Patho ch 12 - disorders of the immune response

(immunodeficiency/autoimmune) disorders are any abnormality within in the immune response - humoral or cell-mediated - that renders a person susceptible to diseases that are normally prevented by an intact system

immunodeficiency

immunodeficiency that is congenital or inherited

primary immunodeficiency

immunodeficiency that is acquired later in life

secondary immunodeficiency

how does malnutrition cause secondary immunodeficiency?

immunoglobulins are made of proteins so a lack of protein means a lack of Igs

malnutrition, infection, neoplastic disease, and immunosuppressive therapy can cause…

secondary immunodeficiency

primary immunodeficiency warning signs are usually seen in (kids/adults)

kids

in general, are characterized by repeated/hard to treat infections or wounds

(B/T) cell immunodeficiency disorders are worse

T cell

humoral immunodeficiency is due to a lack of…

B-cell function and immunoglobulin or antibody production - cannot fight (selective) bacterial infections

defects in humoral immunity increase the risk of recurrent ___ infections

pyogenic (made of dead WBCs and organism cells) - always bacterial

humoral immunity (is/is not) important for defending against intracellular bacteria (mycobacteria), fungi, protozoa

is NOT (those are usually combatted by T lymphocytes)

viral infections (are/are not) usually handled normally when the person has humoral immunodeficiency

are - except enteroviruses

what virus is affected by humoral immunodeficiency?

enteroviruses

the most common primary immunodeficiency (general category)

primary humoral (B-cell) immunodeficiency

• can interrupt the production of one or all Igs

ex. transient hypogammaglobulinemia, X-linked agammaglobulinemia, common variable immunodeficiency

immunoglobulin production depends on:

1. the differentiation of ___ to ___

2. the generation of ___-producing plasma cells

stem cells to mature B lymphocytes

immunoglobulin

secondary humoral immunodeficiencies are caused by loss of __

proteins needed to make the Igs

(loss in GI tract, malnutrition, burns, nephrotic syndrome, side effects of some meds)

cell-mediated immunodeficiency results in a greater risk of __ infections (5)

fungal

protozoan

viral

intracellular bacterial (mycobacteria)

malignant cell proliferation

DiGeorge syndrome immunodeficiency classification

primary cell-mediated (T cells)

lymphomas and viral infections can cause secondary __ immunodeficiency

cell-mediated (T-cell)

CIDS

combined immunodeficiency syndrome (B and T cells)

ataxia-telangiectasia immunodeficiency classification

primary combined

X-linked SCIDs immunodeficiency classification

primary combined (severe combined immunodeficiency)

Wiskott-Aldrich syndrome immunodeficiency classification

primary combined

2 causes of secondary combined immunodeficiency

irradiation (can destroy bone marrow)

cytotoxic drugs

immunodeficiency that has:

• normal B cell count

• reduced ability to produce antibodies (can’t produce plasma cells)

• resolves in 2-4 years

transient hypogammaglobulinemia (primary humoral)

transient hypogammaglobulinemia immunodeficiency classification

primary humoral (B cells)

immunodeficiency that has:

• undetectable levels of immunoglobulins in males

• mutation of genes involved in the production of mature B-cells and antibodies

X-linked agammaglobulinemia (primary humoral)

X-linked agammaglobulinemia immunodeficiency classification

primary humoral (B cell)

immunodeficiency that has:

• terminal differentiation of B-cell to plasma cell is blocked

common variable immunodeficiency (primary humoral)

common variable immunodeficiency classification

primary humoral (B cell)

“bubble baby” has __ type of immunodeficiency

combined

immunodeficiency that has:

• embryonic failure to develop the 3rd and 4th pharyngeal pouches - responsible for thymus and parathyroid glands

• → immature T cells, hypoparathyroidism & hypocalcemia

DiGeorge syndrome (primary cell-mediated)

a patient presents with hypocalcemia and recurrent viral infections. they most likely have…

DiGeorge syndrome

immunodeficiency that has:

• difficulties with gait

• spider-like appearance of blood vessels

• at risk of cancers and infections

ataxia-telangiectasia (combined immunodeficiency)

immunodeficiency that has:

• thrombocytopenia

• eczema

• recurrent infections

Wiskoff-Aldrich Syndrome (combined immunodeficiency)

a patient comes in with complaints of eczema and their gums bleeding when they brush their teeth. they most likely have…

Wiskott-Aldrich syndrome

WAITER

Wiskott-Aldrich Immunodeficiency:

• thrombocytopenia

• eczema

• recurrent pygogenic infections

when you drink whiskey…

Wiskott-Aldrich syndrome:

• IgE and IgA increase (ethyl alcohol goes up)

• IgM decreases (and mental function declines)

primary deficiency of complement proteins is usually autosomal (dominant/recessive)

recessive

hereditary angioneurotic edema is a disorder of…

the complement system

hereditary angioneurotic edema is due to a deficiency of…

C1 inhibitor

C1 inhibitor function

regulates vasoactive substances, including bradykinin (vasodilation, vessel permeability)

when functioning, prevents spontaneous edema

C1 inhibitor is deficient in hereditary angioneurotic edema

patient who presents with spontaneous, non-pitting, non-pruritic subcutaneous or submucosal swelling in the face, tongue, larynx, genitalia, hands, feet, or intestines most likely has…

hereditary angioneurotic edema (primary disorder of complement system)

secondary complement system disorders are due to…

disorders that consume complement factors

• malnutrition, liver disease

2 main phagocytic cells

macrophages, neutrophils

leukocyte adhesion deficiency is an autosomal (dominant/recessive) defecit of (selectins/integrins)

recessive, integrins

chronic granulomatous disease is a disorder of…

the phagocytic system

complement system disorders (2)

primary:

1. hereditary deficiency of complement proteins

2. hereditary angioneurotic edema

secondary causes (malnutrition, liver disease)

defective NADPH oxidase is found in…

chronic granulomatous disease (phagocytic system)

Chediak-Higashi syndrome is a disorder of…

the phagocytic system

disease that is due to a protein trafficking deficit (issues with cytoskeleton tracks)

Chediak-Higashi syndrome

sx include albinism, peripheral neuropathy, risk of infections, defective primary hemostasis, giant cell granules in leukocytes

Chediak-Higashi syndrome

• cells can’t move along cytoskeleton tracks to get to where they need to go

  • melanin in melanocytes doesn’t move to keratinocytes → albinism

  • NTs have difficulty traveling down axons → neuropathy

  • defective platelets → defective hemostasis

  • etc.

• phagocytic disorder

type I hypersensitivity

immediate (minutes to hours)

type II hypersensitivity

antibody-mediated

type III hypersensitivity

immune complex mediated

type IV hypersensitivity

T-cell mediated

hypersensitivity with a free antigen and fixed antibody

type I (immediate)

• antibody stuck on mast cells & basophils lining surfaces of the body that might be exposed to things

immunoglobulin released in type I hypersensitivity

IgE

hypersensitivity with a fixed antigen and free antibody

type II (antibody-mediated)

hypersensitivity seen most commonly in allergies

type I

immunoglobulin released in type II hypersensitivity

IgM, IgG

hypersensitivity with a free antigen-antibody complex

type III (immune-complex-mediated)

immunoglobulin released in type III hypersensitivity

IgM, IgG

hypersensitivity with CD4 or CD8 cells

type IV (T-cell-mediated)

IgE mediated hypersensitivity reaction

type I (immediate)

3 cells responsible for type I hypersensitivity disorders

1. Type 2 helper T cells

2. mast cells/basophils

3. eosinophils

type 1 vs type 2 helper T cells

type 1 are more common, cause B cells to produce IgG and IgM antibodies. also stimulate phagocytic ingestion of microbes

“class switch” occurs when exposed to allergens causing type 1 to convert to type 2 and produce IgE antibodies. activates eosinophils by producing IL-5

phase 1 of type 1 hypersensitivity

initial response that occurs within 5-30 minutes of exposure, subsides within 60. includes:

1. vasodilation (histamine, acetylcholine, kinins)

2. vascular leakage (vessel permeability) (histamine)

3. smooth muscle contraction (histamine, acetylcholine, kinins)

short term

phase 2 of type 1 hypersensitivity

a secondary response with infiltration of tissues by eosinophils and other acute & chronic inflammatory cells. also tissue destruction via epithelial cell damage

occurs in 2-8 hours, can last for days

mediated by leukotrienes and prostaglandins (long term)

mucosal edema, mucus secretion, leukocyte infiltration, epithelial damage, bronchospasm

symptoms of phase 2/late-stage immediate hypersensitivity

due to eosinophils releasing granules

anaphylaxis is caused by a widespread release of __ into the systemic circulation

histamine

systemic hypersensitivity reaction

anaphylaxis

local hypersensitivity reaction

reaction to an antigen confined to a specific site - atopic (inherited)

• allergic rhinitis

• urticaria (hives)

• atopic dermatitis

• food allergies

• some forms of asthma

complement-activated cell destruction is a part of the ___ response and is due to activation of the ___

type II hypersensitivity

MAC (C5b-C9) → lysis of the cell

opsonization by IgG or C3b can cause phagocytosis too

antibody-dependent cell cytotoxicity is part of the ___ response and opsonized via ___

type II hypersensitivity

IgG - not complement/MACs

complement-and-antibody-mediated inflammation is part of the ___ response and results in ___

type II hypersensitivity

inflammation (antibodies/antigens attract leukocytes that release enzymes causing inflammation and tissue destruction) but NOT phagocytosis

Goodpasture’s syndrome is what type of HSN reaction?

type II (complement and antibody mediated inflammation)

Goodpasture’s syndrome targets…

collagen type IV in the basement membranes of the lungs and the kidneys - causes inflammation

antibody-mediated cellular dysfunction is part of the ___ response. mechanism of action?

type II hypersensitivity

antibody binding to target cell receptors causes change in cell function

• Graves Disease, MG

Graves disease is what type of HSN reaction?

type II (antibody-mediated cellular dysfunction)

antibody binds to TSH receptors and causes increased production of thyroid hormone

Myasthenia Gravis is what type of HSN reaction?

type II (antibody mediated cellular dysfunction)

binding of antibody to ACh receptor prevents muscle contraction

type III hypersensitivity is due to the formation of…

insoluble antibody-antigen complexes that deposit in certain parts of the body and cause damage (formed in the plasma, deposit in other tissues)

cause activation of complement system & generate chemotactic factors that attract neutrophils, etc.

• alterations in blood flow

• increased vascular permeability

• destructive action of inflammatory cells

type III HSN reactions present with (systemic/local) manifestations

can be both

sx of systemic immune complex disorders

urticaria, patchy or generalized rash, extensive edema, fever

serum sickness is what type of HSN reaction?

type III (immune complex)

transfused serum (with foreign antigens) reacts with antibodies formed in the recipient

• used to use horse serum to treat diptheria (?)

Arthus reaction

a type III HSN reaction (immune complex) characterized by local tissue necrosis caused by immune complexes

can be due to repeated injections of an antigen on the skin

also hyperacute transplant reaction

type IV hypersensitivity reactions are characterized by… (cells)

T cells (cell-mediated, not humoral!)

____ hypersensitivity reactions are a response to intracellular pathogens (viruses, mycobacterium TB) and fungi, protozoans, other parasites

type IV hypersensitivity reactions

direct cell-mediated cytotoxicity is characterized by ___ cells

CD8 (cytotoxic T) cells without CD4 activation

(part of type IV hypersensitivity)

certain hepatitis forms are (direct/delayed) cell-mediated hypersensitivity

direct

delayed-type hypersensitivity is characterized by ___ cells

CD4 (helper T) cells that recruit macrophages, lymphocytes, fibroblasts, and other inflammatory cells

how long does it take delayed-type hypersensitivity reactions to fully develop?

24-72 hours

PPD reaction, allergic contact dermatitis, hypersensitivity pneumonitis are (direct/delayed) cell-mediated hypersensitivity

delayed

type I latex allergy reaction

systemic

urticaria, bronchospasm, anaphylaxis (same sx as HSN type 1 - allergic)

type IV latex allergy reaction

contact dermatitis

transplant type: donor and recipient are unrelated but share similar HLA types (same species)

allogeneic transplant

transplant type: donor and recipient are identical twins

syngeneic transplant

transplant type: donor and recipient are of different species

xenogeneic transplant

transplant type: donor and recipient are the same person

autologous

hyperacute transplant reactions occur ___ after transplantation, due to (preformed/newly formed) antigens

almost immediately

preformed antigens

hyperacute transplant reaction is considered a type (II/III/IV) reaction

type III (Arthus reaction)