Alterations in the Immune System

What is immunity?

Body’s ability to defend against specific pathogens and/or foreign substances responsible for the development of disease 

Functions of the immune system:

• Defends, against anything foreign 

• Detects, is this supposed to be here or not? 

• Destroys, anything foreign 

Characteristics of the immune system:

• Recognizes, should recognize foreign things (antigens) 

• Remembers 

• Reacts 

Lymhoid organs

• thymus

• lymph nodes

• spleen

• lymphoid tissue

What is the thymus’ function?

• Function- Site where T lymphocytes mature 

• Organ is mature at birth; begins to degenerate in adulthood 

• Thymus selection- Only T cells that are able to detect antigens are allowed to mature (not cells that may detect and attack self) 

What is the lymph nodes function?

Functions-

1) remove foreign material from lymph before it enters the blood stream;

2) hub for reproduction of immune cells

What is the spleens function?

• Functions- 1) Filter antigens from blood; 2) Site of RBC destruction 

• As blood circulates through the spleen it is monitored by T lymphocytes. If invaders are spotted, B cells activate antibodies to destroy the invader 

• Macrophages in the spleen swallow and digest debris in the blood (such as destroyed RBCs)

What is lymphoid tissue?

Contains “standing guard” immune cells 

What WBC…

• Phagocytic 

• 1st responder 

• Respond to bacterial_ invasions 

• Immature neutrophils are called Bands 

Neutrophils (55% - 70% of WBC count) 

What WBC is being described..

• B Lymphocytes 

• T Lymphocytes 

• Natural Killer Cells 

  • Spleen, lymph nodes, bone marrow, blood 

  • Kill tumor cells and virus-infected cells 

  • Natural kills are programmed to KILL, not recognize 

Lymphocytes (20% - 40%) 

What are B lymphocytes

10-20% of lymphocytes; mature in bone marrow, responsible for antibody-mediated (humoral) immunity

What are T lymphocytes

• 60-70% of lymphocytes;

• two main subpopulations

  • (CD4+ and CD8+); provide cell-mediated (cellular) immunity

What kind of cells are being descibed?

1. Spleen, lymph nodes, bone marrow, blood 

2. Kill tumor cells and virus-infected cells 

3. Natural kills are programmed to KILL, not recognize 

natural killer cells

What WBC is…

• Monocytes mature into macrophages that travel and reside in different tissues in the body 

• Once a macrophage resides in a particular tissue, the macrophage will differentiate into a cell that is specific to that tissue. (Liver = Kupffer cells) 

• Macrophages are large, phagocytic leukocytes 

• Macrophages are “presenter cells” – they inform Helper T Cells and Cytokines 

Monocytes / Macrophages (2% - 8%) 

What WBC IS…

• Mostly in GI and respiratory tract 

• Numbers rise with parasitic and allergic responses 

Eosinophils (1% - 4%)

What WBC…

• Numbers rise with inflammatory and allergic/hypersensitivity responses 

• Release histamine from Mast Cells 

  • Histamine (inflammatory mediator), vasodilate and increase capillary permeability 

Basophils (0.5% - 1%) 

What are dendritic cells?

• “Bridge” between innate(born with) and adaptive(aquire over time) immune systems 

• Relatively rare, found mostly in tissues exposed to external environments  

• Circulate in the body as immature cells but become activated when they encounter pathogens “Gossips”  

  • Once activated, they function as key antigen-presenting cells (APCs) capable of initiating adaptive immunity 

  • Responsible for the processing and the presentation of antigens to lymphocytes 

• Like macrophages, these cells are presenter cells. 

What are cytokines?

• Proteins produced during ALL types of immune responses 

• REGULATORS!: Cytokines regulate the host reaction and the leukocyte activities (movement, proliferation, & differentiation) 

• COORDINATORS!: Key role in regulating messages necessary for the coordinated function of the immune response 

• Domino effect: Often, one type of cytokine directly affects subsequent cytokines (excessive cytokine production leads to severe adverse effects, such as in septic shock) 

• Four Main Cytokine Groups 

  • interlukins

  • interferons

  • tumor necrosis factors

  • growth factors

What are interleukins? (one of the main cytokine groups)

• Mediate communication between WBCs (inter = between; leuk = WBC) 

• Many types 

• Primarily responsible for activating T and B lymphocytes 

What are inteferons? (one of the main cytokine groups)

1. Interfere with viral replication 

2. Activate natural killer cells 

What are tumor necosis factors? (one of the main cytokine groups)

1. Activates neutrophils and endothelial cells 

2. Induces acute inflammatory response 

3. Kills cells through apoptosis 

What are growth factors? (one of the main cytokine groups)

stimulate plasma cell production

What is recognition of self?

• Human Leukocyte Antigens (HLA): Proteins on the surface membranes of cells that help identify the cell as “self” 

  • Unique to you no one has the same HLA 

  
  

• Assist in recognizing Self or Non-Self (Pathogens) 

  • If recognized as “self”: It’s all good 

  • If recognized as “non-self”: Immune response is initiated  

  
  

• HLAs markers are found on all tissues except_Red blood cells 

What are the proteins on the surface membranes of cells that help identify the cell as “self” 

Human Leukocyte Antigens (HLA)

• Assist in recognizing Self or Non-Self (Pathogens) 

  • If recognized as “self”:

its all good

• Assist in recognizing Self or Non-Self (Pathogens)

  • If recognized as “non-self”:

Immune response is initiated  

What tissues are HLA markers NOT found on

Red blood cells

 

Recognition of Non-Self (Immune Response) 

• Antigens: Anything that is foreign; generates an immune response 

  • Microbial: bacteria, viruses, parasites, fungus  

  • Non-microbial: pollen, bee stings, venom 

  
  

• Antigenic determinant site- Area on an antigen that provokes an immune response 

• Haptens: Small molecules not capable of producing their own antigenic response, so they link to proteins in order to function as antigens 

Antigens are first identified by a complex system and then “presented” to the immune system. 

What is …

Anything that is foreign; generates an immune response 

• Microbial: bacteria, viruses, parasites, fungus  

• Non-microbial: pollen, bee stings, venom 

antigens

Examples of microbial antigens

bacteria, viruses, parasites, fungus  

Examples of non-microbial antigens

pollen, bee stings, venom 

What is the Antigenic determinant site-

Area on an antigen that provokes an immune response 

What are Haptens?

Small molecules not capable of producing their own antigenic response, so they link to proteins in order to function as antigens 

The Complement System 

• “Complements” the immune system 

• Inactive proteins in the circulatory system are activated in an immune response 

• Assists in recognizing microorganisms 

• Activation and response occur in a predictable sequence or pathway 

  • Opsonization- coating of the cell membrane of an antigen that enhances the binding of phagocytic cells to the organism 

    • Antigen is destroyed 

  • Triggers neutrophil invasion to the site 

  • Stimulates the release of inflammatory mediators 

  • Triggers the membrane attack complex (antigen lysis) 

What is the, coating of the cell membrane of an antigen that enhances the binding of phagocytic cells to the organism

Opsonization

Critically Think: What happens if the recognition of self fails: 

• What happens if the immune system recognizes itself as foreign? 

Going to attack itself= autoimmune disease  

What happens if the immune system fails to recognize a pathogen? 

More prone to infections, body wont fight it off, you get really sick  

What is innate immunity?

• Natural immunity 

• Defenses in place before an encounter with an infectious agent 

• Rapid response to invading agents 

• Differentiates between self and non-self 

• Does not distinguish between invading agents 

  • For ex cant tell diff between flu and varicella virus  

• Examples:

  • Skin 

  • Mucus membranes 

  • WBCs 

  • Enzymes  

What are some examples of innate immunity?

• Skin 

• Mucus membranes 

• WBCs 

• Enzymes

What is passive immunity?

• Acquired Immunity 

• Short-term (3 – 6 months) 

• Immunity to certain diseases is transferred from the mother to the infant through placental circulation and breast milk 

• Does not last a lifetime 

• Passed from one person to another  

• Examples:

  • Mother to baby through breast milk 

  • Donating blood plasma, antibody infusions  

Examples of passive immunity:

• Mother to baby through breast milk 

• Donating blood plasma, antibody infusions  

What is Adaptive Immunity 

• Acquired Immunity 

• Immunity acquired through exposure to foreign and infectious agents 

• Initially a slower response but more capable of destroying pathogens that evade innate immunity 

• Differentiates between self and non-self 

• Ability to distinguish between invading agents 

  • Specific unique antigens 

 

How does adaptive immunity develop?

• Having the disease or receiving vaccinations 

• Production of antibodies: Antibodies develop and are present in the body. May be measured with serum lab tests called “serology” or “titer” 

adaptive immunity components

T and B lymphocytes and their products 

Examples of adaptive immunity

B and T cells

Two types of adaptive immunity:

Humoral and Cell-Mediated 

What is the Humoral Immune Response (B-Lymphocytes) 

1. Antibody mediated immunity 

2. B-Lymphocytes mature in the bone marrow and create antibodies 

3. Defends against extra-cellular microbes and their toxins 

4. B-Lymphocytes differentiate into antibody-secreting plasma cells 

5. Circulating antibodies destroy microbes present in the blood or mucosal surfaces 

6. How does it work? 

   1. Body experiences an initial exposure to an antigen (non-self substance), ex varicella  

   2. Antigens are presented to the B-cells 

   3. B-cells become sensitized to the specific antigen forever 

   4. B-cells split into two new cells: 

      1. One plasma cell: secretes antibodies  

      2. One memory cell: one job, forever remember what that antigen is and what it looks like

      
      

   5.  Plasma cell will continue to produce antibodies for that specific antigen (antibody production peaks at ~ 10 – 14 days after the initial exposure). 

   6. The antibodies produced will circulate in the blood for the rest of the person’s life. 

   7. Any subsequent exposures to the antigen will be recognized by the Memory B-cell, which will result in a rise in the antigen specific antibodies. 

   8. The antibodies fit like a puzzle piece to the specific antigen (Y shape) 

      1. Made to fit specific antigen determinant spot  

   9. When the antibodies bind to the antigens, an “immune complex” is formed. This slows the antigen movement, weakens the antigens cell membrane, and triggers attacks from other WBCs. 

   10. The immune complex forms a “clumping” substance that is removed from the body by phagocytic WBCs. 

   11. Complement system is activated- assisting in the destruction of the antigen 

   12. The humoral immune response is the basis for vaccines 

       1. Vaccines, weakened virus injected into body, won’t make us sick, but it gives us an initial exposure, we will have enough antibodies in 10-14 days to be immune to protect from sickness  

       2. For ex, we get flu vaccine every year because the flu virus mutates 

   13.  Antibodies are protein molecules also known as immunoglobulins 

Humoral Immune Response (B-Lymphocytes) :

B cells split into two new cells:

• One plasma cell: secretes antibodies  

• One memory cell: one job, forever remember what that antigen is and what it looks like  

What does the plasma cell do`

B cell derivative that secrete antibodies

What does the memory cell do?

B cell derivative that has one job, which is to forever remember what that antigen is and what it looks like 

Plasma cell will continue to produce antibodies for that specific antigen (antibody production peaks at ______ ______ days after the inital exposure)

10-14 days

Antibodies are protein molecules also known as

immunoglobulins

IgG

• I “Got the goods” at birth

• Most abundant (~75% of total) 

• Combats viruses, bacteria, and toxins 

• Only Ig that crosses the placenta 

• Protects the newborn 

• Activates complement system & binds to macrophages 

IgA

• “sAlivA, nAsAl, respiratory, breaAstmilk” 

• Found in body secretions, including breastmilk 

• Protects mucous membranes 

IgM

“My blood type”

• Forms antibodies for ABO blood antigens 

• Responds to viral and bacterial invasions 

• Prominent in early immune response- First Ig to appear 

• Activates complement system 

IgD

• “daddy(mature, chronic)” 

• Found on B-Lymphocytes and needed for maturation of B-cells 

• Usually elevated in chronic infections 

IgE

• “EEEw parasites, allergEEEs”

• Binds to mast cells and basophils 

• Involved in parasitic infections, allergic reactions, and hypersensitivity reactions(basically same thing as allegric reaction) 

• Important inflammatory Ig- Activates mast cells and triggers release of histamine and other inflammatory mediators 

Cell-Mediated Immune Response (T-Lymphocytes) 

• Primarily destroy intracellular pathogens (viruses, cancer cells) 

• T-cells develop receptors that recognize viral peptides (antigens) on the surface of infected cells 

• Once an infected cell is recognized, T-cells activate the immune response 

• Helper T Cells (“Master Regulator, the boss”) 

  • Stimulate B cells to produce antibodies 

  • Activates T cell responses 

  • Helper T cells(CD4), Designated as CD4 T cells  

• Regulator (Suppressor) T cells 

  • Suppress the proliferation of immune cells to prevent exaggerated immune responses 

Once an infected cell is recognized, what cells activate the immune response?

T-cells

What are the cells that:

• Stimulate B cells to produce antibodies 

• Activates T cell responses 

• Helper T cells(CD4), Designated as CD4 T cells  

Helper T Cells (“Master Regulator, the boss”) 

Regulator (Suppressor) T cells 

Suppress the proliferation of immune cells to prevent exaggerated immune responses 

Age-Related Considerations of the Immune System 

• Infants

  • IgG crosses the placenta and is the only immunoglobulin present at birth 

  • All other immunoglobulins are produced once exposure to antigens occur 

    • Except: IgA is transferred from the mother to infant through breastmilk 

  • Immature complement system 

• Elderly 

  • Immune system begins to decline with age 

  • Elderly are more susceptible to infection and autoimmune disorders 

  • Older adults may not present with fever during an infection 

 

Age-Related Considerations of the Immune System

INFANTS

• IgG crosses the placenta and is the only immunoglobulin present at birth 

• All other immunoglobulins are produced once exposure to antigens occur 

  • Except: IgA is transferred from the mother to infant through breastmilk 

• Immature complement system 

Age-Related Considerations of the Immune System

ELDERLY

• Immune system begins to decline with age 

• Elderly are more susceptible to infection and autoimmune disorders 

• Older adults may not present with fever during an infection 

What is a hypersensitivity disorder?

An abnormal, excessive response of the immune system that causes injury to the host. 

Type I- Immediate Hypersensitivity Reaction 

• Classic allergic response; most common type 

• IgE mediated (basophils/mast cells) 

• Genetic propensity 

• Onset: Minutes to hours 

Type I- Immediate Hypersensitivity Reaction 

ALLERGENS= Antigens:

• Examples of allergens:  

  • Pet hair, pollen, dust, medications, foods  

Type I- Immediate Hypersensitivity Reaction,

METHODS OF EXPOSURE:

Touch, inhale, ingest, injection 

Type I- Immediate Hypersensitivity Reaction

Mast cells release inflammatory mediators 

• Histamine 

  • Bronchiole constriction, tightening/narrowing of airways 

  • Increased capillary permeability= swelling 

  • Vasodilation, decreased pressure  

Type I- Immediate Hypersensitivity Reaction

• ATOPIC (LOCAL) REACTIONS:

• Occur at the site of exposure 

• Examples: allergic rhinitis, atopic dermatitis 

 

Type I- Immediate Hypersensitivity Reaction

• Type I IgE mediated response may be mild or severe

• mild- Allergic rhinitis(nasal) 

• May be severe- Asthma or Anaphylaxis 

Type I- Immediate Hypersensitivity Reaction 

• Common manifestations for any “allergic reaction”: 

• Inflammation of the eyes, nose, respiratory tract 

• Urticaria(hives) 

• Dermatitis(inflammation of the skin) 

What is anaphylaxis?

LIFE THREATENING EMERGENCY 

1. Systemic IgE-mediated hypersensitivity reaction 

2. Widespread release of histamine 

   1. Massive vasodilation= low bp --> Hypotension --> Arterial hypoxia 

3. Even minute quantities of the allergen can result in an anaphylactic reaction 

   1. The severity of the reaction depends on the degree of previous sensitization (not the quantity of exposure). 

4. Manifestations: 

   1. Erythema (redness) 

   2. Urticaria (hives) 

   3. Angioedema (swelling of the face: eyes, lip, tongue, and sometimes airway) 

   4. Hypotension (low blood pressure) 

   5. Tachycardia (fast heartrate) 

   6. Bronchospasm(bronchioles spasm) & Dyspnea(difficulty breathing) 

   7. GI upset 

   8. Cardiac dysrhythmias... cardiac arrest! 

Manefestations of Anaphylaxis: LIFE THREATENING EMERGENCY 

• Erythema (redness) 

• Urticaria (hives) 

• Angioedema (swelling of the face: eyes, lip, tongue, and sometimes airway) 

• Hypotension (low blood pressure) 

• Tachycardia (fast heartrate) 

• Bronchospasm(bronchioles spasm) & Dyspnea(difficulty breathing) 

• GI upset 

• Cardiac dysrhythmias... cardiac arrest! 

Hypersensitivity disorders:

• Type II, Antibody-Mediated (Cytotoxic) Disorders 

• Mediated by IgG or IgM antibodies reacting to specific antigens on specific cell or tissue surfaces 

• Examples: 

  • Blood transfusion reactions 

  • RH incompatibility  

Hypersensitivity disorders:

• Type III, Immune Complex-Mediated Disorders 

• IgG and IgM mediated  

• Caused by the formation of antigen-antibody immune complexes 

• Immune complexes circulate in the blood stream and “get stuck” in tissues, initiating an inflammatory response

  • Glomerulus, lungs, joints 

  • May damage inner lining of vessels 

• Inflammatory response leads to leukocyte accumulation and vessel/tissue damage 

 

Hypersensitivity disorders:

• Type IV, Cell-Mediated Hypersensitivity Disorders

• T CELL mediated (not antibody mediated) 

• *Cell mediated and delayed* response (24 – 72 hours) 

• May be mild to severe 

• Examples: 

  • Autoimmune disorders 

  • Contact dermatitis (poison ivy, cosmetics, laundry detergent) 

  • Organ transplant 

  • Tb skin test

Hypersensitivity disorders:

• Latex Allergy 

• May present as a Type I (IgE mediated) or Type IV (cell mediated) reaction 

• Frequent exposure to latex or the proteins on latex (gloves, other materials) 

• May range from contact dermatitis to anaphylaxis 

• Cross-sensitivity with foods 

  • Bananas, kiwis, avocados 

In a latecx allergy there is cross sensitivity with foods, list the foods:

banannas, kiwis, avocados

What is a graft?

whatever is donated or transplanted, ex: kidney

What is a donor?

person who is donating the graft

What is a Recipient/host?

person who receives the graft

What is an Allogeneic graft (allograft)  

Transplanted from one person to another  

• donor and recipient share similar HLA but are not identical

What is an Syngeneic graft?

Transplant in which donor and recpient are indetical twins

• wont reject bc twins have same HLA 

What is an Autologous graft (autograft)?

Move something from one part of body to another  

• no risk of rejection

What is transplant rejection?

When graft is being destroyed by immune system

Mechanisms Involved in Transplant Rejection 

• Many cells involved in rejection process: T-cells, B-cells, macrophages, eosinophils, NK cells (T-cells play a major role) 

• Patterns of Rejection 

  • Hyperacute Rejection 

    • Happens immediately, ex: we immediately see kidney dying during transplant 

  • Acute Rejection 

    • A few months/years down the road, body attacks it  

    • Sign: organ failure,  

  • Chronic Rejection 

    • Happens around 10yrs after transplant  

    • Happens to every allograft, for ex: so down the line you will need another kidney transplant 

What is hyperacute rejection?

Happens immediately, ex: we immediately see kidney dying during transplant  

What is Acute Rejection 

• A few months/years down the road, body attacks it  

• Sign: organ failure

What is chronic rejection?

• Happens around 10yrs after transplant  

• Happens to every allograft, for ex: so down the line you will need another kidney transplant 

What is graft-versus host disease (GVHD)?

Condition where immunologically competent transplanted cells attack an immunocompromised recipient; most common with bone marrow or liver transplant

What is autoimmune disease?

•   Body fails to differentiate between “self” and “non-self” and mounts and immunologic response against the host (it attacks itself!)

•     Group of diseases- More than 80 different autoimmune diseases

•     May be organ specific or systemic

  •      Organ Specific: Type I Diabetes, Hashimoto thyroiditis

  •    Systemic: Systemic Lupus Erythematosus (SLE)

organ specific autoimmune disease

Type I Diabetes, Hashimoto thyroiditis

Systemic autoimmune disease

   Systemic Lupus Erythematosus (SLE)

Mechanisms of Autoimmune Disease (Independent Review)

•     Humoral/Cell-mediated response resulting in inflammation and tissue injury or deposits of immune complexes into tissue (resulting in tissue injury) 

•    If cell-mediated, autoantibodies are found in blood stream

  •      Example: Rheumatoid Factor (RF) is an autoantibody found with rheumatoid arthritis

• Both genetic and environmental factors may play a role

•     Other potential causes:

  •   Gender (mostly female... hormones may play a role?)

  •   Heredity

  • Age

  • Environmental factors (viruses, maternal smoking, lack of exposure to maternal antibodies through breastfeeding, exposure to hazardous chemicals)

HUMAN IMMUNODEFICIENCY VIRUS (HIV) & ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

1)    Caused by Human Immunodeficiency Virus (HIV)

2)    Characterized by profound immunosuppression, opportunistic infections(wouldn’t normally make someone sick if they had a normal immune system), malignancies(certain. Cancers), wasting, and CNS degeneration.

• 3)    Present worldwide- Pandemic; one of the leading causes of death among young adults in the U.S.

• a)     In 2024, an estimated 1.2 million people in the U.S. had HIV

• b)    Approximately 13% (1 in 8) did not yet know that had it

Aids characteristics

profound immunosuppression, opportunistic infections(wouldn’t normally make someone sick if they had a normal immune system), malignancies(certain. Cancers), wasting, and CNS degeneration

HIV TRANSMISSION

a)     There is no evidence of casual transmission

           i)     Being near someone with HIV you won’t catch

b)    Transmission can occur through:

                  i)     Sexual contact

                  ii)     Blood-to-blood

                 iii)     Perinatally ( Pregnant woman to fetus)

                iv)     Infected blood, semen, or vaginal secretions are onto

mucous membranes or into the bloodstream

               v)     Break in mucosa (oral, vaginal, anal)

                vi)     Blood transfusions – Risk has drastically reduced since donor screening began in 1985

c)     A person infected with HIV can spread disease even if no symptoms are present.

d)    A person infected with HIV can spread disease even if they do not know they have it.

• Cant be spread through saliva, closed mouth kissing, sweat, tears, hugging, shaking hands, sharing dishes

e: Window Period

      i)   Time period from the initial infection to the point at which the individual tests positive for HIV antibodies

     ii)     Virus may be latent for a period of time

     iii)     Transmission is possible during this period

 

 

f: Seroconversion

        i)     The moment when the infected person converts from being negative for HIV antibodies to being positive for HIV antibodies

      ii)     1 – 3 months, or up to 6 months

Transmission of HIV can occur through?

•   Sexual contact

• Blood-to-blood

•    Perinatally

  • Pregnant woman to fetus

• Infected blood, semen, or vaginal secretions are onto mucous membranes or into the bloodstream

•   Break in mucosa (oral, vaginal, anal)

•   Blood transfusions – Risk has drastically reduced since donor screening began in 1985

Can A person infected with HIV can spread disease even if no symptoms are present?

true