immuno: hypersensitivity, autoimmunity, immunodeficiency

immune system

consists of the cells and molecules responsible for immunity.

normal immune response

the body’s proper reaction to foreign antigens, leading to defense, elimination of invaders, and increased resistance to infection.

abnormal immune response

an altered or inappropriate reaction of the immune system after exposure to a foreign substance, which may result in harmful effects instead of protection.

hypersensitivity

autoimmunity

immunodeficiency

3 types of abnormal immune response

hypersensitivity

__ is an exaggerated or excessive immune response to a foreign antigen that results in tissue damage and clinical disease instead of protection.

harmless

hypersensitivity occurs when the immune system overreacts to substances that are usually __

autoimmunity

__ is an abnormal immune response directed against the body’s own cells and tissues.

self from non-self

autoimmunity happens when the immune system fails to distinguish __, leading to destruction of normal body components.

immunodeficiency

__ is a condition where the immune system has a reduced or absent ability to fight infections.

inadequate immune response

immunodeficiency results in increased susceptibility to diseases due to an __

pathological inflammatory response

instead of providing protection, the immune system triggers a __ against environmental allergens or self-antigens, leading to significant tissue injury

allergic (immediate)

cytotoxic

immune complex

delayed (cell-mediated)

hypersensitivity reactions

• IgE

• mast cells

• bee sting

• peanut

type 1: immediate

IgG, IgM

hemolytic anemia

type 2: cytotoxic

• Ag-Ab complexes

• SLE

• rash

type 3: immune complex

blistering rash

type 4: delayed

type 1

immediate release of histamine from mast cells. it happens almost instantly upon expose

type 2

IgG or IgM-mediated, specifically attack a target cell. (e.g. destruction of rbc)

type 3

focuses on the formation of antigen-antibody complexes. these clumps end up clogging the body’s filters, specifically the kidneys or joints

type 4

this reaction is not mediate. it takes a few days for the t-cells to migrate to the site of the antigen and trigger the response

immediate allergic reaction

type 1 hypersensitivity commonly known as __

allergens

type 1 hypersensitivity is an exaggerated and misdirected immune response to harmless environmental substances called __

IgE antibodies

type 1 hypersensitivity is characterized by the overproduction of __ which bind to the surface of mast cells and basophils.

sensitization phase

allergen cross-linking

degranulation

effector response

steps of hypersensitivity

sensitization phase

During initial exposure, the immune system produces specific IgE antibodies, which bind to high-affinity receptors on the surface of mast cells.

allergen cross-linking

Upon subsequent exposure, the allergen binds to and "cross-links" the IgE molecules already fixed on the mast cell membrane.

degranulation

This signals the mast cell to immediately release stored granules, releasing histamine, proteases, and chemotactic factors into the surrounding tissue.

effector response

histamine triggers rapid vasodilation, increased vascular permeability (edema), and smooth muscle contraction

massive degranulation

Allergen cross-linking triggers a systemic release of Histamine from mast cells and basophils.

vascular effects

Widespread vasodilation and increased permeability lead to a sudden drop in blood pressure.

histamine

__ causes the hepatic veins to constrict, trapping a large volume of blood within the liver and portal circulation.

IgG or IgM antibodies

allergens, Type II involves __ that bind to antigens located on the surface of specific host cells, marking them for immediate destruction.

targeting

Antibodies "tag" host cells, marking them for immediate destruction.

complement activation

Leads to direct cell lysis

opsonization

Targeted cells are coated with antibodies, making them "visible" for removal by macrophages in the spleen and liver.

antibody binding

complement activation

cellular destruction

clinical result

steps of type 2 hypersensitivity

antibody binding

IgG or IgM antibodies bind directly to antigens on the surface of host cells, such as rbc

complement activation

This binding triggers the Classical Pathway, leading to the formation of the Membrane Attack Complex (MAC) that punches holes in the cell membrane

cellular destruction

Target cells are destroyed via intravascular lysis (bursting in the blood) or extravascular opsonization (phagocytosis by macrophages).

severe anemia or organ dysfunction

The massive loss of these cells results in host tissue damage, commonly manifesting as __

complement activation

direct lysis

intravascular hemolysis

opsonization

phagocytosis

extravascular hemolysis

type III hypersensitivity

__ is an immune complex–mediated reaction in which antigen–antibody (IgG or IgM) complexes form in circulation and deposit in tissues, leading to complement activation and inflammation.

soluble IgG or IgM complexes

Type III hypersensitivity is driven by the formation of __ that escape clearance by the mononuclear phagocytic system. These complexes circulate and deposit within tissue basement membranes, typically in small blood vessels, renal glomeruli, or synovial membranes.

localized (arthus reaction)

systemic (serum sickness)

blue eye (corneal edema)

purpura hemorrhagica

clinical examples of type 3 hypersensitivity

localized (arthus reaction)

Occurs in the skin after repeated vaccinations (e.g., in horses or dogs).

systemic (serum sickness)

Occurs when large amounts of foreign protein (like antivenom or antitoxin) are injected.

blue eye (corneal edema)

Observed in dogs with Canine Adenovirus-1 or following live-vaccination.

purpura hemorrhagica

Follows Streptococcus equi (Strangles) infections in horses; causes severe vasculitis and edema.

serum sickness

is a transient syndrome that occurs when a large volume of foreign antigen is introduced intravenously.

antigen phase

Following injection, the level of blood-borne antigen remains high while the body begins the initial immune recognition.

complex formation

As the body produces specific antibodies (Red line), they bind to the circulating antigens. This creates a peak of antigen-antibody complexes.

clinical onset

The shaded blue region identifies the "danger zone" where these complexes deposit in tissues. This results in the simultaneous onset of fever, vasculitis, arthritis, and nephritis.

resolution

As the remaining antigen is cleared and free antibody levels rise (Red line), the symptoms subside, making the condition typically self-limiting.

blue eye

occurs in some dogs after infection or vaccination with canine adenovirus type 1.

It causes anterior uveitis, leading to corneal edema and opacity.

type IV hypersensitivity

hypersensitivity is a delayed, cell-mediated immune response that is independent of antibodies and mediated primarily by sensitized T lymphocytes.

cytokine-mediated inflammation & cytotoxic effects of t cells

tissue injury in type IV sensitivity is caused by __ direct __

macrophages

Activated CD4+ Th1 cells release cytokines that recruit and activate __, resulting in tissue damage,

apoptosis

CD8+ cytotoxic T cells induce __ of target cells.

tuberculin skin test

contact dermatitis

chronic conditions

clinical example of type IV hypersensitivity

tuberculin skin test

A diagnostic reaction showing firm tissue swelling (induration) at the injection site.

contact dermatitis

Inflammation caused by haptens such as chemicals, plant allergens (poison ivy), or metals like nickel.

chronic conditions

Formation of tuberculosis lesions and other persistent intracellular infections.

autoimmunity

Immune system attacks self-antigens

Failure of self-tolerance

Can affect multiple organ systems

Common in domestic animals

genetic predisposition

environmental triggers

loss of self-tolerance

causes of autoimmunity

mechanism of autoimmunity

• starts with loss of self-tolerance

• lead to tissue damage and inflammation

b-cells

produce antibodies

t cells

directly attack body cells

systemic lupus erythematosus

autoimmune thyroiditis

common autoimmune diseases in animals

systemic lupus erythematosus

• affects multiple organs

• immune complex-mediated

skin

joints

kidneys

blood

commonly affected organs of systemic lupus erythematosus

autoimmune thyroiditis

• Thyroid damage = hormonal imbalance

• immune system attacks thyroid tissue

autoimmune thyroiditis

weight gain

lethargy

hair loss

serology

is one of the primary diagnostic tools. It involves the detection of autoantibodies in the blood, which are antibodies directed against the body’s own tissues.

histopathology

it involves the microscopic examination of tissue samples obtained through biopsy. This technique allows visualization of inflammation, tissue destruction, and immune-mediated damage, which are hallmarks of autoimmune disorders.

corticosteroids

__ such as prednisone, are commonly used as first-line therapy. They work by reducing inflammation and suppressing immune system activity, providing rapid relief of symptoms.

immunosuppressive drugs

__ are also widely used to control disease progression. Medications such as azathioprine and cyclosporine inhibit the activity of immune cells, particularly T cells, thereby decreasing the immune attack on the body’s own tissues.

supportive therapy

__ is essential and depends on the specific autoimmune condition. This approach focuses on managing symptoms and complications.

immunodeficiency

A condition in which the immune system’s ability to fight infections and diseases is reduced or absent.

Immune cells (B cells, T cells, phagocytes)

Immune proteins (antibodies, complement system)

immunodeficiency results from defects in

primary immunodeficiency

secondary immunodeficiency

types of immunodeficiency

primary deficiency

• Caused by inherited genetic mutations

• congenital

b cell

t cells

combined

primary immunodeficiency affects specific components

secondary immunodeficiency

• acquired

• caused by external factors affecting the immune system

Malnutrition

Infections (e.g., AIDS (caused by HIV) or chronic leukemia)

Chemotherapy / drugs (immunosuppressants)

Chronic diseases (diabetes, cancer)

common causes of secondary immunodeficiency

pathogenesis

• Failure to eliminate pathogens

• Persistent infections

• Increased severity of disease

b cell defects

bacterial infections (esp. extracellular bacteria)

t cell defects

viral, fungal, intracellular pathogens

phagocyte defects

impaired killing of microbes

complement defects

poor opsonization & lysis

skin testing

• Intradermal or prick tests using suspected antigens.

• Positive result shown by wheal and flare reaction indicates sensitivity.

immunological assays

• Measure numbers and function of B cells, T cells, phagocytes, and complement.

• Identifies which part of the immune system is defective.

clinical evaluation

Based on signs like recurrent, persistent, or opportunistic infections.

antihistamine

• Block H1 receptors and prevent the vasoactive effects of histamine.

• Reduce swelling, redness, and itching.

corticosteroids

• Potent anti-inflammatory agents that suppress the immune response.

• Prevent tissue damage.

epinephrine

Used in severe cases like anaphylaxis to reverse shock and open airways.

antihistamine

corticosteroids

epinephrine

medication for hypersensitivity

immunosuppressive drugs

corticosteroids

medication for autoimmune disease

immunoglobulin therapy

antimicrobial treatment

supportive care

medication for immunodeficiency

immunoglobulin therapy

Replacement of missing antibodies to boost defense mechanisms.