infection 

functions of innate immunity

• Prevention of microbe colonization 

• Prevention of microbe entry 

• Prevention of microbe spread 

pathophysiology of innate immunity

• The first exposure to a microorganism initiates an immune response through the detection of foreign antigens

• An inflammatory response is initiated and receptors on the surface of macrophages recognize components of certain types of microorganisms 

• Inflammation starts the phagocytic process and stimulates the release of chemical mediators 

dendritic cells in innate immunity

• Are important in recognizing hidden antigens; Certain pathogens conceal themselves in envelopes but can be shown to lymphocytes after ingestion by dendritic cells

• Mature dendritic cells = antigen-presenting cells (APCs) that assist recognition of foreign cells

adaptive immunity

• Humoral and cell-mediated immunity that occurs over a lifetime to promote the body’s ability to adapt to the threat of reinfection 

• Primary cell types: B lymphocytes, T lymphocytes, and dendritic cells 

• This system is stimulated by phagocytosis and activation of antigen-presenting cells (APCs; mature dendritic cells)

key properties of adaptive immunity

• Specificity: targeted response to a distinct antigen

• Diversity: recognition of a wide variety of antigens

• Memory: rapid and robust response to previously recognized antigens

• Self and nonself recognition: the ability to distinguish between antigens on body cells and foreign antigens

characterization of adaptive immunity

• A slower response to the introduction of microorganisms than the innate immune system 

• When reintroduction occurs, immune memory can cause a more rapid and intense response 

• includes active and passive immunity

active immunity (adaptive immunity)

• Development of antibodies in response to an antigen

• Achieved through actually having a specific disease or vaccine immunization against a particular disease

• Ex. flu vaccination or having chicken pox

passive immunity (adaptive immunity)

• Immunity transfer from host to recipient

• Achieved via mother-to-infant transfer via placenta or breast milk or injection with high concentrations of antibody, such as immune gamma globulin

humoral immunity

• Adaptive immunity that involves antibodies

  • Antibodies = immunoglobulins that react with an antigen in a specific way

  • B lymphocytes become plasma cells and make immunoglobulins/antibodies

how antibodies protect cells from pathogens

1. Binding of the antigen to the antibody, which prevents the antigen from infecting cells (neutralization). The antigen–antibody complex is removed by agglutination (clumping together) or precipitation (falling out of solution).

2. Promoting phagocytosis and destruction of the pathogen through the phagocyte’s ability to recognize the constant region of the antibody that is bound to or coating the antigen (opsonization).

3. Activating complement, which supplements that of the innate system, further enhances the actions of the antibodies.

immunoglobulins

• Antibodies secreted from plasma cells 

• Composed of the constant region (forms the base of the Y-shaped antibody) and the two variable regions (structured to allow binding to specific antigens) 

• B lymphocytes become plasma cells and make immunoglobulins/antibodies

• GAMED

IgG

• Most abundant immunoglobulin (>70%) 

• It's the smallest of all immunoglobulins and its tiny size allows it to enter body tissues from body fluids 

• The only immunoglobulin able to cross the placenta = provides passive immunity 

• Is detected days after infection and in chronic cases

IgA

• Provides passive immunity from mother to baby through breastmilk 

• Is present in mucous membranes (i.e tears, the mouth, genitalia, and anus)

IgM

• The initial circulating antibody produced in response to antigen challenges (first to rise) and the first to be produced by newborns

• Is massive and the largest of all immunoglobulins

IgE

• On the surface of mast cells and basophils 

• Causes cellular degranulation upon antigen binding, triggering chemical mediator release w/ inflammation and allergies 

IgD

• Located in the B lymphocyte plasma

• Involved in antigen binding and stimulating differentiation of B lymphocytes into plasma cells 

hypersensitivity reactions

• Disorders resulting from excessive immune responses to allergens 

  • Allergens = antigens considered to be harmless 

• response to these allergens is inappropriate, ranging in severity from mild to severe, and it can be potentially life-threatening

• Types of hypersensitivity reactions:

  • Type I = immediate hypersensitivity reaction 

  • Type II = antibody-mediated reaction 

  • Type III = immune complex-mediated reaction 

  • Type IV = cell-mediated hypersensitivity reaction

Immediate hypersensitivity reaction

• Type I reactions; IgE mediated hypersensitivity response 

• Initial exposure to an allergen causes IgE production 

  • Small, dry allergen is often inhaled at low doses 

• dendritic cells are activated by the allergens, causing them to travel to lymph nodes to young T lymphocytes, promoting differentiation 

• IgE produced by the plasma cells within inflamed tissue binds with high affinity to receptors on mast cells and basophils

• IgE encounters and binds an allergen

• mast cells and basophils degranulate, releasing chemical mediators, and causing injury to cells, producing the symptoms associated with allergy

• The reaction is initiated within minutes of allergen exposure 

• Atopic = people who develop symptoms after exposure to a wide number of commonly encountered allergens; IgE responses are stimulated from exposure to usually benign substances 

• Anaphylaxis = extremely serious response to type I immediate hypersensitivity reaction

  • It is characterized by edema and vasodilation and leads to hypotension

  • Severe, life-threatening reaction requiring immediate treatment 

• Examples: 

  • Food allergies 

  • Insect bites

antibody mediated reaction

• Type II reactions; IgG or IgM mediated; “mistaken identity” 

• Usually harmless substances are identified as harmful causing an immune response resulting in cell damage 

• Reaction is tissue-specific, usually involving the destruction of a target cell by antibodies binding to antigens on the cell surface 

  • Cell destruction and tissue damage

•  When the antibody binds to the antigen on the cell, the cell is lysed and destroyed

• Examples: 

  • Drug reactions 

  • Myasthenia graves 

  • Blood transfusion reactions 

  • Graves disease 

  • Newborn hemolytic disease 

  • Anemia 

  • Thrombocytopenia 

  • Leukopenia 

• Treatment:

  • Removal of the antigen 

  • Antigen avoidance 

type I vs. type II hypersensitivity reactions

• type I = anaphylaxis; requires immediate medical treatment

• type II = cell damage; usually resolved by taking allergen/antigen away

immune complex mediated reaction

• Type III reaction; IgG and IgM mediated; cellular and tissue damage indirectly caused by complement activation stimulated by antigen-antibody complexes

• Immune complex activation causes widespread damage:

  • Altered blood flow 

  • Vascular permeability 

  • Inflammatory cell response 

  • Damaged blood vessels 

  • Damage to the kidney glomeruli, small blood vessels of the skin, and synovial lining of the joints

• Causes infiltration of PMN leukocytes/neutrophils 

• Arthus reaction 

  • Complex mediated immune response in the skin resulting in localized tissue necrosis 

  • Initial exposure resolves with time; subsequent exposure can cause serious response 

• Examples: 

  • Systemic lupus erythematosus (SLE) 

  • rheumatoid arthritis (RA) 

  • Drug reactions with antilymphocyte globulin (an immunosuppressive agent used in transplant patients) and streptokinase (thrombolytic agent used with patients having a myocardial infarction)

cell mediated hypersensitivity reaction

• Type IV response; T-cell mediated; two types of these reactions are distinguished by different mechanisms and associated response times

• direct cell mediated toxicity or delayed hypersensitivity reaction

direct cell mediated toxicity (type IV hypersensitivity response)

• Damage occurs in cells and tissues as a direct response to CD8 cytotoxic T lymphocyte destruction of cells with recognized antigens 

• Can be more harmful than the damage inflicted by the pathogen

delayed hypersensitivity reaction (type IV hypersensitivity response)

• Mediated by antigen-specific T lymphocytes 

• Respond to antigens presented responses usually occur in the skin and are mediated by antigen-presenting cells/mature dendritic cells or CD4 helper T lymphocytes 

• phases:

  • Sensitization phase 

    • When the antigen crosses the skin, and is transported to the lymph nodes 

    • Cells develop into mature dendritic cells able to present antigens to helper T lymphocytes and activate them

    • Memory cells are produced and become localized in the dermis.

  • Elicitation phase 

    • Memory T lymphocytes in the dermis are stimulated by subsequent exposure to the antigen 

    •  Cytokines and chemokines are released, stimulating the attraction of macrophages and additional T lymphocytes to the area 

    • Takes between 24-72 hours 

    • AKA contact dermatitis 

steps from antigen to antibody

• Pathogen enters the body 

• Mast cells are on site first and release histamine 

• Macrophages and double nucleated neutrophils come and phagocytize the pathogen 

• The pathogen is broken into antigens which are picked up by dendritic cells

• Dendritic cells take the antigens to give to the T cells and the B lymphocytes

• The B lymphocytes become plasma cells and make immunoglobulins/antibodies

adaptive immunity cells

• Originate with pluripotent hematopoietic stem cells in the bone marrow 

  • Produces two precursor cell types

    • lymphoid progenitor

      • T lymphocytes 

      • B lymphocytes 

    • myeloid progenitor

      • Monocytes 

      • Dendritic cells 

      • Granulocytes 

      • Mast cells

WBCs/leukocytes

• Basic functional units of the immune system 

• Account for 25-35% of the WBCs circulating in the blood; 99% are located in lymphatic fluid 

• Three major categories: T lymphocytes, B lymphocytes, and natural killer cells

T lymphocytes

• Type of WBC that is born in bone marrow but matures and fully differentiates in the THYMUS 

• Are essential in adaptive cell-mediated immunity

• Destruction of cellular antigens 

• Promote antibody production by B lymphocytes

• 60% of blood lymphocytes 

• They require contact with an antigen in order to signal T lymphocyte proliferation and differentiation into different classifications:

  • Helper T lymphocytes = CD4 (TH1, TH2)

  • Cytotoxic T lymphocytes = CD8

  • Suppressor T lymphocytes

helper T lymphocytes

• CD4 

• Enhance humoral and cell-mediated responses of the immune system; activate other cells needed for an appropriate immune response. 

• activate antigen-specific T cells 

• T helper type 1 cells activate macrophages, secrete chemokines and

• cytokines to attract macrophages, promote fusion of lysosomes with

• vesicles containing bacteria, and stimulates phagocytosis

• T helper type 2 cells activate B cells to produce antibodies

cytotoxic T lymphocytes

• CD8 

• Direct the destruction of antigen-carrying cells 

• They attack tumor cells and cells infected with viruses before viral replication is complete, therefore stopping further spread 

suppressor T lymphocytes

• Inhibit humoral and cell-mediated responses

• Provide a balance, limiting immune response

B lymphocytes

• Type of WBC that is born and matures in BONE marrow before migration to the lymphoid tissue to become activated after contact with an antigen 

• Binding of an antigen to the B lymphocyte stimulates differentiation of the B lymphocytes into anti-body secreting plasma cells 

• B-cell receptors on the plasma membrane of B lymphocytes recognise specific antigens, causing specificity in the adaptive immune response 

• After antigen-BCR binding, B lymphocytes differentiate into plasma cells, which proliferate and begin to produce and secrete large quantities of antibodies called immunoglobulins (Ig’s) 

vaccines

• Vaccines help to develop active immunity to particular diseases 

• Live-attenuated vaccines contain weakened (attenuated) forms of the microorganism that causes a disease 

  • Ex. MMR, rotavirus, smallpox, chickenpox, and yellow fever 

• inactivated/dead vaccines use the killed version of the microorganism that causes a disease 

  • Don’t provide immunity as strong as live vaccines so boosters are required

  • Ex. Flu, COVID, hepatitis A, polio, rabies 

myeloid progenator cells

• Originate with pluripotent hematopoietic stem cells in the bone marrow 

• Produce leukocytes essential to immune function: granulocytes and monocytes

granulocytes

• Named for cytoplasmic granules common to all types

• are phagocytic cells

• Include: neutrophils, eosinophils, and basophils 

• Cells do not live long but production is dramtically increased when stimulated

basophils

• Complement the actions of mast cells important in allergic reactions 

eosinophils

• Offer the greatest protection against parasites 

neutrophils

• Present in the greatest number 

• Most important in the rapid response to bacterial infection 

• Phagocytes that are the first responders in inflammatory response

natural killer cells

• Large granular lymphocytes

• Active in innate immunity and circulate until they come in contact with cells they can recognize as a threat

  • such as virally infected cells or tumor cells

• NK cells exert their cytotoxic effect through attack and killing of targeted cells.

monocytes

• Phagocytic cells

• Able to engulf larger quantities of debris than granulocytes 

• large, mononuclear leukocytes, representing 3% to 7% of the total number of circulating leukocytes

• Become activated with in contact with an antigen, causing differentiation into macrophages and migration into the tissues 

• The antigen-carrying cell is ingested by the macrophage, where it undergoes phagocytosis

dendritic cells

• Critical to processing and displaying antigens to T lymphocytes

• Mature dendritic cells take up antigens when encountered in circulation

langerhans cells

• Immature dendritic cells in the skin 

• Carry surface receptors for immunoglobulin and complement

autoimmunity

• Failure or uncontrolled function of the immune system to distinguish “self” from “nonself” directed at a person’s own tissues 

• Occurs through specific recognition of “self” antigens and by overzealous responses to chronic infection

alloimmunity

• occurs when an immune response is stimulated in response to the presence of cells from another individual of the same species

• Ex. skin graft rejection; organ transplant rejection