PART Dr. Muhammd's lecture

What is Immunodeficiency

state in which the immune system’s ability to fight infectious diseases is either compromised or completely absent.

What is Primary Immunodeficiencies

• The defect arises because of a problem with the immune system itself.

• Inherited genetic diseases

• Common in newborns and very young animals

What is Secondary immunodeficiencies

• Secondary to a known cause

• Virus diseases

• Cancers (some exceptions)

• Nutrition

• Toxins

Dutchess is a 1-year-old German Shepherd with repeated bacterial pneumonia, a long-term cough since she was 2 months old, poor weight gain, and occasional diarrhea. Antibiotics helped each time, but the pneumonia kept coming back. At the physical examination, she was thin but alert, and she had a strong odor and discharge in her ears due to frequent scratching. WHAT IS YOUR DIAGNOSiS

selective IgA deficiency

Where is IgA produced

produced at mucosal surfaces and is the predominant antibody produced in response to bacterial colonization of the intestine.

IgA is produced as a dimer in ?

secretions

IgA is produced as a monomer in ?

Blood

How is IgA transported into the lumen

by the polymeric Ig receptor (pIgR).

After IgA is transported what happens in the next step?

the receptor is cleaved, leaving behind the secretory component (J chain), which helps IgA adhere to mucus and protects it from being broken down by enzymes.

•-----------------------deficiency is a common primary immunodeficiency in dogs and humans (~1 in 700 people of European descent).

Selective IgA

How might the ear canal infection seen in Dutchess be related to her IgA deficiency?

without IgA in ear secretions bacteria can move easily grow, attack and invade tissues that IgA would normaly protect

If Dutchess develops allergies to inhaled allergens, describe how her lack of IgA might contribute to this condition.

Airway IgA blocks inhaled allergies from reaching APC and mast cells without IgA allergies more easily trigger allergy especially in genetically susceptible individuals

Do you think that an intranasal vaccine for “kennel cough” (Bordetella bronchiseptica/parainfluenza-3) would be effective in a dog with selective IgA deficiency? If not, would you expect a parenteral vaccine to work better?

An internasal kennel cough vx stimulates mucosal IgA, therefore a dog with selective IgA deficiency should not be vaccinated IN, the injectable vx induces IgG which provides some protection even if ira deficient

Autoimmune diseases is influences by

• Gender

• Age

• Genetics

• Infection

• Normal immune response to abnormal antigen OR

• Abnormal immune response to a normal antigen

Molecular mimicry

may be due to cross-reactions with microbes

Previously hidden (sequestered) antigens become exposed

Tissue injury or inflammation can release intracellular or

previously protected antigens that the immune system has

never encountered, making them appear “foreign.”

Molecular alteration

Chemical modification, infection, or inflammation can alter

normal self-proteins, creating new epitopes that the immune

system recognizes as non-self.

Lymphocytic thyroiditis

Autoantibodies to thyroglobulin, T3, T4, and thyroid peroxidase

Lymphocyte infiltration of thyroid – ADCC leads to cell destruction or CD8+ T -cell cytotoxicity, or both

Equine recurrent uveitis or “Moon Blindness” – periodic ophthalmia

• Autoantigen is a photoreceptor retinoid- binding protein

Pemphigus

Antibody to cell adhesion proteins

Hypersensitivity is what kind of response

exaggerated immune response.

Some hypersensitivity reactions are autoimmune in nature:

•antibodies attack self-cells

•Immune complexes damage tissues

•T cells attack self-tissues

Schistosomes penetrate where

intact skin

What is the function of plasma cells

Produce large amounts of parasite-specific IgE antibodies.

What is the role of Th2 cells

Cells: Orchestrate parasite immunity through IL-4, IL-5, and IL-13, enhancing IgE production and recruiting eosinophils

What do IgE do ?

•IgE binds parasites and arms mast cells and eosinophils for effective killing.

What do eosinophils utilize?

Fc receptors to bind to antibody-coated worms, then degranulate and release their granule contents directly onto the worms.

Eosinophils in Parasite Immunity: what kind of granules do they secrete

• Granules contain major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil neurotoxin (EN).

What is the role of ILC2?

help shape a strong type 2 immune environment that supports IgE production and eosinophil recruitment

Why is CMI crucial

particularly Th1 responses and IFN-γ production, which activate macrophages to eliminate intracellular parasites.

The ultimate antigenic variation process is seen in

Trypanosomes.

Other Immune Evasion Mechanisms

• Resistance to microbicidal products of phagocytes

• Example: Leishmania

• Masking of antigens and suppression of immune system

• Example: Schistosomes

• Immunoglobulin destructions

• Fashiola hepatica (Sheep liver fluke) activates M2 macrophages. It also secretes proteases that digest host interstitial tissue and immunoglobulins.

Immune Evasion Strategies of Plasmodium

• antigenic variation

• sequestration

What is antigenic variation

Switches surface antigens to avoid recognition by host immunity.

What is sequestration

Infected RBCs adhere to vessel walls, helping them bypass splenic filtration and survive longer. Sequestered infected cells can continue to reproduce and release new parasites without being removed from circulation.

What does the plasmodium do once they enter the body

•Disrupts complement activation to prevent lysis or opsonization.

•Phagocytosis escape

•Modulates and weakens immune signaling to enhance the survival of parasites.

The barrier of the intestinal tract includes:

1. Mucus layer

2. Tight Junctions

3. Peristalsis

4. Commensal microbiota or microbiome

In the intestinal tract, there are

local or resident phagocytic cells that play a crucial role in the immune defense of the mucosal lining.

What are some examples of phagocytes in the GI

• macrophages

• dendritic cells

What is the role of primary lymphoid organs

such as the bone marrow, are responsible for the production and maturation of lymphocytes.

What is the role of secondary lymphoid organs

create a favorable environment for the presentation of antigens.

Phagocytic cells release what when a salmonella enters the body

CXCL8, summoning neutrophils, which are produced by the bone marrow, via selectin- mediated rolling and integrin- mediated-adhesion.

Macrophages then enter the scene, transitioning into

M1 macrophages, which release nitric oxide to kill Salmonella.

What happens if the macrophages fail doing their jobs

Cytotoxic cells will be recruited

The complement system becomes activated through

the innate pathway, leading to the destruction of bacteria via cell lysis.

Fragments of the defeated Salmonella are collected by

dendritic cells, which migrate to local lymph nodes to present foreign bacterial antigens to naive T cells, thereby igniting the adaptive immune response.

What does IgA do ?

immunity protects mucosal surfaces by generating IgA antibodies that neutralize bacteria and prevent their attachment and invasion

IgM and IgG are generated in most

bacterial infections; their proportions shift depending on the severity and site of the infection.

What does M2 macrophages do in the gut

step in to repair the damaged tissue, contributing to the healing process and restoration of normal tissue function.

Antigen-presenting cells (APCs), such as dendritic cells, process fungal antigens and present them using

MHC class II molecules.

What T help is in Virus

Th1

What T helper is in parasites

Th2

What T helper is in bacteria

Th2 + Tfh

What T helper is found in fungi

th17

Activated Th17 cells produce specific cytokines, what are they

particularly interleukin-17A (IL-17 A) and interleukin-22 (IL-22).

IL-17A and IL-22 play a key role in recruiting

neutrophils and other immune cells to the site of infection.

Th17 responses have also been implicated in several

canine and human immune-mediated diseases (rheumatoid arthritis and inflammatory bowel disease).

What is immunodeficiency

Immunodeficiency is a state in which the immune system’s ability to fight infectious diseases is either compromised or completely absent.

What is Primary Immunodeficiencies

• The defect arises because of a problem with the immune system itself.

• Inherited genetic diseases

• Common in newborns and very young animals

What is Secondary immunodeficiencies

• Secondary to a known cause

• Virus diseases

• Cancers (some exceptions)

• Nutrition

• Toxins

Clinical conditions that may indicate immunodeficiency in animals include:

• Recurrent infections with a history or primary immune deficiency in the blood line (inherited).

• Two or more episodes of pneumonia within 1 year.

• Infections with opportunistic organisms (e.g. Cryptosporidium parvum, Pneumocystis jirovecii, Candida spp., adenovirus).

• Multiple sites of infection (pneumonia + sinusitis).

• Recurrent pyodermatitis, deep skin or organ abscesses.

• Single episode of meningitis or osteomyelitis.

• Two or more months on antibiotics with little or no effect. (no immune cells to eliminate the infections)

Dutchess is a 1-year-old German Shepherd with repeated bacterial pneumonia, a long-term cough since she was 2 months old, poor weight gain, and occasional diarrhea. Antibiotics helped each time, but the pneumonia kept coming back. At the physical examination, she was thin but alert, and she had a strong odor and discharge in her ears due to the frequent scratching.

the diagnosis is selective IgA

Functional IgG, IgM, and cell-mediated immunity are sufficient to prevent the IgA deficiency from becoming life-threatening.

It is produced as a dimer in

secretions

It is produced as a monomer

in blood

How are IgA transported to the lumen

by the polymeric Ig receptor (pIgR).

After IgA is transported what is the next step

the receptor is cleaved, leaving behind the secretory component (J chain), which helps IgA adhere to mucus and protects it from being broken down by enzymes.

Autoimmune diseases are influenced by what

• Gender

• Age

• Genetics

• Infection

• Normal immune response to abnormal antigen OR

• Abnormal immune response to a normal antigen

Molecular mimicry

may be due to cross-reactions with microbes

Previously hidden (sequestered) antigens become exposed when

Tissue injury or inflammation can release intracellular or previously protected antigens that the immune system has never encountered, making them appear “foreign.”

Abnormal Immune Response due to failure of

regulatory control

What happens to the Central tolerance:

Self-reactive lymphocytes are eliminated.

What happens to the Peripheral tolerance:

(anergy or Treg suppression)

What causes Lymphocytic thyroiditis

Autoantibodies to thyroglobulin, T3, T4, and thyroid peroxidase

Lymphocyte infiltration of thyroid

ADCC leads to cell destruction or CD8+ T -cell cytotoxicity, or both

What causes Equine recurrent uveitis or “Moon Blindness” – periodic ophthalmia

Autoantigen is a photoreceptor retinoid- binding protein

What causes Pemphigus

Antibody to cell adhesion proteins

Some hypersensitivity reactions are autoimmune in nature:

•antibodies attack self-cells

•Immune complexes damage tissues

•T cells attack self-tissues

•Genetic and environmental factors can trigger these responses.